HEAD AND NECK PATHOLOGY
NASAL CAVITY, SINUSES, NASAPHARYNX
NORMAL
§ Staphyloccocus aureus can colonize nasal cavity without causing problems (Robbins).
NASAL GLIAL HETEROTOPIA (nasal glioma)
Clinical
§ Developmental malformation of displaced normal glial tissue without intracranial connection
§ Newborns and infants within first few years
§ Extranasal (60%), intranasal (30%), both sites (10%)
Imaging
Treatment
§ Curettage with surgery
Micro
§ Astrocytes[3] and neuroglial fibers
§ Fibrosis
§ FV connective tissue stroma
§ Occasional multinucleated GLIAL cells simulating neurons[4]
IHC
§ Glial tissue (Astrocytes and glial fibers): S100+, GFAP+
DD
§ Encephalocele : same histology, use imaging and clinical history
MYOSPHERULOSIS
§ Foreign-body reaction to petrolatum present in preparations used for hemostatic packing (Steinberg)
§ Etio: petrolatum results in formation of baglike spaces within tissue containing spherules that come to resemble yeast (Steinberg). Such spherules are denatures RBC (Steinberg)
DD
§ Rosai-Dorfman syndrome: sinus histiocytosis with massive lymphadenopathy (Steinberg)
§ Leprosy (Steinberg): may be histologically indistinguishable (Steinberg)
MUCOCELE
§ Obstruction of outflow, often in frontal sinus and ant ethmoid sinus-> accumulation of mucus in absence of bacterial infection-> mucocele
SINONASAL POYP
Clinical
§ Allergic rhinitis (aka hay fever, type I HS)
§ Elevated serum IgE (Robbins).
§ Sinuses (aka choanal polyps): antrochoanal, sphenochoanal, ethmoidochoanal (Rosai).
§ Bone destruction possible
Mechanism
§ Recurrent rhinitis[5]à focal protrusions of mucosa-> nasal polypsà if large, can result in sinusitis or can be infected or ulcerated
Etio[6]
§ Allergic rhinitis
§ Vasomotor rhinitis
§ Infectious rhinosinusitis
§ DM
§ Nickel exposure
§ CF
§ ASA allergy[7]
Micro
§ Respiratory epithelium[8]
§ Edematous LP
§ Decreased number but hyperplastic mucous glands[9]
§ Lymphoplasmacytic[10] infiltrate+/-eosinophils[11], mast cells, PMN[12]
§ Occasional bizarre stromal cells (MFB)
§ Secondary change[13]
§ Rule out koilocytosis, dysplasia and inverted papilloma (Manley)
Variants (Steinberg, Rosai)
§ Antrochoanal
Ø Arise from cysts of maxillary sinus protruding into nasal cavity through maxillary meatus (Steinberg)
Ø Sometimes with prominent dilated BV, thrombosis and infarct (called angiomatous or angiectatic polyps) (Rosai)
Ø
§ Associated with CF
Ø Nasal polyps in kids should raise suspicion for CF (Steinberg)
Ø Contain acid mucin (Alcian blue+) vs netural mucin (PAS+) in inflammatory polyp (Rosai)
§ Inflammatory (no1)
Ø Usually in >30
Ø Invariably multiple and bilateral
Ø Associated with asthma, chronic rhinitis, ASA allergy[14] in 20% (Steinberg)
ALLERGIC RHINITIS (hay fever)
§ Allergy to pollens, fungi, animal, dust, mites-> IgE with early and LATE phase response-> EOSINOPHILS
§ In 20% population
CHRONIC RHINITIS
§ Recurrent acute rhinitis (ALLERGIC or infectious)-> chronic rhinitis-> nasal polyps or deviated nasal septum-> bacterial infection-> surface ulceration, mixture of acute and chronic inflammations (PLASMA cells)
NAME 3 NECROTIZING LESIONS OF NOSE
§ Wegener’s granulomatosis
§ Lethal midline granuloma (angiocentric lymphomaNK/T cell lymphoma)
§ Mucormycosis, Mycobacterial
§ SCC, BCC
CHRONIC SINUSITIS
Micro:
§ Polypoid mucosa with eosinophilia
§ (polyps)
Ø Glandular hyperplasia of seromucus
§ glands
Ø Inflammation
Ø Submucosal fibrosis
ALLERGIC FUNGAL SINUSITIS (eosinophilic fungal rhinosinusitis)
Clinical
§ Allergic response within sinonasal tract to fungal allergens
§ Peripheral eosinophilia
§ Must obtain culture to assist with desensitization
Micro
§ Alternating tide-lines[15] with degenerated inflammatory debris (eosinophils and PMN)
§ +/-Charcot-Leyden crystals
§ +/-fungal hyphae[16]
DD
§ Invasive fungal sinusitis: fungi within BV or deep in stroma
§ Inflammatory nasal polyps: no tide-lines
§ Mycetoma (fungus ball): fungal elements with limited inflammatory response, no invasion
ALLERGIC SINUSITIS
§ Allergic mucin (eosinophils with laminated mucus and Charcot-Laden). Always do fungal stain to rule out Aspergillus.
§ Tons of eosinophils with laminated mucus and Charcot-Laden crystals (Osler). Thick mucus (Osler)
IHC
§ Remember to do fungal stains (Osler)
CHRONIC ADENOIDITIS
§ Resembling tonsillitis but covered by respiratory epithelium instead of squamous (Dexter)
COCAINE USE
§ Mimic clinically NK/T lymphoma, ddx NK/T lymphoma and Wegener,
§ Ssx: mimic clinically NK/T lymphoma (Rosai)
§ Nonspecific inflammation and necrosis without vasculitis
DD
§ Nasal-type NK/T cell lymphoma (Rosai)
§ Wegener’s granulomatosis (Rosai): vasculatiits
WEGENER’S GRANULOMATOSIS
Clinical
§ Type of small vessel vasculitis
§ Relapse coincides with c-ANCA[17] rise
Mechanism
§ Genetics + environmentsà abnormal immune response (pauci-immune)
Gross
§ Ulceration with necrosis
Micro
§ Geographic necrosis (blue, granular debris)
§ Vasculitis often difficult to see in nose[18]
§ Granulomas not easy to see although sometimes MGC
§ Use elastic stains to highlight destroyed BV
MYOSPHERULOSIS
§ FB reaction to iatrogenic petroleum, lanolin, traumatized fat tissue resulting artifactually encysted RBC
Micro
§ Pseudocysts with dense fibrosis
§ Large (100µm) cysts, non-refractile thin membrane containing brown discolored misshapen RBC
IHC
§ Hb+
§ Fungal stains-
INFECTIONS
INFECTIOUS RHINITIS (common cold)
§ Adenovirus, echovirus, rhinovirus-> can be superimposed by bacterial infection-> goes in 1 wk if treated but after 1 wk if ignored
MALAKOPLAKIA
§ Etio: Rhodococcus equi (Osler)
PHARYNGITIS/TONSILLITIS
§ Rhinovirus, echovirus, adenovirus, respiratory syncytial virus, influenza-> superimposed by bacterial infection-> often in CONJUNCTION WITH URTI
§ Immunosuppression results severe pharyngitis
MUCORMYCOSIS
§ Fungal sinusitis (mucormycosis), often in DM-> severe sinusitis-> NECROTIZING ULCERATING lesions
RHINOSPORIDIOSIS
§ Infection by Rhinosporidium seeberi (blue-green algae)
§ Dense lymphoplasmacytic infiltrate when ruptured cysts
§ Subepithelial, large (300µm) cysts with thick birefringent walls
§ Numerous small endospores when mature
RHINOSCLEROMA
Clinical
§ Chronic progressive upper aerodigestive tract infection by Klebsiella rhinoscleromatis
§ Endemic in central America, tropical Africa, india, Indonesia
§ Quite destructive[19]
Gross
§ Friable polyp!
Micro
§ Sheets of foamy macrophages[20] (Mikulicz cells)
§ Other chronic inflammation[21]
§ Coccobacilli within macrophages
IHC
§ PAS or silver (Warthin-Starry, Steiner)
§ IHC against Klebsiella
SINUSITIS
§ Acute/chronic rhinitis, periapical abscess-> acute sinusitis or empyema of sinus-> chronic sinusitis-> osteomyelitis, septic thrombophlebitis of dural venous sinus-> consequence?
RHINOPHYMA
Clinical
§ Hypertrophy of sebaceous glands in long-standing acne roseacea
§ Facial flushing with drinking hot liquids, ROH, eating spicy foods
Micro
§ HP of sebaceous glands
§ Follicular plugging
§ Focal folliculitis/perifolliculitis
§ Telangiectasia
§ No atypia, no invasion
HIV TONSILLITIS
Micro
§ Florid follicular HP+/-follicular lysis
§ MGC
§ Late: effaced architecture, no follicles, plasma cell infiltrate
SINUS HISTIOCYTOSIS WITH MASSIVE LYMPHADENOPATHY (Rosai-Dorfman disease)
Clinical
§ Idiopathic
§ Young black women
Micro
§ Abundant lymphoplasmacytic infiltrate
§ Marked dilation of lymphoid sinuses
§ Pale histiocytes in sinuses with emperipolesis (lymphophagocytosis)
IHC
§ S100+
§ CD68+
§ LeuM3+
§ Lysozyme+
§ CD1a-
BENIGN EPITHELIAL TUMORS
SINONASAL PAPILLOMAS*** (Schneiderian papillomas)
Micro
§ 2 types of epithelium (Steinberg)
Ø Squamous: arises from vestibule, keratinizing squamous epithelium
Ø Schneiderian: heterogeneous[22]
Clinical
§ Papillomas derived from Schneiderian membrane
§ HPV6 and 11[23]
INVERTED (endophytic)
Gross
§ Lateral walls[24]
Complications
§ Intracranial invasion
§ Malignant transformation in 10-15%
Clinical
§ Same demographics as exophytic
§ 60% recurrences (Goldblum)
Micro
§ Thick endophytic epithelium[25] without invasion
§ Transitional/squamous epithelium[26] with intraepithelial microcysts containing macrophages, mucin and cell debris
§ Distinct cell borders with glycogenation
§ No seromucinous glands in stroma
§ Look for dysplasia
ONCOCYTIC (cylindrical)
§ Exophytic and endophytic lined by multilayered oncocytes
§ Lateral walls
§ Rare cases of malignant transformation
§ Equal gender, 60
EXOPHYTIC
Complications[27]
§ Obstruction
§ Epistaxis
Clinical
§ 4x males, 60
§ Up to 50% recurrences (Goldblum)
§ More and more evidence showing relationship with HPV 6 and 11 (less with 16 and 57b) (WHO)
Gross
Micro
§ Branching papillae with FV cores
§ WD squamous[30] lining with residual intraepithelial goblet cells[31],
§ No keratinizing or inflammation unless irritated
§ Intraepithelial or luminal ciliated or goblet cells
§ Seromucinous glands in stroma
§ Malignant: mitoses and dysplasia (rare)
DD
§ Verruca vulgaris[32]: keratinizing, more anterior location in nasal vestibule, no mucocyte, no respiratory or transitional epithelium, no underlying seromucinous glands or septal cartilage
HAIRY POLYP
SQUAMOUS PAPILLOMA
ECTOPIC PITUITARY ADENOMA
§ Rare
SALIVARY GLAND ANLAGE TUMOR
CRANIOPHARYNGIOMA
§ Benign?
SALIVARY GLAND-TYPE ADENOMAS
PLEOMORPHIC ADENOMA
MYOEPITHELIOMA
ONCOCYTOMA
MALIGNANT EPITHELIAL TUMORS
SCC
§ No1 malignancy of sinonasal tract
§ More PD in sinuses than in nasal cavity
§ Worse in sinuses
VERRUCOUS
PAPILLARY
BASALOID
SPINDLE CELL
ADENOSQUAMOUS
ACANTHOLYTIC
LYMPHOEPITHELIAL
SNUC
Clinical
§ 2x males
§ 20% 5-year survival
Micro
§ UD by definition (no squamous or glandular differentiation)
§ High N/C
§ Macronucleoli
§ Tumor necrosis
§ Mitoses
IHC
§ CKAE1/3+
§ CK7+
§ EMA-
§ NE markers-
§ S100-
§ CD99-
DD
§ Small cell NE carcinoma
ADENOCARCINOMA
Clinical
§ Def: any sinonasal malignant tumors with glandular structures (Steinberg)
§ No2 malignancy in sinonasal tract
§ Sinuses >nasal cavity
Variants (Goldblum)
§ Salivary: arising from seromucinous glands, 40-60% mortality
§ Non-salivary: arising from respiratory epithelium, 60% mortality but grade-dependent
Ø Intestinal subtype
Ø Non-intestinal subtype
INTESTINAL-TYPE ADENOCARCINOMA (ITAC)
§ Same IHC as colorectal carcinoma
§ Association: long-term exposure to fine wood dust (Steinberg)
§ Etio: HPV genome found in minority of cases; contribution unknown (Steinberg)
§ Incidence: rare
§ Locations: maxillary antrum (no1, 58%), nasal cavity (30%), others (Steinberg). Ethmoid sinus (Steinberg)
§ Outcome: locally aggressive neoplasm
§ RF: nickel refiners (gives mostly squamous cell carcinoma, Steinberg), WOOD WORKERS (mostly intestinal-type adenocarcinoma, Steinberg)
§ Scenario: biopsy of mass in left ethmoid sinus reveals carcinoma characterized by glandular structures in 65yo retired WOOD WORKER (Steinberg)
§ Morphologically resembling colonic adenocarcinoma (Steinberg)
IHC (Goldblum, WHO)
§ CDX2+
§ CK7+/20+ mostly
NON-INTESTINAL-TYPE AENOCARCINOMA (non-ITAC)
§
SALIVARY GLAND-TYPE CARCINOMAS
AdCC
§ No1 among salivary gland type carcinomas
AcCC
MEC
EPITHELIAL-MYOEPITHELIAL CARCINOMA
CLEAR CELL CARCINOMA
MYEOPITHELIAL CARCINOMA
CXPA
POLYMORPHOUS LOW-GRADE ADENOCARCINOMA
NASOPHARYNGEAL PAPILLARY ADENOCARCINOMA
NASOPHARYNGEAL CARCINOMA NPC
Clinical
§ Aka lymphoepithelioma (erroneous term) (Steinberg)
§ 3x males, African kids, SE Asia adults 40-60
§ Strong association with EBV[33] and nitrosamines in foods[34]
§ Cervical LN often+
§ Only in nasopharynx
Variants (Robbins, Outlines)
§ Keratinizing (WHO type 1): not associated with EBV
Ø Obvious squamous differentiation and keratinization
Ø Distinct borders
Ø Intercellular bridges
§ Non-keratinizing (WHO type 2)
Ø SCC without keratinization
Ø Variable lymphocytes
§ Undifferentiated (WHO type 3): EBV+,
Ø Solid sheets, islands and nests with intimate lymphocytic infiltrate
Ø Syncytial[35] large cells, vesicular nuclei, red macronucleoli, scant cytoplasm
Ø Lots of mitoses
Ø Necrosis
Mechanism
§ Age, EBV, geography[36]à distinct anatomic distribution[37]à
Etio
§ EBV[38], environment, genetics
IHC
§ CKAE1/3+
§ CK5/6+
§ EMA+
§ CEA+
§ 34βE12+
§ EBER+ in situ hybridization (Goldblum, Rosai)
§ Patterns of spread: regional lympn nodes, trigeminal nerve, distant mets
§ Treatment: radiotherapy
Treatment
§ Radiotherapy[39]
§ Chemotherapy for advanced stage
Prognosis
§ Stage
§ Complete remission in 80%, poor if anaplastic, ↑mitoses, ↓lφ, ↑S100
DD
§ Lymphoma
§ RMS
NONKERATINIZING
Micro
§ Small nests surrounded by lymphocyte-rich fibrous septa (Regaud pattern)
§ Diffuse sheets (Schminke pattern[40]) (Steinberg)
§ PD SCC often containing rich lymphocytic infiltrate,
KERATINIZING
BASALOID
NE TUMORS
TYPICAL CARCINOID
ATYPICAL CARCINOID
SMALL CELL NE CARCINOMA
BENIGNG SOFT TISSUE TUMORS
MYXOMA
§ Rare
LEIOMYOMA
HEMANGIOMA
SCHWANNOMA
NF
MENINGIOMA
§ Remember this one because common. Can invade from cranial cavity to nose, see neuro
§ Incidence: not uncommon (Osler)
NASOPHARYNGEAL ANGIOFIBROMA
Clinical
§ Associated with FAP
§ Young males[41], 10-25
§ Tend to bleed easy
§ Benign vascular tumor
§ Nasopharynx[42] (not nasal cavity)!
§ Profuse epistasis
§ Can expands in all directions, following least resistance path into nasal cavity, pterygomaxillary fossa, cheek, maxillary antrum, orbit (Steinberg, WHO)
Outcome
§ Up to 60% recurrences!
Variants
§ Giant cell
§ Cellular)
Staging (Goldblum)
§ 1. Limited to nasopharynx, no bone destruction
§ 2. Invades nasal cavity, sinuses but no bone destruction
§ 3. Invading local bones
§ 4. Invades cranial cavity, optic chiasm or pituitary fossa
Treatment
§ Surgery +/- radiation
§ Embolization
§ Hormonal therapy
Gross
§ Deceptive avascular
§ WC but no capsule
Micro[43]
§ Combination of abnormal BV, fibrous stroma and stromal cells
§ Fibrous stroma of variable cellularity with hyalinized or myxoid change
§ Thin-walled BV[44] from small slitlike to large dilated
§ Stellate stromal cells instread of bipolar fibroblasts as in aggressive fibromatosis (Steinberg)
§ No inflammation usually
§ +/-multinucleated ganglion-like cells resembling proliferative myositis (Steinberg)
IHC
§ CD34+
§ AR+ (Steinberg)
DD
§ Hemangioma[45]: no stellate cells, not as much fibrous stroma
BORDERLINE AND LOW MALIGNANT POTENTIAL TUMORS
DESMOID-TYPE FIBROMATOSIS
IMT
GLOMANGIOPERICYTOMA
Clinical
§ Sinonasal tumor demonstrating perivascular myoid phenotype
§ Lateral walls
§ Indolent with >90% 5-year survival but recurrences up to 30%, 2% malignant transformation (Goldblum)
Micro
§ …
SFT
MALIGNANT SOF TISSUE TUMORS
FIBROSARCOMA
MFH
LMS
RMS
Clinical
§ Nasopharynx, sinonasal tract common
§ Kids and young adults (embryonal), adults (alveolar)
Treatment
§ Radiation, chemotherapy and surgery together
Prognosis
§ Age
§ Histologic subtype: botryoidà embryonalà pleomorphicà alveolar
§ Stage
Micro
§
AS
MPNST
MALIGNANT BONE TUMORS
CS
MESENCHYMAL CS
OS
CHORDOMA
BENIGN BONE TUMORS
GIANT CELL LESION
GCTB
CHONDROMA
OSTEOMA
CHONDROBLASTOMA
CHONDROMYXOID FIBROMA
OSTEOCHONDROMA (EXOSTOSIS)
OSTEOID OSTEOMA
OSTEOBLASTOMA
AMELOBLASTOMA
NASAL CHONDROMESENCHYMAL HAMARTOMA
LYMPHOID
EXTRANODAL NK/T CELL LYMPHOMA (midline lethal granuloma[46])
Clinical
§ No1 nonepithelial malignancy in sinonasal tract
§ Nasal cavity and sinuses[47]
§ Non-healing ulcer
§ 3x males, endemic in Asians and Latin Americans, 60
§ NK cell lymphomaà necrotizing ulcerating lesion, often superimposed by INFECTIONà sometimes difficult to ddx from granulomatous inflammation
Treatment
§ Combined chemoradiation
Micro
§ Angiocentric and angioinvasive
§ Small to large lymphocytes
IHC
§ CD2+
§ CD56+
§ CD3e+ (cytoplasmic)
§ Perforin+
§ TIA1+
§ Granzyme B+
§ EBER ISH+
DD
§ Small round blue cell tumors
§ Wegener
§ Reactive
DLBCL
PLASMACYTOMA
MYELOID SARCOMA
LANGERHANS CELL HISTIOCYTOSIS
Clinical
§ Young <20
§ Flat bones or jaws
Prognosis
§ Stage (localized or systemic)
Treatment
§ Surgery for localized diseaseà excellent prognosis
§ Chemotherapy if systemicà poor prognosis
Micro
§ Langerhans cells[48]
§ Eosinophils +/- microabscess formation
EM
§ Birbeck granules[49]
IHC
§ CD68+
§ S100+
§ CD1a+
HD
FOLLICULAR DENDRITIC CELL SARCOMA
NEUROECTODERMAL
PNET/EWS
§ 20% occur in HN
§ Sinuses> nasal cavity
§ Better prognosis in HN
IHC
§ VIM+
§ CD99+
§ FLI1+
§ Maybe+: NE markers, S100, NF
PNET
OLFACTORY NEUROBLASTOMA (esthesioneuroblastoma)
Clinical
§ Malignant neuroectodermal tumor from olfactory epithelium
§ Bimodal: 10-20, 50-60
§ Dumbbell-shaped growth on either side of cribriform plate[50]
§ Anosmia, HA, epistaxis
Genetics
§ Lack of EWS/FLI1 gene fusion
Treatment
§ Combo surgery and radiation (Rosai)
Prognosis
§ Stage
§ Grade
EM
§ Membrane-bound neurosecretory granules
§ Neurofilaments and neurotubules
Micro
§ Uniform small to medium round-oval blue cells[51]
§ Scanty cytoplasm
§ Lobules
§ Highly vascular stroma to neurofibrillary matrix
§ Salt and pepper chromatin
§ Rosettes[52]
Ø Homer-Wright[53]: neurofibrillary
Ø Flexner-Wintersteiner[54]: true lumen
§ +/-melanin in some tumor cells[55]
Grading (Hyam’s)
§ See end
IHC
§ NE markers+
§ S100+ only confined to periphery of tumor nests (sustentacular pattern)
Gross
§ Reddish highly vascularized soft polypoid mass in roof of nasal cavity (Rosai)
DD
§ Lymphoma (Steinberg, Rosai): especially when small cells are predominant
§ Ewing/PNET (Rosai)
§ Plasmacytoma (Rosai)
§ Alveolar and embryonal RMS (Rosai)
§ Poorly differentiated carcinoma (Rosai, Steinberg): especially when large cells with abundant cytoplasm are predominant. Or basaloid carcinoma (me)
MELANOTIC NEUROECTODERMAL TUMOR OF INFANCY
MUCOSAL MELANOMA
GCT
IMMATURE TERATOMA
TERATOMA WITH MALIGNANT TRANSFORMATION
YST
TERATOMA
DERMOID CYST
BONE TUMORS
CHORDOMA
MELANOMA
§ Sinonasal tract, from normal melaoncytes of mucosa, look for junctional component,
§ Locations (in sequence): nasal cavity, antrum, ethmoid, frontal sinuses (Rosai)
§ desmoplastic (HMB45-) melanoma can also occur (Osler)
§ Origin: melanocytes normally located in stroma or epithelium of respiratory mucosa (Rosai)
§ often misdiagnosed if diffuse pattern, lack of pigmentation, pleomorphic or prominent spindle cell appearance (Rosai). Therefore, keep your ddx wide!!!
§ always look for theque-like growth (nests) of junctional component (good hint, Rosai)
Micro
§ Peritheliomatous[56] growth in necrotic tumor
§ Small cell, spindle, pleomorphic, epithelioid morphology
§ Macronucleoli
§ INCI
EM
§ Melanosomes and premelanosomes
DD
§ AS
§ SNUC
§ LMS
§ RMS
§ Lymphoma
§ Mets
§ Olfactory neuroblastoma
METS
ORAL CAVITY, OROPHARYNX
PERIODONTITIS
§ Facultative G+ in healthy
§ Anaerobic and microaerophilic G- in plaques
HETEROTOPIA (Rosai)
§ Gastric
§ Intestinal
§ Sebaceous (Aka Frodyce’s disease)
§ Nerve tissue
§ Lingual thyroid
§ Organ of Chievitz: due to epithelial nests in intraoral sensory nerve endings (Rosai). Resembling invasive SCC with perineural invasion (Rosai). Can be paraparotid or extraoral (Rosai). Can form mass (Rosai)
FORDYCE GRANULES
AMALGAM TATTOO
ECTOPIC THYROID
GINGIVAL HYPERPLASIA
§ Etio: Dilatin, cyclosporin A, inherited, idiopathic (Rosai)
INFLAMMATORY PAPILLARY HYPERPLASIA
§ Etio: dentures (Rosai)
§ Locations: 4/5 in palate (Rosai)
§ Hyperplastic epithelium, chronic inflammation, fibrous tissue, +/-ulceration (Rosai).
§ sometimes isolated squamous cell nests in stroma due to inflammation on pegs; do not diagnose as invasive malignancy (Rosai)
Variants
§ Irritation fibroma: if prominent fibrous proliferation (Rosai)
§ Giant cell fibroma: if scattered stellate or multinucleated giant cells (Rosai)
IRRITATION FIBROMA
§ Aka fibroma (Robbins)
§ Incidence: no1 fibrous oral lesion (Robbins)
§ Locations: buccal mucosa along bite line and gingivodental margin (Robbins)
§ Treatment: curative excision (Robbins)
§ Fibrous tissue with few inflammatory cells, covered by squamous mucosa (Robbins).
CHEILOSIS
§ Fissuring or cracking of mucosa, typically at corner of mouth (Robbins)
§ Sometimes due to B2 (riboflavin) deficiency (Robbins)
NICOTINE STOMATITIS
§
GLOSSITIS
§ Associations: Plummer-Vinson or Paterson-Kelly if with iron-deficiency and esophageal dysphagia (Robbins)
§ Etio: malnutrition, traumatic (denture, caries), syphilis, inhalation burns, corrosive chemicals (Robbins)
§ RF: B2, B3, B6, B12 deficiencies, sprue, iron-deficiency anemia (Robbins).
§ Ssx: beefy red to ulceration (Robbins).
Micro
§ Atrophy of papillae and squamous mucosa exposing underlying vasculature (“beefy red”) (Robbins)
§ +/- ulcerations (Robbins).
Variants
§ Median rhomboid glossitis
GEOGRAPHIC TONGUE
§ Unknown cause but due to loss of filiform papillae, similar to psoriasis with psoriasiform hyperplasia with surface microabscesses,
§ Aka erythema migrans, benign migratory glossitis (Rosai)
§ Incidence: common, in 2% population (Rosai)
§ Etio: unknown but due to loss of filliform papillae (Rosai)
§ Nature: similar to psoriasis of skin (Rosai)
§ Psoriasiform hyperplasia, surface microabscess formed by PMN, mild inflammation in LP (Rosai)
NECROTIZING SIALOMETAPLASIA
§ Clin: painful
§ Micro: necrosis of salivary glands replaced with squamous metaplasia
§ -retains lobular architecture!
§ Can look like SCC!!→ imp ddx
§ Leukoplakia- white patch does not wipe off, assoc/ keratosis, may be dysplastic
§ Erythoplakia-red patch, more likely to be dysplastic than leukoplakia
Epiglottitis
§ -H. flu, β-hemolytic streptococci
HPV
§ -some papillomas, condylomas
CROHN’S DISEASE
§ Initial manifestation, noncaseating granuloma,
§ can be initial manifestation (Rosai)
§ Incidence: 1/20 Crohn’s have oral lesions (Rosai)
§ Locations: lips, gingiva, vestibular sulci, buccal mucosa (Rosai)
§ Ssx: ulcer, edema, polypoid (Rosai)
§ Edema, chronic inflammation, scattered giant cells, noncaseating granulomas (Rosai)
VERRUCIFORM XANTHOMA
§ Demo: elderly (Steinberg)
§ Lipid-laden macrophages covered by hyperplastic epithelium (Steinberg)
EPITHELIAL CYSTS
Name THREE epithelial cysts.
Dentigerous cyst
§ -unerupted teeth in young adults
§ -keratinzed squamous epithelium + thin fibrous rim
Odontogenic cyst
-ghost cells + peripheral palisading
Radicular cyst
§ -post-extraction
§ -stratified squamous epithelium + ulceration
ORAL LYMPHOEPITHELIAL CYST
MUCOCELE
§ Clin: pooling of salivary glands mucous secondary to obstructed duct
§ Micro: cystic cavity with mucin
§ -not true cyst like retention cyst which as epithelial lining
§ Extravasation (granulation tissue) vs retention (epithelium), ddx oral focal mucinous,
§ Aka mucous cyst (Rosai)
2 types (Rosai)
§ Extravasation: due to traumatically injured minor SG, often in youngs, lower lip classic location (Rosai). Granulation tissue surrounding pools of mucin (Rosai)
§ Retention: in olders, floor of mouth or cheek, mucus-filled cyst lined by flat-cuboidal-columnar epithelium (Rosai)
HAIRY LEUKOPLAKIA
Etio
§ EBV in immunosuppressed[57]
Micro
§ Can be superinfected by Candida.
§ Hyperkeratosis
§ Acanthosis
§ Balloon cells[58] in upper layer
Clinical
§ Foretells upcoming AIDS within 2-3yrs.
§ Any malignant risk?
Gross
§ Bilateral linear striation
POSTOPERATIVE SPINDLE CELL NODULE
§ Same as in GU
§ Overdiagnosed as LMS
PYOGENIC GRANULOMA
Micro
§ Lobular architecture
§ Central BV surrounded by cellular lobules of closely packed capillaries
§ Mitoses common!
§ Often ulcerated
Clinical
§ Nose
§
FOLLICULAR TONSILITIS
§ Rule out SCC and lymphoma,
§ asymmetric growth must rule out SCC or lymphoma, especially in older population (Dexter)
§ Reactive lymphoid hyperplasia
GRANULOMATOUS TONSILLITIS
§ NO organism found (must rule out organisms)
§ Outcome: benign (Rosai)
§ NO organism found (Rosai)
LEUKOEDEMA
§ Cheek to lips, intracellular edema of squamous cells,
§ Ssx: diffuse opalescent lesion (Rosai)
§ Nature: degenerative (Rosai)
§ Locations: cheek mucosa extending to lips (Rosai)
§ Vacuolization or intracellular edema of squamous epithelium (Rosai)
APHTHOUS ULCER
§ MONONUCLEAR infiltrate except bacterial superinfection,
§ Aka canker sore (Robbins).
§ Demo: young but any age possible (Robbins).
§ Outcome: spontaneous resolution in 7-10 days (Robbins)
§ Ssx: recurrent superficial ulcerations with erythematous rim and central white exudate (Robbins).
§ Etio: not infectious, probably auto-immune (Robbins). Some family more prevalent (Robbins)
§ Exudate mainly mononuclear except superimposed by bacterial infection (Robbins)
TONGUE ULCERATION WITH EOSINOPHILIA
§ Aka eosinophilic ulcer, due to tongue muscle trauma
§ Aka eosinophilic ulcer, ulcerative eosinophilic granuloma, Riga-Fede disease (Rosai, Steinberg)
§ Ssx: ulcer (Steinberg)
§ Etio: tongue muscle trauma (biting) (Rosai)
§ Polymorphous inflammation rich in eosinopihls in submucosa, muscle and minor SG (Rosai, Steinberg)
LICHEN PLANUS
§ Usually coexists with skin lesions (Robbins).
§ Whitish plaques that may ulcerate (Robbins)
§ Intense submucosal chronic inflammation (Robbins)
MUCOUS MEMBRANE PEMPHYGOID
PEMPHIGUS VULGARIS
MELANOTIC MACULE
AMYLOIDOSIS
§ Incidental finding in tongue
§ Locations: common in tongue (Rosai)
§ Ssx: often incidental (Rosai)
SUBMUCOSAL ORAL FIBROSIS
§ Subepithelial fibrosis with some chronic inflammation and loss of vascularity (Rosai). Increased risk of SCC
§ Complications: increased risk of SCC (Rosai)
§ Etio: unkonwn (Rosai)
§ Subepithelial fibrosis, chronic inflammation, hyalinization and loss of vascularity (Rosai). Overlying epidermis can be either atrophic or hyperplastic, often with hyperkeratosis (Rosai)
ATYPICAL HISTIOCYTIC GRANULOMA
§ Reactive nodule characterized by heavy histiocytic infiltration
§ Nature: reactive nodule characterized by heavy histiocytic infiltration (Rosai). May be cellular and mitoses, simulating malignancy (Rosai).
WALDEYER’S RING LYMPHOID HYPERPLASIA
§ Due HIV and causes symptoms, giant cells under tonsillar crypt epithelium,
§ Etio: symptomatic complication of HIV (Rosai)
§ Scattered multinucleated giant cells adjacent to tonsillary crypt epithelium (Rosai)
INFECTIONS
ACTINOMYCES
§
CANDIDIASIS
§ Aka oral thrush (Robbins).
§ RF: immunocompromised, DM, neutropenic (Robbins).
§ Scenario: 35 HIV+ man complains about bad taste in mouth and dtongue discoloration, adherent, yellow-tan, circumscribed plaques, can be scraped off as pseudomembrane to show underlying granular, erythematous base (Robbins).
§ 1/2 normal people have oral candida (Robbins)
§ Virulence: immune status of host, strand of Candida and composition of host’s oral flora (Robbins)
§ Ssx: superficial (Robbins). Yellowish plaque (Robbins)
Micro
§ Budding pseudohyphae (perpendicularly to mucosal surface) and spores within superficial parakeratin, neutrophilic exocytosis.
Variants (Robbins)
§ Pseudomembranous (thrush)
§ Erythematous
§ Hyperplastic
IHC
§ PAS stain
CMV
DISSEMINATED FUNGAL INFECTION
§ Histoplasmosis-> bug-laden, foamy histiocytes with necrosis, non-specific inflammation
§ Blastomycosis-> giant cells, PMN, pseudoepitheliomatous hyperplasia simulating SCC
§ Cryptoccosis, coccidioidomycosis
EBV
§ Aka mononucleosis (Robbins)
ENTEROVIRUS
§ Aka HERPANGINA, hand-foot-and-mouth disease, acute lymphonodular pharyngitis (Robbins)
HISTOPLASMOSIS
§ Locations: anywhere (Rosai)
§ Ssx: indurated ulcers, nodular or verrucous masses (Rosai). Clinically simulating SCC (Rosai)
§ Granuloma
HPV
§ HPV16/18à SCC of tonsils and oropharynx
Ø Tongue, gingiva, soft palate
§ Papilloma (papillary growth)
§ Verrucae (coarse keratohyaline granules, hyperkeratosis
§ Condyloma (koilocytes, broader papillations and branching)
HSV
§ Dormant in local GANGLIA,
§ Aka “cold sore” when reactivated (Robbins)
§ Demo: 2-4yo kids when primo-infection (Robbins)
§ Ssx: primo-infection ASYMPTO except acute herpetic gingivostomatitis (LN, fever, anorexia) in 1/5 (Robbins)
§ Locations: keratinized mucosa (gingiva no1) (Robbins)
§ Lab: acantholytic multinucleated cells in Tzanck test (Robbins)
§ Ssx: vesicles which ulcerate (Robbins).
§ Spreads: virus becomes dormant in local GANGLIA (trigeminal) (Robbins)
Micro
§ Mulitinucleated cells with ground glass chromatin and intranuclear eosinophilic inclusions (Robbins)
Variants (Robbins)
§ Acute herpetic gingivostomatitis
Ø primo-infection only (me)
Ø Outcome: self-limited within 1month (Robbins)
§ Recurrent herpetic stomatitis
§ Locations: either at site of primary inoculation or adjacent mucosa innervated by same ganglion (Robbins)
§ Outcome: much short, lasting up to 10 days just like aphthous ulcer (Robbins)
SYPHILIS
§ Granuloma with giant cells, numerous plasma cells, prominent vascular changes, painless mass on tongue or palate,
§ Ssx: painless indurated mass (Rosai).
§ Locations: tongue or palate (Rosai)
§ Granuloma with giant cells, numerous plasma cells, prominent vascular changes (Rosai)
TB
§ Painful ulcer on tongue
§ Ssx: painful ulcer (Rosai)
§ Locations: usually tongue (Rosai)
EPITHELIAL PRECURSOR LESIONS
ERYTHROPLAKIA
Clinical
§ 50% progress to SCC (Steinberg)
Micro
§ 90% superficial erosions
§ HG dysplasia, CIS or SCC in the surrounding margins
§ Intense inflammation
§ Dilated BV (reason why red)
LEUKOPLAKIA
Variants (Rosai)
§ Speckled (aka erythroleukoplakia): >3/5 superinfected by Candida
§ Erythroplakia
§ Proliferative verrucous
Outcome
§ <10% dysplasia, <20% SCC[59]
Clinical
§ Oral counterpart of keratosis[60]
§ ≡white patch/plaque >5mm that cannot be removed by scraping
Locations: where highest rate of dysplasia?
§ Mouth floor[61], lower lip border but buccal gingival gutter
Etio
§ Smoking
§ Pipe
§ Cigars
§ Chewing tobacco
§ Chronic irritation/inflammation
Micro
§ Hyperkeratosis
§ Acanthosis
LICHENOID DYSPLASIA
§
§
BENIGN EPITHELIAL TUMORS
PAPILLOMAS
SQUAMOUS CELL PAPILLOMA/VERRUCA VULGARIS
§ Def: benign non-neoplastic lesion (Steinberg)
§ Etio: partially HPV and partially idiopathic (WHO)
§ Location: most often in soft or hard palate (Steinberg)
CONDYLOMA ACUMINATUM
FOCAL EPITHELIAL HP
GRANULAR CELL TUMOUR
§ Pseudoepitheliomatous HP over a granular cell tumour may be confused with SCC
KERATOACANTHOMA
MALIGNANT EPITHELIAL
SCC
RF
§ Smoking, ROH[64][65], betel nuts, sun exposure (lip)
§ Questionable: toxins, iron deficiency[66], chronic trauma[67], chronic inflammation[68] (Steinberg)
Clinical
§ 90% in >50yo males who smoke and drink[69]
§ Location: ventral surface of tongue, floor of mouth, lower lip, soft palate, gingiva
Outcome
§ Field effectà incredibly high rate of second primary (3-7%/yr)
Genetics
§ LOH in conjunction with promoter hypermethylation at 3p and 9p21?à inactivation of p16 gene (inhibitor of CDK)à hyperplasia and hyperkeratosisà LOH at 17p with mutation of p53 (tumor suppressor gene)à dysplasiaà deletions on 4q, 6p, 8p, 11q, 13q, 14q, amplification and overexpression of CyclinD1 on chromosome 11q13à malignancy
§ EGFR often overexpressed
Prognosis (Steinberg)[70]
§ Growth/invasion pattern (irregular frond and discohesive cells vs rounded well-defined border)
§ Depth of invasion (use Breslow-like method; regional mets rare with <4mm but common with >8mm)
§ Vascular and perineural invasions
Micro
§ Variable grade
§ Dysplasia does not require full-thickness (CIS) before invasion
IHC
§ P16+: in basaloid SCC in <40yo (Lester, WHO)
VERRUCOUS
RF
§ All heavy consumers of tobacco[71]
Locations: where else?
§ Oral cavity[72] but also GI (nasal cavity, tonsils, larynx, esophagus, anogenital areas) (Steinberg)
Clinical
§ Locally invasive without metastatic ability (Steinberg)
Treatment: what not to do?
§ NEVER radiate (Manley)
DD
§ Squamous papilloma
Gross
§ Exophytic, papillary, with red and white areas (Steinberg)
Micro
§ Orderly maturation
§ Broad (bulbous or blunt) downward-pushing rete pegs
§ Coexist with SCC (1/5 cases).
BASALOID
Diagnosis
§ PCR for HPV16 (Lester)
Clinical
§ More aggressive (Steinberg)
§ Tonsils (often P16+) (Lester)
Micro
§ Islands of basaloid cells with central abrupt squamous differentiation (and keratinization) with peripheral palisading and thick BM
When should you suspect SCC to be tonsil origin?
§ P16+
§ HPV+ by PRC
§ Basaloid morphology
PAPILLARY
SPINDLE CELL (sarcomatoid)
ACANTHOLYTIC
ADENOSQUAMOUS
CARCINOMA CUNICULATUM
LYMPHOEPITHELIAL CARCINOMA
SALIVARY GLAND TUMORS
SALIVARY GLAND CARCINOMAS
AcCC
MEC
AdCC
PLGA
BASAL CELL ADENOCARCINOMA
EPITHELIAL-MYOEPITHELIAL CARCINOMA
CLEAR CELL CARCINOMA
CYSTADENOCARCINOMA
MUCINOUS ADENOCARCINOMA
ONCOCYTIC CARCINOMA
SALIVARY DUCT CARCINOMA
MYOEPITHELIAL CARCINOMA
CXPA
SALIVARY GLAND ADENOMAS
PLEOMORPHIC ADENOMA
MYOEPITHELIOMA
BASAL CELL ADENOMA
CANALICULAR ADENOMA
DUCT PAPILLOMA
CYSTADENOMA
SOFT TISSUE TUMORS
KAPOSI SARCOMA
LYMPHANGIOMA
ECTOMESENCHYMAL CHONDROMYXOID TUMOR
FOCAL ORAL MUCINOSIS
§ Nature: oral counterpart of cutaneous focal mucinous (Rosai)
§ Locations: anywhere in oral cavity else than lips (Rosai)
§ Mucin but no granulation tissue wall or inflammation in contrast to extravasation mucocele (Rosai)
§ No granulation tissue, no inflammation,
CONGENITAL GRANULAR CELL EPULIS
§ Non-neoplastic
§ Is this called congenital gingival granular cell tumor which is S100-???
PERIPHERAL GIANT CELL GRANULOMA[73] (osteoclastoma)
Clinical
§ Bilateral=cherubism (AD)
§ Young women
§ Erodes into or displace tooth
§ Gingiva at site of chronic inflammation
§ Probably reactive but can recur
§ Easily excised because WC
Gross
§ Same appearance as pyogenic granuloma except more bluish
Imaging
§ Peripheral “cupping” of bone characteristic[74]
Micro
§ Vascular stroma containing numerous osteoclast-like giant cells and hemosiderin deposits
§ WC but Unencapsulated
IHC
§ CD68+ (giant cells)
LYMPHOID
DLBCL
MANTLE CELL
FOLLICULAR
MALTOMA
BURKITT
T-CELL
PLASMACYTOMA
LANGERHANS CELL HISTIOCYTOSIS
MYELOID SARCOMA
FOLLICULAR DENDRITIC CELL SARCOMA
MELANOMA
METS
JAWS
NORMAL
§ http://obm.quintessenz.de/index.php?doc=html&abstractID=9558
OSTEOMYELITIS
OSTEORADIONECROSIS
FISSURAL CYSTS
§ Nature: including nasopalatine, nasolabial, globulomaxillary, median palatal (Steinberg).
§ Locations: mostly in maxilla (Steinberg). Rarely mandible can have median mandibular cyst (Steinberg). At points of embryological junction between head and neck structures (Steinberg)
NASOPALATINE
NASOLABIAL
GLOBULOMAXILLARY
MEDIAN PALATAL
ODONTOGENIC CYSTS
§ from tooth germ, degenerated epithelium around impacted tooth, epithelial rests, remnant of dental lamella (Steinberg).
§ Incidence (in sequence): periapical, dentigenrous, paradental, keratocyst, lateral periodontal, calcifying odontogenic, gingival, eruption (Steinberg)
§
CALCIFYING ODONTOGENIC CYST (Gorlin cyst)
Variants
§ Odontogenic ghost cell tumor when solid (USCAP)
DENTIGEROUS
§ Association: develops in close association with unerupted teeth (Steinberg)
§ Imaging: around crown of UNERUPTED tooth, unilocular
§ Location: typically third molar (Robbins)
§ Mechanism: separation of dental follicle
§ Nature: odontogenic developmental cyst (Robbins)
§ Ssx: swelling and less frequently pain (Steinberg)
§ Treatment: curative with complete removal but recurrence or neoplastic transformation (ameloblastoma or SCC) if incomplete removal
§ Very common; 1% of all adults (Steinberg)
Micro
§ Lined by thin, nonkeratinizing layer of squamous epithelium (Robbins). Dense chronic inflammatory infiltrate in stroma (Robbins). Thin layer of stratified squamous epithelium with dense chronic inflammation. Lined by ameloblastic-type epithelium (stratified and keratinizing with conspicuous basal layer, Steinberg)
§ Hemorrhage, infection and tangential cut may impair visualization of characteristic epithelial lining (Steinberg)
ERUPTION
GINGIVAL CYST OF ADULT
GINGIVAL CYST OF NEWBORN
GLANDULAR CYST
LATERAL PERIODONTAL CYST
§ Nature: developmental (think that “periodontal” is in periodontal tissue vs “paradental” just next to tooth, therefore periodontal is developmenta vs paradental is inflammatory) (Robbins)
ONDONTOGENIC KERATOCYST OKC
§ Aka keratocystic odontogenic tumor KCOT (new term from WHO)
§ Demo: typically in 10-40yo male
§ Def: benign uni or multicystic intra-osseous tumor of odontogenic origin with characteristic PARAKERATINIZED (orthokeratin does not count) squamous epithelium and prominent BASAL layer (WHO).
§ Genetic: PTCH gene mutations (tumor suppressor gene)-> multiple keratocysts-> Gorlin (nevoid basal cell carcinoma syndrome)
§ Locations: posterior mandible
§ Nature: odontogenic developmental cyst (Robbins)
§ Origin: arises from rests of odontogenic epithelium within jaw (Robbins).
§ Prognosis: more AGGRESSIVE than dentigerous cyst. Benign but can reccur upon inadequate excision (Robbins).
§ Treatment: aggressive removal because 60% RECURRENCE rate if incomplete removal (Robbins)
Gross
§ Unilocular or multilocular, well-defined
Micro
§ Looks like normal squamous epithelium with thin layer of parateratosis on bland fibromuscular cyst stroma (Robbins). PARAKERATINIZED stratified squamous epithelium, PROMINENT BASAL cell layer (hallmark) with nuclei polarized away from BM, corrugated epithelial surface (WHO, Robbins). Any granular layer?
PRIMORDIAL
PERIAPICAL CYST (INFLAMMATORY)
§ Aka periapical granuloma (Robbins). Inflammatory lesion tha develops at apex of teeth as complications of longstanding pulpitis (Robbins).
§ Nature: odontogenic inflammatory cyst (Robbins)
§ Demo: no1 cyst among all odontogenic cysts (Steinberg). Mostly in 20-30 adults (Steinberg)
§ Etio: develop from cystic degeneration of dental granulomas (granulation tissue, not real granuloma, Steinberg)
§ Nature: inflammatory
§ Mechanism: pulpitis-> abscess-> periapical granulation tissue-> periapical cyst (may be pseudocyst), not true granuloma)
§ Imaging: well-defined radiolucent defects around tooth apex (Steinberg)
§ Location: mostly in maxillary incisors and mandibular molars (Steinberg)
Micro
§ Cyst lined by cells of Malassez rests, which are normally presents within dental granulomas (Steinberg). Lining epithelium also contains keratinized foci, goblet cells and peculiar hyaline bodies called Rushton bodies (Steinberg)
PARADENTAL CYST (INFLAMMATORY)
RESIDUAL CYST (INFLAMMATORY)
BENIGN EPITHELIAL TUMORS WITHOUT ECTOMESENCHYME
AMELOBLASTOMA
Clinical
§ No1 tumor arising from odontogenic epithelium
§ Borderline (LG malignant)à locally invasive with recurrence[75]
§ Mostly in jaws[76] but also in oral cavity and sinonasal tracts[77]
Imaging
§ Most often multicystic[78] but can be unicystic (Steinberg).
Micro
§ Peripheral palisading columnar cells → CK+ve
§ Stellate reticular stroma → calretinin+ve
§ Cyst formations
§ No: atypia, mitoses[79]
§ Paucicellular fibrous stroma
§ Follicular, plexiform
DD
§ Ameloblastoid HP within dentigerous cyst (vs cystic ameloblastoma) (Steinberg)
AMELOBLASTOMA, SOLID/MULTICYSTIC
AMELOBLASTOMA, EXTRAOSSEOUS
AMELOBLASTOMA, DESMOPLASTIC
AMELOBLASTOMA, UNICYSTIC
SQUAMOUS ODONTOGENIC TUMOR
CALCIFYING EPITHELIAL ODONTOGENIC TUMOR CEOT (Pinborg tumor)
§ Benign
§ Amyloid droplets, dystrophic calcification (USCAP)
ADENOMATOID ODONTOGENIC TUMOR
KERATOCYSTIC ODONTOGENIC TUMOR
BENIGN EPITHELIAL TUMORS WITH ECTOMESENCHYME
AMELOBLASTIC FIBROMA
AMELOBLASTIC FIBRODENTINOMA
AMELOBLASTIC FIBRO-ODONTOMA
ODONTOMA
§ -look like misshapen teeth
§ Most common odontogenic tumor (Robbins). Composed of calcified enamel and dentin (Robbins).
§ remember presence of calcified enamel/dentin in this tumor (Steinberg)
COMPLEX
§ Nature: hamartoma (Robbins)
§ Origin: odontogenic epithelium (Robbins)
§ Contains enamel, dentin and cementum (Steinberg)
COMPOUND
§ Aka composite odontoma (Steinberg).
§ Nature: hamartoma (Robbins)
§ Origin: odontogenic epithelium (Robbins)
§ Characterized by complete differentiation of ameloblasts and odontoblasts to produce enamel and dentin to form small teeth (Steinberg).
ODONTOAMELOBLASTOMA
CALCIFYING CYSTIC ODONTOGENIC TUMOR
DENTINOGENIC GHOST CELL TUMOR
§ Solid variant of calcifying odontogenic cyst (USCAP)?
ODONTOGENIC CARCINOMAS
METASTASIZING AMELOBLASTOMA
AMELOBLASTIC CARCINOMA-PRIMARY[80]
AMELOBLASTIC CARCINOMA-SECONDARY
SCC-SOLID
SCC DERIVED FROM KERATOCYSTIC ODONTOGENIC TUMOR
SCC DERIVED FROM ODONTOGENIC CYSTS
CLEAR CELL ODONTOGENIC CARCINOMA
GHOST CELL ODONTOGENIC CARCINOMA
ODONTOGENIC SARCOMAS
AMELOBLASTIC FIBROSARCOMA
MESECHYMAL TUMORS
ODONTOGENIC FIBROMA
ODONTOGENIC MYXOMA/MYXOFIBROMA
CEMENTOBLASTOMA
BONE TUMORS
PERIPHERAL OSSIFYING FIBROMA
Clinical
§ Reactive
§ More recurrence
§ From long-standing pyogenic granuloma,
§ Incidence: very common in mouth (Robbins)
§ Nature: REACTIVE (Robbins)
§ Etio: unknown but some result from long-standing pyogenic granuloma (Robbins)
§ Demo: young females (Robbins)
§ Ssx: red ulcerated gingival nodule, misdiagnosed clinically as pyogenic granuloma (Robbins)
§ Treatment: excision down to periosteum (Robbins).
§ Outcome: recurrence up to 1/5 (Robbins)
§ Precursor: pyogenic granuloma (Robbins)
Micro
§ Fibrous connective tissue with numerous trabeculated bone within. Osteoid production.
FIBROUS DYSPLASIA
OSSEOUS DYSPLASIA
REPARATIVE GIANT CELL GRANULOMA
§ Aka SOLID variant of ABC (Rosai, WHO, AFIP). Not same as GCT of bone, GCT of tendon sheath or GCT of soft tissue (Rosai).
§ Nature: overlaps histologically and pathogenetically with ABC (Steinberg).
Variants
§ By locations (Rosai, WHO): impossible to ddx based on histology alone (Steinberg)
§ Central (intra-osseous)
§ Peripheral (extra-osseous)
CENTRAL GIANT CELL GRANULOMA
§ Aka central giant cell lesion, central giant cell granuloma (WHO, AFIP).
§ Nature: resembling “brown tumors” in hyperPTH (Robbins)
§ Locations: jaws (Robbins).
CHERUBISM
ANEURYSMAL BONE CYST
SIMPLE BONE CYST
OTHERS
MELANOTIC NEUROECTODERMAL TUMOR OF INFANCY
SALIVARY GLANDS
CONGENITAL ANOMALIES
HETEROTOPIA
§ Intraoral vs extraoral, high vs low sites, Warthin’s tumor no1 in extraoral SG,
§ most LN near or within parotids contain SG tissue, especially in kids (Rosai). Often in medulla of LN and composed of intercalated ducts (Rosai)
§ Can undergo oncocytic metaplasia, cystic formation, ductal hyperplasia and neoplasms (Rosai). Most common neoplasm is Warthin’s tumor (Rosai)
Variants (Rosai, Steinberg)
§ Intranodal: more common
§ Extranodal: divided into high and low sites (Rosai).
Ø High: ear, mandible, palatine tonsils, pituitary gland, mylohyoid muscle, cerebellopontine angle (Rosai). Probably due to abnormal SG migration due embryogenesis (Rosai)
Ø Low: in associated with cysts and sinuses of lower neck, often in medial border of SCM muscle or in thyroid (Rosai). From branchial pouches (Rosai)
METAPLASIA
§ Chondroid
§ Oncocytic
Ø Defined as solitary or small groups of acinar cells that become oncocytes (Goldblum). Practically universal after 70yrs of age (Goldblum). No alteration of glandular architecture (?, not too sure, Goldblum). Possibly age-related degenerative change because number increases with age and shows minimal secretory activity (Rosai)
§ Oncocytic, clear cell
Ø If majority of oncocytes have clear cytoplasm (Goldblum)
§ Sebaceous
§ Squamous
Ø Can occur in excretory ducts and acini of injured salivary glands (not to confused with squamous cell carcinoma, Steinberg).
INFLAMMATION
Sialadenitis
§ Name 3 causes:
§ Viral: paramyxovirus (mumps)
§ Bacterial: S. aureus, S.viridans
§ Sjrogren’s syndrome (chapter7)
Sialolithiasis
§ -stones in the salivary ducts
LYMPHOEPITHELIAL CYST
§ Multicystic lesion lined by squamous or glandular epithelium with lymphoid hyperplasia and germinal centers, ddx of cystic lesions in SG, in parotid or cervical LN, probably acquired, HIV-associated variant also has solid lymphoepithelial lesions, epithelium infiltrated by lymphocytes (reason why “lymphoepithelial” cyst),
§ ddx of cystic lesions in SG include polycystic disease (developmental disorder, more in females, characterized by bilateral gland enlargement), sclerosing polycystic adenosis, cystic changes in tumors (MEC, sebaceous lymphadenoma, PA) (Rosai)
§ Def: multilocular cystic lesions lined by glandular or squamous epithelium surrounded by florid lymphoid hyperplasia and prominent germinal centers (Rosai)
§ Etio: probably acquired from proliferation of branchial pouch-derived epithelium induced by lymphoid hyperplasia (Rosai). Process similar to branchial cleft cyst of head and neck region (Rosai)
§ Locations: parotid, upper cervical LN (Rosai, Steinberg).
§ Scenario: cyst removed from parotid of 23yo man, multilocular cyst lined by squamous epithelium with florid lymphocytic infiltrate with germinal center formation, immunostains showing mixed B and T lymphocytes (Steinberg).
Micro
§ Multilocular cystic spaces containing mucoid fluid and lined by glandular and/or squamous epithelium (Steinberg). Intervening solid areas show lymphocytic infiltration with germinal centers (Steinberg).
§ important to see cyst lining heavily infiltrated by lymphocytes (important hint and reason why “lymphoepithelial cyst”, Rosai)
Variants (Rosai)
§ Warthin’s tumor: some people view Warthin’s tumor as oncocytic variant of benign lymphoepithelial cyst (Rosai)
§ HIV-associated lymphoepithelial cyst: characterized by combination of lymphoepithelial cysts and solid lymphoepithelial lesions (epimyoepithelial islands) of Mikulicz’s disease (Rosai).
MUCOCELE
§ Always include cystic mucoepidermoid carcinoma in ddx, especially in parotid
§ Variant: ranula is just a mucocele from rupture of sublingual gland
§ Def: mucocele vs sialocele (Rosai)
§ Mechanism: trauma-> rupture or blockage of salivary gland duct, most commonly on lower lip-> cystlike space lined by inflammatory granulation tissue or fibrous tissue, filled with mucin and macrophages-> recurrence if minor salivary gland lobule is not excised. In minor*** SG (Robbins).
§ The case I saw: lined by squamous epithelium, acute inflammation
DD
§ Always include cystic mucoepidermoid carcinoma in ddx, especially in parotid (Rosai)
ONCOCYTOSIS
§ Cystic or nodular, multiple, benign, unkown etio but probably age-related, cystic vs nodular,
§ 2 forms (Rosai)
Ø Cystic: multiple parotid cysts lined by oncocytic epithelium containing tyrosine crystals (Rosai)
Ø Nodular: multiple well-defined clusters of oncocytic cells scattered throughout parotid (Rosai). Sometimes may be diffuse (Goldblum)
§ Aka oncocytic hyperplasia, multionodular oncocytoma, multifocal adenomatous oncocytic hyperplasia (Rosai, Goldblum).
§ Nature: uncertain, maybe degenerative with increasing age (Rosai)
§ Prognosis: no pathologic significance (Steinberg).
§ Intimate, unencapsulated relationship between glandular parenchyma and oncocytic nodule (Goldblum)
MIKULICZ’S DISEASE
§ White large gland with small cysts, lymphocytic infiltrate with germinal centers + epimyoepithelial islands, localized vs associated with Sjogren’s syndrome, more in HIV+,
§ Aka benign lymphoepithelial lesion, myoepithelial sialadenitis “MESA” (Rosai)
§ Ssx: slow enlargement of SG and lacrimal glands to striking size of SG (Rosai). Usually bilateral and symmetric but can be localized unilateral (Rosai)
§ Locations: SG, lacrimal glands (Rosai)
§ Complications: lymphomas (DLBCL, MZBCL, others) (Rosai)
§ RF: HIV+ (Rosai)
§ Etio: unknown but probably autoimmune given polyclonal growth (Rosai).
§ Enlarged gland with white cut surface and occasional cysts (Rosai)
Micro: 2 cardinal changes
§ Epimyoepithelial islands (more precisely lymphoepithelial lesions because no MEC): solid epithelial nests surrounded and infiltrated by lymphoid cells, mainly monocytoid B cells (Rosai)
§ Lymphocytic infiltrates: with well-formed germinal centers (Rosai)
Variants
§ Without Sjogren (localized)
§ With Sjogren (systemic): see rheum for Sjogren
DD
§ Chronic lymphocytic sialadenitis in HCV-related chronic liver disease can resemble Mikulicz’s disease in microscopy (Rosai)
§ Lymphoepithelioma-like carcinoma (Rosai)
ACUTE SIALADENITIS
§ Etio: localized infection or from systemic infection (Rosai).
Ø Viral: paramyxovirus, EBV, coxsackievirus, influenza A, parainfluenza (Rosai).
Ø Bacteria: Staphy aureus, Strep, GNB (Rosai). Cause acute suppurative sialadenitis (Rosai).
Ø Traumatic: mucocele
Ø Autoimmue: Sjogren-> more chronic sialadenitis
§ RF: malnutrition, immunosuppression, dehydration, lithiasis (Rosai)
§ Complications: abscess (Rosai)
§ 2 types
Ø Acute in viral, bacterial and traumatic but chronic in Sjogren (also enlarged parotid, lymphoid follicles with germinal center, fibrosis and scarring, acinar atrophy).
§ Locations: minor SG (Robbins)
§ Ssx: localized tender nodule (Robbins).
§ Scenario: 76 man schizophrenic on thioridazine (neuroleptic with anticholinergic side effect resulting in dry mouth and sialolithiasis), bothered by pain in side face, CT shows cystic and solid texture in enlarged parotid, histology shows acute and chronic inflammation with fibrosis and abscess and atrophy of acini, Staph aureus positive in tissue (Robbins).
§ Acute inflammation and abscess (Robbins). When chronic, fibrosis, chronic inflammation and acinar atrophy (Robbins, Rosai)
CHRONIC SIALADENITIS
§ Etio: partial obstruction by lithiasis, autoimmue (Sjogren, RA) (Rosai)
§ Kuttner’s tumor (aka chronic sclerosing sialadenitis of submandibular gland): characterized by lymphoplasmacytic infiltrate leading to dense fibrosis encasing ducts (Rosai).
§ Locations: major SG (Rosai)
§ Ssx: often asymptomatic unless due to lithiasis (Rosai)
§ Mild lymphocytic infiltrate, acinar atrophy, fibrosis, microliths (Rosai).
GRANULOMATOUS SIALADENITIS
§ Etio: TB, mycosis, sarcoidosis, obstruction from stone or malignancy (Rosai)
§ Variant: xanthogranulomatous sialadenitis (Rosai)
§ Pools of mucin if obstructive causes (Rosai).
SIALOLITHIASIS
§ Submandibular because of higher Ca, squamous metaplasia, ductal dilation, chronic inflammation, acinar destruction, carbonate apatite,
§ Etio: unknown reason or dehydration. Some stones have foreign body or bacterial nidus (Rosai)
§ Composition: some are carbonate apatite (Rosai)
§ Bilaterality: possible and also multicentric (Rosai)
§ Locations: submandibular gland no1 because saliva more saturated with Ca salts (Rosai)
§ Complications: nonspecific bacterial (suppurative) sialadenitis (S aureus and S viridans)-> suppurative necrosis or abscess
§ Imaging: US, sialography (Rosai)
§ Ssx: painful, indurated, sometimes gland enlargement (but no mass effect) (Robbins)
§ Treatment: surgical removal of stone or ESWL (Rosai)
§ Dilation of ducts, sometimes squamous metaplasia, chronic inflammation, variable degree of acinar destruction (Rosai, Robbins).
NECROTIZING SIALOMETAPLASIA NSM
§ Oral cavity but also in larynx, ischemic, both minor and major SG, typically on hard palate, misdiagnosed as SCC or MEC, ulceration on hard palate, preserved LOBULAR architecture,
§ Etio: likely ischemic (Steinberg)
§ Locations: both minor and major SG but mostly minor SG of hard palate (Steinberg) Mostly in oral cavity but also in nasal caivity, lip, hypopharynx, maxillary sinus, larynx (Rosai)
§ Ssx: ulcer on hard palate (Steinberg, Rosai)
§ Vascular proliferation, prominent chronic inflammation, partial necrosis of SG with regeneration, focal squamous metaplasia of adjacent ducts and acini (Rosai)
§ Patterns: preserved LOBULAR architecture (Steinberg).
§ squamous metaplasia found in center of SG and develops from pre-existing ducts (Steinberg). Necrosis and inflammation more in periphery (Steinberg)
§ often misdiagnosed as SCC or MEC due to prominent squamous metaplasia (Rosai, Steinberg)
§ overall changes quite similar to radiotherapy-induced changes (Rosai)
DD
§ SCC (Rosai)
§ Mucoepidermoid carcinoma (Rosai)
XEROSTOMIA
§ Sjogren syndrome, radiation therapy
§ Chronic fibrosing inflammation, typically non-suppurative (vs suppurative in sialadenitis, Robbins)
TUMORS
Clinical
§ SG tumor weirdly higher malignancy incidence in kids,
§ Bilateral and multifocal: Warthin’s (no1), PA, AcCC
§ FNA[81] can induce necrosis, repair change and oncocytic change
§ Unknown etiology
§ 12x more in parotid than submandibular, not explained by gland size difference (Rosai).
§ Malignant: sublingual> minor SG (palate, 44%)> submandibular (38%)> parotid (17%)
§ Incidence of malignancy much higher in kids than in adults (paradoxical but important)
Ø Benign tumors in kids: PA still no1 (Rosai).
Ø Malignancy in adults: MEC (Rosai)
Ø Malignancy in kids: MEC> AdCC and AcCC (Rosai)
Ø Malignancy in parotid: MEC> undifferentiated adenocarcinoma> AcCC> AdCC (Rosai). Remember aCinic=C position, aDenoid=D position (me)
Ø Malignancy in submandibular and minor SG: AdCC> MEC (Rosai)
§ Locations: anywhere in mouth including tonsils and lip, nasal cavity, sinuses, ear, jaw, pharynx, larynx, trachea, bronchi (Rosai). Also in bresat and sweat glands (Rosai)
Ø palate no1 location for minor SG tumors due to highest normal SG density (Ross). Location of minor SG tumors is proportional to amount of normal glandular tissue in that area (Rosai).
RF
§ Childhood radiation[82]
§ Ssx: facial nerve palsy almost diagnostic of malignancy except LG AcCC and MEC because these latters often have similar clinical presentation to benign neoplasms (Rosai)
§ Prognosis: clinical staging, tumor type, location (Rosai). Submandibular gland tumors have higher recurrence rate and mets (Rosai). Facial paralysis for parotid tumors ominous (Rosai).
§ Prognosis by tumor types (Rosai)
Ø Good: LG MEC and AcCC (Rosai)
Ø Bad: any HG tumors, AdCC, carcinosarcoma, salivary duct carcinoma, squamous cell carcinoma, CXPA (Rosai)
§ Treatment
Ø Submandibular gland tumor: total gland removal with no need of prior biopsy and no matter benign or malignant (Rosai). Reason is higher recurrence rate due to close relation with mandible (Rosai)
Ø Parotid tumor: superficial parotid tumor can be management with superficial parotidectomy with frozen section (Rosai).
Ø if skin invasion, local biopsy can nail diagnosis (Rosai).
Ø type of surgery for parotid tumor depends on tumor type and relationship with facial nerve (Rosai)
Name the types of benign and malignant salivary gland tumours.
Benign
§ Pleomorphic adenoma, monomorphic
§ Oncocytoma
§ Warthin tumour
§ Myoepithelioma
§ Lymphoepithelioid cyst (see above)
§ Sebaceous adenoma
Malignant
§ Mucoepidermoid carcinoma
§ Adenocarcinoma (NOS)
§ Acinic cell carcinoma
§ Adenoid cystic carcinoma
§ Squamous cell ca
§ Polymorphous low grade carcinoma
BENIGN EPITHELIAL TUMORS
§ Pleomorphic adenoma
§ Basal cell adenoma
§ Sebaceous adenoma
§ Warthin tumour
§ Oncocytoma
§ Ductal papilloma
§ -inverted papilloma
§ -intraductal papilloma
PLEOMORPHIC ADENOMA
§ -parotid/submandibular
§ -radiation exposure
§ -encapsulated (risk of recur. if not completely removed)
§ ▪ stromal (chondromyxoid)
Ø +
§ ▪ epithelial (usu occur as tubules/nests) & myoepithelial (may be seen at basal aspect of tubules)
§ -squamous & cartilagenous metaplasia
§ Biphasic (epithelium and stroma), looks carcinomatous change, mainly in parotid and submandibular, not in sublingual, more in superficial lobe of parotid, 40 females, rubbery bosselated, consistency depends on relative proportions, grossly well-circumscribed but microscopically nasty digits into capsule, 4 components including capsule, glands, MEC and stroma, glands is epithelial, focal squamous metaplasia and keratin plugs, sheet is MEC, can be locally invasive with rare mets, malignant if mitoses, necrosis and significant atypia, CXPA vs carcinosarcoma, PAP/PSA+ in 1/2, recurrence depends on primary excision adequacy, CXPA absolutely requires microscopic presence of PA (clinical history not sufficient), always thorough sampling, monomorphic adenoma should not be used,
§ Aka bening mixed tumor composed of epithelial (ducts) and myoepithelial cell prolifeation within mesenchymal stroma (Goldblum).
§ “biphasic” refers to epithelium (ducts and MEC) and stroma (Rosai, Robbins).
§ Complications: facial nerve dysfunction and Frey’s syndrome (gustatory sweating).
§ Def: tumor marked by morphologic diversity including varying cellularity, cell morphology, matrix type and encapsulation (Goldblum).
§ Demo: 40-50 females but also <20 males and extreme ages of either sex (Goldblum, Rosai).
§ Genetics
Ø 8q12 rearrangement leading to PLAG1 fusion in >50% (Lester). PLAG1 means “pleomorphic adenoma gene 1″ (Web)
Ø 12q15 rearrangement leading to HMG1C oncogenes in <20% (Lester)
§ Incidence: no1 salivary gland neoplasm (54-76%) (Goldblum). 60% of parotid tumors (Steinberg)
§ Locations: parotid (4/5, mostly superficial lobe), minor SG (10%, especially in palate), submandibular gland (10%) (Rosai, Steinberg, WHO). Extremely rare in sublingual gland (Rosai). Tumors arising in deep lobe of parotid presents as pharyngeal mass without external mass (Rosai)
§ Origin: epithelial and MEC cells of salivary glands (Robbins). Stromal cells actually modified MEC, which secrete stroma (Ross, Rosai). From normal intercalated ductal cells (Rosai). Solid evidence based on EM, IHC and molecular analysis that epithelial and mesenchymal components share same origin (Rosai)
§ Outcome: 4% recurrence with excision vs up to 45% with enucleation due to tongue-like peripheral extension (Goldblum). Extremely high recurrence with enucleation and depends on adequacy of primary excision (20-45%, Goldblum). Recurrences often multifocal, more difficult to remove and leading to more recurrences (Goldblum; a real vicious cycle). Time of recurrence extremely variable (up to 50yrs, Rosai). Usually recur with same histomorphology but multiple recurrences increase malignant transformation risk (Goldblum).
§ Prognosis: recurrence rate depends heavily on adequacy of primary excision (Rosai)
§ RF for malignant transformation (1/20): recurrences, elderly (>40), male, large (>2cm), submandibular, deep-seated tumor, prominent hyalinization, increased mitoses (Rosai, Goldblum).
§ RF for PA: radiation (radiation also increases incidence of other salivary gland tumors, Steinberg)
§ Scenario: 65 woman slowly enlarging nodule on face, nontender mobile discrete mass anterior to ear and just superior to mandible, ductal epithelial cells in myxoid straom containing islands of chondroid and bone (Robbins). Local invasion and recurrence hugely problematic (Robbins).
§ Spread: recur often locally but rarely can mets to LN, lungs, bone and other organs (Rosai). Curiously, kidney is favorite site for isolate mets (Rosai)
§ Ssx: asymptomatic slow growing (Goldblum) but may have pain or paralysis due to infarcted tumor (Ross, WHO). Mucosal ulceration and paresthesia rare (Goldblum). 5-10% PA become malignant with sudden growth, pain and facial paralysis (Rosai).
§ Treatment: superficial or partial parotidectomy with nerve preservation is standard with nearly zero recurrence if tumor is in superifical lobe (Rosai, Goldblum). Some propose to radiate if suspicion of tumor spillage (Rosai). Neck dissection if clinical evidence of LN involvement (Rosai)
§ Well-circumscribed, rubbery (depending on proportion of stroma and epithelium, Rosai) nodule with blue translucent (chondroid) areas with variable encapsulation (Goldblum, WHO, Lester). Capsule of highly variable thickness (may be focally absent, WHO). Despite well circumscription, often small extensions to adjacent normal tissue (Goldblum). Sometimes hemorrhage and necrosis (WHO). Cystic degeneration and diffuse infiltration suspicious for AcCC or mucoepidermoid carcinoma (Lester). Nontender mobile slowly-growing mass (Robbins). Variegated surface with myxoid and blue-gray areas (Steinberg)
§ solitary if primary, multifocal if recurrent (Goldblum, Lester, WHO).
§ Often plasmacytoid in minor salivary glands (Goldblum). Mucochondroid matrix most common with variable collagenation (Goldblum). Tendency for pericapsular parallel cleft (WHO).
§ 2 malignant variants: always contains at least malignant epithelial component, usually squamous (Rosai). All salivary gland types possible: MEC, AdCC, salivary duct carcinoma, myoepithelioma, undifferentiated carcinoma, high-grade adenocarcinoma (Rosai). Rule: whenever you see high-grade malignancy in salivary glands, always think of tumor arising from PA (Rosai)
Ø Carcinosarcoma: biphasic with ductal carcinoma and chondrosarcoma (Rosai). No pre-existing PA visible (Rosai). Rapidly lethal (Rosai)
Ø CXPA: more common, in 1/10 of PA, diagnosis requires presence of PA in same neoplasm (positive clinical history of PA not sufficient), therefore throrough sampling, sometimes pre-existing PA becomes totally hyalinized round nodule
§ 4 components (WHO)
Ø Capsule: variable thickness and can be partial or even entirely absent in mucoid variant (WHO). Despite benign in nature, most tumors have finger-like processes extending into capsule (WHO).
Ø Epithelium: extremely variable morphology including cuboidal, basaloid, spindle, squamous, plasmacytoid and clear cells (WHO). Forming sheets or ducts (WHO). Focal squamous metaplasia +/- luminal keratin plugs common (Rosai, WHO). So, best hint for epithelial cells is to look for ducts/glands (Hurlbut). Usually minimal compared to MEC or stroma (Goldblum)
Ø MEC: variable morphology including cuboidal, flattened, spindle, plasmacytoid, epithelioid, stellate, basaloid and can be individual, solid, trabecular, abluminal (WHO, Rosai). In sheets or reticular patterns (WHO). Often gradual transition from MEC to stromal cells because of same cell origin (Rosai)
Ø Stroma: mucomyxoid, chondroid, hyalinized, osseous, fatty (WHO). Recent molecular studies showed stromal component has same origin as epithelial cells and are in fact modified MEC (Rosai). Sometimes crystals, amyloid (Rosai)
§ “metastasizing” PA (caused by iatrogenic manipulation of PA), which is not real mets (Goldblum).
§ areas of spontaneous infarction (hemorrhage, necrosis, inflammation, reactive cellular atypia, squamous/mucus metaplasia) can mimic CXPA (Goldblum). Remember you must try to find intercellular bridges and keratin to confidently call squamous metaplasia, otherwise it’s more squamoid rather than squamous (me)
§ chondroid stroma useful because never found in AdCC, basal cell adenoma (Rosai)
§ either stroma-rich or MEC-rich because ductal components (i.e. epithelial) usually minor (Goldblum)
Ø Stroma-rich (80% of tumor is myxoid stroma)
Ø Cellular (80% of tumor is myoepithelial cells)
Ø Ductal component usually minor
§ often misdiagnosed as carcinoma because of extreme cellularity, scattered bizarre tumor cells, partial penetration of capsule, sometimes tumor clusters in BV (Rosai)
§ some atypia, high cellularity and partial capsular penetration permitted and do not change prognosis (Rosai). Minor fat extension accepted (Goldblum).
§ sometimes EXTREMELY cellular (Rosai)
§ usually no mitoses or atypia but cytological atypia permitted (Rosai)
§ Malignant: increased mitoses, necrosis (Rosai). Nuclear atypia, mitoses in atypical PA; tumor necrosis, atypical mitoses, severe atypia in CXPA in situ (Goldblum). Malignant form always has epithelial component and most are salivary duct carcinoma or poorly differentiated carcinoma (Rosai).
Immuno (epithelial component has similar expression as intercalated duct cells, Rosai)
§ Two types of mucin: neutral glycoprotein and glycosaminoglycans (Rosai).
§ Basement membrane always present (Rosai) Low proliferation index using Ki67, PCNA (proliferating cell nuclear antigen) or AgNOR (silver-staining nucleolar organizer region) or flow cytometry (Rosai)
§ Ductal cells: CK+ (Goldblum), EMA+ (Rosai), GCDFP+ (Rosai), PAS+/PAP+ (50%, great source of confusion, Rosai)
§ MEC: CK+ (Rosai, Goldblum), vimentin+ (Goldblum), S100+ (Goldblum), SMA+ (Goldblum), GFAP+ (difficult to explain but seems to relate to capacity of this tumor for cartilaginous differentiation; useful in differentiating PA from PLGA, AdCC and basal cell adenoma, Goldblum)
§ Stroma: Giemsa highlights mucochondroid material (Goldblum).
§ P53+ (overexpression) and HER2/neu overexpression in malignant form but not in PA (Rosai)
Variants
§ Atypical: diagnose as atypical PA if some atypia (pleomorphism, prominent nucleoli), increased mitoses (Goldblum).
§ Metastasizing (WHO)
DD
§ Basal cell adenoma (Goldblum): unencapsulated, mostly in palate, may be infiltrative,
§ Adenoid cystic carcinoma (Goldblum, WHO): especially in biospy
§ Myoepithelioma (Goldblum):
§ Epithelial-myoepithelial carcinoma (WHO):
§ Polymorphous low-grade adenocarcinoma (Goldblum)
MONOMORPHIC ADENOMA
§ -dermal annalage
-basal cell adenoma
§ -looks like skin adnexal tumor
§ -periphery of nests have palisading with ↑ basal lamina material (like cylindroma!)
§ Avoid this term (Rosai). People tend to use this term to refer to basal cell adenoma only (Rosai). Not in WHO (Rosai)
BASAL CELL ADENOMA
§ Benign, elderly (60) females, congenital to ddx from embryoma (sialoblastoma), parotid, small encapsulated cystic, basaloid cells with palisading in periphery, larger polygonal pale cells in center, 4 patterns (solid, trabecular, membranous, tubular), membranous variant resembling cylindroma, 3 ddx (basal cell adenocarcinoma, AdCC, PA), benign, excision curative, transform into basaloid carcinoma or basal cell adenocarcinoma, malignant if infiltrative, mitoses, vascular invasion, perineural invasion and atypia, can transform into malignant myoepithelioma,
§ Aka: monomorphic adenoma (Outlines, Lit)
§ Associations: dermal cylindromas (Rosai)
§ congenital form to differentiate from embryoma (sialoblastoma) (Rosai)
§ Complications: malignant transformation, sometimes into malignant myoepithelioma (Rosai)
§ Def: benign epithelial salivary gland neoplasm composed of small basaloid cells in solid, trabecular, tubular or membranous growth patterns (Goldblum).
§ Demo: adults with peak 60 (Rosai, Goldblum). Slightly more in females (Goldblum, Rosai).
§ Evolution: slow growth mass
§ Incidence: 2% of all SG neoplasm (Goldblum).
§ Locations: parotid (2/3), minor SG (upper lip), submandibular (Goldblum, Rosai, Steinberg). Sometimes in periparotid LN (Rosai)
§ Origin: intercalated ducts or basal cells of striated ducts based on EM (Rosia, Goldblum)
§ Outcome: 25% recurrence (due to capsular invasion and multicentricity) (Goldblum)
§ Prognosis: small risk for malignant transformation for membranous form but low for other forms (Goldblum).
§ Ssx: often asymptomatic.
Ø membranous pattern has different presentation: more in males, multicentric and association with skin adnexal tumors such as cylindroma (same cytogenetic abnormalities in 16q region, Rosai), trichoepithelioma and eccrine spiradenoma and form skin/salivary gland tumor diathesis (Goldblum).
§ Treatment: excision curative (Rosai)
Gross
§ Small encapsulated cystic (Rosai). May simulates enlarged LN (Goldblum).
Micro
§ WELL-circumscribed, usually encapsulated (Goldblum). Well-defined basement membrane (Steinberg)
§ 2 cells (Goldblum, Rosai). Best hint is peripheral palisading (Steinberg).
Ø Smaller basaloid cells with peripheral palisading
Ø Larger polygonal/angular cells with abundant cytoplasm and pale round nuclei in center.
§ diagnose as basal cell adenocarcinoma if cytological atypia, mitoses and infiltrative growth (Steinberg)
§ membranous pattern may be multifocal and unencapsulated (Goldblum). Solid variant looks like cylindroma.
§ PAS+ material sometimes found between epithelial cells or within stroma (Steinberg)
§ sometimes squamous metaplasia with keratinization (Goldblum).
§ Malignant (basal cell adenocarcinoma): rare (Rosai). Cutaneous cylindroma has higher rate of malignant transformation (Rosai). Infiltrative, perineural invasion, vascular invasion, perineural invasion, cytologic atypia, mitoses (Rosai, Steinberg)
§ NO: MEC (vs PA), myxoid matrix (vs PA) (Outlines, Lit)
§ Patterns: can coexist (Goldblum, Rosai, Steinberg)
Ø Membranous: interesting because resembles cylindroma with solid/jigsaw puzzle separated by dense PAS+ hyaline band (Rosai, Goldblum). Cases of multiple skin cylindromas with multiple parotid “cylindromas” have been reported (Rosai). Probably same lesion because same cytogenetic abnormalities in 16q (Rosai)
Ø Solid:
Ø Trabecular (aka canalicular adenoma): most common (2/3). Bilayered strands of columnar cells in looser stroma. More tendency to occur in minor SG.
Ø Tubular: similar to solid but with lumina. No2 common (1/4).
Variants (Steinberg)
§ Nesting: more common; 2/3 of cases
§ Tubular
IHC
§ CEA+ (Steinberg), EMA+ (Steinberg)
DD
§ Basal cell adenocarcinoma (Goldblum; main ddx, Rosai): no matrix
§ Adenoid cystic carcinoma (Goldblum, Rosai): atypia, stromal infiltration, perineural invasion, lack of encapsulation in AdCC
§ Pleomorphic adenoma (Rosai, Steinberg, Outlines): myxoid stroma, no fibrous stroma, MEC present, no peripheral palisading
WARTHIN TUMOUR
§ Clinical: smokers, males
§ -parotid exclusively
§ -can be bilateral (10%)
§ Gross: mult. cystic spaces, -lobulated, can be multifocal
§ Micro: double layer of oncocytic cells overlying lymphocytic stroma with germinal centres often
§ Treatment: surgery
§ Prognosis: excellent, rarely recur
§ Papillary cystadenoma lymphomatosum, only in parotid but may be extraparotid, male smokers, multicentric and bilateral (1/10), no1 bilateral tumor, multicystic with brown oil fluid (due to spontaneous hemorrhagic infarct), much OLDER (60) population than PA (40), dual-layered oncocytic epithelium, sometimes ciliated, papillary-cystic, lymphoid follicles, giant cell reaction due to hemorrhagic infarct, well-circumscribed, lymphoid stroma can be absent, squamous metaplasia often misinterpreted as SCC or necrotizing sialometaplasia, never recurs, malignant transformation possible but extremely rare, nature controversial,
§ Aka papillary cystadenoma lymphomatosum (Goldblum, Rosai).
§ Associations: syndronously occurring with other tumor types than other salivary tumors (Goldblum). SMOKING strong association (8x) (WHO, Goldblum).
§ biphasic tumor (oncocytes and lymphoid stroma) (Goldblum).
§ if a parotid tumor is bilateral, Warthin tumor is most likely diagnosis (Steinberg)
§ Def: characterized by double layers of oncocytic epithelium, papillary-cystic architecture and dense lymphoid stroma with germinal centers (Goldblum).
§ Demo: caucasians 60-70yo (rare before 40) (WHO). MALE predilection (2-10:1 vs female predominance in other salivary gland neoplasms) (Steinberg).
§ EM: mitochondria (Steinberg)
§ Incidence: no2 SG neoplasm (WHO).
§ Locations: only in parotid (lower portion of superficial lobe) (Goldblum, Rosai). Also in oral cavity, larynx, and cervical lymph nodes (Outlines).
§ Nature: neoplastic or reactive still controversial (Rosai). May be a cousin of oncocytosis but with lymphoid stroma (Rosai)
§ Genetics: molecular studies indicate it is not clonal (Outlines).
§ Origin: arise from entrapped salivary ducts (striated ducts because full of mitochondria, Steinberg) in intra/peri-parotid LN (Goldblum; most accepted theory although under debate, Steinberg).
§ Prognosis: nearly never recurs (Rosai). 2-5.5% post-excision recurrence rate (WHO). Malignant transformation rare but possible (1%; from either epithelial or lymphoid elements, WHO).
§ Rules of 10: 10% multicentric (synchronous or metachronus), 10% bilateral (no1 bilateral salivary gland tumor (Rosai, Robbins).
§ Ssx: asymptomatic slow growing mass (Goldblum). Uncommon and indolent (Robbins).
§ Treatment: lumpectomy (Goldblum), superifical parotidectomy (WHO) or enucleation (WHO). Resection almost always curative (Outlines)
§ Well-circumscribed, multicystic lesion with brown oil fluid (due to spontaneous hemorrhagic infarct, Goldblum, Rosai, Steinberg). Sometimes clear fluid, Lester).
§ Double-layered oncocytic epithelium (cuboidal to columnar with palisaded nuclei, creating tram-tracking nuclear appearance (Goldblum). No MEC (Rosai, Lit). Sometimes ciliated (Rosai). Dense LN-like stroma with germinal centers (mainly polyclonal B cells with some T, mast cells and dendritic cells) (Rosai). Occasionally lymphoid component minimal/absent (Rosai).
§ cystic spaces filled with fluid, desquamated epithelial or lymphoid cells (Goldblum).
§ dual-layered oncocytes are different immunohistochemically (Rosai)
§ hemorrhagic infarct common, either spontaneous or due to FNA, leading to foreign body giant cell reaction, fibrosis, squamous metaplasia and necrosis (Goldblum). Often misinterpreted as SCC or necrotizing sialometaplasia (Rosai)
§ thin capsule (WHO).
§ Malignant transformation: possible but extremely rare (Rosai). Both components possible: lymphoid stroma (lymphoma), epithelium (MEC, adenocarcinoma, SCC, oncyctic carcinoma, Merkel cell carcinoma) (Rosai)
§ Patterns: papillary-cystic architectures (WHO)
IHC
§ CK+ (Rosai)
DD
§ Squamous cell carcinoma (Rosai): careful not to overinterpret degenerative changes (squamous metaplasia) in Warthin’s tumor (Rosai)
Variants
§ Tumor, Warthin, metaplastic
§ Just infarcted or infected Warthin’s tumor with significant foreign body giant cell reaction, inflammation, squamous metaplasia, fibrosis, coagulative necrosis, increased atypia and mitoses following cyst rupture
ONCOCYTOMA (oxyphilic adenoma)
§ Clin: old women in parotids
§ Micro -small and brown
§ -oncocytic cells
§ SS:-PASD+granules
§ EM:mitochondria
§ Ddx: acinic cell ca, clear cell ca
Clinical
§ Uniform, associated with oncocytosis, benign tumor, elderly white, parotid mostly, cured with excision, exclusively of oncocytes, no atypia, no mitoses, no infiltrative, well-circumscribed, sometimes clear cytoplasm, characteristic tan-colored well-circumscribed mass, RF=radiation, malignant equivalent exists,
§ Aka oncocytoma, oncocytic adenoma, mitochondrioma (Rosai, Goldblum).
§ malignant form is oncocytic carcinoma (Rosai)
§ Associations: often with oncocytosis (oncocytic hyperplasia, Goldblum).
§ Def: benign tumor exclusively composed of oncocytic cells (Rosai).
§ Demo: 70-80yo Caucasians (Goldblum)
§ RF: 1/5 with radiation exposure (therapeutic or occupational) (Rosai, Goldblum).
§ Incidence: 1% of all benign parotid tumors (Goldblum).
§ Locations: parotid (80-90%), sometimes submandibular gland (Goldblum, Rosai). 7% bilateral (Goldblum).
§ Nature: putative neoplastic process (therefore not sure, Goldblum).
§ Prognosis: recurrence minimal (Goldblum). Curative with local excision (Rosai)
§ Ssx: slow-growing mass (Goldblum).
§ Treatment: superficial/total parotidectomy (Goldblum)
§ Soft, well-circumscribed nodule (Goldblum). Characteristic tan-colored (Rosai) (remember oncocytoma of kidney is mahogony-colored with central stellate scar, me)
§ Oncocytes are large UNIFORM polygonal cells containing uniform, round, centrally nuclei with/without nucleoli and abundant oncocytic (deeply eosinophilic and finely granular; may be clear due to processing artifacts) cytoplasm (Goldblum).
§ no atypia (mild pleomorphism permitted), no mitoses, no infiltrative growth (Rosai).
§ sometimes clear cytoplasm due to cystic dilation of mitochondria (Rosai).
§ Malignant: inflitrative, mitoses, atypia (Rosai)
§ sometimes intraluminal psammoma bodies or tyrosine-rich crystals (Rosai)
§ well-circumscribed with variably thick encapsulation (Goldblum).
§ Patterns: solid, acinar, trabecular, papillary-cystic or follicular (Goldblum)
IHC
§ Some oncocytes may contain glycogen (Rosai)
DD
§ Warthin tumor (Goldblum): Warthin has lymphoid elements and oncocytic hyperplasia often blending with surrounding parenchyma
§ Acinic cell adenocarcinoma (Goldblum)
§ Oncocytic hyperplasia (Goldblum)
§ Renal cell carcinoma (Goldblum): vs clear cell variant of oncocytoma.
§ Oncocytic carcinoma (Goldblum): atypia (Rosai), necrosis (Goldblum), mitoses (Rosai), infiltrative growth (Rosai)
Variants
§ Clear cell: if majority of oncocytes have clear cytoplasm (Goldblum). You STILL can find some scattered cells with eosinophilic granular cytoplasm (Goldblum)
CANALICULAR ADENOMA
§ Minor salivary glands,
§ Benign epithelial salivary gland neoplasm characterized by chains of columnar cells and almost invariable preference for MINOR SALIVARY GLANDS (Goldblum; was thought to be a variant of basal cell adenoma but separated now due to minor salivary gland predisposition, Rosai). Classically in upper lip of old female Blacks (70yo) (Goldblum). Second most common benign salivary gland neoplasm of upper lip (Goldblum). Usually solitary (Goldblum). Asymptomatic. 1% of all salivary gland tumors but 4% of all minor salivary gland tumors (Goldblum). Treated with simple excision; low recurrence (Goldblum)
§ Well-circumscribed but non-encapsulated. Solid or cystic (Goldblum)
§ Mass composed of long single layered strands or tubules of variable size within loose lightly collagenized stroma (Goldblum). These strands run parallel to each other with thin canal-like space in between , then attach to each other and separate (see Fig 11.13 in Goldblum), creating a beaded appearance (Goldblum). Cells usually columnar but can be cuboidal to basaloid with eosinophilic cyto and basophilic oval nuclei (Goldblum). Minimal atypia and mitoses (Goldblum).
DD
§ PA (Goldblum)
§ Basal cell adenoma (Goldblum)
§ AdCC (Goldblum)
§ PLGA (Goldblum)
SEBACEOUS ADENOMA
§ Purely sebaceous, always in parotid, sebaceous lymphadenoma variant if lymphoid stroma, fat+, ddx include all clear cell neoplasm from clear cell myoepithelioma, RCC, mucoepidermoid carcinoma, acinic cell carcinoma,
§ Def: benign epithelial neoplasm PURELY composed of proliferating, incompletely differentiated sebaceous glands (Goldblum).
§ Incidence: <1% of all SG neoplasms (Goldblum).
§ Locations: rare outside of parotid (Goldblum).
§ malignant counterpart called sebaceous carcinoma (Rosai)
§ Variant: sebaceous lymphadenoma if with prominent lymphoid stroma (Rosai). May be unilocular cystic mass (Rosai)
Immuno
§ + for fat (Rosai)
Ddx
§ Clear cell myoepithelioma (Rosai): + for glycogen
§ Met RCC (Rosai): + for glycogen, CD10, vimentin but – for HMK and CEA
§ Acinic cell carcinoma (Rosai): – for all nonimmune stains
§ Mucoepidermoid carcinoma (Rosai): + for mucin
LYMPHADENOMA
§ Same as sebaceous lymphadenoma but not sebaceous differentiation,
§ Epithelial glandular cells with lymphocytes but lack sebaceous differentiation (Rosai)
SEBACEOUS
§ Variant of sebaceous adenoma,
§ Etio: possibly arising from entrapped salivary gland tissue within intra/peri-parotid LN (Goldblum, Rosai).
§ malignant counterpart called sebaceous lymphadenocarcinoma (Rosai)
§ Ssx: other clinicopathologic features are similar to sebaceous adenoma
§ Def: rare variant of sebaceous adenoma with dense lymphoid stroma (Goldblum).
§ Basically sebaceous adenoma with prominent lymphoid stroma (Rosai).
NON-SEBACEOUS
DUCTAL PAPILLOMA
§ Locations: usually in minor SG (Rosai). Only case reports in major SG (Rosai)
§ Precursor to what???
INVERTED
INTRADUCTAL
SIALADENOMA PAPILLIFERUM
CYSTADENOMA
MYOEPITHELIOMA (not in WHO)
§ -benign tumor
§ -spindle and/or plasmacytoid cells with herringbone/stroriform/swirling pattern
§ -CK,S-100 + essential for diagnosis
§ Ddx: BFH, PNST, LM
§ ENTIRELY of MEC, 3 types including spindle, plasmacytoid and clear cell, malignant if invasion and atypia, BENIGN,
§ Def: benign epithelial SG neoplasm composed predominantly/ENTIRELY of MEC (Goldblum, Rosai).
§ Etio: de novo or from malignant transformation of PA or basal cell adenoma (Rosai)
§ Locations: mainly parotid for spindle and clear cell types but mostly minor SG for hyaline cell type (Rosai)
§ Origin: may represents end of spectrum of PA without or with rare ductal structures (Goldblum).
§ Prognosis: most hyaline cell variant benign but still with rare exceptions (Rosai). Spindle and clear cell variants more often malignant (Rosai). Some even say that all clear cell myoepithelioma (aka epithelial-myoepithelial carcinoma) should be regarded as potentially malignant (Rosai)
§ Spreads: local invasion, LN, distant mets (Rosai)
§ Plasmacytoid or spindle cells prevail (Goldblum)
§ 3 cell types by morphology (Rosai): intermediate or combined forms possible (Rosai).
Ø Spindle cell: stormalike spindle cells often confused with lesions of fibroblasts, Schwann cells or smooth muscle cells (Rosai).
Ø Hyaline (plasmacytoid) cell: eccentric nuclei, some degree of atypia, no mitoses (Rosai). Abundant DIFFUSELY eosinophilic cytoplasm which differs from fine GRANULAR cytoplasm in oncocytes (Rosai). Polygonal cells with sharp outlines (Rosai). Resembles neoplastic plasma cells or skeletal muscle cells (Rosai)
Ø Clear cell (aka epithelial-myoepithelial carcinoma, Rosai): small tubules lined by one layer of cuboidal cells surrounded by one or more layers of clear cells. Hyalinlike material separating into nests (Rosai). Good pattern recognition. Contains glycogen but no fat (Rosai).
§ Malignant: invasion and atypia (Rosai)
Variants (Rosai)
Ø Oncocytic: granular eosinophilic cytoplasm in scanty collagen stroma. Microcystic formation or lipomatous metaplasia sometimes (Rosai). Collagenous crystalloids sometimes (Rosai)
IHC
§ Glycogen+ in clear cell variant (Rosai)
DD
§ Sebaceous neoplasm (vs clear cell myoepithelioma, Rosai): + in fat vs + in glycogen in clear cell myoepithelioma
§ Metastatic RCC (vs clear cell myoepithelioma, Rosai)
§ Mucoepidermoid carcinoma (vs clear cell myoepithelioma, Rosai)
§ Acinic cell carcinoma (vs clear cell myoepithelioma, Rosai)
MALIGNANT EPITHELIAL TUMORS
§ Acinic cell carcinoma
§ Mucoepidermoid carcinoma
§ Adenoid cystic carcinoma
§ Polymorphous low grade adenocarcinoma
§ Clear cell adenocarcinoma
§ Sebaceous carcinoma
§ Carcinoma ex pleomorphic adenoma
§ Squamous cell carcinoma
§ Small cell carcinoma
§ Large cell carcinoma
§ Hemangioma
§ Lymphoma
§ -Hodgkin lymphoma
§ -Extranodal marginal zone lymphoma
§ -Diffuse large B cell lymphoma
MALIGNANT
***perineural invasion common theme in all malignant salivary gland tumours
ACINIC CELL CARCINOMA
§ Clin: parotid, facial nerve paralysis, recurrence
§ Micro:-abundant granular, basophilic cytoplasm with small nuclei
§ -resemble the serous glands of the salivary gland
§ -parotid usu
§ -can be bilateral
§ SS: DPAS+ zymogen granules
§ EM: secretory zymogen granules
§ IHC: CK, not useful
§ Treatment: surgery
§ Prognosis: good
§ Incidence (no2 tumor, no2 malignancy in kids, no2 malignancy in parotid) (think of locations of normal serous cells). Gross (small friable mass, sometimes cystic). Dx (acinar cells basophilic and always present, lymphoid follicles in tumor periphery, EM for zymogen granules, look for anaplasia/dedifferentiation, grading controversial). Outcome (slow-growing but can locally recur and mets mostly to LN).
Clinical
§ Aka acinous cell carcinoma, acinic cell adenocarcinoma (WHO).
§ Def: epithelial neoplasm with at least some cells demonstrating serous acinar cell differentiation with cytoplasmic zymogen secretory granules (WHO, Goldblum).
§ Demo: slightly more in females (3:2) (WHO). Wide range of age distribution (peak 30, Rosai) without sparing ados and kids (WHO). 20-70yo with mean of 44 (Goldblum). Males predominance with peak in 30 (Rosai).
§ EM: zymogen granules similar to normal serous acinar cells (Goldblum, Rosai)
§ Genetic: largest study (n=25) shows that 84% have LOH at about 20 different loci on chromosomes 1, 4, 5, 6 and 17 but mostly affecting 4p, 6p, 17p regions (WHO). Read WHO p218 for molecular genetics.
§ Grade: LG (Lester)
§ Incidence: 6% of all SG neoplasms and 7-17% of all malignant ones (Goldblum). No2 malignancy in kids (Goldblum). 1-3% of all SG tumors (Rosai). No2 malignancy in parotid (Rosai)
§ Locations: parotid (80%)> minor SG (17%)>>> others (WHO, Steinberg). Rare in minor SG because serous cells rare in normal minor SG (Steinberg). No2 malignancy in parotid (Rosai)
§ Nature: by definition, low grade tumor (Lit); but high grade reported (Goldblum).
§ Origin: most think it’s neoplastic transformation of terminal duct cells (intercalated duct cells) with serous acinar differentiation (WHO).
§ Prognosis: 35% local recurrence with 82%, 68%, 55% of 5-, 10- and 20-yr survival (Goldblum, Rosai). Behavior not correlated with growth pattern (Goldblum). Probable poor prognosis if large, deep, multifocal, severe atypia, mitoses, necrosis and neural invasion (Goldblum) and stromal hyalinization (WHO). Ki67 maybe independent prognosticator (Goldblum, WHO). Focal but rare anaplastic (dedifferentiated) component associated with accelerated clinical tempo (Rosai). Related to degree of anaplasia (Steinberg). Generally poor on long-term follow-up (Steinberg). Well-encapsulated tumor of small size more likely to have benign course (Steinberg). Aggressivity: submandibular> parotid> minor SG (WHO). Adequacy of initial excision most important: wide excision has lower recurrence rate than local excision (Rosai).
Ø Prognostic factors: pain or fixation, gross invasion, desmoplasia, atypia, increased mitoses, adequacy of initial excision (most important) (Rosai)
§ preads: can locally recur and mets (mostly to cervical LN but also lungs (Rosai, WHO). Usually small but about 1/6 metastasize to regional LN (Robbins). Slow growing (up to several decades) but 10% with facial nerve involvement (Goldblum). Spread to local LN, lung and bone (Goldblum).
§ Ssx: slow-growing mass sometimes with pain (1/3) and palsy (1/10) (WHO).
§ Treatment: excision with clear margins ideally (Goldblum). Neck dissection necessary only if LN clinically involved (Rosai). Radiation controversial (Rosai).
Gross
§ Small (<3cm) encapsulated mass with friable, grayish cut surface (Rosai, WHO). Cystic sometimes (Rosai, Lester).
Micro
§ Most tumors have mixture of all cell types and patterns although serous acinar and intercalated ductal cells tend to prevail (WHO).
§ 4 patterns (WHO, Rosai)
Ø Follicular: closely mimicking thyroid follicular carcinoma: cystic spaces lined by intercalated duct-like cells with scalloped eosinophilic proteinaceous fluid in lumina (Goldblum).
Ø Microcystic: no1 pattern, small spaces within tumor, giving lattice-like appearance; resembling solid lobule punched with numerous small spaces ranging from microns to mm; most often composed of mixture of acinar/vacuolated/intercalated cells (WHO)
Ø Papillary-cystic: larger cystic spaces than microcystic, partially filled with intraluminal papillary projections; sometimes hobnailing appearance; usually quite vascular with common intraluminal hemorrhage/hemosiderin (WHO)
Ø Solid: often predominantly composed of serous acinar cells (WHO). Solid growth composed of cells resembling normal serous cells of salivary glands (Steinberg).
§ 5 cell types (WHO, Rosai): tumor differentiates into all components of terminal ductular-acinar unit of SG (Rosai)
Ø Clear cells: from myoepithelial cells (Rosai). Similar in shape and size to acinar cells but clear cytoplasm with PAS- (WHO). No cytoplasmic glycogen but due to artifact or rough ER dilatation (WHO). Usually only FOCAL and should not cause diagnostic difficulty (WHO). Resembles RCC when clear cell predominate (Rosai). Contains glycogen but no fat (Rosai)
Ø Intercalated ductal cells: from intercalated duct cells (Rosai). Smaller cuboidal cells containing less, eosinophilic, central nuclei and surrounding variably sized luminal spaces (WHO)
Ø Nonspecific glandular cells: polygonal/round, smaller than serous acinar cells, PAS/D-, no zymogen granules, often form sheets with indistinct borders (WHO)
Ø Serous acinar cells: from serous acinar cells (Rosai). Always present (WHO). Resembling normal serous acinar cells (WHO). Large, polygonal cells containing basophilic, granular cytoplasm with grayish/blue zymogen granules, round eccentric, sometimes vesicular nuclei, PAS+/D- cytoplasmic zymogen-like granules (mucicarmine-) (WHO). Relatively uniform with granular or clear cytoplasm reminiscent of serous cells (Steinberg). Cells have abundant, slightly basophilic, granular cytoplasm with centrally placed small nucleus (Steinberg).
Ø Vacuolated cells: common, similar size to intercalated ductal cells, contains PAS/D- cytoplasmic vacuoles, sometimes zymogen granules (WHO, Goldblum).
§ intraluminal psammoma sometimes and numerous (Goldblum, Rosai, WHO).
§ prominent lymphoid follicles common and often in tumor periphery (Rosai, Goldblum). No prognostic value but should not be interpreted as nodal mets, WHO).
§ secretory or clear vacuoles are positive for PAS (Steinberg)
§ sometimes well-circumscribed and encapsulated (Goldblum).
§ Dedifferentiation (anaplasia): omninous event (Rosai)
§ Grading: not universally accepted and no correlation with prognosis and the four major growth patterns (Goldblum). Brief, staging often better outcome predictor than histomorphologic grading (WHO, Goldblum).
IHC: usually unpredictable and not helpful (Goldblum)
§ Acinic cells: CK+ (Rosai, WHO), PAS+/D- zymogen granules (Goldblum, WHO; should be useful in diagnostic, me), CEA+ (WHO) amylase+/antichymotripsin+/transferrin+/lactoferrin+/IgA+ (Rosai, WHO), S100- (but 10% cases can be +, Goldblum), PAS-/PAP- (sometimes +, WHO), ER/PR- (sometimes +, WHO)
DD
§ Normal salivary gland (Goldblum): sometimes a problem. Zymogen granules, vacuolated cells and intercalated cells help
§ Sialadenitis (Goldblum): sometimes a problem. Zymogen granules, vacuolated cells and intercalated cells help
§ Cystadenocarcinoma (Goldblum): vs papillary-cystic or microcystic variants. Zymogen granules, vacuolated cells and intercalated cells help
§ Mucoepidermoid carcinoma (Goldblum): vs microcystic variant sometimes
§ Thyroid carcinoma (Goldblum): vs follicular variant. Use thyroglobulin staining
§ Clear cell tumors (Goldblum, Rosai): vs clear cell variant of AcCC. Rarely a problem because clear cells in AcCC are usually focal (Goldblum)
MUCOEPIDERMOID CARCINOMA
§ -usu in the parotid
§ Gross: well-circ., solid and cystic,no capsule, infiltrative margins
§ Micro:
§ -squamoid nests with “mucous cells” (mucicarmine +),
§ note: mucous cells often contained within the epidermal nests
§ note: Mayer’s mucicarime +, so, background is blue and the stain is red
§ Grade: (neural invasion, cystic <20%, MAN)
§ Treatment: surgery
§ Prognosis: dependent on grade
§ Gross (blue cyst if LG but poorly circumscribed solid if HG). Dx (3 components including squamous/mucin-producing/intermediate, grading important). AFIP grading (>4/10, anaplasia, intracystic <20%, neural invasion, necrosis). Incidence (several no1′s including no1 malignancy in all ages and all SG except minor SG where AdCC is no1. Outcome (not as aggressive as AdCC, parotid mostly, 50 females but also in kids). Spreads (LN). Ddx…
§ Def: characterized by mucous, intermediate and squamous cells with columnar, clear cell and oncocytic cells (WHO).
§ Demo: wide uniform age distribution but most in 50yo females (3:2) (Goldblum, WHO). Relatively more common in kids than other SG tumors (Steinberg)
§ EM: both luminal epithelial and myoepithelial cells present (Rosai; odd, Steinberg p416 says no myoepithelial cells because mucoepidermoid carcinoma arises from ductal segment lacking myoepithelial cells).
Genetics
§ T(11;19) MECT1-MAML2: in >50% (translocation also found in acute leukemia) (Lester, WHO). This fusion transcript formed by MECT1 (mucoepidermoid carcinoima translocated gene-1 at 19p13, unknow function) with MAML2 (mastermind-like gene family at 11q21) (WHO). This chimeric transcript activates notch target genes (WHO).
Clinical
§ Grade: variable (Lester)
§ Incidence: no1 malignancy in all ages (both kids and adults) and in major SG (Lit, Goldblum, Steinberg, Rosai, WHO). No2 malignancy in minor SG (after AdCC) (Rosai). 15% of all SG tumors (Lit).
§ Locations: parotid (45%, WHO)> minor SG (palate and buccal mucosa, WHO)> submandibular (7%, WHO)> sublingual (1%, WHO). Where else can this occur beside in salivary gland?
§ Prognosis: grade (no1), margins, locations (submandibular, mouth floor and tongue worse), LN, staging (Lit, Goldblum). Better if young, female, in parotid (Rosai). Bad if extraglandular invasion, vascular invasion, necrosis, high mitoses, high proliferation index, DNA ploidy, activation of ERK1/ERK2 pathway? (Rosai). LG good prognosis (>95% 5-year survival) vs HG bad (55% with high grade) (Rosai, Robbins, Goldblum). Most recurrences/mets occur within 5 first years vs continuous over 20 years in acinic cell and adenoid cystic carcinomas (Rosai). Not as aggressive as adenoid cystic carcinoma (Steinberg).
§ Spread: via nodal drainage (parotid-> preauricular-> submandibular LN (WHO); submandibular SG-> submandibular LN-> upper jugular lymphatic chain; palate-> upper respiratory tract and skull base; lip-> submental LN; intraoral tumors-> submandibular LN-> post-auricular-> upper accesory LN) (WHO).
§ Ssx: painless, fixed, slow growing mass with accelerating growth immediately before clinical presentation (Goldblum). Pain, otorrhea (skull base erosion), dysphagia, trismus possible (Goldblum).
§ Treatment: surgery still ideal (Goldblum).
§ Intraoral tumor often BLUISH-red and fluctuant, resembling mucocele (Goldblum). Overlying mucosa sometimes papillary (WHO). Well-circumscribed blue cyst containing mucin if LG vs infiltrative solid if HG (Goldblum, Rosai).
§ although traumatic sialoceles and mucoceles can occur, any mucin-filled cystic spaces in parotid require additional sections to rule out well-differentiated MEC (Rosai)
§ Cysts lined by mixture of all 4 cell types and filled with mucus (Goldblum).
3 cell types (Rosai, Goldblum, Steinberg)
§ Squamous cells: uncommon, scattered, with rare keratin pearl (Goldblum). Keratinization extremely rare (Goldblum, WHO)
§ Mucus-producing cells: larger, pale, with clear abundant cytoplasm, peripheral nuclei, singly or clustered, may be scanty but highlightable with mucicarmine or Alcian blue (Goldblum). Typically <1/10 of tumor cells (WHO).
§ Intermediate cells: dominant cell population (WHO). Ranging from basaloid cells to larger more oval cells with abundant eosinophilic cytoplasm (WHO). In clusters or sheets (WHO).
§ Clear cells: 4th cell type only listed by Rosai but not by Goldblum or Steinberg
§ Minor cell types: clear (D sensitive/PAS+ clear cytoplasm indicating glycogen and no sialomucin, small centrally placed nuclei, focal and quite common, WHO), columnar cells (rare) and oncocytes (occasionally) (Goldblum; occasionally constitute dominant population, WHO). Mucuous cells prevails in low-grade but intermediate, squamous and clear cells predominate in high grade tumors (Rosai). Quite confusing here: high grade tumor has necrosis, high mitoses, severe atypia (Goldblum); but Rosai says marked atypia, frequent mitoses and extensive necrosis often not typical of mucoepidermoid carcinoma of any grade and should think about poorly differentiated adenocarcinoma and adenosquamous carcinoma (Rosai). Quite variable proportion of different cell types and architectures (including cyst formation) (WHO). Neural invasion, necrosis, increased mitoses and anaplasia uncommon (WHO).
Micro
§ difficult to differentiate from mucocele; sometimes better diagnose as mucus-producing lesion (Goldblum).
§ lymphocytic infiltration common and can mimick nodal invasion at periphery of tumor (WHO, Goldblum).
§ marked atypia, numerous mitoses, extensive necrosis NOT typical of mucoepidermoid carcinoma of ANY grade (Rosai). Alternative diagnosis such as PD adenocarcinoma or adenosquamous carcinoma should be considered (Rosai). Recently a case with dedifferentiation has been reported (Rosai)
§ remember multicystic with solid areas (sometimes solid predominates, WHO).
§ secondary changes such as inflammation, hemorrhage, cholesterol clefts and fibrosis (sometimes extensive) if mucin or keratin escape into stroma (Rosai, Goldblum).
§ stromal hyalinization common (Goldblum).
Grading (AFIP): intracystic component greater than 20% (2 points), neural invasion (2 points), necrosis (3 points), >4/10 mitoses (3 points), anaplasia (4 points) (last 3 form “MAN”) (Rosai, AFIP).
§ Grading important but none universally accepted (Lit, WHO). Recent grading system using 5 histomorphologic criteria (apparently quite reproducible, WHO; grading system not predictive of prognosis in submandibular tumors, Lester): intracystic component <20%, neural invasion, necrosis, mitoses >4/10HPF, anaplasia (Goldblum says this system is less reliable for submandibular gland). Goldblum says grading relies on subjective evaluation of relative proportions of various cell types, atypia, mitoses, necrosis and invasion. Low grade often cystic with abundant mucocytes and minimal atypia and mitoses but invasion often obvious (Goldblum). High grade is more cellular, less cystic, only few mucocytes (predominately squamous cell carcinoma-like cells) (Goldblum). However, interobserver reproductibility for tumor grading is moderate to poor even among Head and Neck Pathologists (Lit).
§ HG (7 and above): more solid with infiltrative border (Rosai). Squamous, intermediate and clear cells predominate in microscopy (Rosai). About 50% 5-year survival (Rosai)
§ IG (5-6)
§ LG (0-4): well-circumscribed mass with cystic areas containig mucin (Rosai). Mucin-producing cells predominate in microscopy (Rosai). About 100% 5-year survival (Rosai)
§ Permitted: focal sebaceous differentiation (Rosai)
Variants
§ Oncocytic: rare (Rosai)
§ Sclerosing (WHO)
Immuno (no diagnostic value, Goldblum)
§ CK+ (pos for intermediate, squamous and columnar cells, inconsistent for clear cells, neg for mucocytes, Goldblum). EMA+ (most tumor cells, Goldblum), PAS/mucicarmine/alcian blue+ (sialomucin in mucocytes, WHO, Goldblum). Mucicarmine highlight mucinous component (Steinberg)
§ Squamous cells: HMK+ (very useful because squamous cells quite scattered, WHO)
DD
§ Necrotizing sialometaplasia (Goldblum, WHO): both have squamous proliferation and mucocytes in inflamed fibrous stroma. NSM usually lobular distribution without intermediate cells or cyst formation (Goldblum).
§ Cystadenoma (Goldblum, WHO)
§ Cystadenocarcinoma (Goldblum)
§ Squamous cell carcinoma (Goldblum, WHO): especially vs high grade MEC. But presence of rare mucocytes (use immuno) can differentiate MEC from SCC. Furthermore, it’s extremely rare for MEC to show keratinization
§ Mets (WHO
ADENOID CYSTIC CARCINOMA
Gross
§ Solid, gray-pink, small, not WC
§ Palate > PG, SMG> nose, sinus, upper airways
Micro
§ Nests of cells with punched out pseudocysts “cylinders” (mucopolysaccharide) “cribriform”
§ Solid, tubular, cribriform[83]
§ Small cells, dark angulated nuclei, scant cytoplasm
§ PNI common
IHC
§ “ Blue goo” pseudocystsà PAS+, AB+
§ Epithelialà LMK
§ MECà p63, SMA, S100
Prognosis
§ Recurrent, mets to lungs, rarely LN, 60% 5yr
Clinical
§ No1 malignancy in MSG
§ No3[84] SG cancer in adults
§ Basaloid[85] tumor composed of epithelial and MEC, cribriform with pseudocysts filled with BM-like material and true glands filled with mucus
§ All age, peak 40-60
§ Painful (from PNI)
§ Slow growing, stubborn recurrences, ultimately fatal[86]
§ Spreads to lung, bone, brain and liver[87]
§ MSG (50%, especially palate)> PG[88] (20%)> SMG (15%)> sinonasal (10%)> lacrimal glands, trachea
§ Origin: MEC[89] (Steinberg)
Treatment
§ Wide local excision[90]
Outcome
§ 60% 5-year, 40% 10-year (Goldblum)
Prognosis
§ PNI[91]
§ Grading[92] (Lit says important to grade this…)
§ Site[93]
§ Stage[94]
§ Primary surgery failure
EM
§ Combined features of intercalated ducts, MEC, secretory cells and pluripotent reserve cells, similarly to PA, suggesting similar histogenesis (Rosai)
Genetics (Rosai)
§ P53 uncommon unless during dedifferentiation
§ Alterations at 6q, 9p, 17p and t(6;9) (WHO).
§ 6q translocations and deletions in >50% (Lester)
Gross
§ Solid[95]
§ Invariably infiltrative border
Micro
§ Basaloid cells
Ø Small cells, uniform, dark compact nuclei, scant cytoplasm
§ Nests separated by hyalinized[96] BM-like material
§ Pink PAS+ in ?
§ True glands required for diagnosis
§ PNI
§ 2 cell types (Goldblum, WHO)
Ø Abluminal MEC: uniform, dark angulated nuclei, indistinct borders, blue to clear cytoplasm, more in number
Ø Luminal ductal cells: cuboidal with more abundant pink cytoplasm, round uniform nuclei, +/-small nucleoli
§ 3 patterns[97]
Ø Cribriform (no1): nests or columns of bland but dark (MEC) cells around pseudocystic spaces filled with granular basophilic mucoid or PAS+ eosinophilic hyaline material (WHO, Rosai). Basophilic is mucin/glycoaminoglycans; hyaline eosinophilic is duplicated basement membrane (Goldblum, Rosai).
Ø Tubular (no2): ducts/tubules surrounded by inner ductal cells and outer MEC (WHO). TUBULAR variant is double-layered with more conspicuous ductal differentiation (Goldblum).
Ø Solid: many are mixed, either in primary or recurrent disease (Goldblum, Rosai). Solid variant: sheets of basaloid cells with larger and less angular nuclei; comedonecrosis common (Goldblum).
§ can coexist with other tumor types (Rosai)
§ combination of cystic and glandular spaces required for diagnosis (Steinberg)
§ mitoses possible but more in solid variant (Goldblum).
§ perineural invasion nearly always present (Steinberg) and accounts for recurrences 10-20 years after resection (Steinberg)
§ remarkable propensity for PERI/INTRA-NEURAL INVASION (can extend along nerves for considerable distance beyond clinically apparent tumor boundaries, WHO) to the point that you must question this diagnosis if perineural invasion absent (Rosai).
§ smaller TRUE glandular lumina/ducts always present in all forms (Rosai, WHO). Identification of both pseudocysts and true glandular lumina are required for diagnosis (Rosai, Lit).
§ look for anaplasia because can dedifferentiate (Rosai). Associated with p53 mutation (Rosai)
§ Grading based on pattern (Rosai)
Ø Cribriform: 90% recurrence
Ø Solid: 100% recurrence
Ø Tubular: 60% recurrence
§ Grading based on solid area (Lit): most common used grading criteria is proportion of solid area (Lit). However tumor grading on prognosis is still controversial (Lit). TMN staging is still the best indicator (Lit).
Ø Grade 1: no solid
Ø Grade 2: <30% solid area
Ø Grade 3: >30% solid area (Lit).
IHC
§ Cells around true glandular lumina express intercalated duct phenotype: CK+, CEA+, lysozyme+, lactoferrin+, antichymotrypsin+, S100+, CD117+ (Rosai; C-kit overexpression and biological implication remains unknown, WHO)
§ Cells around pseudocysts express myoepithelial phenotype: S100+, SMA+ (muscle marker), p63+, calponin+ (smooth muscle marker), variable CK+ (epithelial component of MEC) (Rosai)
§ Inner membrane of pseucysts: strong laminin+, collagen IV+, heparan sulfate proteglycan+ (Rosai)
§ PAS+ (eosinophilic pseudocyst content), Alcian blue+ (basophilic pseudocyst content)
DD
§ PA (Rosai, WHO): can be difficult and immuno does not help (Rosai). But AdCC often has perineural invasion and more infiltrating and lack mesenchyme and squamous metaplasia of PA (Rosai)
§ PLGA (Goldblum, Rosai, WHO): similar patterns of growth but PLGA has more uniform cell population and bland cytology (vs more angulated and hyperchromatic nuclei in AdCC). Immuno CD117 and galectin3 may help because neg in PLGA (Goldblum, Rosai). Should be an easy differential because nearly never occur in major salivary glands (Rosai)
§ Basaloid SCC (Goldblum): vs solid variant of AdCC. Basaloid SCC more often in hypopharynx and glottic region and shows squamous differentiation and involvement of overlying squamous epithelium
§ Epithelial-myopeithelial carcinoma (Goldblum): vs tubular variant of AdCC. Both have tubular structures but other cytologic features will ddx them
§ Basal cell adenoma/adenocarcinoma (WHO)
POLYMORPHOUS LOW GRADE CARCINOMA
§ -minor salivary glands (hard and soft palate)
Micro
§ Low power: well circ. w/ focal areas of infiltration
High power:
§ -mult. salivary gland patterns, none predominate
§ -bland cytology
§ -targetoid pattern around nerves, bv, normal salivary gland structures
§ Architectural diversity, cytologic uniformity, infiltrative growth but low grade, only in minor SG, ddx include PA and AdCC,
§ Aka terminal duct carcinoma, lobular carcinoma (WHO, Rosai).
§ Grade: LG (Lester)
§ no myoepithelial differentiation (Lit).
§ Def: low grade tumor characterized by architectural diversity, cytological uniformity, infiltrative growth and low metastic potential (Lit, Goldblum, WHO).
§ Incidence: relatively common (about 1/4 of all minor salivary gland malignancies, Lit, Goldblum). No2 intraoral SG malignancies (WHO).
§ Locations: only minor SG of palate (60% cases, no1 site; especially at junction of hard/soft palates), buccal mucosa, upper lip, retromolar areas (Lit, Goldblum). Cases in major SG always occur in background of PA (Rosai)
§ Demo: mostly females (2:1) from 16-94yo (peak 60 and most between 50-70, WHO, Lit).
§ Ssx: painless, slow-growing, firm, palatal mass; ulceration, bleeding and pain rare (Lit, Goldblum).
§ Outcome: excellent (Goldblum). 9-17% local recurrence (Goldblum, WHO). 9-15% regional LN but distant mets very rare with very low disease specific death (Goldblum, WHO).
§ Treatment: conservative surgery (with neck dissection if proven regional mets, WHO, Goldblum).
§ Most <2cm (Lit). Bone invasion possible (Lit). Often circumscribed but non-encapsulated (Goldblum, WHO). Intact overlying epithelium (Goldblum)
§ WELL-CIRCUMSCRIBED, non-encapsulated with peripheral infiltration (infiltration always present despite bland cytology, Lit, WHO, Goldblum). Overlyig intact epithelum (Goldblum; sometimes ulcerated, WHO). Composed of combination of patterns: LOBULAR, PAPILLARY-CYSTIC (typically focal, WHO), SOLID NESTS/THEQUES, CRIBRIFORM (resembling AdCC, WHO), DUCTAL (lined by single layer of cuboidal cells, WHO). Central area usually solid, cribriform and tubules (Lit). Tubules and ducts lined by single layer of simple cuboidal cells. Perivascular/perineural involvement quite common, often in TARGETOID arrangement (Lit; but less around blood vessels, Goldblum). Psammona sometimes (Lit). Invariably bland cytology (Lit). Mitoses rare (<1/10, WHO). Metaplastic changes (oncocytic, clear, squamous, mucous) sometimes (WHO)
§ Normal salivary gland parenchyma often incarcerated within tumor (Goldblum). Characteristic stromal HYALINIZATION with slate-gray appearance or mucinous stroma common (Goldblum; Lit says always present, Lit). Mitoses and necrosis uncommon (Goldblum, WHO). Cells are uniform, small-medium with vesicular, round-oval nuclei and occasional nucleoli (Goldblum, WHO; in one word, BLAND)
Immuno (rarely of diagnostic value, Goldblum)
§ LMK+ (Lit), CK (100%, WHO, Goldblum), vimentin+ (Goldblum), S100+ (97%, WHO, Goldblum), EMA- (12%+, WHO), actin+ (only weak and focal), GFAP- (good antibody because pleomorphic adenoma is GFAP+ usually, Lit, Goldblum; 15%+, WHO), CEA+ (57%, WHO), MSA- (13%+, WHO), calponin- (Goldblum), galectin3+ (WHO), CD117 can be positive (therefore positive staining does not help differentiate from AdCC). BCL2+ (overexpressed in most cases, WHO, Goldblum)
DD
§ Plemorphic adenoma (Rosai, Lit, Goldblum, WHO): difficult in small biopsies. PLGA has lack of tubules with two cell layers or squamous differentiation, lobules of cartilage, caplonin and GFAP (Lit, WHO). Always circumscribed, triphasic proliferation (epithelial, myoepithelial and stromal) in PA (WHO). Perineural and stromal invasion not seen in PA. Even if both can have myxoid stroma, myxochondroid/chondroid matrix only in PA (WHO). Typical plasmacytoid myoepithelial cells typically seen in palatal PA not present in PLGA (WHO)
§ AdCC (Rosai, Lit, Goldblum, WHO): difficult in small biopsies. AdCC has two cell layer lining. More atypical cytology with higher NC (Lit). More destructive growth (Goldblum). Trabecular/papillary growth uncommon in AdCC (WHO)
§ Papillary variant of cystadenocarcinoma (Goldblum): more atypia and mitoses
§ Adenocarcinoma NOS (Lit)
EPITHELIAL-MYOEPITHELIAL CARCINOMA
§ Aka clear cell myoepithelioma???
§ Def: low-grade, biphasic, tumor characterised by duct-like structures formed by inner duct-like lining cells and outer myoepithelial-like cells (Lit, Goldblum, WHO).
§ Demo: females (2:1) 13-89yo with peak at 60-70 without sparing kids (Lit, Goldblum, WHO).
§ Incidence: 1% of all salivary gland neoplasms (Goldblum, WHO).
§ Locations: mostly in major SG, notably parotid (60%) but can rarely occur in minor SG of mouth and upper/lower respiratory tracts (Lit, WHO).
§ Prognosis: moderately aggressive with high recurrence (40%, Goldblum, WHO) and mets to regional LN, lung, liver and kidney in 15% (Goldblum, WHO). 80%, 72% for 5- and 10-year survival (Goldblum, WHO). Poor prognosis if incomplete excision (major prognostic indicator, WHO), large size, rapid growing, minor SG (mostly due to incomplete excision, WHO), atypia, mitoses, aneuploidy (Goldblum).
§ Ssx: slowly enlarging painless mass (facial pain and palsy in high-grade tumors, Goldblum, WHO).
§ Characteristically multinodular with expansive (well-circumscribed, usually non-encapsulated) borders (WHO, Lit, Goldblum) but poorly-circumscribed in minor SG (WHO). Hemorrhage and necrosis rare (Lit). Typically firm and white grossly (Lit). Often lobulated with cystic areas (Goldblum, WHO)
§ Lobulated growth with mixed tubular (hallmark double-layered duct-like structures) and solid arrangements (WHO, Goldblum). Papillary-cystic areas in 20% cases (WHO). Tumor in minor SG often have infiltration of surrounding tissue and surface ULCERATION (40%, WHO). Luminal cells (DUCTAL CELLS) often single, uniform, cuboidal/columnar with finely granular, eosinophilic cytoplasm and central round/oval nuclei (Goldblum, WHO). Outer cells (MYOEPITHELIAL CELLS) often single or multi-layered, large, polygonal with characteristically CLEAR cytoplasm (glycogen) and eccentric vesicular nuclei; sometimes spindly (Goldblum, Lit, WHO). Variable arrangement and proportion (Goldblum). Lumen often contains PAS+, mucicarmine- eosinophilic proteinaceous material.
§ foci of EMC can be found within CXPA as part of carcinomatous component (WHO).
§ Most often myoepithelial cells prevails over ductal cells in number (Lit). Ductal cells can be nearly absent (Lit). Low mitoses (<2/10) (Lit, Goldblum; especially in clear cell population, WHO). HYALINE or fibrous stroma (Goldblum). Perineural and vascular involvement common (Goldblum, WHO). Can dedifferentiate (WHO)
IHC
§ Ductal cells: LMK+/CAM5.2+/EMA+ (Goldblum, WHO)
§ MEC: PAS+ (glycogen, Lit), calponin+/SMA+/p63+ (Goldblum, WHO), S100 less reliable (Goldblum)
DD (include all clear cell tumors of SG, WHO)
§ Pleomorphic adenoma (Goldblum, WHO):
§ Myoepithelioma (WHO)
§ Oncocytoma (WHO)
§ Mucoepidermoid carcinoma (WHO)
§ Metastatic RCC and thyroid carcinoma (WHO): CD10+/HMK+ in RCC and TTF1+/thyroglobulin+ in thyroid carcinoma
CLEAR CELL CARCINOMA
§ Mostly minor SG, low grade, basket diagnosis, prominent hyaline stroma,
§ accompanied by prominent fibrohyaline stroma (therefore the proposed new term hyalinizing clear cell carcinoma) (Rosai)
§ Def: basket diagnosis because only descriptive (Rosai)
§ Incidence: rare (Goldblum).
§ Locations: oral cavity rather in major SG (Rosai)
§ Prognosis: low grade tumor (Lit).
Variant
§ Hyalinizing HCCC
Ø Uncommon. No myoepithelial differentiation (Lit). >90% in minor salivary glands (Lit). Low grade tumor with recurrence rate of 17%. 20% mets to neck LN. But no patient died (weird, Lit).
Ø Exclusively composed of round to polygonal cells containing abundant glycogen (Lit). Arranged in trabeculae, cords, nests and sheets surrounded by hyalinized PAS+ stroma (Lit). Focal loose myxoid stroma sometimes (Lit). No ductal or glandular differentiation (Lit).
Ø Immuno: LMK+, EMA+, CEA+ (Lit), LACK of myoepithelial differentiation (SMA-), S100-, calponin-
BASAL CELL ADENOCARCINOMA
§ Malignant counterpart of basal cell adenoma, infiltrative, perineural invasion, vascular invasion, cytologic atypia and mitoses,
§ Aka basaloid carcinoma (Rosai)
§ Associations: dermal cylindromas similarly to benign counterpart (Rosai)
§ Def: malignant counterpart of basal cell adenoma (Rosai). Low grade (Lit, not sure, me).
§ Demo: peak 60 (Rosai)
§ Grade: LG (Lester)
§ Incidence: rare with only case reports (Rosai, Goldblum).
§ Locations: same as in benign counterpart (Rosai)
§ Infiltrative, perineural invasion, vascular invasion, cytologic atypia, mitoses (Rosai)
§ Patterns: same 4 patterns as in benign counterpart (Rosai)
SEBACEOUS CARCINOMA
SEBACEOUS LYMPHADENOCARCINOMA
CYSTADENOCARCINOMA
LOW-GRADE CRIBRIFORM CYSTADENOCARCINOMA
MUCINOUS ADENOCARCINOMA
ONCOCYTIC CARCINOMA
§ Infiltrative, mitoses, atypia
§ Aka malignant oncocytoma, oncocytic adenocarcinoma (Rosai)
§ Incidence: rare (Goldblum)
§ Infiltrative, mitoses, atypia (Rosai)
ADENOCARCINOMA NOS
§ -infilatrative ducts
§ -no salivary gld features
SALIVARY DUCT CARCINOMA
§ -looks like breast ca (cribriform, comedonecrosis, papillary)
§ IHC: CK, Her2/neu
§ Ddx: breast ca.
§ Elderly males, parotid but sometimes in submandbular, microscopically resembling all cancers of breast, express weird markers such as GCDFP15, androgen receptor, PSA, de novo or from prior PA, must grade,
§ Def: HG tumor by definition (Lit). Careful, its name refers to growth pattern and not anatomical location (Rosai).
§ Demo: 22-91yo with peak at 50 (Goldblum; usually in elderly, Rosai). Striking male preponderance (>4:1, Goldblum).
§ Diagnosis: FNA can diagnose HG SDC but LG SDC often false negative (Rosai)
§ Etio: de novo or from pre-existing PA (aka salivary duct carcinoma ex pleomorphic adenoma, Goldblum, Rosai).
§ Grade: variable although mostly HG (Lester)
§ Incidence: uncommon but not rare: 9% of all SG malignancies (WHO, Goldblum).
§ Locations: mostly in major SG (96%) (Rosai). Mostly in parotid but sometimes submandibular>>> sinonasal tract and larynx (Rosai, Goldblum).
§ Outcome: very aggressive for HG SDC (Rosai). Most die within 4 years (Goldblum, WHO). Mortality 70% (Rosai). Most present in advanced stages (III and IV) with 60% positive LN (WHO)
§ Prognosis: bad if large, mets, HER2 overexpression but p53, proliferation index and anueploidy no value (Goldblum). P16 seems to play a role (WHO). Grade (Rosai)
§ Spread: local recurrence in 1/3 (Goldblum, WHO). Mets to regional LN in 60% (Goldblum). Mets to lung and bone in 45% (Goldblum, WHO).
§ Ssx: sudden rapid growing mass with/without skin ulceration and facial palsy (Goldblum).
§ Treatment: total parotidectomy with neck dissection and adjuvant radiation (Goldblum).
§ Solid mass with hemorrhage and necrosis (Goldblum). Mostly ill-defined (but not all, Goldblum). Macro features of preexisting CXPA may be present (Goldblum).
§ Cytoarchitecturally resembling DCIS and IDC (not only IDC but also metaplastic with sarcomatoid differentiation and mucinous breast carcinoma, WHO) of breast (Goldblum, Rosai). Most characteristic is large ducts with cribriform configurations, Roman-bridging and intraductal comedonecrosis (Goldblum, WHO). Solid, papillary focally possible with psammoma bodies and squamous differentiation (Goldblum, WHO). Stromal fibrosis and lymphocytic infiltration common (Goldblum). Cells large, pleomorphic, with abundant pink granular cytoplasm (epithelioid, WHO), large dark nuclei and prominent nucleoli (Goldblum, WHO). Oncocytic metaplasia common (Goldblum). Usually high mitoses (Goldblum). Goblet cells not seen (WHO). Occasionally resembling metaplastic breast carcinoma with sarcomatoid growth pattern (Goldblum, WHO). Perineural invasion (60%, WHO) and vascular invasion (30%, WHO). Mets recapitulates morphology of primary lesion (WHO).
Grades (Rosai): important to grade (Rosai)
§ LG
Ø Relatively new entity. Mostly in parotids (Lit). Lit says important to recognize because different prognosis from usual salivary duct carcinoma (Lit).
Ø Cystic ducts with micropapillary, tufted, plaque-like intraluminal projections and ducts distended by solid or pseudocribriform cellular projections (Lit). Tumor cells cuboidal to columnar with bland cytology and abundant intracytoplasmic vacuoles (Lit).
§ HG: extremely aggressive
§ resembles all variants of breast malignancies including DCIS and IDC (Rosai)
Immuno (same as ductal type adenocarcinoma, Rosai)
§ LMK+/HMK+ (WHO; including CK14+, Rosai, Goldblum), CEA+ (Goldblum, Rosai, WHO), EMA+ (Goldblum, WHO), androgen receptor AR+ (strong, 100% cases, Goldblum, Rosai, WHO), LeuM1+ (WHO), PSA/PAP (prostatic acid phosphatase) variable (Goldblum; Rosai says +), peroxisome proliferator-activated receptor gamma PPAR gamma+ (80%, cytoplasmic, Goldblum), HER2/neu overexpression common (Goldblum, Rosai), GCDFP15 (focally, especially intraductal component, Rosai, WHO; apocrine marker, WHO)
§ Myoepithelial markers-, ER-/PR- (Goldblum, Rosai), S100- (WHO)
§ MIB1 proliferative index 25-80% with average 40% (WHO)
DD
§ Metastatic breast carcinoma (Goldblum, WHO):
§ Papillary cystadenocarcinoma (Goldblum)
§ Mucoepidermoid carcinoma (WHO): goblet cells not present in SDC (WHO)
§ Oncocytic carcinoma (Goldblum, WHO)
§ Squamous cell carcinoma (Goldblum, WHO): easily differentiated as soon as you see ducts or cirbriforming (features not present in SCC) (WHO). Presence of sialodochodysplasia supports parotid origin (WHO)
ADENOCARCINOMA NOS
§ No2 malignancy after MEC, diagnosis of exclusion, parotid and minor SG, slow growing, can arise from prior PA, inconsistent reporting in literature, it is called adenocarcinoma NOS,
§ Incidence: 17% of all SG carcinomas (Goldblum, WHO). No2 maligancy after mucoepidermoid carcinoma (WHO).
§ Def: characterized by ductal differentiation but lacking other morphologic features of other specific tumors (therefore diagnosis by exclusions, Goldblum, WHO). Suffers from inconsistent reporting in litterature (WHO).
§ Grade: variable (Lester)
§ Locations: 60% in major SG (mostly parotids, WHO) and 40% in minor SG (hard/soft palatal junction, buccal mucosa and lips, WHO).
§ Demo: more in females 58 and extremely rare in kids (WHO).
§ Ssx: slow growing, painless but 20% have facial nerve involvement (Goldblum).
§ Prognosis: grading, stagie and location (minor SG better prognosis) (Goldblum).
§ Precursor: can arise from pre-existing PA.
§ Must sample thoroughly (Rosai)
§ Always conspicuous duct-like structures with infiltrative pattern but by definition lacks features of specific tumor types (Goldblum, WHO).
§ Patterns: widely variable growth patterns including ductal, theques, sheets and trabeculae (Goldblum).
§ Grading (Goldblum): can be done
Ø LG: ova/cuboidal cells with minimal atypia and mitoses
Ø IG: more atypia, higher NC, mitoses, hemorrhage and necrosis.
Ø HG: stroma often fibrous and cellular but scanty in high grade.
IHC
§ No specific but used to rule out other types (Goldblum). PSA+ have been reported (WHO)
MYOEPITHELIAL CARCINOMA
CARCINOMA EX PLEOMORPHIC ADENOMA (MALIGNANT MIXED TUMOR)
§ -high grade tumour juxtaposed to pleomorphic adenoma
§ One decade after PA, non-invasive and minimally invasive CXPA same prognosis as PA, non-invasive vs minimally invasive vs invasive, sample thoroughly because need to measure capsular invasion and find pre-existing PA, all tumor types possible, hints include severe atypia, necrosis, mitoses, infiltrative pattern, 1.5mm cut-off, careful with infarcted PA and metastasizing PA,
§ Aka malignant mixed tumor is misnomer because true malignant mixed tumor should be carcinosarcoma (Goldblum).
§ Def: PA from which an epithelial malignancy is derived (WHO).
§ Incidence: 4% of all salivary tumors, 12% of salivary malignancies and 6% of all PA (Goldblum, WHO).
§ Locations: parotid (67%)> minor glands (18%, mostly palate)> submandibular (15%)> sublingual (<1%) (Goldblum).
§ Demo: 60-70yo mostly (one decade later than PA, WHO, Goldblum). Equal gender (Goldblum).
§ Ssx: 40% with facial palsy (Goldblum).
§ Prognosis: noninvasive CXPA same prognosis as conventional PA (Goldblum). Invasive CXPA aggressive (25-50% local recurrence within 5 years and 70% mets (Goldblum). Minimally invasive CXPA relatively good prognosis with rare mets (WHO, Goldblum). Tumor grade correlates with prognosis (WHO). Read on cyto-/molecular genetics (WHO p243). Prognosis depends on microscopic grade, extent of capsular invasion and proliferative index (Rosai). Tumor size and grade have prognostic value in widely invasive carcinoma (WHO).
§ Spread: regional LN, lung/bone/liver/brain (Goldblum).
§ Treatment: local excision with continguous LN dissection with radiation if widely invasive (radiation not necessary for minimally invasive carcinoma, WHO). Invasive CXPA requires neck LN dissection and adjuvant radiotherapy (WHO). Must grade (WHO)
§ Poorly circumscribed and extensively infiltrative (sometimes well-circumscribed, WHO). Sample thoroughly (because diagnosis depends on evidence of preexisting PA and degree of capsular invasion, Rosai, Goldblum).
§ Variable proportion of preexisting PA and CXPA; PA sometimes difficult to find or involutes into hyalinized round nodule; therefore clinical history important (Rosai, Goldblum).
§ 3 types (Goldblum, WHO)
Ø Non-invasive (aka intracapsular carcinoma, in situ CXPA, severely dysplastic PA): PA with diffuse or focal areas of severe dysplasia without invasion into surrounding tissue (Goldblum). Same clinical behavior as PA (Lit). Closer follow-up and no change in overall prognosis (Goldblum)
Ø Minimally invasive: <=1.5mm (Goldblum). Exactly same prognosis as PA (Lit).
Ø Invasive: >1.5mm) (Goldblum)
§ diagnosis relies on presence of residual PA or clinical history of PA (Lit). Rosai says it’s absolutely necessary to see pre-existing PA; clinical history not sufficient (Rosai)
§ Hints: infiltrative pattern, severe nuclear atypia, necrosis and mitoses especially if atypical (Goldblum, WHO, Rosai).
§ Reporting: pathologic stage, extent of invasion (extension of carcinoma in mm beyond capsule; study showed <5-8mm, no patient died, Lit), tumor size, proprotion of CXPA, proliferative index (Lit). Also, important to provide tumor grading (Lit).
§ Tumor types: often poorly differentiated carcinoma, high grade adenocarcinoma NOS, salivary duct carcinoma, AdCC, MEC, myoepithelial carcinoma (Rosai, Goldblum). Any type possible (WHO).
DD
§ Spontaneous infarcted PA (Goldblum)
§ “Metastasizing” PA (Goldblum): not real mets but caused by iatrogenic manipulation of PA
CARCINOSARCOMA
METASTASIZING PLEOMORPHIC ADENOMA
§ -even benign appearing can mets.
SCC[98]
§ Most are mets, may be squamous cell component of PA or HG MEC,
§ Incidence: true primary SCC of parotid very rare (Rosai).
§ sometimes in situ component in ducts (Rosai)
§ Grade: HG when primary (Lester)
§ Treatment: surgery (Rosai). Radiation also effective (Rosai)
§ Outcome: 1/2 5-year survival (Rosai)
§ Ssx: fast growing (Rosai)
§ Etio: most represent mets in intra-parotid LN of oral cavity tumors, upper aerodigestive tract or skin (Rosai). Others are malignant component from PA or squamous cell component of HG MEC (Rosai)
Variants
§ SCC, adenosquamous carcinoma
Ø Rare and aggressive variant of SCC (Steinberg)
Ø Origin: minor salivary glands (Steinberg)
Ø Mixed glandular-squamous pattern (Steinberg)
SMALL CELL CARCINOMA
§ Keratin (EMA, CK) and neuroendocrine (NSE, CHR, SYN) expression
§ EM: dense-core granules (Rosai)
§ Patterns: solid (Rosai)
§ pure or associated with areas of glandular or squamous differentiation (Rosai)
IHC
§ Keratin (EMA, CK)+ and neuroendocrine (NSE, CHR, SYN)+ (Rosai)
LARGE CELL CARCINOMA
LYMPHOEPITHELIAL CARCINOMA
§ Eskimo and Chinese, subtype of undifferentiated carcinoma,
§ Aka lymphoepithelioma-like carcinoma (WHO).
§ Association: nearly 100% association with EBV (WHO).
§ Def: important subtype of undifferentiated carcinomas (Rosai).
§ Demo: particularly in Chinese and Eskimos, maybe due to familial clustering (Rosai)
§ Genetic: analogous to nasophagryngeal counterpart (Steinberg)
§ Outcome: wide variation in mortality although overall better than other types (Rosai)
§ Spreads: regional LN very common, distant mets to lung, liver and bone (Rosai)
§ Low power, looks at Mikulicz’s disease with mixture of epithelial solid islands and lymphoid tissue except at high power, epithelial component is frankly malignant (Rosai). Nonkeratinizing large cell caricnoma with occaionsal spindly areas, reminiscent of lymphoepithelioma of nasopharyngeal tumor (Rosai).
§ sometimes perineural invasion (Rosai)
§ reactive lymphocytic infiltrate may form germinal centers (Rosai)
SIALOBLASTOMA
§ Aka embryoma (Rosai)
§ Def: highly cellular epithelial parotid tumor of infancy with embryona or blastomatous appearance (Rosai)
§ Incidence: extremely rare (Goldblum)
§ Nature: benign neoplasm.
§ Outcome: may recur (Rosai)
Micro
§ Small round blue cells
SOFT TISSUE TUMORS
HEMANGIOMA
LYMPHOID
§ Parotid, MZBCL and CLL/SLL, Sjogren,
§ Incidence: uncommon (up to 3% of all salivary gland tumors, Lit).
§ Locations: parotid most common but other sites including minor salivary glands possible (Lit, Rosai).
§ Origin: intraparotid LN or parotid itself (Rosai).
§ Etio: primary vs secondary (Rosai)
§ Ssx: unilateral mass (Rosai)
§ RF: Sjogren’s syndrome, Mikulicz’s disease, transplant patient, Kuttner’s tumor (chronic sclerosing sialadenitis) (Lit, Rosai).
§ Types: mostly marginal zone lymphoma and CLL/SLL (me). But other types such as follicular lymphoma, DLBCL, plasmacytoma, T-cell lymphoma, HD can also occur (Rosai)
§ 3 morphologies: spindle, hyaline (plasmacytoid) and clear cells
§ sclerosis quite common, especially in large cell type lymphomas, and can simulates Kuttner’s tumor (chronic sclerosing sialadenitis) (Rosai)
§ not uncommon for MZBCL to recur in controlateral parotid, skin or other sites several years later (Rosai)
IHC
§ Myoepithelial cells: keratins+ (Rosai), S100+ (Rosai), SMA- (often neg, Rosai)
HD
DLBCL
MALTOMA
METS
§ SCC from oral cavity/upper aerodigestive tract/skin, melanoma, lung, kidney and breast tumors,
§ Locations: mostly to intraparotid and intrasubmandibular LN (Rosai)
§ Origin: SCC from oral cavity/upper aerodigestive tract/skin, melanoma, lung, kidney and breast tumors (Rosai)
LARYNX
NORMAL
§ True cord: vocalis muscle
§ False cord: numerous minor SG
ACUTE EPIGLOTTITIS
§ Aka acute supraglottitis (Rosai)
§ Acute inflammation causing airway obstruction (Robbins). Abrupt onset of pain (Robbins).
LARYNGEAL KERATOSIS
§ Aka simple hyperplasia, epithelial hyperplasia, squamous hyperplasia, leukoplakia (Rosai)
Micro
§ Acanthosis (often with granular layer), hyperkeratosis, NO atypia (Rosai)
§ Malignant (dysplasia or CIS): atypia, loss of orderly maturation, loss of stratification (Rosai)
Variants
§ Verrucous keratosis: with undulating warty configuration (Rosai)
§ Pachyderma laryngis: with extensive keratinization (Rosai)
LARYNGITIS
§ Etio: allergy, viral (URTI), bacterial (TB, diphteria), smoking, voice overuse, alcohol, tabacco, other irritants (Steinberg)
§ Evolution: most often self-limited but can be serious in kids (epiglottitis)
§ Complication: may cause laryngeal keratosis (Steinberg)
Variants
§ Chronic
Ø Etio: infection, voice overuse, chemical or physical agents, tobacco and alcohol (Rosai)
§ Mycotitc
Ø Etio: histoplasmosis, blastomycosis, aspergillosis and cryptococcosis (Rosai). Actimyocosis rare (careful not same as Actinomyces) (Rosai). No1 mycotic laryngitis in US are histoplasmosis and blastomycosis (Rosai).
§ TB
LARYNGEAL NODULE
§ Aka vocal cord polyp (Steinberg, Robbins), reative nodule (Robins)
§ by convention, singers’ nodules is bilateral but nodule is unilateral.
§ Demo: mostly in men who are heavy smokers or abuse vocal cords (Robbins).
§ Evolution: virtually never maligant transformation. Not premalignant (Robbins).
§ Location: mostly on vocal cord (Steinberg)
§ Mechanism: reactive change
§ RF: abuse of vocal cord (Steinberg). Heavy SMOKER, SINGERS,
§ Scenario: 28 man singer, recent voice change (hoarser), afebrile, no mass in head and neck, no cough/sputum, smoker (Robbins).
§ Scenario: 45yo attorney presenting with hoarseness and vocal cord nodule, histology showing hyalinized stroma containing dilated BV with perivascular fibrinous exudate (Steinberg)
Gross
§ SMOOTH (NOT papillary), rounded, sessile or pedunculated nodules, usually on true vocal cords. Generally only a few mm in size (Robbins).
Micro
§ Covered by SQUAMOUS epithelium, maybe keratinizing, myxoid core or fibrotic, surface may be ulcerated. Fibrovascular core cored by hyperplasia and hyperkeratotic squamous epithelium (Robbins).
§ early stage composed of edematous stroma with fibroblastic hyperplasia (gelatinous type) (Steinberg). Later, hyalinization of stroma develops (leading occasionally to misdiagnosis of localized amyloidosis) and vascular proliferation (prompting confusion with pyogenic granuloma or angioma) (Steinberg)
§ almost all angioms develop in supraglottic location; vessels in angiomas are thick walled, whereas singer’s nodule has thin-walled BV (Steinberg)
ADULT LARYNGEAL PAPILLOMA***
§ Quite similar to JLP except solitary and does not spread and recurs less, same viral serotypes,
§ Etio: much less frequently associated with HPV in adults (Steinberg)
§ Evolution: does not recur as often as in kids (Steinberg).
§ Complication: recur less but more associated with dysplasia and SCC (Steinberg)
§ Soft RASBERRY-like growth on true vocal cords (Steinberg)
§ Single in adult (unless recurrent) but MULTIPLE in KIDS (laryngeal papillomatosis) (Steinberg)
JUVENILE LARYNGEAL PAPILLOMATOSIS***
§ Caused by HPV11 and 6, respiratory difficulty, kids, spreads from true cords to false cords, epiglottis, subglottis and even trachea and bronchi, can be INVASIVE,
§ not related with voice abuse (Robbins). No congenital nor part of syndrome (Robbins).
§ Complication: when extensive, can obstruct airway (Robbins).
§ Etio: usually HPV 6 and 11 (Robbins, Steinberg). HPV genome detectable in all cases either by IHC or ISH (Steinberg)
§ Evolution: frequently recurs after excision (Robbins). May regress after puberty (Robbins). In contrast, laryngeal papilloma arising in adulthood usually solitary and do not recur (Robbins). Benign and does not have malignant potential (Robbins).
§ Location: can be found anywhere in airway (Robbins).
§ Mechanism: increased expression of EGFR probably contributory (Steinberg)
§ Scenario: 22yo with multiple resections of laryngeal papillomas since age of 16, histology showing well-differentiated squamous epithelium with papillary architecture, mild nuclear atypia with koilocytosis (Steinberg)
§ Scenario: 6yo boy with increasing difficulty breathing and voice change, papillary lesion in subglottis (Robbins).
§ Treatment: no effective antiviral therapy against HPV (Robbins).
§ Multiple laryngeal papillomas which recur repeatedly (Steinberg)
§ Orderly squamous epithelium on fibrovascular cores (Robbins). HPV6 immunostain+ (Robbins)
§ mild atypical change and koilocytosis consistently present (Steinberg)
§ those arising from respiratory epithelium may not show orderly maturation and often mistaken for carcinoma in situ (Steinberg)
§ Invasive papillomatosis: extends into soft tissue or tracheostomy stroma (Rosai). Rare (Rosai).
INFECTIONS
CROUP
§ Aka acute laryngeotracheobronchitis (Robbins). In kids (Robbins). Produces airway narrowing with inspiratory stridor (Robbins). Caused by parainfluenza virus (Robbins). Inflammation may be severe enough to obstruct airways (Robbins). Scenario: 3yo kid with difficulty breathing for 24h, febrile, harsh cough with prominent inspiratory*** stridor, lungs clear***, subglottic edema on XR, saturation normal, improves over next 3 days with nebulized CTSD (Robbins).
§ Inflammatory narrowing of airway-> inspiratory stridor-> self-limited
DIPHTERIA
§ Caused by Corynebacterium diphtariae (Robbins). Dirty grey membrane which may slough and be aspirated (Robbins).
MALIGNANT EPITHELIAL
§ RF: smoking with contributing factors (alcohol, nutritional factors, asbestos, radiation, HPV)
§ 5 locations
Ø Glottic: from true cord, manifest in early stages with hoarseness, good prognosis (Steinberg)
Ø Pyriform sinus: often invades posterior edge of thyroid cartilage, worse prognosis (Steinberg)
Ø Subglottic: below true cord, rare in incidence (Steinberg)
Ø Supraglottic: regions above true cord, including false cords, epiglottis, ventricular band and aryepiglottic fold (Steinberg)
Ø Transglottic: crosses ventricle vertically between true and false vocal cords, higher regional mets and worse prognosis (Steinberg)
§ Mechanism: sequence of hyperplasia-dysplasia-carcinoma
§ Prognosis: anatomical location important for prognosis (Steinberg). 5-year survival: glottic 90%, supraglottic 65%, transglottic 50%, subglottic 40% (Steinberg)
§ Types: divided into intrinsic (within larynx) and extrinsic (outside larynx)
§ White or red thickening
§ Usually WELL-differentiated SCC but 5% can be adenocarcinoma (arising from mucous glands)
SQUAMOUS CELL CARCINOMA
§ Risk factors: smoking, maybe HPV
§ Etio: only 5% patients have HPV (Robbins).
§ Prognosis: location, stage, LN and histologic type (Steinberg)
§ RF: smoking (no1), alcohol (contributing) (Robbins).
§ Scenario: 70yo man with increasing horseness, hemoptysis, firm nontender cervical LN, laryngectomy and neck dissection (Robbins).
§ Treatment: radiation (Dexter) sometimes to shrink it
§ Fungating (Robbins).
§
VERRUCOUS
BASALOID
§ Rare but extremely aggresssive
PAPILLARY
SPINDLE CELL
ACANTHOLYTIC
ADENOSQUAMOUS
LYMPHOEPITHELIAL CARCINOMA
GIANT CELL CARCINOMA
SALIVARY GLAND-TYPE TUMORS
MEC
AdCC
NE TUMORS
TYPICAL CARCINOID
§ Demo: elderly males (Rosai)
§ Locations: nearly always supraglottic on arytenoid cartilage (Rosai)
§ RF: smoking (Rosai)
§
ATYPICAL CARCINOID
SMALL CELL NE CARCINOMA
COMBINED
BENIGN EPITHELIAL
SINGER’S NODULE (REACTIVE NODULE)
§ -occurs on the vocal cord
§ -epithelium +/- hyperplastic/keratotic
SQUAMOUS PAPILLOMA
§ -assoc/ HPV 6,11
§ -if mult→juvenille laryngeal papillomatosis (can die from this) (recurring papillomas)
PAPILLOMATOSIS
SALIVARY GLAND-TYPE ADENOMAS
PLEOMORPHIC ADENOMA
ONCOCYTIC PAPILLARY CYSTADENOMA
MALIGNANT SOFT TISSUE TUMORS
FIBROSARCOMA
MFH
LPS
LMS
RMS
AS
KAPOSI SARCOMA
MPNST
SS
BORDERLINE SOFT TISSUE TUMORS
IMT
BENIGN SOFT TISSUE TUMORS
SCHWANNOMA
NF
LIPOMA
LM
RHABDOMYOMA
HEMANGIOMA
LYMPHANGIOMA
GRANULAR CELL TUMOR
LYMPHOID
BONE TUMORS
CS
OS
CHONDROMA
GCTB
MELANOMA
METS
§
NECK
THYROGLOSSAL DUCT CYST
Micro
§ -squamous or pseudostratified epithelium (may be keratinized!!!)
§ -+/-mucous and thryoid glands in stroma
BRANCHIAL CLEFT CYST
Micro
§ Squamous 90%> respiratory 8% or both 2%
§ Keratin debris
§ Lymphoid tissue (nodular or diffuse)
§ -+/-mucous and thryoid glands in stroma
§ Keratin debris+inflammatory cells[99]=branchial celft cyst on FNA
§ Fibrous wall usually lined by SQUAMOUS, sometimes RESPIRATORY epithelium (Rosai). Lymphoid tissue with germinal centers (Rosai, Isotalo)
§ cysts located in lower neck may contain mucinous, seromucinous and sebaceous glands (Rosai)
§ no thyroid tissue (vs present in thyroglossal duct cyst, Robbins).
§ epithelium infiltrated by lymphocytes (important hint, Rosai)
§ secondary infection common (Rosai)
§ Malignant transformation: extremely rare (Rosai). Any SCC in neck should be considered LN mets with cystic degen until proven otherwise (Rosai). Occult SCC primary sites include tonsil, posterior tonsillar pillar, retromolar tongue and nasopharynx (Rosai)
Clinical
§ Developmental anomalies from 2nd branchial apparatus
§ Lateral neck mostly near mandibular angle
§ Aka lymphoepithelial cyst (Robbins).
§ Also see salivary gland, can be fistula, sinus, cyst or cartilage, any level from ear to sternum, no thyroid tissue, mostly SQUAMOUS but also RESPIRATORY epithelium infiltrated by lymphocytes (reason why aka lymphoepithelial cyst)
§ Origin: remnants of branchial arches or developmental salivary gland inclusions within cervical LN (Robbins, RISE, Rosai).
§ Scenario: 21yo woman with neck side mass, stable in size, painless, beneath skin of left lateral neck just above level of thyroid cartilage, granular and keratinaceous cellular debris on FNA
§ Ssx: patent fistula, sinus, cyst, island of cartilage (Rosai)
Gross
§ Circumscribed cysts with serous to mucinous content
Locations
§ Locations: depend on which arch (Rosai). To make matter even more complicated, lymphoepithelial cysts can also be found in thyroid, especially if Hashimoto’s thyroiditis (Rosai)
Ø 1st: preauricular or below ear lobe (Rosai). Can be connected to external auditory canal (Rosai)
Ø 2nd: anterior to SCM in mid neck (Rosai).
Ø 3rd and 4th: suprasternal (“behind sternum”) or supraclavicular in lower neck (Rosai)
DD
§ Metastatic SCC
§ Thyroglossal duct cyst: thyroid tissue present
CAT SCRATCH DISEASE
NODULAR FASCIITIS
LYMPHOEPITHELIOID CYST
§ -cyst lined by squamous epithelium with florid lymphoid HP
TUMORS
PARAGANGLIOMA
§ note: paraganglia are clusters of NE cells assoc. with symp and parasymp NS.
§ -most are found in the adrenal where they give rise to pheochromocytomas
§ Carotid body tumours occur where? Bifurcation of the carotid artery.
§ Gross: red-brown
§ Micro:- zellballen (gps of polygonal cells with nuc: salt and pepa, round, uniform)
§ -cytoplasm is granular
§ -surrounded by fibrovascular strands
§ IHC: NSE, synapto, chrA
§ -S100+ sustentacular cells
SPINDLE CELL/PLEOMORPHIC LIPOMA
SS
CHORDOMA
METASTATIC CYSTIC SCC
§ Cystic SCC to cervical LN[100]
§ 80% are from Waldeyer’s ring
§
§ 4x males, 60
§ Thick desmoplastic fibrous capsule
METS OF UNKNOWN PRIMARY
§ 10% of neck LN metastasis
§ Waldeyer’s ring, nasopharynx, larynx, esophagus, melanoma, sarcoma[101]
§ DD should include lymphoma, ectopic tissue in LN, developmental cysts
§ CK, CD45, S100, HMB45, SMA, desmin as initial workup
EAR
SPECTACLE FRAME ACANTHOMA
§ Aka granuloma fissuraum (Steinberg).
§ Etio: due to irritation from eyeglasses (Steinberg)
§ Location: behind ears or on nose (Steinberg)
CHOLESTEATOMA
§ 2 forms: congenital (usually closed and arises from epidermoid cell rests, Steinberg) or acquired (most common, is open, develops in context of chronic otitis media and tympanic perforation, Steinberg).
§ Complication: erosion of ossicles (Steinberg)
§ Etio: complication of chronic otitis media (Robbins).
§ Evolution: despite non-neoplastic, can enlarge and erode middle ear (Robbins).
§ Mechanism: acute or CHRONIC RHINITIS-> ingrowth of squamous epithelium or metaplasia of secretory epithelium-> cystic lesion lined by KERATINIZING squamous epithelium or metaplastic mucus-secreting epithelium, filled with amorphous debris (mostly squames) with giant cells, sometimes cholesterol crystals-> perforation of tympan-> erosion of ossicles. Still unclear but probably involve epidermal invasion from external canal into middle ear, retraction pockets from tympanic membrane and trauma (Steinberg)
Ø Not neoplasm but inflammation. Ingrowth of squamous epithelium or metaplasia of secreting epithelium lining of middle ear secondary to chronic otitis.
§ Nature: not real neoplasm (Robbins).
§ Prognosis: no risk for malignant transformation (Robbins).
§ Scenario: 5yo boy with bouts of earache, red bulging tympanic membrane, either unilaterally or bilaterally, perforated tympanic membrane recently, responds to antibiotic (Robbins: this boy is at risk for cholesteatoma).
§ Cystic lesion lined by squamous epithelium (Robbins). Desquamated epithelium and keratin degenerate, resulting in cholesterol formation and giant cell reaction (Robbins). Cysts containing pearly keratin and lined by epidermal layer devoid of adnexae (Steinberg). The case I saw is mostly orthokeratin. The material is loose and fibrillary
§ morphologically, they are epidermoid cysts (Steinberg). Squamous epithelium lining cyst wall is morphologically similar to epidermis but shows increased proliferative index (increased Ki-67) (Steinberg)
§ not always contain cholesterol (Robbins).
ACUTE AND CHRONIC OTITIS MEDIA
§ Viral or bacterial (Strep pneumoniae, non typeable H influenza, Moraxella catarrhalis)-> acute otitis-> superimposed by bacteria (Pseudomonas, Staph aureus, fungus)-> chronic otitis-> perforation of tympan-> possibly temporal cerebritis or brain abscess
DESTRUCTIVE NECROTIZING OTITIS MEDIA
§ P aeruginosa in DM-> very aggressive otitis
OTOSCLEROSIS
§ Involves otic capsule and extends to footplate of staes, where characteristic morphologic changes may be seen when whole stapedectomy is performed (Steinberg). Abnormal bone deposition in ossicles of middle ear resulting in bone deafness in adults (Robbins)
§ Etio: autosomal dominant with variable penetrance->
§ Evolution: severe form leads to conductive hearing loss (Steinberg)
§ Location: usually bilateral.
§ Mechanism: bone resorption-> fibrosis and vascularization of temporal bone in immediate vicinity of oval window-> dense new bone anchoring footplate of stapes-> marked hearing loss
§ Increased new woven bone and neovascularization typical microscopic findings (Steinberg). Spongiosis (formation of ample marrow cavities) occurs in early stages (Steinberg)
§ because these changes are limited to footplate, partial stapedectomies (limited to crura and head) would not show any pathologic abnormalities (Steinberg)
DD
§ Paget disease (Steinberg)
§ Osteogenesis imperfecta (Steinberg)
AURAL POYP
§ Know ddx, reactive growth,
§ Aka otic polyp (Goldblum)
§ Associations: destructive lesions such as cholesteatoma (Goldblum)
§ Def: benign prolifeation of grnaulation tissue with chronic inflammation, lined by squamous metaplastic or cuboidal glandular epithelium, in response to chronic mid-ear inflammation (Goldblum)
§ Demo: males 2x, 30 mean (Goldblum)
§ Outcome: good unless concomittant lesions such as cholesteatoma (Goldblum)
§ Treatment: antibiotics followed by polypectomy (Goldblum)
§ Edematous granulation tissue with lymphocytes, plasma cells, eosinophils, +/-cholesterol granulomas, calcifications, giants (Goldblum)
DD
§ Plasmacytoma (Goldblum)
§ RMS (Goldblum)
§ Middle ear adenoma (NAME) (Goldblum)
§ Ceruminous adenoma (Goldblum)
EXTERNAL EAR TUMORS
BENIGN TUMORS OF CERUMINOUS GLANDS
ADENOMA
CHONDROID SYRINGOMA
SYRINGOCYSTADENOMA PAPILLIFERUM
§ Demo: characteristically in kids and young adults (Steinberg)
§ Histologically similar to those occurring on face (Steinberg)
CYLINDROMA
MALIGNATN TUMORS OF CERUMINOUS GLANDS
ADENOCARCINOMA
AdCC
MEC
SCC
RMS
OSTEOMA AND EXOSTOSIS
ANGIOLYMPHOID HYPERPLASIA WITH EOISNOPHILIA
MIDDLE EAR TUMORS
ADENOMA OF MIDDLE EAR
§ Aka ceruminoma (Steinberg), adenoma of middle ear?
§ Ssx: Mass blocking ear canal (Steinberg).
§ Regular glands with two-layered epithelium (epithelial/myoepithelial) (Steinberg). Epithelial cells show apocrine features (Steinberg)
PAPILLARY TUMORS
AGGRESSIVE PAPILLARY TUMOR
SCHNEIDERIAN PAPILLOMA
INVERTED PAPILLOMA
SCC
MENINGIOMA
INNER EAR TUMORS
1. VESTIBULAR SCHWANNOMA
2. LIPOMA OF INTERNAL AUDITORY CANAL
3. HEMANGIOMA
4. ENDOLYMPHATIC SAC TUMOR
Clinical
§ Non-metastasizing adenocarcinoma, slowly invading petrous bone
§ Associated with VHL
Micro
§ Papillae with thin FV cores
HEREDITARY
MELKERSSON-ROSENTHAL SYNDROME
§ “Mr syndrome”, triad of orofacial swelling, facial nerve paralysis, plicated tongue, ddx other granulomatous diseases such as sarcoidosis or Crohn’s
§ Triad: orofacial swelling, peripheral facial nerve paralysis, plicated tongue (Rosai). Think about this, this is all consequence of diffuse granulomatous inflammation (Rosai)
Micro
§ Granulomatous inflammation in stroma of lips (Rosai)
Variants
§ Granulomatous cheilitis: abortive variant (Rosai)
DD
§ Sarcoidosis (Rosai)
§ Crohn’s (Rosai)
BEHCET SYNDROME
§ Dx (leukocytoclastic VASCULITIS of skin, mucosa, eyes). Etio (idiopathic).
§ Etio: idiopathic disease characterized by relapsing ulcers (Steinberg).
§ Locations: skin, oral mucosa, eyes (Rosai)
§ Nature: leukocytoclastic vasculitis (Rosai)
§ Necrotizing vasculitis with swollen endothelial cells, fibrinoid necrosis, lymphocytic perivascular infiltrate (Steinberg).
CHERUBISM (AD)
§ Ssx: bilateral peripheral giant cell granulomas of jaws (Steinberg)
CRI DU CHAT SYNDROME (5p-)
§ Due to microdeletion,
§ Laryngeal dysplasia resulting in cat cry (Osler)
KARTAGENER SYNDROME
§ Sinusitis, bronchiectasis, situs inversus
IHC OF EAR TUMORS (Goldblum)
| Paraganglioma | NE adenoma | RCC | Meningioma |
| CG+ | CG+ | - | - |
| SYN+ | SYN+ | - | - |
| S100+ (s) | - | - | Rare |
| - | CK+ | CK+ | Rare |
| - | EMA+ | EMA+ | EMA+ |
| Unknown | Unknown | CD10+ | Unknown |
CYSTS IN MOUTH[102]
§ Salivary duct cyst
§ Fissural cyst
§ Odontogenic cyst
Ø Developmental
Ø Inflammatory
§ Retention cyst[103]
GRANULOMAS IN MOUTH
§ Infectious (Yersinia, Spirochetes, Blastomyces, Leprosy, TB)
§ Sarcoid
§ IBD
§ Foreign body
LYMPHOMA OF SINONASAL TRACTS
§ 3 main types of lymphomas of sinonasal tract and nasopharynx including NK/T, B and peripheral T (Rosai). Strong geographic difference (Rosai). See LN
TYPES OF ADENOCARCINOMAS IN SINONASAL TRACTS
| Non-salivary | Salivary |
| M>>>F, 60-70 | 30-80, equal gender |
| Industrial exposure[104] | No |
| From respiratory epithelium | From seromucinous glands |
| 60% mortality[105], grade-dependent | 40-60% mortality[106], stage-dependent |
| 60% recurrences | |
| Surgery+radiation | Surgery+/-radiation |
| Fungating ulcerated mass | Submucosal mass |
| Divided into intestinal vs non-intestinal type | AdCC most common |
SMALL ROUND BLUE CELLS IN SINONASAL TRACT
§ SCC (basaloid)
§ SNUC
§ Melanoma
§ Olfactory neuroblastoma
§ Extranodal NK/T cell lymphoma
§ RMS
§ PNET/EWS
§ Plasmacytoma
§ Small cell NE carcinoma
PROGNOSIS OF EWS/PNET
§ Stage
§ Size
§ HN better than thoracoabdominal
§ EWS-FLI1 better
SPINDLE CELL NEOPLASMS OF SINONASAL TRACT
§ FS
§ MFH
§ Sarcomatoid carcinoma
§ Spindle cell melanoma
§ SFT: plump FB, collagenous stroma, HPC vasculature, mitoses rare, CD34+
§ MPNST: often higher grade than FS, S100+, skeletal differentiation in Triton tumor
§ SS: biphasic, t(X;18)
§ RMS
§ Glomangiopericytoma:
§ IMT: extensive inflammation
§ Fibromatosis (desmoid-type): kids, no metastatic potential, lacks infiltration, mature FB, no nucleoli, rich collagenous matrix
CYSTS IN ORAL CAVITY
§ Oral lymphoepithelial cyst
§ Mucocele
ULCERS IN ORAL CAVITY
§ Aphthous stomatitis
§ HSV
§ Trauma
§ Herpangina
§ Behcet (ocular, orogenital ulcers)
CYSTIC LESIONS IN NECK
§ Non-neoplastic
§ Thyroglossal duct cyst
§ Branchial cleft cyst
§ Lymphoepithelial cyst
§ Multinodular goitre
§ Neoplastic
§ Cystic degeneration of an adenoma
§ Metastatic SCC (esp if in l.n.)
§ Carcinoma
NECK CYSTS WITH SQUAMOUS DEBRIS (Goldblum)
§ Metastatic cystic SCC
§ Branchial cleft cyst
§ Thymopharyngeal cyst
§ Thymic cyst
§ Bronchial cyst
STAGING LARYNX[107] (Goldblum)
| Supraglottis | Suprahyoid epiglottis
Infrahyoid epiglottis Aryepiglottic folds Arytenoids Ventricular bands |
| Glottis | True vocal cords
Anterior commissure Posterior commissure |
| Subglottis | Anything ≥1cm below true vocal cords |
3 MOST COMMON LARYNGEAL POLYPS
§
FIBROUS LESIONS IN ORAL CAVITY
§ Irritation fibroma
§ Peripheral ossifying Fibroma
§ Pyogenic granuloma
§ Peripheral giant cell granuloma
PLUMMER-VINSON SYNDROME (Paterson-Kelly)
§ Iron-deficiency anemia
§ Glossitis
§ Esophageal dysphagia (due to web)
AFIP GRADING FOR MEC[108][109]
§ Intracystic component present <20%à 2
§ PNIà 2
§ Necrosisà 3
§ ≥4/10à 3
§ Anaplasia[110]à 4
MODIFIED AFIP GRADING FOR MEC (Lester)
§ See Lester
STAGING FOR SALIVARY GLAND
§ See Lester 487
HYAMS’ GRADING FOR OLFACTORY NEUROBLASTOMA (Goldblum)
| Grade 1 | Grade 2 | Grade 3 | Grade 4 | |
| Architecture | Lobular | Lobular | Lobular | Lobular |
| Mitoses | Absent | Present | prominent | Marked |
| Atypia | Absent | Moderate | Prominent | Marked |
| Fibrillary matrix | Prominent | Present | Minimal | Absent |
| Rosettes | Homer Wright | Homer Wright | Flexner-Wintersteiner | Flexner-Wintersteiner |
| Necrosis | Absent | Absent | +/-present | Common |
[1] If bone defect present, it is encephalocele (Rosai)
[2] Biopsy and aspiration of nasal polyps in newborns are contra-indicated before imaging because of risk of meningitis or removal of normal brain or CSF leak from encephalocele
[3] Gemistocytic change
[4] Usually no neurons although can be present
[5] Allergic or infectious
[6] Multifactorial
[7] ASA allergy, asthma, nasal polyps (Sampter’s triad)
[8] Usually intact+/-focal squamous metaplasia
[9] Not to overdiagnose as LG adenocarcinoma (Steinberg)
[10] Mainly CD8
[11] No correlation between number of eosinophils and allergic etiology (Steinberg, Rosai).
[12] Depending on etiology
[13] Pseudoangiomatous change, infarction, organization, secondary infections, fibrosis
[14] Asthmatic attack on ASA ingestion due to defective prostaglandin metabolism
[15] “Allergic mucin”
[16] Must do silver stain
[17] AB against proteinase-3 (PR3) in cytoplasmic pattern
[18] Easier in lungs and kidney
[19] May extend to orbit, pharynx, larynx and GI tract, causing extensive ulcerations
[20] Characteristic
[21] Russell bodies=pink globules
[22] Nonkeratinizing squamous or transitional epithelium, less commonly by ciliated or mucus secreting epithelium
[23] Controversial (Steinberg)
[24] Can be in sinuses
[25] Can extend into seromucinous glands and ducts
[26] +/-respiratory epithelium and keratinization
[27] No malignant risk (Steinberg)
[28] Anterior portion
[29] Never in sinuses!!!
[30] Variable epithelium despite “schneiderian”
[31] Sometimes transitional or respiratory epithelium
[32] Aka keratinizing squamous papilloma (WHO)
[33] Only in non-keratinizing variant (Steinberg)
[34] Smoking not RF
[35] Indistinct borders
[36] Common in African kids and Chinese adults
[37] Close to lymphoid tissue
[38] EBER ISH
[39] Cornerstone
[40] Easily mistaken for lymphoma but vesicular nuclei with centrally placed prominent nucleoli support a diagnosis of carcinoma
[41] Always males. Maybe testosterone-dependent
[42] Lateral nasopharynx>>> posterolateral nasal cavity (WHO). These are areas with specialized form of erectile FV tissue (Steinberg)
[43] Diagnosis sometimes impossible on biospy due to surface ulceration (simulating granulation tissue) (Steinberg)
[44] SM walls can be completely or focally absent
[45] Important differential because of different evolution
[46] Umbrella that includes several pathogenetically unrelated conditions, characterized by extensive necrosis of midline structures of nasopharynx, palate, paranasal sinuses (Steinberg). Etio: cocaine abuse, Wegener granulomatosis, angiocentric lymphoma, other lymphomas, infections, idiopathic (Steinberg). Diagnosis: idiopathic IMG is diagnosis of exclusion (Steinberg). Care must be taken to rule out treatable causes (Steinberg)
[47] Also on hard palate???
[48] Large cells with pale cytoplasm, vesicular nuclei, grooves
[49] Formed from cell membrane invagination
[50] Roof of nasal cavity
[51] Maturation into ganglion cells possible but rare (Rosai)
[52] Evidence of neuronal differentiation (synaptophysin+, Homer-Wright rosettes, neurite formation, dense-core granules on EM) (Steinberg)
[53] Pseudorosettes
[54] Rare
[55] Do not confuse with melanoma! (Rosai)
[56] Forming mantle-like coat around BV because tumor cells survive better in proximity to BV
[57] Not directly caused by HIV (Steinberg)
[58] With chromatin marginalization, +/-koilocyte-like cells
[59] Vs 50% for erythroplakia
[60] Squamous hyperplasia
[61] Highest rate of dysplasia (Rosai)
[62] Dysplasia can extend into SG ducts
[63] LG, IG, HG
[64] Chronic irritation, infections, ROH are promoters, not initiators (Rosai)
[65] At least 50% of oral SCC are due to smoking and ROH (Steinberg)
[66] Plummer-Vinson syndrome
[67] Denture
[68] Lichen planus, lupus
[69] Nonsmoking/non-drinking cases mostly in elderly females (Steinberg)
[70] Tumor grade, host responses (desmoplasia or inflammation), degree of keratinizationà not good predictor of nodal mets (Steinberg)
[71] Not related to alcohol but HPV+ and TABACCO related (Steinberg)
[72] Mandibular buccal mucosa (no1)
[73] Giant cell epulis (Robbins)
[74] Superficial erosion of underlying bone in edentulous patient
[75] Distant mets is called malignant ameloblastoma
[76] Central.
[77] Peripheral.
[78] Either macro or microcysts
[79] If mitoses or atypia, must diagnose as malignant ameloblastoma (Steinberg)
[80] Not same as malignant ameloblastoma (Robbins)
[81] Needle core higher risk of implantation but not FNA (Rosai)
[82] Increases PA and some SG tumors (Rosai)
[83] Only these 3 patterns exist
[84] After MEC and adenocarcinoma NOS
[85] Small cuboidal cells with dark nuclei and scant cytoplasm
[86] Much more aggressive than MEC
[87] LN spread rare
[88] No3 parotid SG malignancy after MEC and AcCC
[89] Reason why can produce BM material
[90] Sometimes quite radical because cure after recurrence nearly impossible
[91] Controversial but large nerve invasion bad
[92] Grading incorporates growth pattern. Based on % of solid areas: tubular 59%, cribriform 89%, solid 100%
[93] SMG worse than parotid. Isn’t palate worst???
[94] Stage, site and primary surgery failure probably most important
[95] Not cystic (Rosai, Lester). Hemonecrosis rare vs common in MEC and AcCC (Lester)
[96] Sometimes mucomyxoid
[97] Most tumors have mixture of 3 patterns
[98] Remember this can exist in SG!
[99] Must not have atypia
[100] 1/3 of cervical metastatic SCC are cystic
[101] Not lung, GI, breast, pancreas, prostate because not drain to HN
[102] All jaw cysts are subdivided into fissural or odontogenic (Steinberg). I think odontogenic cysts can be further subdivided into inflammatory vs developmental.
[103] Can occur in tonsil
[104] Wood and leather workers
[105] 80% 5-year survival for papillary ITAC but 40% 5-year survival for PD
[106] 50% 10-year survival for AdCC
[107] Pyriform sinus malignancies are staged as pharynx lesions
[108] LG 0-4, IG 5-6, HG 7 or more
[109] Not usable for submandibular tumors
[110] Nuclear pleomorphism, increased N/C, macronucleoli, anisochromia, hyperchromasia