COLON PATHOLOGY
COLLAGENOUS COLITIS
-Females
-Chronic watery diarrhea and crampy abdominal pain
-Normal endoscopy
Microscopy
-Patchy
-Thickened subepithelial BM>10μm (type I and III) (N<5μm)
- Intraepithelial lymphocytes
-LAMINA PROPRIAà plasma cells, eosinophils
Differential diagnosis: tangential sectioning, lymphocytic colitis
LYMPHOCYTIC COLITIS
Clinical: watery diarrhea, crampy abdominal pain; normal scope, associated with AI disorders.
Microscopy
- Intraepithelial lymphocytes, LAMINA PROPRIA
-Normal architecture
-Surface epithelial degeneration
-No acute inflammation
Treatment: CTSD, sulfasalazine
Differential diagnosis
| IBD | No INTRAEPITHELIAL LYMPHOCYTES, cryptitis, apoptosis |
| SRUS | No INTRAEPITHELIAL LYMPHOCYTES |
| Ischemia | No INTRAEPITHELIAL LYMPHOCYTES |
| Lymphoma | Tons of INTRAEPITHELIAL LYMPHOCYTES |
| Bowel prep | No INTRAEPITHELIAL LYMPHOCYTES |
SOLITARY RECTAL ULCER SYNDROME
-20-30, constipation with difficulty in defecation, blood & mucous
-AbN anorectal floor musculature during defecationà rectal mucosal prolapseà intussusception
Gross: polypà ulcer on anterior or anterolateral wall
Microscopy
-Mucosa: superficial ulceration (pseudomembrane), villiform change, crypt HYPERPLASIA, ectatic capillaries
-LAMINA PROPRIA: fibromuscular HYPERPLASIA with edema, pauci-inflammatory, +/-colitis cystica profunda
-MM: thickened with splayed fibers
Px: responds to bulk laxatives and stool softeners
Differential diagnosis
| SRUS | Mucinous carcinoma |
| Rounded mucin pool | Infiltrative |
| No | Floating epithelial nests |
| Bland, simple epithelium | Stratified, atypia, complex |
| No | Desmoplasia |
| Hemorrhage, hemosiderine | No |
| Supporting LAMINA PROPRIA sometimes | No |
DIVERTICULAR DISEASE
Left: mostly sigmoid and can be more proximal but never in rectum (if present, should query coexisting Crohn).
Right: isolated, mid-aged Asians, unrelated to left-sided disease, congenital or acquired
Congenital: all 3 layers of bowel wall (includes Meckel’s diverticulum)
Acquired: lack or have attenuated MP
Microscopy: acute and chronic inflammation+/-granulomas = diverticulitis
Complications: hemorrhage, perforation, diverticulitis, fistula, obstruction
Differential diagnosis: CD
ALLERGIC COLITIS
Cause cow’s milk, eggs, soyà infants/kids
Microscopy: rectal biopsy shows mucosal edema, prominent eosinophils (>60 per 10 HYPERPLASIAF)
COLITIS CYSTICA PROFUNDA
Microscopy: cysts containing mucus in colonic wall, mucosal prolapse change
Differential diagnosis: mucinous adenocarcinoma
ENDOMETRIOSIS OF COLON
Microscopy: endometrial glands, stroma, hemosiderin in deeper layers
INFARCTED EPIPLOIC APPENDAGES
-twisting of thick pedicles of fat
-like fat necrosis in the breast
Gross: firm, gray-white nodules resembling metastatic tumor
Microscopy: central infarcted adipose tissue with peripheral fat necrosis and calcification
CEROIDOSIS (brown bowel syndrome)
-Associated with severe malabsorption
-Lipofuscin in MP and MM
MELANOSIS COLI
-Anthracene-type laxatives
Microscopy: macrophages containing lipofuscin (melanin-like pigment) in LAMINA PROPRIA or deeper in muscle
PNEUMATOSIS CYSTOIDES INTESTINALIS PCI
-“A finding, not a diagnosis”
-Both SB and LB
Infants (fulminant): ischemiaà NECà gas-forming bacteriaà PCI
2. Adults (most benign): drugs, chemotherapy, ischemia, C. difficile, COPD, anything leading to increased luminal pressure (diverticular disease,…)
Gross: polypoid grapelike masses
Microscopy: submucosal cysts lined by multinucleated giant cells; mucosa contains cryptitis, crypt abscesses, granulomas
Differential diagnosis
| Pseduolipomatosis | Fat in LAMINA PROPRIA |
VASCULAR ECTASIA OF COLON/ANGIODYSPLASIA
-Elderly, 20% of lower GI bleeds
-Right colon and cecum, acquired (associated with aortic stenosis or vWD)
Microscopy: dilated and thin BV in mucosa and submucosa (quite superficial), often with cholesterol emboli. Difficult surgical diagnosis (best by contrast imaging).
DD: colonic varices due to portal HTN
XANTHELASMA OF COLON
-Foamy cells without mucin
Negative stains: DPAS, Alcian blue (pH 2.5 or 1.0), mucicarmine
EM: electron-dense globules
Differential diagnosis muciphages (positive mucin stains)
ISCHEMIC COLITIS
Etiology
Embolus/thrombus
-Arterial -> thrombosis or embolism
-Venous embolism
Ischemia (ie. hypoperfusion)
Mechanical (eg. volvulus, stricture, herniation)
Distribution
-dependent of vessel involved (ie/ celiac, SMA, IMA)
-transmural: entire thickness
-mural: mucosa and submucosa
-mucosal infarction: mucosa
Gross
-Arterial occlusion: sharply defined
-Venous occlusion: poorly defined
-Serosa: purple-red, small-large ecchymoses
-Wall: edematous, thickened, hemorrhage
-Patchy, serpiginous ulcersà strictures
-Must sample BV
Microscopy
Acute
-Patchy or diffuse
-Superfical coagulative epithelial necrosis (pseudomembrane) with loss of nuclei but preserved deep crypts
-Hemorrhage/hemosiderin in LAMINA PROPRIA
-Look for vasculitis or thrombosis
-Ulceration, transmural necrosis only when severe
-Granulation tissue
-Pauci-inflammatory, no basal plasmacytosis
2. Chronic
-Full-thickness fibrosis (including MP), hemosiderin
Differential diagnosis
| IBD | Acute: ulceration, transmural, no necrosis, more inflammatory, basal plasmacytosis, lymphoid aggregate, no hemorrhage/hemosiderin
Chronic: fibrosis sparing MP, no hemosiderin |
| E coli | More inflammatory |
| C difficile | More inflammatory |
RADIATION COLITITIS
-Weeks to years after radiation
Microscopy
-Atrophic mucosa
-Vascular ectasia
-Hyalinized fibrosis
-Atypical FB
-Endothelitisà fibrointimal HYPERPLASIAà occlusion
NECROTIZING ENTEROCOLITIS
-Necrotizing inflammation of SB or LB
-Onset within 10days of life in prematures
Gross: necrotic mucosa, submucosal gas-filled cysts
Microscopy: early – mucosal edema, hemorrhage, necrosis, pneumatosis cystoides intestinalis
late – hemorrhagic and gangrenous bowel wall with strictures if patient survives
EOSINOPHILIC GASTROENTERITIS
-Children and young adults
Endoscopy
-Furrow, rings
Ssx
-Malabsorption, diarrhea, bowel obstruction, ascites
Microscopy
-Eosinophils deep in submucosa and MPà diagnosis usually requires resection specimen
-Eosinophils: groupings, cryptitis, crypt abscesses, MP infiltration
-No chronicity change
Differential diagnosis
| IBD | Crypt distortion, metaplasia |
| NHD | |
| Parasites | |
| Drugs |
BOWEL PREPARATION
-Mild increase in mitoses and apoptosis
-Mucin deplEtiologyn
-PMN in surface and crypts
ACTIVE COLITIS
Microscopy
-PMN in LAMINA PROPRIA, cryptitis, crypt abscesses
-Irregular luminal border
-Prominent mucin deplEtiologyn
Differential diagnosis
-Diffuse active colitis: UC, infectious
-Focal active colitis: Crohn, bowel preparation, ischemia, NSAIDs, diverticular-associated
| Active IBD | Infectious | Diverticular |
| Chronic change | No chronic change | Rectal sparing, only next to divertiula |
CHRONIC COLITIS
Microscopy
-Metaplasia (Paneth)
-Crypt distorsion (branching/budding)à careful with mucosa above lymphoid follicles and from lower rectum
-Crypt atrophy (¯ number and shorter because does not touch MM)
-Irregular luminal border
-Basal plasmacytosis
-Fibrosis
-Goblets unaffected
Differential diagnosis
-IBD
-Ischemia
-Radiation
-TB
-Schistosomias
Diagnosis: Clinicalicopathologic
INFLAMMATORY BOWEL DISEASE
1. CROHN DISEASE
-HLA DR1/DQw5, white, jews, smokers
Location: throughout GI tract, most common in SB and also in LB with rectal sparing
Symptoms: episodic mild diarrhea, pain
Extraintestinal symptoms:
Arthritis (migratory polyarthritis)
SI
Ank spon
PSC
Erythema Ndosum
Complications: fibrosing strictures; fistulas to bowel, bladder, vagina and perianal skin; protein losing enteropathy, malabsorption, vitB12 deficiency, bile salt malabsorption with steatorrhea, carcinomas (in SB and LB, after 20 years of disease) (SB cancers aggressive but average for LB cancers)
Treatment: steroids, surgery eventually
Gross
-Mucosa: aphthous & linear ulcers, skip lesions (sharp demarcation), cobblestone
-Wall: edema, thickening, fibrosis,
-Serosa: sinus tracts, fistulae, creeping fat
-More right-sided, rectal sparing
Microscopy
1. Mucosa
-Superficial or deep ulcers, crypt abscesses
-Paneth cell and pyloric gland metaplasia
-Features of chronicity
2. Wall
-Non-necrotizing granulomas (poorly formed, next to BV or lymphatics)à need serial sections
-Transmural inflammation with lymphoid aggregates
-Fibrosis of submucosa, m. propria; HYPERPLASIA of m. propria
3. Serosa
-Serositis
-Does disease at anastomosis predict recurrence? No
Dysplasia and carcinoma
Poor prog: long duration and severe disease
2. ULCERATIVE COLITIS
Location: rectum, progressing proximally, continuous
Symptoms: relapsing, bloody mucoid diarrhea
Extraintestinal symptoms:
Arthritis (migratory polyarthritis)
SI
Ank spon
PSC
Complications: perforation, toxic megacolon, carcinoma, lymphoma
Treatment: steroids, surgery eventually
Gross
-Ulcers, inflammatory pseudopolyps, diffuse continuous disease in LB from rectum proximally (distal worse)
-Backwash ileitis
-No mural thickening, no serositis, no fissuring ulcers, no transmural lymphoid follicles
-Transmural inflammation, fissuring ulcers in fulminant colitits
Microscopy
Mucosa
-Inflammation and ulcers, nf with crypt abscesses
-Ulceration to submucosa
-Features of chronicity
Wall and serosa
-Submucosal fibrosis
Dysplasia and carcinoma
-Fat mucosa, poorly diff. or mucinous ca, high stage
Variants
-Ulcerative proctitis: good prognosis
Poor px: young, length of bowel inv., duration
3. INDETERMINATE COLITIS (used in colectomy)
Diagnosis: cannot distinguish between CD and UC
DIVERSION COLITIS
-Stasis, lass of trophic factors in feces (short-chain FA)àerythematous, granular, friable
Microscopy
-Lymphoid follicles
-Crypt abscess
-Mild inflammation
CHEMORADIATION
-Same histology for chemotherapy and radiation
Microscopy
Acute (starts within 2 weeks after treatment, subside after 1-2 months)
-Necrosis, ulcer, acute and chronic inflammation
-Large cells, large nuclei, mucin deplEtiologyn, apoptosis
2. Chronic (after acute phase)
-Mucosal atrophy
-Variable fibrosis in submucosa, MP, serosaà can be hyalinized
-Ectatic BV in LAMINA PROPRIA
-Atypical FB and BV
-Vascular changes: fibrointimal HYPERPLASIA, foamy macrophage in walls, hyalinized wall, stenosis
-Others: chronic inflammation, ulcer, stricture, fistula
Differential diagnosis
| Chemoradiation | Dysplasia |
| Preserved mucosal architecture | |
| Atypia beyond carcinoma | |
| Low or normal N/C | |
| No mitoses despite apoptosis | |
| Atypia in FB and BV | |
| No infiltrative growth |
GRANULOMA
-Infectious: viral, bacterial, mycobacterial, fungal, parasitic
-FB: polarize, amyloid
-Vasculitis: Wegener, Giant cell arteritis
-Neoplastic
-IBD
-Pneumatosis cystoides intestinalis?
-Idiopathic: sarcoid
DYSPLASIA IN IBD (intraepithelial neoplasia)
Clinical: multiple biopsy for flat lesions, precedes cancer almost all
Gross: flat, villous or nodular
Microscopy
Negative for dysplasia
regular surveillance (yearly after 10 years of disease)
LGD: basal nuclei; mild nuclear (enlargement, crowding and hyperchromasia), ¯ intracellular mucin
close surveillance
2. HGD: apical nuclei, loss of polarity, more atypia (darker, more pleomorphic), architecture distortion (villous or nodular) (CIS if cribriform)
colectomy (requires either second opinion or confirmation biopsy)
Indefinite for dysplasia: epithelial changes in a background of active inflammation with regeneration
repeat colonoscopy shortly with aggressive treatment
Differential diagnosis
| Dysplasia | Repair |
| Large nuclei | Same |
| Dark | Same |
| Mitoses | Same |
| Mucin deplEtiologyn | Same |
| Irregular nuclei | Rounded, smooth |
| Pleomorphic in size | Same nuclear size |
| Basal nuclei for LG but stratified for HG | Basal |
| Loss of polarity | No |
| No | Evenly spaced nuclei |
| Increased | Decreased N/C |
| No | Nearby cryptitis/abscess |
DALM
-Algorithm…
-Colectomy required even if LG dysplasia
POLYPS
Classify polyps
-Hamartomatous: lymphoid polyp
-Inflammatory/reactive: mucosal prolapse, inflammatory polyp
-Hyperplastic
-Neoplastic
HYPERPLASTIC POLYP
-Rectum mostly, often at top of mucosal folds, can be pedunculated
-Right-sided associated with MSI. >1cm right-sided HYPERPLASIA significant association with CRC
Microscopy
-Serration
-Bland basal nuclei, brush border, mitoses to crypt base (never on surface),
-Mixture of eosinophilic enterocytes and goblets, +/-Paneth
-Crypt cells more crowded with darker nuclei
-Can have invaginated glands (not cancer!)
-Thick subepithelial collagen layer
HYPERPLASTIC POLYPOSIS SYNDROME
-≥5HYPERPLASIA proximal to sigmoid, 2 of which ≥1cm or
-Any number in patient with first-degree relative
-≥30HYPERPLASIA of any size throughout colorectum
INFLAMMATORY POLYP
Where can you find?
-UC, Crohn, ischemia, amebiasis, schistosomiasis, adjacent to ulcers, adjacent to anastomosis
Why misdiagnosis?
-Can mimicks sarcoma due to bizarre stroma cells (epithelioid, spindle, ganglion-like, multinucleated giants)
Differential diagnosis from malignancy
| Inflammatory polyp | Malignancy |
| Rare mitoses | |
| Never atypical mitoses | |
| Zonation of bizarre cells | |
| Small size |
SESSILE SERRATED ADENOMA
-exaggerated serration
-crypt branching
-hypermucinous epithelium
-horizontal extension of the crypt base along the m. mucosa
Classification
SERRATED ADENOMA
MIXED HYPERPLASIA/ADENOMATOUS POLYP
Gross: small, <1cm
Microscopy: surface epithelial nuclear dysplasia (elongation, increased N/C ratio, nucleoli, atypia) and serration of >20%
TUMORS
ADENOMA
Name FIVE steps of adenoma-carcinoma sequence
“First hit”: germline or somatic mutations to:
-APC, mismatch repair genes (MSH2)
2. “Second hit”: methylation/inactivation of normal alIntraepithelial lymphocyteses: APC, B-catenin, MSH2à Adenomas:
Protooncogene mutation: k-ras
Homozygous loss of other tumour suppressor pr-: p53
Carcinoma: many genes
Gross morphology of adenoma. Why important?
-Pedunculated, sessile, flat. Flat has 10x HGD
Criteria for flat adenoma
-Flat with height less than half of diameter endoscopically
-Tubular, never thicker than 2x normal epithelial thickness Microscopyscopically. Diagnosis requires endoscopic correlation
Differentiate LG vs HG dysplasia
| LG | HG |
| Elongated nuclei | Branching, budding, cribriform |
| Large dark or vesicular with nucleoli | |
| Basal nuclei, apical mucin | Apical nuclei, no mucin |
| More mitoses, somestimes necrosis |
Define intramucosal vs invasive carcinoma and how to recognize them. Why important?
-Intramucosal: invasion to LAMINA PROPRIAà no metastatic potential
-Invasive: invasion to submucosaà metastatic potential
| HGD | Cancer |
| Desmoplasia | |
| Infiltrative pattern | |
| Ulceration |
How to report cancer on biopsy?
-Invasive or not
-Grade
-LVI
-Margin: not reportable on piecemeal polypectomy
When polypectomy is curative for invasive cancer in polyp?
-WD-MD
-No LVI
-Negative margin
-2mm from margin?
-Not villous?
Differentiate pseudoinvasion (misplacement)
| Pseudoinvasion | True |
| Glands in submucosa are wrapped by LAMINA PROPRIA (LAMINA PROPRIA contains usual inflammatory cells) | Glands not wrapped by LAMINA PROPRIA |
| No | Desmoplasia |
| Cystic dilation and rupture | |
| Hemorrhage, hemosiderin | |
| Acellular mucin pool | Floating tumor cells in mucin pool |
| Same degree of dysplasia |
Pathways to colorectal carcinoma
Chromosome instability pathway (adenomaà cancer)
Microscopysatellite instability pathway
MYH pathway
CG island methylation pathwayà imp mech. of inactivating tumor suppressor genes in
ADENOCARCINOMA OF COLON
RF?
-Hereditary syndromes, age, UC, Crohn’s, family history
Ssx?
-Right: polypoid exophytic massesà Fe-def anemia w/, weakness and fatigue
-Left: annular lesionsà obstructive symptoms (diarrhea)
-Rectosigmoid tumors: more advanced
Gross?
-Ulcerative, polypoid, infiltrative. Ulcerative more advanced stage usually
Microscopy: well to poorly differentiated tumor cells with marked desmoplasia, mucin prod. inflm NE cells
Grading? Where cutoff?
-20%-60%-80% glands. Also nuclear polarity and uniformity
-PD significantly worse than WD and MD
IHC?
-CK7-/20+, MUC1+/MUC3+, CDX2, hCG, CEA
Variants?
-Adenocarcinoma
-Mucinous
-Signet ring
-Small cell
-Adenosquamous
-Squamous
-Undifferentiated (medullary)
Poor prognostic factors
-Stage, grade, highly infiltrative growth pattern at margin, margins, angiolymphatic & perineural invasion, types (small cell, mucinous, anaplastic or signet ring)
INDICATIONS FOR GENETIC TESTING
-Kindreds of FAP and HNPCC
-Sporadic cancer satisfying Amsterdam
Amsterdam
1 with CRC <50 of age
2 successive generations
3 relatives with CRC (one first-degree)
-Hints: endometrial cancers
-Only send blood for testing
MUCINOUS CARCINOMA
What’s special about this tumor Clinicalically?
-Associated with MSI, younger onset, villous adenomas, 2nd to radiation, UC, more in developing countries
-More advanced stage, more extensive peritoneal spread, higher LN+, poorer prognosis
Microscopy?
-Mucinous >50% of tumor mass (floating tumor cells) +/-signet rings
-Often bland morphology
MEDULLARY/UNDIFFERENTIATED CARCINOMA
Genetics and behavior?
-Strongly associated with MSI-H but no/few nodal metastasesà better prognosis
-Sporadic or associated with HNPCC
Microscopy
-Expansive sheets of cells
-No or minimal mucin production
-No tubule formation
-Lymphocytic infiltration
-Uniform, small to medium-sized, round, nucleoli, lots of mitoses
Positive IHC: CK, CEA, EMA
Negative IHC: NE markers, MLH1, MSH2
Differential diagnosis for ugly tumors in bowels. Workup?
| Primary carcinoma | |
| Primary sarcoma | |
| Primary NE | |
| Lymphoma | |
| Melanoma |
-Don’t forget EM
SIGNET RING CARCINOMA
-Poor prognosis
Microscopy
-Diffuse growth of signet ring cells with little glandular formation (>50% of tumor cells)
SMALL CELL CARCINOMA
-Poor prognosis
Microscopy
-Same as small cell NE carcinoma of lung
IHC: NSE, syn, chrA
EM: few dense-core secretory granules
RECTAL CANCER AFTER NEOADJUVANT THERAPY
Microscopy? How to find tumor cells?
-Often just acellular mucin pools, inflammation and fibrosis.
-Use CK for tumors in tissue and also LN
How to report tumor size?
-Extent of mucin pools and fibrosis
GIST
-Interstitial cells of Cajal (pacemaker cells)
-By definition, CD117+ except few negative due to improper fixation, inadequate sampling, prior Gleevec treatment.
-50-70, equal except in Carney complex (parachondrogist, multiple, strikingly young females)
Genetics
-c-kit (transmembrane TK) OR PDGFR-α mutationsàauto-phosphorylationà signalling cascadeà altered cell proliferation and differentiation
Risk level
-Benign: <2cm, <5/50
-Borderline: in between
-Malignant: >5cm, >5/50
Treatment: Gleevec (imatinib) inhibits ABL, BCR-ABL, KIT, PDGFR. Only CD117+ by IHC responds to it; what about PDGFR+?
Gross: WC, intramural, fish-flesh, hemorrhage, necrosis, cystic softening
Microscopy
-Epithelioid: rounded cells, clear-eosinophilic cytoplasm, sheet but sometimes in nests
-Spindle (20%): interlacing fascicles, cigar-shaped, vesicular nuclei, sometimes palisading, less eosinophilic than adjacent SM, juxtanuclear cytoplasmic vacuoles in 5%
-Skenoid fibers (extracellular collagen globules)
Positive stains: CD117, CD34
Negative stains: desmin, actins
Diagnosis: C-KIT screening test
EM: long interdigitating cytoplasmic processes, intercellular junctions, dense core granules
Differential diagnosis of all GI spindle cell tumors
| Inflammatory fibroid polyp | Zonation, CD34+, SMA+ |
| Schwannoma | Diffuse S100+ |
| Fibromatosis | SMA+, CD117- |
| IMT | ALK+, SM markers-, S100- |
| GIST | CD117+, CD34+, SMA+, desmin- |
| GANT | CD117+. EM: neuron-like cells with neurosecretory granules |
| SM tumors | SMA+, desmin+ |
| Kaposi | |
| Melanoma |
APPENDIX
NORMAL
-Same 4 layers as gut
-Histologically similar to LB
-LAMINA PROPRIAà irregularly distributed crypts (glands)
-Rich lymphoid tissue in mucosa and submucosa
GROSSING
-Longitudinal serial sections of 1cm tip (in toto basically)
-2 cross sections from mid and proximal portions (always include resection margin)
INFLAMMATION
ACUTE APPENDICITIS
Clinical: young adults with periumbilical to RLQ pain, N&V, fever, ↑WBC
Gross: fibrinopurulent exudate on serosa, perforation, fecalith
Microscopy
Early: focal PMN collections in lumen and LAMINA PROPRIA
Later: erosion, cryptitis, crypt abscess, PMN in wall
Late: granulation, xanthogranulomatous
-Concomittant Actinomyces
-Large amount of eosinophils suggests appendiceal involvement by eosinophilic GE
INFECTIONS
1. ENTEROBIUS VERMICULARIS
Clinical, pinworm, ages 7-11, incidental
Microscopy: narrow lateral cuticular alae; causes granulomas
2. YERSINIA
3. SCHISTOSOMIA
TUMORS
FIBROUS OBLITERATION
-Not secondary to appendicitis
Gross: white tip
Microscopy
-Spindle cells and myxoid component
-Neuronal and NE cell proliferation
IHC: S100, chr, NSE
Differential diagnosis
| NE hyperplasia | Carcinoid |
| Definite insular growth with extension to muscular wall | |
| Gross nodule |
INFLAMMATORY MYOFIBROBLASTIC TUMOR
FIBROMATOSIS
IDIOPATHIC RETROPERITONEAL FIBROSIS
Name the different types of mucous lesions in the appendix
Simple mucocele
Hyperplastic polyp / mucinous hyperplasia
Mucinous cystadenoma
Mucinous cystadenocarcinoma
MUCOCELE
-Dilated lumen filled with mucous
Causes:
-Mucinous HYPERPLASIA (looks like hyperplastic polyp)
-Mucinous cystadenoma
-Mucinous cystadenocarcinoma
-Obstruction of the appendix (eg. fecolith, tumour)
HYPERPLASTIC POLYP/MUCINOUS HYPERPLASIA
-Looks like colonic hyperplastic polyp
MUCINOUS CYSTADENOMA
-Intestinal type epithelium w/ minimal atypia
MUCINOUS CYSTADENOCARCINOMA
-Like ovarian mucinous tumor
-Associated with pseudomyxoma peritonei, particularly if ruptures
Gross: resembles cystadenoma
Microscopy:
-Complex papillary fronds
-Stratification
-Destructive invasion wall
PSEUDOMYXOMA PERITONEI
-extravasation of mucin into abdominalmen
-thought to be clonally derived from associated mucinous tumor, usually of appendix
-also assoc/ ovarian mucinous tumors (thought to be met. from appx or GI)
ANUS
POLYPS
INFLAMMATORY CLOACOGENIC POLYP
Microscopy
-Mucosal prolapse change
CARCINOID
-Associated with Meckel’s, AIG, ZEN
Px: metastases, size
Stomach: AIG, ZEN, sporadic,
Small intestine: depth of invasion, location in small intestine
Appendix: >2 cm, mesoappendix invasion
goblet cell carcinoid = poorer prog
Rectum: >2 cm, invasion of muscularis propria, mitoses, angiolymphatic invasion, anaplasia
1. ESOPHAGUS
Very rare
Microscopy: nests, islands and trabeculae of uniform cells, may have Paneth cell differentiation
2. STOMACH
Clinical:
Types
-ECL carcinoids
| I (no1) | II | III (no2) |
| AIG | ZES | Sporadic |
| About 50 of age | ||
| 2.5x in F | Equal | 3x in M |
| Body, LVI possible | Parietal cell HYPERPLASIA | Anywhere |
| Favorable (regress with antrectomy) | Intermediate if sporadic; bad if MEN1 | Poor |
| Malignat if >2cm, myoinvasion, LVI | ||
-Gastrinomaà antrum
Gross: look like polyps
Microscopy
-Acinar, insular, trabecular
-≥5mm
Treatment: antrectomy, tumor resection
3. SMALL INTESTINE
Clinical: assoc/ MEN, ZES, sporadic
-assoc/ carcinoid syndrome if liver mets present
Treatment: surgical excision of tumor and regional lymph nodes, excise solitary liver metastases
5 year survival: 50-65% (85% if confined to bowel wall vs. 5% if serosal invasion)
Gross: submucosal, can ulcerate
-bright yellow after formalin fixation
Microscopy: arch: insular (nests), acinar, trabecular
| duodenum | jejunoileal |
| <2cm | >2cm |
| indolent | aggressive |
| muc/submucosa | muc/submucosa |
| somatistatinomas(periampullary with psam. bodies) | serotonin-prod |
| gastrinoma | gastrinoma |
Location: ileum>jejunum> duodenum
4. APPENDIX
-No1 tumor here, often at tip
-Sporadic
Gross: tip, < 1 cm; gray or yellow, firm, intramural nodule
Microscopy:
insular (nests)
trabecular
adenocarcinoid
tubular
goblet cell (mucicarmine, PAS-D, Alcian Blue)
Treatment
Appendectomy: if < 1cm
Indications for right hemicolectomy:
>2 cm
2. positive margin
3. mesoappendiceal spread
What about goblet cell carcinoid?
Poor prog: >2 cm, mesoappendix invasion
goblet cell carcinoid (mucicarmine, CEA +)
5. RECTUM
Clinical: most common site of colonic carcinoid
-assoc/ ovarian carcinoid, Crohn (multiple), UC (multiple)
Poor prog.: >2 cm, invasion of muscularis propria, mitoses, angiolymphatic invasion, anaplasia
Treatment: local excision; partial colectomy if have malignant potential (see above)
Gross: <5mm
Microscopy: insular, trabecular
CARCINOID SYNDROME
-Caused by liver mets, ovary and lung primaries (all bypass portal venous system)
“Biologically active substances” released→ serotonin, tachykinin, bradykinin, histamine, prostaglandins
Clinical: flushing, hypertension, sweating, palamina propriaitations
Gross: fibrosclerosis of RV +TV/PV “carcinoid heart disease”, tumour itself
Microscopy: smooth muscle cells + mucopolysaccharide matrix
Why only right-side of heart?
-5-HT and bradykinin are degraded by monoamine oxidases in the pulmonary circulation
Why only liver mets?
-bioactive substances released into the portal system and therefore not degraded by the liver
ENTEROPATHY-ASSOCIATED T-CELL LYMPHOMA (ulcerative jejunoileitis)
Ssx
-Malabsorption, perforation, hemorrhage, pain, fever
Microscopy
-Villous atrophy
-Low threshold for ordering TCR rearrangement analysis
AMYLOID
-Common
Diagnosis
-Abdominalminal fat or rectal biopsy
Microscopy
-AL: BV walls and MP
-AA: mostly in LAMINA PROPRIA and BV walls
GROSSING
COLECTOMY
1. “Make sure the name and unique number match on the requisition and bucket.”
2. Sample the following areas (going through the TNM stages):
Polyps
-section through surgical margin of stalk
-in toto
Colectomy – tumor
-can remove mesentery and dissect lymph nodes while fresh
-can do fat digestion in alcohol
-open bowel (don’t cut through tumor) and pin overnight to fix
Sections:
Tumor deepest point of invasion
IBD: section every 10cm
Resection Margins
Proximal
Distal
Radial margin
Lymph nodes
peritumoral
proximal to tumor
distal to tumor
Representative sections
bowel
anorectal junction
subserosal connective tissue
STAGING
COLON
Difference with other GI tumors?
-Tis: carcinoma in situ (intraepithelial or invasion of LAMINA PROPRIA)
-T1: tumor invades submucosa only
4 margins?
-2 ends, radial, peritoneal (only valid if tumor on peritoneal surface or ulcerated surface or reactive mesothelials with tumors close to, but not at, serosal surface)
Node numbers? Minimal number?
-N1: ≥1, N2: ≥4 (remember 1, 4)
-12 but more LN will increase predictive probability
How to sample margins?
-Must do longitudinal sections if tumor close to margins. Otherwise, en face acceptable
Define positive radial margin and why so important?
-≤1mm. Because postoperative adjuvant therapy needed
LN equivalent?
-Tumor found in fat but with form and smooth contour of LN
-If irregular, should be classified in T category
Current standpoint for Microscopymetastasis?
-Not considered standard of care. So no need to stain with CK
How many sections needed to assess depth of invasion?
-At least 3
REST OF GI TRACT
TX: cannot be assessed
T0: no primary tumour
Tis: carcinoma in situ (intraepithelial only)
T1: tumor in LAMINA PROPRIA OR submucosa
T2: tumor invades MP
T3: tumor invades through MP into the subserosa
T4a: tumor directly invades other organs
T4b: perforates visceral peritoneum
Note: pT4 (serosal involvement) includes (a) tumor close to or at, serosal surface due to mesothelial inflammatory or HYPERPLASIA reaction
Regional lymph nodes (N)
NX: cannot be assessed
N0: none
N1: 1-3
N2: 4+
Classify tumour nodule as:
lymph node: if form and smooth contour of a lymph node
tumour: if irregular contour
Notes: 12-15 lymph nodes are required for accurate staging
Distant Metastasis (M)
MX: distant metastasis cannot be assessed
M0: no distant metastasis
M1: distant metastasis
SYNOPTIC REPORT
COLORECTAL CARCINOMA
Tumor extent: depth of invasion (TNM stages)
Lymph nodes: sentinel, non-sentinel
Margins: proximal, distal, radial
Host response
Perforation
Pre-existing polyp
TNM stage
HEREDITARY
FAP (Classic)
When all get cancer?
-~100% adenocarcinoma by age 50
Inheritance, genetics, mechanism?
-AD. APC mutation on 5q. Tumour suppressor geneà non-functional APC cannot bind b-cateninà b-catenin binds to Tcf-Lef proteinsà proliferation and anti-apoptosis
Diagnostic criteria
>100 colorectal polyps (not always adenoma!)
Germline APC mutation
Family history of APC
At least one of following: epidermoid cyst, osteoma or desmoid tumor
GI tumors
-Stomach: FGP, adenomas
-SB: adenomas
-GI: adenomas
Extracolonic tumours
-Fibroma, supernumerary teeth, congenital hypertrophy of retinal pigment epithelium
-Gardner’s syndrome: periampullary adenocarcinoma, lymphoid polyps of ileum, cancers of thyroid and adrenals + extraGI lesions (desmoid tumors, epidermoid cyst, osteoma)
-Turcot’s syndrome: + medulloblastoma
Microscopy: adenomas, may have adenomatous flat epithelium
AFAP (Attenuated)
What genetic difference?
-MAPC mutation on 5q, on exon 9 (both 5’ and 3’ ends)
-Also mutations to MYH (base excision repair gene)
Gross difference? Onset difference?
-Flat, plaque-like, >100, right colon
-Cancer 15yrs later than FAP but 10yrs earlier than sporadic
HNPCC
Define MSI-H. Name all MMR
-Loss of ≥2 MMR markers
-MSH2, MLH1, PMS1, PMS2, MSH6
Onset?
-~45yrs.
Genetics
-MLH1, MSH2, PMS1/2 mutationsà MSI (expansion or contraction of tandem repeats of 1-4 nucleotides)
Extracolonic? “CEO”
-Cholangiocarcinoma
-Endometrial carcinoma
-Ovarian
Amsterdam criteria?
-3 members (one must be 1st degree)
-2 successive generations
-1 under 50
Bethesda criteria?
-Steinberg p1573
Microscopy
-Right-sided
-Undifferentiated (medullary)
-Signet ring differentiatino
-Lymphocytic infiltration
-Mucinous differentiation
-No dirty necrosis
Prognosis compared to sporadic?
-Paradoxically better prognosis despite uglier tumors
IHC: hMLH1, hMSH2à loss of staining suggests mutation in gene with additional DNA testing for MSI expansion/contraction
What’s Muir-Torre?
-HNPCC+sebaceous tumors
COWDEN’S SYNDROME
-AD
Features
-Multiple GI hamartomas including in stomachà no malignant potential
-Risk of breast and thyroid cancers
-Trichilemmomas, acral keratoses, oral papillomatosis
Microscopy
-LAMINA PROPRIA divided into lobules by SM from MM (~PJ polyps or SRUS)
Genetics: PTEN mutations in 70%
Differential diagnosis: Peutz-Jeghers
JUVENILE POLYPOSIS SYNDROME
Locations?
-Rectum>>> SB, stomach
Inheritance?
-Sporadic or AD
Diagnostic criteria?
->5 colorectal juvenile polyps
-Juvenile polyps in entire GI tract
-Any polyps in patient with family history of JPS
Sessile or pedunculated? Cut surface?
-Peduculated (sessile is rare). Cysts
Microscopy?
-Eroded surface with reactive and regenerative epithelium
-Cystically-dilated glands
-Prominent stroma with mixed inflammatory infiltrate (granulation tissue stroma)
Any cancer risk?
-Considered non-neoplastic if solitaryà therefore, no risk
-30-40% CRC if syndromic. Cancer can be in colon, stomach and pancreas
Name 2 genetic mutations?
-SMAD4, PTEN muations
PEUTZ-JEGHERS SYNDROME
-AD, incomplete penetrance, most diagnosed at 20 of age
Genetic mutation?
-STK11
Diagnostic criteria?
-≥3 PJ polyps or
-Any combo of 2 elements of following: any number of PJ polyps, family history, mucocutaneous pigmentation
Sessile or pedunculated?
-Large, lobulated, pedunculated polyps resembling adenomatous polyps
Microscopy?
-Epithelium of HYPERPLASIA + arborizing SM
-Surface regenerative changes with erosion
-Invagination possible
Cancers in which organs? What surveillance?
-95% overall cancer risk
GI: colon, pancreas, stomach
2. Breast: very high
Gyn: ovary (sex cord tumors with annular tubules), cervix (adenoma malignanum), testis (Sertoli cell tumors)
TURCOT
Genetics for both variants and tumors?
-AD
| HMPCC | FAP |
| No polyps | Polyps |
| GBM | Medulloblastoma |
GANGIONEUROMA
SB and LB
Forms
Solitary
Ganglioneuromatous polyps
Diffuse ganglioneuromatosis (with NF1, MEN2b)
Microscopy
CRONKITE-CANADA
Inheritance:
Nonhereditary
Manifestations?
Alopecia, nail atrophy, skin hyperpigmentation
What’s special about onset compared to other genetic disorders?
Late after 50
Microscopy
Same as JP
Cancer risk?
Very rare
REPORT COLON
CAUSES OF FEWER LYMPH NODE THAN EXPECTED
Unusual patient with fewer LN (least likely possibility)
Neo-adjuvant therapy
Surgeons fail to remove enough tissue
Pathologists fail to find LN