Esophagus

ESOPHAGUS

Mucinous glands In submucosa 

~ salivary glands
Cardiac mucosa In Lamina Propria
Inlet patch
Mislabeled sample
Sebaceous glands Heterotopia
Normal cardiac mucosa Within 2cm from GEJ
Z-line Squamocolumnar junction 

Normally up to 2-3cm above GEJ
GEJ Where tubular esophagus meets saccular stomach 

Covered by cardiac mucosa
Cardia Ill-defined distal limit 

Between Z-line and proximal margins of gastric rugae

Basal layer

3 cell thick and <15% total thickness

Papillae <2/3 total thickness

CYSTS

  • Bronchogenic: foregut-derived bronchial tissue, not communicating with esophageal lumen, ciliated with SM wall, mucous glands and cartilage
  • Duplication: all layers (mucosa, submucosa, muscular layer)
  • Retention: from occluded submucosal mucinous glands
  • Diverticulosis
  • Neuroenteric: lined by intestinal mucosa
  • Developmental: ciliated or squamous lining with SM
  • Inclusion: squamous lining

WHITE PATCHES IN ESOPHAGUS

  • Glycogenic acanthosis
  • Caustic injury
  • Cancer
  • Infectious

CONGENITAL ABNORMALITIES

  • Tracheo-esophageal fistulas
    • Trisomy 21
    • Trisomy 13
    • Trisomy 18
  • Atresia
  • Diaphragmatic hernia
  • Omphalocele
    • Incomplete closure of abdominal musculature
    • Abdominal viscera herniate into ventral membranous sac
    • 40% other birth defects, diaphragmatic hernia, cardiac anomalies
  • Gastroschisis
    • Involves all of layers of abdominal wall, from peritoneum to skin
    • Most common to R of umbilicus
    • Trisomy 18 (Edwards)
  • Ectopia
    • Gastric, pancreatic, sebaceous
    • Inlet patch
    • Gastroduodenal junction
    • Meckel’s diverticulum
  • Pyloric stenosis
  • Hirschprung’s disease

TRACHEO-ESOPHAGEAL FISTULA

  • 5 types
  • VACTERL: vetebral anomalies, anal atresia, cardiac abnormalities, tracheoesophageal fistula, renal agenesis, limb deformities

ESOPHAGEAL OBSTRUCTION AND MOTILITY ABNORMALITIES

  • Diverticula
    • Zenker
    • Midesophagus/traction
    • Above lower esophageal sphincter/epiphrenic
  • Nutcracker esophagus
  • Diffuse esophageal spasm
  • Achalasia
  • Hiatus hernia
  • Webs
  • Schatzki rings
  • Lacerations
    • Mallory-Weiss
    • Boerhave’s

DIVERTICULA

  • Zenker (pulsion) – posterior, above UES, mass in neck, aspiration pneumonia, secondary to dysfunction in cricopharyngeal muscle
  • Mid-esophageal (traction)
  • Epiphrenic (pulsion)à above LES

ACHALASIA

  • Primary
    • T cell-mediated destruction of myenteric plexus
    • Progressive peristalsis and LES relaxation
      • Resting tone of LES
      • Dilation proximal to LES
  • Secondary
    • Chagas (Trypanosoma cruzii)
    • Scleroderma
    • Amyloidosis
    • Sarcoidosis
    • Malignancies
    • Inflammatory conditions
  • Micro
    • No myenteric ganglion cells but nerves remain
    • Chronic inflammation attacking ganglion cells
    • Hyperplasia or thinning of muscularis
    • Lewy bodies

HIATAL HERNIA

  • Sliding
  • Paraesophageal
  • Complications
    • Ulcer, bleed, perforation strangulation of paraesophageal hernias

MALLORY-WEISS TEAR

  • Characteristic longitudinal laceration
  • RR
    • Iatrogenic instrumentation
    • Intractable vomiting

SCLERODERMA

  • Excessive collagen deposition throughout body
  • Intimal fibrosis resulting in microvascular disease
  • CREST syndrome
    • Calcinosis
    • Raynaud’s
    • Esophageal dysfunction
    • Sclerodactyly
    • Telangiectasia
  • 2 specific ANA’s
    • DNA topoisomerase I (very specific)
    • Anti-centromere AB
  • Skin
    • Thinning of epidermis
    • Dermal appendage atrophy
    • Fibrosis of the dermisà claw like flexion deformity
  • Esophagus
    • MP replaced by collagen
    • garden hose tube
    • GERD, Barrett, dysplasia
  • Intestine
    • Loss of villi/microvilli
    • malabsorption
  • Joints
    • Synovial HP and hypertrophy with fibrosis
  • Kidneys
    • Intimal thickening and concentric proliferation of intimal cells
    • Malignant HTN
    • Fibrinoid necrosis with thrombosis and infarction
    • ARF
  • Lungs
    • Pulmonary fibrosis and vascular changes
    • Pulmonary HTN and RHF
  • Heart
    • Myocardial fibrosis
    • Thickening of intramyocardial arterioles
    • CHF, arrhythmias
  • Varices
    • Secondary to portal HTN
    • DDx portal HTN
      • Cirrhosis
        • EtOH
        • Viral
        • Schistosomiasis
        • Hemochromatosis
        • Alpha-1-AT deficiency
        • Cystic fibrosis
        • CHF
        • Budd Chiari
        • Mass obstructing portal vein
GERD
Infections Not limited to immunosuppressed
Crohn Aphthous ulcers, granulomas
GVHD Apoptosis, no inflammation
Eosinophilic
Corrosive
Pill Antibiotics, NSAIDs, K, Fe, alendronate
Radiation Hyalinized collagen, atypical FB

ESOPHAGITIS

CANDIDA

  • X2 features seen in true infection (vs. colonization)
  • Tissue invasion or ulcer formation

HSV

CMV

  • Viral inclusions in fibroblasts and endothelial cell in ulcer bed

PILL

  • Direct caustic effects + other systemic
  • Midesophagus
  • Micro
  • Erosions, ulcers
  • Granulation tissue
  • Polarizable FB with giants

RADIATION

  • Micro changes in acute and chronic
  • Acute
  • Necrosis
  • Submucosal edema
  • Chronic (>60Gy)
  • Submucosal fibrosis/hyalinized collagen
  • Telangiectasia
  • Thick hyalinized arterioles
  • Atrophic mucous glands

GASTROESOPHAGEAL REFLUX DISEASE

  • Changes in gastro-esophageal junction and distal esophagus distension with reflux of gastric or duodenal contents into esophagus
  • Clinicopathologic diagnosis
  • Well-oriented specimens bx essential!
  • Micro x3 criteria
    • Elongated papillae
      • >2/3 of the thickness of the mucosa
      • Basal cell hyperplasia
        • >15% of the thickness of the mucosa
        • Intraepithelial granulocytes (at least one type)
          • Neutrophils
          • Eosinophils
          • > 5/HPF (consider EE)
        • If some but not all features present, findings can be considered consistent with or suggestive of reflux
  • Nonspecific findings
    • Intraepithelial lymphocytes
    • Ballooning degeneration of squamous cells
    • Multinucleated squamous cells
    • Capillary dilation and extravasation
    • Mild chronic inflammation normal in GEJ
  • Ulceration
    • R/O HSV and CMV
  • PMNs in squamous mucosa
    • R/O fungi such as Candida
  • PMNs in glandular mucosa
    • R/O Helicobacter, unless gastric antral bx available
  • Goblet cells
    • R/O Barrett esophagus
  • Pancreatic metaplasia frequently seen in EGJ
    • No clinical significance

EOSINOPHILIC ESOPHAGITIS

  • AKA allergic esophagitis
  • Marked eosinophil infiltration restricted to esophagus
  • 20-40 years
  • Associated allergy, asthma, atopy, eosinophilia
  • May have dysphagia, focal strictures, food impaction
  • Endoscopic findings
    • Longitudinal furrows
    • Multiple rings (feline esophagus)/trachealization
    • Fragile and inelastic (crepe paper esophagus)
    • White granular exudates
      • Rich in eosinophils
      • Focal strictures and long segment strictures
  • Failure to thrive in infants
  • Pediatric treatments
    • Elemental (amino acid) diet or dietary restrictions
    • Anti-reflux therapy
    • Oral steroids
  • Adult treatments
    • Antihistamines
  • Topical steroids
  • Micro criteria
    • Intraepithelial eosinophils 15-20/HPF
      • Diffuse or in clusters
      • Microabscess > 4 clustered eos.
      • Eosinophils in superficial layers of mucosa
      • Superficial epithelium containing sheets of eosinophils may slough
  • No eosinophils in rest of GI tract
    • Generalized GI infiltrates = eosinophilic gastroenteritis
  • Surgical pathology report
    • Number of eosinophils/HPF
    • Presence or absence of microabscesses
    • Distribution: diffuse or accentuated at surface
    • Presence or absence of squamous hyperplasia
    • Papillary or basal cell
  • Eosinophils in other diseases
    • Food impaction
    • Pill esophagitis
    • Drug hypersensitivity (Abx, MTX)
    • Hypereosinophilic syndrome
    • Parasitic disease (stool parasites & ova)
    • Crohn disease
      • Eosinophils do not predominate
      • Very rare in esophagus
      • Milk protein enteropathy (infants)
      • Systemic diseases
        • Churg Strauss vasculitis
        • Polyarteritis nodosa
        • Scleroderma
        • Stevens-Johnson syndrome

ESOPHAGEAL POLYPS

BENIGN EPITHELIAL

-   Squamous papilloma

  • Gastro-esophageal junction
  • Variants x3
    • Exophytic
      • HPV 80%
      • Spiked
        • HPV 50%
        • Endophytic
          • AKA inflammatory polyp
          • HPV 30%

-   Polypoid dysplasia in Barrett’s esophagus

-   Adenoma

-   Gastric heterotopia

-   Glycogenic acanthosis

MALIGNANT EPITHELIAL

-   Carcinoma

  • Squamous cell
  • Adenocarcinoma
  • Spindle cell
    • Mid-esophagus
    • Middle-aged men
    • AKA
      • Carcinosarcoma
      • Polypoid carcinoma
      • Sarcomatoid carcinoma
      • Spindle cell variant of squamous cell
      • Biphasic
        • Dominant spindle cell component
        • Focal squamous cell carcinoma
        • Focal squamous dysplasia
        • Adenosquamous
        • Basaloid
        • Small cell
        • SGTs
        • Melanoma
          • Junctional melanocytic activity
          • KIT positive
          • KIT gene mutations

BENIGN MESENCHYMAL

-   Leiomyoma

-   Granular cell tumor

  • S100+
  • PAS-D+
  • Schwann-cell origin
  • Infiltrative
  • Pseudoepitheliomatous hyperplasia

-   Fibrovascular/fibroepithelial polyp

  • Proximal
  • Mass effect
  • Large
  • Mixed mesenchymal components
    • Adipose

-   Inflammatory fibroid polyp

  • Antrum > duodenum
  • Young
  • Obstruction (ball and valve effect)
  • Sessile, pedunculated
  • PDGFRalpha gene mutations
  • Micro
    • Submucosal proliferation of FB
    • Perivascular hypocellularity around muscular BV
    • Fibrous or myxoid background
    • Uniformly scattered mixed inflammation (eosinophils, lymphocytes, plasma cells, macrophages, mast cells)
    • Rare mitoses (up to 2/HPF!), no giants
    • IHC
      • CD117-
      • CD34+
      • SMA/MSA+
      • Desmin-

MALIGNANT MESENCHYMAL

-   GIST

-   Inflammatory myofibroblastic tumor

-   Leiomyosarcoma, other (rare)

ESOPHAGEAL CYSTIC AND DIVERTICULAR LESIONS

CYSTS

-   Duplication cyst

-   Bronchogenic cyst

DIVERTICULA

-   Upper

  • Zenker’s

-   Mid

  • Traction

-   Lower

  • Epiphrenic

-   Pseudodiverticulosis

Barrett Esophagus

  • Clinicopathological diagnosis
    • Endoscopic identification of columnar mucosa extending proximally into tubular esophagus
    • Histopathologic identification of columnar epithelium with goblet cells
      • Distended, sharply defined, mucin-filled cytoplasm
      • Alcian blue positive at pH 2.5
  • Barrett esophagus defined by its length
    • Long segment at least 3 cm
    • Short segment <3 cm
    • Ultra-short segment <1 cm
  • Fundic or cardiac type mucosa may be present
  • Dysplasia in Barrett esophagus related to development or presence of adenocarcinoma
  • GEJ
    • Anatomic junction of saccular stomach with tubular esophagus
  • Squamo-columnar junction
    • Where glandular mucosa meets squamous mucosa
  • LES
    • Distal 1 cm of tubular esophagus
    • A region of increased pressure
  • Hiatal hernia
    • Portion of saccular stomach above diaphragmatic notch
    • Difficult to distinguish from an irregular GEJ
  • Pancreatic metaplasia frequent in biopsies from GEJ
    • No clinical significance
  • DDx
    • Esophageal submucosal glands
      • Alcian blue positive
      • Nests of glands below muscularis mucosae
      • Distended foveolar cells
        • Weakly Alcian blue positive
        • Form a linear array
        • Form a spectrum with obvious non-distended foveolar cells
        • Cardiac intestinal metaplasia
          • Requires clinical correlation of site of biopsy
        • Cervical inlet patch with intestinal metaplasia
          • Requires clinical correlation of site of biopsy

Practice Parameters Committee, American College of Gastroenterology, 2008 Recommendations

  • No dysplasia
    • Endoscopy + bx in one year then at 3 years
  • Indeterminate or low grade dysplasia
    • Anti-reflux therapy
    • Endoscopy + bx at 6 mos
  • High grade dysplasia
    • Anti-reflux therapy
    • Endoscopy + bx at 3 mos
    • 30-40% carcinoma on resection
  • Intramucosal carcinoma
    • Consider EMR or equivalent
  • Adenocarcinoma invasive into submucosa
    • Consider surgery

Dysplasia in Barrett Esophagus

  • 4 criteria to assess dysplasia
    • Surface maturation: critical because some basal atypia already present with Barrett
    • Architecture: ­number, ­shape (budding, cribriform)
    • Cytology
    • Inflammation/ulceration: serves as reference on how much atypica can be accepted
  • 10% GERD have Barrett esophagus
  • Barrett esophagus
    • 10% dysplasia at initial diagnosis
    • 10% adenocarcinoma at initial diagnosis
  • Low grade dysplasia
    • 10% progress to high grade dysplasia
    • 3% progress to carcinoma
  • High grade dysplasia
    • 40% develop carcinoma
    • 87% intramucosal
    • 13% invasive into or beyond submucosa
  • Dysplasia best evaluated in areas without significant acute inflammation
  • Dysplastic features should be present on luminal surface
  • Reactive atypia rarely extends to luminal surface
  • Dysplasia may be focal, requiring adequate sampling
  • Diagnosis of dysplasia should be confirmed by an experienced GI pathologist
  • Negative for dysplasia
    • Orderly glandular architecture
    • Regenerative basal glands may have cytologic atypia
    • Hyperchromasia
    • Pleomorphism
    • Nuclear stratification
    • N/C ratio normal or slightly increased
    • Atypia more uniform than in dysplasia
    • Preserved surface maturation
    • Most dysplasia is of intestinal type, resembling changes seen in colonic adenomas
  • Low grade intestinal type dysplasia
    • Architecture preserved or minimally abnormal
    • Nuclei elongated and crowded at base but not at apex of cells
    • Pseudostratification
    • Nuclear enlargement
    • Mild to moderate nuclear hyperchromasia and irregularity
    • Mitotic figures may be present at surface
    • Cytologic atypia extends to cells on luminal surface
    • Surface villous transformation may be present
  • High grade intestinal type dysplasia
    • Marked cytologic atypia
    • Nuclear stratification to surface of cell with loss of polarity
    • Nuclei no longer radially oriented
    • Abnormal architecture
    • Lateral budding
    • Branching
    • Intraglandular bridging
    • Villus formation
    • Dilated glands containing necrotic debris
    • No single cell or small cluster infiltration (intramucosal carcinoma)
  • Indefinite for dysplasia
    • Technical
    • Lesion suggestive but not diagnostic of dysplasia
    • Significant atypia with lack of surface maturation in context of inflammation
    • Significant atypia with surface maturation in absence of inflammation
    • Significant atypia with partial surface maturation
    • If acute inflammation is present, dysplasia should be diagnosed with caution and then only if the dysplastic findings are clearly disproportionate to the degree of inflammation
  • Recently proposed grading criteria based on nuclear size (Mahajan et al, 2010)
    • AKA
      • Non-adenomatous dysplasia
      • Gastric foveolar-type dysplasia
      • 20% of Barrett cases
      • Low grade foveolar-type dysplasia
        • Nuclei enlarged to 2-3x size of lymphocytes
        • Variably prominent nucleoli
        • Pleomorphism absent to mild
        • Full thickness population of uncrowded glands
        • Cytoplasm is usually mucinous
        • High grade foveolar-type dysplasia
          • Nuclei enlarged to 3-4x size of lymphocytes
          • Prominent nucleoli
          • Pleomorphism mild to moderate
          • Glandular crowding
          • Cytoplasm frequently eosinophilic/oncocytic
          • Variable features
          • Villiform growth
          • Cribriform glands
          • Dilated glands with luminal debris

ESOPHAGEAL TUMORS

SQUAMOUS CELL CARCINOMA

Risk Factors: alcohol, smoking, dietary, betel nuts, HPV, genetics, rare (achalasia, strictures)

Spreads by lymphatics, BV, perineural spaces, longitudinal intramural spread

Precursor: squamous dysplasia

Prognosis: depth, LN. Other minors (grade, LVI, growth pattern, inflammation, aneuploidy)

Gross: distal, ulcer, plaque or exophytic

Microscopy: Moderately differentiated to well differentiated

Immunohistochemistry: CKs

Differential Diagnosis:

Repair around ulcers: atypical mesenchymal cells are CK-, surface maturation, nuclei NOT dark, polarity maintained, monomorphic – rebiopsy

Radiation

Variants

Sarcomatoid: biphasic, heterologous differentiation. Stromal VIM+/-CK positivity. Better prognosis

Basaloid: large nests of basaloid cells, central necrosis, peripheral palisading, mitoses, hyalinized BM stroma. Often mixed with other tumors. CK+, NE markers-

Verrucous: large exophytic with papillae, bulbous invasion, WD

ADENOCARCINOMA

- esophageal when tumor epicenter is >2-3cm above GEJ. Barrett favors esophageal. CK7/20 useless

Risk Factors: Barrett esophagus, maybe (EtOH, smoking)

Prognosis: depth, nodes, margins

Gross: distal, flat

Microscopy: Moderately differentiated to well differentiated

Intestinal type epithelium

Papillae

+/- Signet, squamous, Paneth, germ cell, Neuroendocrine differentiation

Adjacent Barrett’s mucosa with high grade dysplasia

May be from ectopic gastric mucosa

Immunohistochemistry: CK7+/CK20-, PAS/Alcian blue (for mucin to confirm it), CDX2?

Variants

ESOPHAGECTOMY GROSSING

-   Cut along greater curvature of stomach

-   Measure tumour midpoint from

  • GEJ
  • Resection margins

-   Pin/fix overnight

-   Sections

  • Resection margins
    • Proximal
    • Distal
    • Radial soft tissue
    • Serosal if proximal stomach
    • Deepest invasion
    • Serosa, wall, mucosa

Staging

T1     Lamina propria, submucosa

T2     Muscularis

T3     Adventia

T4     Adjacent organs

Surgical pathology report (biopsy, excision)

-   Fragment number

-   Tumour size

-   Histologic type, grade

-   Margins

-   Depth

References:

1. Robbins & Cotran Pathologic Basis of Disease, 8th edition. Vinay Kumar, MBBS, MD, FRCPath; Abul K. Abbas, MBBS; Nelson Fausto, MD; Jon Aster, MD. Saunders. Published June 2009.

2. Sternberg’s Diagnostic Surgical Pathology, 5th edition. Darryl Carter, Joel K. Greenson, Victor E. Reuter , Mark H. Stoler. Lippincott Williams & Wilkins. Published Aug 26 2009.

3. College of American Pathologists Cancer Protocols and Checklists:

http://www.cap.org/apps/cap.portal?_nfpb=true&cntvwrPtlt_actionOverride=/portlets/contentViewer/show&_windowLabel=cntvwrPtlt&cntvwrPtlt{actionForm.contentReference}=committees/cancer/cancer_protocols/protocols_index.html&_pageLabel=cntvwr

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