Esophagus

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Esophagus connects the pharynx to the stomach. It is afflicted by tumours on occasion. For some reason or another, it seems everyone at SMH gets a esophageal biopsy... yet patients at SB don't have esophagi.

Normal

General:

  • Stratified squamous non-keratinized epithelium.

Normal (esophageal) squamous epithelium:

  • Should "mature" to the surface like good stratified squamous epithelium does.
    • No nuclei at luminal surface.
    • Cells should become less hyperchromatic as you go toward the lumen.
    • Mitoses should be rare and should NOT be above the basal layer.
  • Inflammatory cells should be very rare.

Diagnoses

Common

  • Normal.
  • Metaplasia (Barrett's esophagus).
  • Dysplasia.
  • Adenocarcinoma.

Less common

  • Squamous cell carcinoma.
  • Eosinophilic esophagitis.
  • Candidiasis.
  • CMV esophagitis.

Indications

  • Pyrosis = heartburn.[1]

Infection

Main article: Microorganisms

Is a relatively common problem, especially in those that live at the margins (EtOH abusers) and immunosuppressed individuals (HIV/AIDS).

Useful stains

  • PAS.
  • Gram stain.

Overview

  • Candida - worms.
  • HPV - koilocytes.
  • CMV - large nuclei.
  • HIV - non-specific.

Candidiasis

Gross (endoscopic)

Features:

  • White patches.

Microscopic

Features:

  • Worm-like micro-organisms.
    • Pseudohyphae (single cells).
    • Thickness ~ 1/3-1/2 of squamous cell nucleus.
    • Should be within (squamous) epithelium.
      • On top of epithelium does not count,[2] i.e. it is likely an artifact.

Image: Esophageal candidiasis (WC).

Cytomegalovirus esophagitis

  • AKA CMV esophagitis.

Clinical:

  • Classically at the base of the ulcer; within endothelial cells.

Herpes esophagitis

General

Etiology:

  • Herpes simplex virus.

Microscopic

Features (3 Ms):

  • Moulding.
  • Multinucleation.
  • Margination of chromatin.

Images:

Human papilloma virus esophagitis

General:

  • AKA HPV esophagitis.

Microscopic

Features:

  • Koilocytes:
    • Perinuclear clearing.
    • Nuclear changes.
      • Size similar (or larger) to those in the basal layer of the epithelium.
      • Nuclear enlargement should be evident on low power, i.e. 25x. [7]
      • Central location - nucleus should be smack in the middle of the cell.

Images:

Barrett's esophagus

Definition

  • Metaplastic transformation of stratified squamous epithelium to simple columnar epithelium with goblet cells.

Microscopic

Features:

  • Columnar epithelium.
  • Goblets cells -- key feature.

Significance

  • Increased risk of adenocarcinoma of the esophagus.

Management

  • Long term follow-up/repeat esophagogastroduodenoscopy.

Dysplasia

Classification

  • Low grade.
  • High grade.

Microscopy

Features:

  • Nuclear changes.
    • Nuclear hyperchromatism.
    • Nuclear crowding.
    • Cigar-shaped (ellipical) nuclei.
  • Nuclear changes present at surface (not only in gland crypts).[3]
    • If changes are present at the base but not at the luminal surface -- it "matures" and is not dysplasic.

Notes:

  • Changes similar to those see in colorectal tubular adenomas.
  • Presence of goblet cells is mildly reassuring its not dysplasia.[4]

Management

Low grade dysplasia.

  • Follow-up.

High grade dysplasia.

  • Endoscopic mucosal resection.[5]
  • Surgical resection ???

Gastroesophageal reflux disease

General

  • Abbreviated GERD and GORD (gastro-oesophageal reflux disease).

Clinical:

  • Treated with proton pump inhibitors (PPIs).

Microscopic

Features:

  1. Basal cell hyperplasia.[6]
  2. Papillae elongation.
  3. Inflammation, esp. eosinophils, lymphocytes with convoluted nuclei ("squiggle cells").
  4. +/-Spongiosis.

Notes:

  • Eosinophilic esophagitis is characterized by similar histomorphologic features -- key difference: more eosinophils.

Eosinophilic esophagitis

General

Clinical:

  • Dyspepsia.
    • Often mimics gastroesophageal reflux (GERD).[7]
  • Dysphagia.[8]

Treatment:

  • Avoid exacerbating antigens.
  • Topical corticosteroids, e.g. fluticasone.

Biopsies:

  • Should be taken from: upper, mid, lower and submitted in separate containers (eosinophilia present through-out-- to differentiate from GERD).

Associations:

  • Atopy.[9]
  • Celiac disease.[10]
  • Oral antigens, i.e. particular foods.[7]
  • Familial association.[7]

Gross/endoscopic

  • Trachealization; eosphagus looks like trachea.[11]
  • White.

Image: Trachealization - radiograph (nih.gov).

Microscopy

Features:[9]

  • Mucosa with "abundant eosinophils".
  • Basal cell hyperplasia.
  • Papillae elongated.

Notes:

  • Criteria for number of eosinophils/area is highly variable; there is a 23X fold variation in published values and only 11% of studies actually define an area (most studies, embarassing, only give the number of eosinophils per "HPF")![13]
    • The group that published the article cited above did another one... [14]
  • The Foundation Series book[9] says: "> 20/HPF"; VL sees this definition as garbage, as "HPF" is not defined (see rant in the basics article).
  • The most commonly reported cut points are 15, 20 and 24 eosinophils/HPF, without defining HPF.[13]
  • Most resident microscopes at the Toronto teaching hospitals have 22 mm eye pieces and have for their highest magnification objective a 40X. De facto, this means most people in Toronto are using the Liacouras et al. definition.[15]

Image: Eosinophilic esophagitis (nih.gov).

Erosive esophagitis

DDx

Work-up

  • GMS.
  • PAS.
  • IHC for HSV, CMV.

Pill esophagitis

Classic causes:

  • Alendronate (Fosamax) - for osteoporosis.
  • Iron (can be demonstrated with Prussian blue stain).
  • Doxycycline.

Cancer

General

Risks:

  • EtOH.
  • Barrett's esophagus.
  • Smoking.

Adenocarcinoma of the esophagus

General

  • Often a prognosis poor - as diagnosed in a late stage.
  • May be difficult to distinguish from adenocarcinoma of the stomach.

Tx

  • Adenocarcinoma in situ (AIS) - may be treated with endoscopic mucosal resection & follow-up.[5]
  • Surgery - esophagectomy.

IHC

Adenocarcinoma:

  • CK7 +ve, CK20 +ve.

Weird stuff

  • Inflammatory polyp - assoc. trauma/previous intervention.
  • Giant fibrovascular polyp - loose connective tissue covered with squamous epithelium.
  • Granular cell tumour.
  • Squamous papilloma - koilocytes.
  • Heterotopic gastric mucosa ("inlet patch") - benign appearing gastric mucosa.

Granular cell tumour

General

  • Rare.
  • Usually benign.

Microscopic

Features:

  • Abundant eosinophilic granular cytoplasm.

Special stains

  • PAS +ve.

IHC

Features:[16]

  • S100 +ve.
  • CD68 +ve (cytoplasmic).
  • Vimentin +ve (membranous).

Images:

See also

References

  1. ↑ URL: http://dictionary.reference.com/browse/pyrosis. Accessed on: 21 June 2010.
  2. ↑ ALS. 4 October 2010.
  3. ↑ GAG Jan 2009
  4. ↑ GAG Jan 2009
  5. ↑ 5.0 5.1 Sampliner RE (March 2009). "Endoscopic Therapy for Barrett's Esophagus". Clin. Gastroenterol. Hepatol.. doi:10.1016/j.cgh.2009.03.011. PMID 19306943.
  6. ↑ Steiner, SJ.; Kernek, KM.; Fitzgerald, JF. (May 2006). "Severity of basal cell hyperplasia differs in reflux versus eosinophilic esophagitis.". J Pediatr Gastroenterol Nutr 42 (5): 506-9. doi:10.1097/01.mpg.0000221906.06899.1b. PMID 16707971.
  7. ↑ 7.0 7.1 7.2 PMID 19596009.
  8. ↑ URL: http://www.medicinenet.com/eosinophilic_esophagitis/page2.htm#tocc. Accessed on: 1 December 2009.
  9. ↑ 9.0 9.1 9.2 Iacobuzio-Donahue, Christine A.; Montgomery, Elizabeth A. (2005). Gastrointestinal and Liver Pathology: A Volume in the Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 19. ISBN 978-0443066573.
  10. ↑ Leslie C, Mews C, Charles A, Ravikumara M (April 2010). "Celiac disease and eosinophilic esophagitis: a true association". J. Pediatr. Gastroenterol. Nutr. 50 (4): 397–9. doi:10.1097/MPG.0b013e3181a70af4. PMID 19841598.
  11. ↑ Al-Hussaini, AA.; Semaan, T.; El Hag, IA.. "Esophageal trachealization: a feature of eosinophilic esophagitis.". Saudi J Gastroenterol 15 (3): 193-5. doi:10.4103/1319-3767.54747. PMID 19636182.
  12. ↑ URL: http://www.ajronline.org/cgi/reprint/164/4/900.pdf. Accessed on: 4 October 2010.
  13. ↑ 13.0 13.1 Dellon ES, Aderoju A, Woosley JT, Sandler RS, Shaheen NJ (October 2007). "Variability in diagnostic criteria for eosinophilic esophagitis: a systematic review". Am. J. Gastroenterol. 102 (10): 2300–13. doi:10.1111/j.1572-0241.2007.01396.x. PMID 17617209.
  14. ↑ PMID 19830560.
  15. ↑ Liacouras CA, Spergel JM, Ruchelli E, et al. (December 2005). "Eosinophilic esophagitis: a 10-year experience in 381 children". Clin. Gastroenterol. Hepatol. 3 (12): 1198–206. PMID 16361045.
  16. ↑ Rekhi, B.; Jambhekar, NA. (Jun 2010). "Morphologic spectrum, immunohistochemical analysis, and clinical features of a series of granular cell tumors of soft tissues: a study from a tertiary referral cancer center.". Ann Diagn Pathol 14 (3): 162-7. doi:10.1016/j.anndiagpath.2010.01.005. PMID 20471560.
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