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.

Tabular summary

Entity Key feature Other features IHC/Special Clinical Image
Normal squamous epi. matures to surface no inflammation, no atypia - - [1]
GERD inflammation (eosinophils, lymphocytes) elongated (epithelial) papillae, basal cell hyperplasia incr. risk of Barrett's
Eosinophilic esophagitis abundant eosinophils elongated (epithelial) papillae, basal cell hyperplasia, lymphocytes unresponsive to PPIs microscopic, endoscopic
Barrett's type change goblet cells no dysplasia Alcian blue +ve incr. risk of adenocarcinoma [2]
Dysplasia, low grade nuclear crowding at surface hyperchromasia, mild arch. complexity incr. risk of carcinoma
Dysplasia, high grade cribriforming marked nuc. crowding, hyperchromasia marked incr. risk of carcinoma

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

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

General

  • Diagnosis is clinical.
    • Pathologic correlate:
      • Metaplastic transformation of stratified squamous epithelium to simple columnar epithelium with goblet cells.
  • Associated with chronic reflux.

Significance of Barrett's esophagus

  • Increased risk of adenocarcinoma of the esophagus.
    • Need on-going surveillance, i.e. long term follow-up/repeat esophagogastroduodenoscopy.

Microscopic

Features:

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

Images:

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;[3] > 3 cells thick or >15% of epithelial thickness.
  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).[4]
  • Dysphagia.[5]

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.[6]
  • Celiac disease.[7]
  • Oral antigens, i.e. particular foods.[4]
  • Familial association.[4]

Gross/endoscopic

  • Trachealization; eosphagus looks like trachea.[8]
  • White.

Image: Trachealization - radiograph (nih.gov).

Microscopy

Features:[6]

  • 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")![10]
    • The group that published the article cited above did another one... [11]
  • The most commonly reported cut points are 15, 20 and 24 eosinophils/HPF, without defining HPF.[10]
    • The Foundation Series book[6] says: "> 20/HPF"; VL sees this definition as garbage, as "HPF" is not defined (see rant in the basics article).
    • There is a consensus paper[12] that makes note of HPFitis... and then goes on to ignore to whole issue by defining EE as 15/HPF. It blows my mind that the people could so will fully blind and that the reviewers didn't understand this.
    • 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.[13]

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.

Dysplasia

Classification

  • Indefinite for dysplasia.
    • Diagnose used in the context of uncertainty (like ASCUS and ASAP); usually used in the context of inflammation.
  • Low grade dysplasia.
  • High grade dysplasia.

Management

Low grade dysplasia.

  • Follow-up.

High grade dysplasia.

  • Endoscopic mucosal resection.[14]
  • Surgical resection.

Microscopy

Features:

  • Nuclear changes.
    • Nuclear hyperchromatism.
    • Nuclear crowding.
    • Cigar-shaped (ellipical) nuclei.
  • Nuclear changes present at surface (not only in gland crypts).[15]
    • 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.[16]

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.[14]
  • Surgery - esophagectomy.

Esophagus vs. stomach

The convention is it's esophageal if both of the following are true:[17]

  1. Epicenter of tumour is in the esophagus.
  2. Barrett's mucosa is present.

Microscopic

Features:

  • Adenocarcinoma:
    • Cell clusters that form glands.
    • Nuclear atypia of malignancy:
      • Size variation.
      • Shape variation.
      • Staining variation.
    • Mitoses common.

Images:

Grading

Graded like other adenocarcinoma:[17]

  • >95 % of tumour in glandular arrangement = well-differentiated.
  • 95-50% of tumour in glandular arrangement= moderately-differentiated.
  • <50% of tumour in glandular arrangment = poorly-differentiated.

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

Main article: Granular cell tumour

Microscopic

Features:

  • Abundant eosinophilic granular cytoplasm key feature.
    • Granules:
      • Size: 1-3 micrometers.
      • Poorly demarcated.
  • Usu. bland (cytologically non-malignant) nuclei.

Images:

See also

References

  1. ↑ URL: http://dictionary.reference.com/browse/pyrosis. Accessed on: 21 June 2010.
  2. ↑ ALS. 4 October 2010.
  3. ↑ 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.
  4. ↑ 4.0 4.1 4.2 PMID 19596009.
  5. ↑ URL: http://www.medicinenet.com/eosinophilic_esophagitis/page2.htm#tocc. Accessed on: 1 December 2009.
  6. ↑ 6.0 6.1 6.2 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.
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ URL: http://www.ajronline.org/cgi/reprint/164/4/900.pdf. Accessed on: 4 October 2010.
  10. ↑ 10.0 10.1 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.
  11. ↑ PMID 19830560.
  12. ↑ Furuta GT, Liacouras CA, Collins MH, et al. (October 2007). "Eosinophilic esophagitis in children and adults: a systematic review and consensus recommendations for diagnosis and treatment". Gastroenterology 133 (4): 1342–63. doi:10.1053/j.gastro.2007.08.017. PMID 17919504.
  13. ↑ 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.
  14. ↑ 14.0 14.1 Sampliner RE (March 2009). "Endoscopic Therapy for Barrett's Esophagus". Clin. Gastroenterol. Hepatol.. doi:10.1016/j.cgh.2009.03.011. PMID 19306943.
  15. ↑ GAG. January 2009.
  16. ↑ GAG. January 2009.
  17. ↑ 17.0 17.1 Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 168. ISBN 978-0781765275.
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