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

Simplified overview

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, no necrosis incr. risk of carcinoma
Dysplasia, high grade cribriforming and/or necrosis nuclei often round & large, hyperchromasia marked incr. risk of carcinoma

Columnar dysplasia

Entity Surface maturation Architecture Cytology Other Clinical Image
Normal matures round glands no nuclear atypia - - Image
Barrett's eosphagus matures round glands, normal gland density +/-scant nuclear atypia goblet cells clinical diagnosis Image
Indefinite for columnar dysplasia moderate-to-minimal maturation round glands, normal gland density mild nuclear atypia, nuclear pseudostratification, no necrosis - follow-up Image
Low-grade columnar dysplasia minimal-to-scant maturation round glands, +/-rare budding, increased gland density mild-to-moderate nuclear atypia, nuclear pseudostratification, no necrosis - follow-up Image
High-grade columnar dysplasia no maturation incr. density of irregular glands with budding and/or rare cribriforming and/or gland dilation moderate-to-marked nuclear atypia (usu. plump round nuclei), hyperchromasia, +/-necrosis - EMR, surgery Image
Intramucosal adenocarcinoma no maturation single cells or back-to-back irregular glands with budding and/or cribriforming and/or gland dilation or glands with long axis along muscularis mucosae moderate-to-marked nuclear atypia - usu. round large nuclei, hyperchromasia, +/-necrosis - EMR, surgery Image

Columnar dysplasia - another table

Feature Indefinite for columnar dysplasia Low-grade columnar dysplasia High-grade columnar dysplasia Intramucosal carcinoma (IMCa) Utility
Depth of glands superficial only superficial only superficial/deep deep low vs. high
Gland density normal near normal increased back-to-back low vs. high vs. IMCa
Gland morphology round round irregular/rare cribriforming irregular/cribriform/sheeting low vs. high vs. IMCa
Necrosis none none may be present may be present low vs. high & IMCa
Hyperchromasia +/- present present present indef. vs. low
Palisaded/crowded nuclei present present absent/present uncommon low vs. high
Round nuclei + enlargement absent absent present/absent present low vs. high
Desmoplasia absent absent absent +/- (uncommon) high vs. IMCa
Surface involvement present (required) present (required) +/- +/- low vs. high

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

Microscopic:

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

Note:

  • Biopsying the the base of an ulcer usually just yields (non-diagnostic) necrotic debris; so, clinicians are told to biopsy the edge of the lesion. A suspected CMV infection is the exception to this rule!

Herpes esophagitis

General

Etiology:

Microscopic

Features (3 Ms):

  • Moulding.
  • Multinucleation.
  • Margination of chromatin.

Images:

Human papillomavirus esophagitis

General:

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:

Other

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 elongated; papillae reach into the top 1/3 of the epithelial layer.[4]
  3. Inflammation, esp. eosinophils, lymphocytes with convoluted nuclei ("squiggle cells").
  4. +/-Spongiosis.
  5. +/-Apoptotic cells.[5]

Notes:

  • Eosinophilic esophagitis is characterized by similar histomorphologic features -- key difference: more eosinophils.
  • "Squiggle cells" may mimic neutrophils.

Images:

Eosinophilic esophagitis

General

  • The current thinking is that it is a clinico-pathologic diagnosis.[6]

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).

Microscopic

Features:[9]

  • Mucosa with "abundant eosinophils".
  • Basal cell hyperplasia.
    • Three cells thick or >15% of epithelial thickness.
  • Papillae elongated.
    • Papillae that reach into the top 1/3 of the epithelial layer - definition for GERD.[4]

Notes "abundant eosinophils":

  • 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 for pathologists that understand this issue, only give the number of eosinophils per "HPF")![13]
    • The group that published the article cited above did another one... [14]
  • The most commonly reported cut points are 15, 20 and 24 eosinophils/HPF, without defining HPF.[13]
    • The Foundation Series book[9] says: "> 20/HPF"; VL sees this definition as garbage, as "HPF" is not defined (see HPFitis).
    • There is a consensus paper[15] 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 be so will fully blind and that the idiotic 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.[16]

Images:

Erosive esophagitis

DDx

Work-up

Pill esophagitis

Classic causes:

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

Preneoplastic

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:

Neoplastic

Columnar dysplasia

General

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.[17]
  • Surgical resection.

Microscopic

Features to assess:[18]

  1. Lack of surface maturation.
    • Lack of lighter staining at surface.
    • Nuclear crowding at surface.
    • Nuclei at the surface not smaller.
  2. Architecture - esp. at low power.
    • Glands not round.
      • Low-grade feature: gland budding.
      • High-grade features: cribriforming, cystic dilation, necrotic debris.
    • Gland density:
      • Increased & round - think low-grade dysplasia.
      • Increased & irregular - think high-grade dysplasia.
  3. Cytology, esp. at high magnification.
    • Nuclear abnormalities in: size, staining, shape.
    • Loss of "nuclear polarity" = high-grade feature
      • Loss of palisaded appearance, rounding-up of nuclei.
  4. Inflammation, erosions & ulceration.
    • Marked inflammation should prompt consideration of knocking down the diagnosis one step, i.e. low-grade becomes indefinite or high-grade becomes low-grade.

Negatives:

  1. No desmoplasia.
    • Stromal fibrotic reaction to the tumour.
      • Desmoplasia is rare in the superficial esophagus.[19]
  2. No single cells.
  3. No extensive back-to-back glands.

Notes:

  • Changes similar to those see in colorectal tubular adenomas; however, what would be low-grade dysplasia in the rectum is high-grade dysplasia in the esophagus.
  • Presence of goblet cells is mildly reassuring its not dysplasia.[20]
  • Desmoplasia present = invasive adenocarcinoma.[21]

Image:

Leiomyoma of the esophagus

Main article: Leiomyoma

DDx:

  • [[[Gastrointestinal stromal tumour]].

Cancer

General

Risks:

Squamous cell carcinoma

Main article: Squamous carcinoma

Like squamous cell carcinoma elsewhere.

Note:

  • Just to make things confusing, the Staging of early SCC differs from that of early adenocarcinoma!

Esophageal adenocarcinoma

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.[17]
  • Surgery - esophagectomy.

Esophagus vs. stomach

The convention is it's esophageal if both of the following are true:[23]

  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:[23]

  • >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.

Staging

Early esophageal adenocarcinoma has its own staging system:[24][25]

  • M1 = lamina propria.
  • M2 = superficial muscularis mucosae.
  • M3 = submucosa.
  • M4 = muscularis propria.

IHC

  • CK7 +ve.
  • CK20 +ve.

To rule-out SCC:

  • p63 -ve.
  • HWMK -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:

Esophagitis dissecans superficials

General

  • Rare & benign condition that resolves without last pathology.[26]
    • Case report - chronic with strictures.[27]
  • Sloughing of large fragments of the esophageal mucosa - seen on endoscopy.

Microscopic

Features:[26]

  • Flaking of superficial squamous epithelium.
  • Focal bullous separation of the layers.
  • Parakeratosis.
  • Variable acute or chronic inflammation.

Glycogenic acanthosis of the esophagus

General

  • Uncommon.
  • Benign.
  • Possible association with ingestion of hot liquids.[28]

Gross/endoscopic

  • Distinctive endoscopic appearance - grey/white raised lesion.[28]

Microscopic

Features:[28]

  • Squamous epithelium with:
    • Superficial clearing of the cytoplasm.
    • Thickening.

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 Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 804. ISBN 0-7216-0187-1.
  5. ↑ Wetscher GJ, Schwelberger H, Unger A, et al. (December 1998). "Reflux-induced apoptosis of the esophageal mucosa is inhibited in Barrett's epithelium". Am. J. Surg. 176 (6): 569–73. PMID 9926792.
  6. ↑ 6.0 6.1 6.2 Genevay, M.; Rubbia-Brandt, L.; Rougemont, AL. (Jun 2010). "Do eosinophil numbers differentiate eosinophilic esophagitis from gastroesophageal reflux disease?". Arch Pathol Lab Med 134 (6): 815-25. doi:10.1043/1543-2165-134.6.815. PMID 20524860. http://www.archivesofpathology.org/doi/full/10.1043/1543-2165-134.6.815.
  7. ↑ 7.0 7.1 7.2 Rothenberg, ME. (Oct 2009). "Biology and treatment of eosinophilic esophagitis.". Gastroenterology 137 (4): 1238-49. doi:10.1053/j.gastro.2009.07.007. 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. ↑ 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.
  16. ↑ 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.
  17. ↑ 17.0 17.1 Sampliner RE (March 2009). "Endoscopic Therapy for Barrett's Esophagus". Clin. Gastroenterol. Hepatol.. doi:10.1016/j.cgh.2009.03.011. PMID 19306943.
  18. ↑ 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. 46. ISBN 978-0443066573.
  19. ↑ 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. 49. ISBN 978-0443066573.
  20. ↑ GAG. January 2009.
  21. ↑ 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. 54. ISBN 978-0443066573.
  22. ↑ URL: http://www.hopkins-gi.org/GDL_Disease.aspx?CurrentUDV=31&GDL_Disease_ID=46159D68-6ED3-4F76-895B-99D8BBBB46EF&GDL_DC_ID=E25BDF77-223D-4B6F-9700-5BE41DBDE28B. Accessed on: 7 August 2011.
  23. ↑ 23.0 23.1 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.
  24. ↑ Pech, O.; May, A.; Rabenstein, T.; Ell, C. (Nov 2007). "Endoscopic resection of early oesophageal cancer.". Gut 56 (11): 1625-34. doi:10.1136/gut.2006.112110. PMC 2095648. PMID 17938435. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2095648/.
  25. ↑ Thosani, N.; Singh, H.; Kapadia, A.; Ochi, N.; Lee, JH.; Ajani, J.; Swisher, SG.; Hofstetter, WL. et al. (Nov 2011). "Diagnostic accuracy of EUS in differentiating mucosal versus submucosal invasion of superficial esophageal cancers: a systematic review and meta-analysis.". Gastrointest Endosc. doi:10.1016/j.gie.2011.09.016. PMID 22115605.
  26. ↑ 26.0 26.1 26.2 Carmack, SW.; Vemulapalli, R.; Spechler, SJ.; Genta, RM. (Dec 2009). "Esophagitis dissecans superficialis ("sloughing esophagitis"): a clinicopathologic study of 12 cases.". Am J Surg Pathol 33 (12): 1789-94. doi:10.1097/PAS.0b013e3181b7ce21. PMID 19809273.
  27. ↑ Coppola, D.; Lu, L.; Boyce, HW. (Oct 2000). "Chronic esophagitis dissecans presenting with esophageal strictures: a case report.". Hum Pathol 31 (10): 1313-7. doi:10.1053/hupa.2000.18470. PMID 11070124.
  28. ↑ 28.0 28.1 28.2 Lopes, S.; Figueiredo, P.; Amaro, P.; Freire, P.; Alves, S.; Cipriano, MA.; Gouveia, H.; Sofia, C. et al. (May 2010). "Glycogenic acanthosis of the esophagus: an unusually endoscopic appearance.". Rev Esp Enferm Dig 102 (5): 341-2. PMID 20524767.
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