Esophagus

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Esophagus connects the pharynx to the stomach. It is afflicted by tumours on occasion. Probably the most common affliction is gastroesophageal reflux disease (GERD). Most biopsies revolve around the questions: 1. intestinal metaplasia? 2. dysplasia? and 3. cancer?

Normal esophagus

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.

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ESOPHAGUS, DISTAL, BIOPSY:
- COLUMNAR EPITHELIUM WITH MODERATE CHRONIC INFLAMMATION.
- REACTIVE SQUAMOUS EPITHELIUM.
- NEGATIVE FOR INTESTINAL METAPLASIA.
- NEGATIVE FOR DYSPLASIA AND NEGATIVE FOR MALIGNANCY.

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 - -
 
Normal esophagus. (WC)
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
 
Eosinophilic esophagitis. (WC/Nephron)
Barrett's type change goblet cells no dysplasia Alcian blue +ve incr. risk of adenocarcinoma
 
Barrett's esophagus. Alcian blue. (WC)
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 esophagus matures round glands, normal gland density +/-scant nuclear atypia goblet cells clinical diagnosis Image
Indefinite for columnar dysplasia minimal maturation or cannot see surface 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

Decision tree for columnar dysplasia

Odze has made an algorithm - see: Diagnostic algorithm (nih.gov).[1]

Indications

  • Pyrosis = heartburn.[2]

Infectious esophagitis

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.

Candida esophagitis

  • AKA esophageal candidiasis.

Gross (endoscopic)

Features:

  • White patches.

DDx (endoscopic):[3]

Microscopic

Features:

  • Worm-like micro-organisms - key feature.
    • Pseudohyphae (single cells).
    • Thickness ~ 1/3-1/2 of squamous cell nucleus.
    • Should be within (squamous) epithelium.
  • Superficial inflammation - esp. neutrophils - important.

Notes:

  • On top of epithelium does not count,[4] i.e. it is likely an artifact.
  • Bacilli and cocci may accompany the candida. They are typically ignored.

DDx:

Image

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ESOPHAGUS, BIOPSY:
- ESOPHAGITIS WITH FUNGAL ORGANISMS CONSISTENT WITH CANDIDA.
ESOPHAGUS, BIOPSY:
- ACUTE ESOPHAGITIS WITH FUNGAL ORGANISMS CONSISTENT WITH CANDIDA.
- NEGATIVE FOR INTESTINAL METAPLASIA.
- NEGATIVE FOR DYSPLASIA.

Cytomegalovirus esophagitis

Microscopic

Features:

  • 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:

Gross/endoscopic

Features:

  • Ulcers with a "punched-out" appearance with a brown/red edge.
Images

www:

Microscopic

Features (3 Ms):

  • Moulding.
  • Multinucleation.
  • Margination of chromatin.
Images

IHC

  • HSV-1 +ve.[5]
    • Occasionally HSV-2 +ve.

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

The group of conditions doesn't fit neatly with the others. It is a mixture of different non-neoplastic conditions.

Gastroesophageal reflux disease

  • Abbreviated GERD or GORD (gastro-oesophageal reflux disease).
  • AKA reflux esophagitis.

Eosinophilic esophagitis

  • Abbreviated EE.

Erosive esophagitis

DDx

Work-up

Pill esophagitis

Classic causes:

Esophageal varices

Acute esophagitis

Benign esophageal stricture

Preneoplastic

Barrett esophagus

Neoplastic

Columnar dysplasia of the esophagus

  • AKA esophageal columnar dysplasia, abbreviated ECD.[6]
  • AKA dysplasia in the columnar-lined esophagus.[7]
  • AKA columnar epithelial dysplasia.[8]

General

Classification

  1. Indefinite for dysplasia.
    • Diagnosis used in the context of uncertainty (like ASCUS and ASAP); the classic reason for its use is: the surface (epithelium) cannot be seen (which precludes assessment of maturation); may be used in the context of inflammation.
  2. Low grade dysplasia.
  3. High grade dysplasia.

Management

Low grade dysplasia & indefinite for dysplasia:

  • Follow-up.

High grade dysplasia:

  • Endoscopic mucosal resection.[9]
  • Surgical resection (esophagectomy).

Microscopic

Features to assess:[10]

  1. Lack of surface maturation - very common, occasionally absent.[11]
    • 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.[12]
  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 suggests it is not dysplasia.[13]
  • Desmoplasia present = invasive adenocarcinoma.[14]
  • Some literature suggests community pathologists should not make this call, i.e. it should be diagnosed by an expert.[15]

DDx:

Images

Indefinite for columnar dysplasia:

Low-grade columnar dysplasia:

High-grade columnar dysplasia:

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ESOPHAGUS, DISTAL, BIOPSY:
- LOW-GRADE COLUMNAR EPITHELIAL DYSPLASIA, SEE COMMENT.
- COLUMNAR EPITHELIUM WITH GOBLET CELL METAPLASIA.
- REACTIVE SQUAMOUS EPITHELIUM.

COMMENT:
This was reviewed with Dr. X and they agree with the diagnosis.

Alternate

ESOPHAGUS, 30 CM, BIOPSY:
- LOW-GRADE COLUMNAR DYSPLASIA WITH INTESTINAL METAPLASIA AND MILD CHRONIC
  INFLAMMATION.
- NEGATIVE FOR MALIGNANCY.

Squamous dysplasia of the esophagus

  • AKA eosphageal squamous dysplasia.

General

Microscopic

Features:

  • Squamous cell nuclear atypia.
  • Lack of maturation to the surface.

Note:

  • Grading differences between Western pathologists and those of the east.[18]

DDx:

Images

A set of cases from Japan:[19]

IHC

  • Ki-67 may be useful:[20]
    • Reactive changes/normal: ~98% negative, ~2% intermediate.
    • Low-grade esophageal squamous intraepithelial neoplasia (LGESIN): ~80% intermediate, ~20% negative.
    • High-grade esophageal squamous intraepithelial neoplasia (HGESIN): ~37% intermediate, ~63% strong.

Definitions:[20]

  • Negative defined as: < 25% of epithelium +ve and staining only in lower quarter of epithelium.
  • Intermediate defined: >=25% and <=50% of epithelium +ve and only in the lower half of the epithelium.
  • Strong defined: >50% of epithelium +ve or upper half of epithelium.

Leiomyoma of the esophagus

General

  • Benign.
  • Uncommon.
    • Before the time of GISTs - this was a relatively common diagnosis.
  • Like leiomyomas elswhere.

Microscopic

See: Leiomyoma.

DDx:

Gastrointestinal stromal tumour

Cancer

General

Risks:

Squamous cell carcinoma of the esophagus

  • AKA esophageal squamous cell carcinoma, abbreviated esophageal SCC.

Esophageal adenocarcinoma

  • AKA adenocarcinoma of the esophagus.

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

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 lasting pathology.[21]
    • Case report - chronic with strictures.[22]
  • Sloughing of large fragments of the esophageal mucosa - seen on endoscopy.

Microscopic

Features:[21]

  • 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.[23]

Gross/endoscopic

  • Distinctive endoscopic appearance - grey/white raised lesion.[23]

Image:

Microscopic

Features:[23]

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

Images:

Achalasia

General

Clinical:

  • Dysphagia (difficulty swallowing) liquids and solids.[25]

DDx:

Microscopic

Features:[27]

  • Mucosa typically normal - even in long-standing achalasia.

Note:[27]

  • Achalasia seen in the context of a resection usually has inflammation.
  • Post-Heller myotomy often has inflammation.

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ESOPHAGUS, BIOPSY:
- SQUAMOUS EPITHELIUM WITH A MILD DEEP LYMPHOCYTIC INFILTRATE, EDEMA, AND
  REACTIVE CHANGES, NO EOSINOPHILS APPARENT.
- SCANT COLUMNAR EPITHELIUM WITH MINIMAL STROMA, NO APPARENT SIGNIFICANT PATHOLOGY.
- NEGATIVE FOR INTESTINAL METAPLASIA.
- NEGATIVE FOR DYSPLASIA AND NEGATIVE FOR MALIGNANCY.

Alternate

GASTROESOPHAGEAL JUNCTION, BIOPSY:
- COLUMNAR EPITHELIUM WITH MODERATE CHRONIC INFLAMMATION.
- REACTIVE SQUAMOUS EPITHELIUM.
- NEGATIVE FOR INTESTINAL METAPLASIA.
- NEGATIVE FOR DYSPLASIA AND NEGATIVE FOR MALIGNANCY.

Esophageal inlet patch

  • AKA inlet patch, AKA cervical inlet patch.

General

  • Benign and likely not of any significance.[28]

Gross

  • Proximal esophagus - salmon coloured lesion.[28]

Microscopic

Features:

Image:

Squamous papilloma of the eosphagus

  • AKA esophageal squamous papilloma.

General

  • Uncommon.

Microscopic

Features:

  • Papillomaous projections - low power.

Image

www:

See also

References

  1. Odze, RD. (Oct 2006). "Diagnosis and grading of dysplasia in Barrett's oesophagus.". J Clin Pathol 59 (10): 1029-38. doi:10.1136/jcp.2005.035337. PMID 17021130.
  2. URL: http://dictionary.reference.com/browse/pyrosis. Accessed on: 21 June 2010.
  3. Odze, Robert D.; Goldblum, John R. (2009). Surgical pathology of the GI tract, liver, biliary tract and pancreas (2nd ed.). Saunders. pp. 244. ISBN 978-1416040590.
  4. ALS. 4 October 2010.
  5. Canalejo Castrillero, E.; García Durán, F.; Cabello, N.; García Martínez, J. (Jul 2010). "Herpes esophagitis in healthy adults and adolescents: report of 3 cases and review of the literature.". Medicine (Baltimore) 89 (4): 204-10. doi:10.1097/MD.0b013e3181e949ed. PMID 20616659.
  6. Feng, W.; Zhou, Z.; Peters, JH.; Khoury, T.; Zhai, Q.; Wei, Q.; Truong, CD.; Song, SW. et al. (Aug 2011). "Expression of insulin-like growth factor II mRNA-binding protein 3 in human esophageal adenocarcinoma and its precursor lesions.". Arch Pathol Lab Med 135 (8): 1024-31. doi:10.5858/2009-0617-OAR2. PMID 21809994.
  7. Levine, DS. (Sep 1997). "Management of dysplasia in the columnar-lined esophagus.". Gastroenterol Clin North Am 26 (3): 613-34. PMID 9309409.
  8. Hamilton, SR.; Smith, RR. (Mar 1987). "The relationship between columnar epithelial dysplasia and invasive adenocarcinoma arising in Barrett's esophagus.". Am J Clin Pathol 87 (3): 301-12. PMID 3825997.
  9. Sampliner RE (March 2009). "Endoscopic Therapy for Barrett's Esophagus". Clin. Gastroenterol. Hepatol.. doi:10.1016/j.cgh.2009.03.011. PMID 19306943.
  10. 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.
  11. Lomo, LC.; Blount, PL.; Sanchez, CA.; Li, X.; Galipeau, PC.; Cowan, DS.; Ayub, K.; Rabinovitch, PS. et al. (Apr 2006). "Crypt dysplasia with surface maturation: a clinical, pathologic, and molecular study of a Barrett's esophagus cohort.". Am J Surg Pathol 30 (4): 423-35. PMID 16625087.
  12. 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.
  13. GAG. January 2009.
  14. 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.
  15. Alikhan, M.; Rex, D.; Khan, A.; Rahmani, E.; Cummings, O.; Ulbright, TM. (Jul 1999). "Variable pathologic interpretation of columnar lined esophagus by general pathologists in community practice.". Gastrointest Endosc 50 (1): 23-6. PMID 10385717.
  16. 16.0 16.1 Odze, RD. (Aug 2009). "Barrett esophagus: histology and pathology for the clinician.". Nat Rev Gastroenterol Hepatol 6 (8): 478-90. doi:10.1038/nrgastro.2009.103. PMID 19581906.
  17. Riddell, RH.; Odze, RD. (Oct 2009). "Definition of Barrett's esophagus: time for a rethink--is intestinal metaplasia dead?". Am J Gastroenterol 104 (10): 2588-94. doi:10.1038/ajg.2009.390. PMID 19623166.
  18. 18.0 18.1 18.2 Dry, SM.; Lewin, KJ. (Feb 2002). "Esophageal squamous dysplasia.". Semin Diagn Pathol 19 (1): 2-11. PMID 11936262.
  19. 19.0 19.1 19.2 Terada, T. (2013). "A clinicopathologic study of esophageal 860 benign and malignant lesions in 910 cases of consecutive esophageal biopsies.". Int J Clin Exp Pathol 6 (2): 191-8. PMID 23330004.
  20. 20.0 20.1 Wang, WC.; Wu, TT.; Chandan, VS.; Lohse, CM.; Zhang, L. (Oct 2011). "Ki-67 and ProExC are useful immunohistochemical markers in esophageal squamous intraepithelial neoplasia.". Hum Pathol 42 (10): 1430-7. doi:10.1016/j.humpath.2010.12.009. PMID 21420715.
  21. 21.0 21.1 21.2 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.
  22. 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.
  23. 23.0 23.1 23.2 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.
  24. Zendehdel, K.; Nyrén, O.; Edberg, A.; Ye, W. (Jan 2011). "Risk of esophageal adenocarcinoma in achalasia patients, a retrospective cohort study in Sweden.". Am J Gastroenterol 106 (1): 57-61. doi:10.1038/ajg.2010.449. PMID 21212754.
  25. 25.0 25.1 Blatnik, JA.; Ponsky, JL. (Jan 2014). "Advances in the Treatment of Achalasia.". Curr Treat Options Gastroenterol. doi:10.1007/s11938-013-0007-2. PMID 24395614.
  26. Pantanali, CA.; Herbella, FA.; Henry, MA.; Mattos Farah, JF.; Patti, MG. (Jan 2013). "Laparoscopic Heller myotomy and fundoplication in patients with Chagas' disease achalasia and massively dilated esophagus.". Am Surg 79 (1): 72-5. PMID 23317615.
  27. 27.0 27.1 Kjellin, AP.; Ost, AE.; Pope, CE. (2005). "Histology of esophageal mucosa from patients with achalasia.". Dis Esophagus 18 (4): 257-61. doi:10.1111/j.1442-2050.2005.00478.x. PMID 16128783.
  28. 28.0 28.1 Chong, VH. (Jan 2013). "Clinical significance of heterotopic gastric mucosal patch of the proximal esophagus.". World J Gastroenterol 19 (3): 331-8. doi:10.3748/wjg.v19.i3.331. PMID 23372354.
  29. 29.0 29.1 Behrens, C.; Yen, PP. (2011). "Esophageal inlet patch.". Radiol Res Pract 2011: 460890. doi:10.1155/2011/460890. PMID 22091379.