Gastric type adenocarcinoma

Cervix
Carcinoma
Gastric type adenocarcinoma

Topic Completed: 1 August 2016

Revised: 28 December 2018, last major update August 2016

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Table of Contents

Cite this page: Parra-Herran C. Gastric type adenocarcinoma. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/cervixGAS.html. Accessed December 14th, 2019.

Definition / general

Approximately 10% of primary endocervical adenocarcinomas are unrelated to high-risk HPV infection
HPV-independent adenocarcinomas include: gastric, clear cell and mesonephric
Minimal deviation adenocarcinoma (MDA, adenoma malignum) is part of the spectrum of adenocarcinomas with a gastric phenotype

Pathophysiology

The following have been postulated as a non-obligatory precursor lesions of gastric-type adenocarcinoma:
- Gastric metaplasia of the endocervix (simple gastric-pyloric metaplasia, type A-tunnel clusters)
- Lobular endocervical hyperplasia (LEGH, complex pyloric metaplasia)
  - LEGH has been documented adjacent to the tumor in 20% of gastric type adenocarcinomas, and up to 50% of MDAs
- Atypical LEGH has been identified in 30% of MDAs
  - Characterized by LEGH with nuclear enlargement, irregular nuclear contours, loss of polarity, mitoses and intraluminal papillary projections

Gastric-type adenocarcinoma-in-situ (G-AIS) is the (likely) preinvasive form of gastric endocervical neoplasia
- Cytologically abnormal (similar to atypical LEGH), but involving endocervical glands – architecturally similar to adjacent normal endocervix, and lacking the lobular architecture of atypical LEGH

Clinical features

Mean age at presentation is ~50 years (range 30-66)
History of Peutz-Jeghers syndrome is documented in a subset of patients

Prognostic factors

Gastric-type endocervical adenocarcinoma and MDA have a worse prognosis and adverse outcome compared to usual-type adenocarcinoma:
- Rate of LVI: 48%
- Regional LN metastases: 50%
- Ovarian metastases: 35%
- Abdominal spread: 20%
- > stage I at presentation: 60%
- Fatal outcome: 39%

Treatment

Treatment does not significantly differ from other forms of adenocarcinoma, since this entity is relatively infrequent and only recently characterized
Stage I tumors at presentation are treated with complete surgical excision (trachelectomy, radical hysterectomy) and regional lymphadenectomy
Advanced stage tumors receive chemo-radiation therapy with subsequent consideration for surgery

Microscopic (histologic) description

Histologic criteria of gastric differentiation, as defined by Kojima et al (Am J Surg Pathol 2007;31:664) are:
- Cells with clear and/or pale eosinophilic cytoplasm
- Distinct cell borders
- Comprising the majority of the tumor
Minimal deviation adenocarcinoma is characterized by:
- Low grade morphology
  - Minimal to absent cytologic atypia
  - Abundant apical mucin
  - Well-defined glands (claw-like pattern)
- Stromal invasion
  - Deep haphazard gland distribution
  - Minimal to no desmoplastic reaction
- The above changes need to be present in >90% of the tumor volume (if less, tumor is classified as gastric adenocarcinoma, NOS)

Gastric-type adenocarcinoma NOS (GAS) displays variable range of cytologic atypia, stromal infiltration and differentiation

Microscopic (histologic) images

Images hosted on Pathout server:

Gastric type, contributed by Carlos Parra-Herran, M.D.

Images hosted on other servers:

Adenocarcinoma and Related Lesions

Positive stains

PAS-Alcian blue: Neutral mucin staining pattern (red staining)
MUC6: >90% (expression can be focal)
HIK1083: >90% (expression can be focal)
p53: Abnormal expression (overexpressed) in 45% of GAS
PAX2: Loss in MDA
mCEA: 100% (expression can be focal)

Negative stains

p16 (not overexpressed), ER, PR, CDX2

Differential diagnosis

Usual type endocervical adenocarcinoma: Mucin depletion, hyperchromasia and abundant apical mitoses, lack of pyloric-type mucinous differentiation, acid mucin staining (dark purple staining with PAS-Alcian blue stain), p16 overexpression, HPV detection by ISH, MUC6/HIK1083 negative
Intestinal (goblet cell) type endocervical adenocarcinoma: Intestinal (goblet cell) mucinous phenotype instead of gastric (pyloric), acid mucin staining (dark purple staining with PAS-Alcian blue stain), p16 overexpression, HPV detection by ISH, MUC6/HIK1083 negative
Clear cell adenocarcinoma: Clear cell cytoplasm without evidence of mucinous differentiation, mCEA negative

Additional references

Am J Surg Pathol 2015;39:1449, Am J Surg Pathol 2007;31:664, Adv Anat Pathol 2013;20:227, Histopathology 2007;50:843, Pathol Int 2005;55:412