Gastric type adenocarcinoma

Author: Carlos Parra-Herran, M.D. (see Authors page)

Revised: 26 August 2016, last major update August 2016

Copyright: (c) 2003-2016, PathologyOutlines.com, Inc.

PubMed Search: Gastric type adenocarcinoma cervix
Cite this page: Gastric type adenocarcinoma. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/cervixGAS.html. Accessed September 25th, 2018.
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 adenocarcinoma with a gastric phenotype
  • The following have been postulated as non-obligatory precursor lesions of gastric type adenocarcinoma:
    • Gastric metaplasia of the endocervix (simple gastric pyloric metaplasia, type A tunnel clusters)
    • Lobular endocervical glandular hyperplasia (LEGH, complex pyloric metaplasia)
      • LEGH has been documented adjacent to the tumor in 20% of gastric type adenocarcinomas, and in 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 lymphovascular invasion/LVI: 48%
    • Regional lymph node metastases: 50%
    • Ovarian metastases: 35%
    • Abdominal spread: 20%
    • Beyond stage I at presentation: 60%
    • Fatal outcome: 39%
  • 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 or pale eosinophilic cytoplasm and 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 and 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

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Minimal deviation adenocarcinoma

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
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