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Table of Contents
Definition / general | Pathophysiology | Clinical features | Prognostic factors | Treatment | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Negative stains | Differential diagnosis | Additional referencesCite this page: Gastric type adenocarcinoma. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/cervixGAS.html. Accessed June 18th, 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
Pathophysiology
- 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
- 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
Images hosted on other servers:
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)
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
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