Gastric-type Endocervical Adenocarcinoma: An Aggressive Tumor With Unusual Metastatic Patterns and Poor Prognosis

Abstract

Gastric-type adenocarcinoma of the uterine cervix (GAS) is a rare variant of mucinous endocervical adenocarcinoma not etiologically associated with human papillomavirus (HPV) infection, with minimal deviation adenocarcinoma (MDA) at the well-differentiated end of the morphologic spectrum. These tumors are reported to have worse prognosis than usual HPV associated endocervical adenocarcinoma (UEA). A retrospective review of GAS was performed from the pathology databases of 3 institutions spanning 20 years. Stage, metastatic patterns, and overall survival were documented. Forty GAS cases were identified, with clinical follow-up data available for 38. The tumors were subclassified as MDA (n=13) and non-MDA GAS (n=27). Two patients were syndromic (1 Li-Fraumeni, 1 Peutz-Jeghers). At presentation, 59% were advanced stage (FIGO II to IV), 50% had lymph node metastases, 35% had ovarian involvement, 20% had abdominal disease, 39% had at least 1 site of metastasis at the time of initial surgery, and 12% of patients experienced distant recurrence. The metastatic sites included lymph nodes, adnexa, omentum, bowel, peritoneum, diaphragm, abdominal wall, bladder, vagina, appendix, and brain. Follow-up ranged from 1.4 to 136.0 months (mean, 33.9 mo); 20/38 (52.6%) had no evidence of disease, 3/38 (7.9%) were alive with disease, and 15/38 (39.5%) died of disease. Disease-specific survival at 5 years was 42% for GAS versus 91% for UEA. There were no survival differences between MDA and non-MDA GAS. GAS represents a distinct, biologically aggressive type of endocervical adenocarcinoma. The majority of patients present at advanced stage and pelvic, abdominal, and distant metastases are not uncommon.

Figure 1

Figure 1A. Gastric type endocervical adenocarcinoma with voluminous clear cytoplasm and basally located nuclei with moderate cytologic atypia, adjacent small invasive tumor clusters (H&E 100×). Figure 1B. Lobular endocervical glandular hyperplasia with central dilated gland and smaller glands proliferating along the periphery, similar to pancreatic ducts (H&E 40×) Figure 1C. Goblet cell and neurosecretory-like granules in glands of gastric type adenocarcinoma (H&E 200×)

Figure 2

Disease stage distribution at presentation (GAS vs. UEA). Abbreviations: GAS=gastric type adenocarcinoma of the uterine cervix. UEA=usual endocervical adenocarcinoma.

Figure 3

Figure 3A. Kaplan-Meier disease-specific survival estimates for UEA vs. GAS, all stages. Figure 3B. Kaplan-Meier disease-specific survival estimates for UEA vs. GAS, stage I only. Abbreviations: GAS=gastric type adenocarcinoma of the uterine cervix. UEA=usual endocervical adenocarcinoma.

Figure 4

Kaplan-Meier disease-specific survival estimates for MDA vs. non-MDA GAS. Abbreviations: GAS=gastric type adenocarcinoma of the uterine cervix. MDA: minimal deviation adenocarcinoma.

Figure 5

Metastatic gastric type adenocarcinoma to brain; tumor appears well differentiated with small basally located nuclei with little cytologic atypia infiltrating glial tissue (H&E 20×).

Figure 6

Metastatic gastric type adenocarcinoma to omentum; well differentiated glands with eosinophilic and mucinous cytoplasm diffusely infiltrating adipose tissue and eliciting desmoplastic reaction (H&E 40×).

Figure 7

Figure 7A. Well formed glands of gastric type adenocarcinoma diffusely infiltrating cervical wall (H&E 20×). Figure 7B. Tumor shows moderate to severe nuclear atypia with voluminous clear cytoplasm and distinct cell membranes; the severe nuclear atypia is incongruous with well differentiated glands (H&E 100×)