A retrospective study on incidence, diagnosis, and clinical outcome of gastric-type endocervical adenocarcinoma in a single institution

Abstract

Background: Gastric-type endocervical adenocarcinoma is rare but the most common subtype of cervical adenocarcinoma not associated with human papillomavirus. It is more aggressive with a shorter five-year survival rate compared to human papillomavirus-associated usual type endocervical adenocarcinoma. The objectives of our study were to determine the incidence and clinical-pathological characteristics of Gastric-type endocervical adenocarcinoma in a single institution.

Methods: Twenty four cases of invasive cervical adenocarcinoma were identified between January 2000 and December 2015, from the Saskatoon Health Region pathology database using International Endocervical Adenocarcinoma Criteria and Classification to retrospectively classify endocervical adenocarcinoma. Immunohistochemistry was performed with antibodies for Gastric mucin-6 (MUC-6), p16^INK4a, cyclin-dependent kinase inhibitor 2A (p16), p53 protein (p53), estrogen and progesterone receptors. Clinical and pathological data was retrieved from pathology reports and charts. Statistical analysis was performed using Mann-Whitney U test and Chi-Square test.

Results: Using the International Endocervical Adenocarcinoma Criteria and Classification criteria, 19 cases (79.2%) were classified as human papillomavirus-associated usual type endocervical adenocarcinoma, and five cases (20.8%) as Gastric-type endocervical adenocarcinoma. In our study 40% of Gastric-type endocervical adenocarcinoma cases presented at stage III compared to none of the usual type endocervical carcinoma cases. All the Gastric-type endocervical adenocarcinoma cases were positive for MUC-6, and negative for p16. 60% Gastric-type endocervical adenocarcinoma cases demonstrated mutant type p53 staining. In contrast, 84.2% of human papillomavirus-associated usual type endocervical adenocarcinoma cases showed block like nuclear and cytoplasmic positivity with p16 antibodies. The Gastric-type endocervical adenocarcinoma group had significantly shorter median survival time than human papillomavirus-associated usual type endocervical adenocarcinoma group, Gastric-type endocervical adenocarcinoma is 22 months compared to human papillomavirus-associated usual type endocervical adenocarcinoma at 118 months (p = 0.043).

Conclusions: In this study, Gastric-type endocervical adenocarcinoma accounted for 20.8% of all cervical adenocarcinoma with higher stage at presentation and shorter overall survival. Criteria proposed by International Endocervical Adenocarcinoma Criteria and Classification (IECC) are simple and reproducible in differentiating between, HPV- associated (HPVA) and non HPV associated (NHPVA) endocervical adenocarcinoma. Although none of the IHC assays is specific for GAS, but p16, MUC-6, ER, PR and p53 may further aid in confirming GAS and to differentiate it from benign and malignant mimics.

Fig. 1

Classification and association of tumors of the uterine cervix

Fig. 2

Images from well-differentiated MDA (B), arising on the base of LEGH (A) with centrally dilated duct surrounded by small proliferating glands. B. MDA with intraluminal papillary infoldings lined by columnar pale cells with abundant mucin, distinct cell borders and very mild nuclear enlargement. C. Focus on stromal invasion by single and small clusters of neoplastic cells. D. HE of moderately-differentiated GAS with columnar pale to eosinophilic cells with nuclear enlargement, stratification and hyperchromasia. Dispersed goblet cells are present Single images of IHC with different antibodies E. CEA, F. MUC-6 G.p16 H.p53 and I.CDX2

Fig. 3

Primary tumor was composed mostly of irregular glands, nests of cells, and occasional invasive single cells. The nuclei varied in size and shape and there was prominent variation from vesicular to highly hyperchromatic nuclei. Nucleoli were present in many cells, but not in all. Occasional goblet cells were also present. Mitotic figures and apoptotic bodies were frequent. Hypocellular and edematous stroma was dominant in many areas of the tumor. The morphology is nearly identical in the primary tumor (A) and metastasis in skin (B) a year after the diagnosis

Fig. 4

Kaplan-Meier Curve of the time to death in months among the GAS and UEA patients. Test of equality of the survival distributions was assessed using the Log Rank test (p = 0.043)