Endometrial Endometrioid Adenocarcinoma of the Uterine Corpus Involving the Cervix: Some Cases Probably Represent Independent Primaries

Abstract

The majority of endometrial endometrioid adenocarcinomas involving the cervix have tumor morphology that is similar in the endometrium and the endocervix. There are, however, some cases in which the morphology of the tumor in the endocervix is different from the endometrial carcinoma, in which it is more invasive than the endometrial carcinoma, or in which invasion only occurs in the endocervix while there is no or only minimal myometrial invasion. The goal of this study was to investigate whether tumors involving the endometrium and the endocervix are similar or 2 independent primaries by hematoxylin and eosin stain, immunohistochemistry (IHC), human papillomavirus (HPV) DNA in situ hybridization, RNA reverse transcriptase in situ polymerase chain reaction (PCR) analyses to reveal HPV, and DNA clonality studies. We selected 14 cases of endometrial endometrioid adenocarcinomas involving the cervix with complete pathology material available from the years between 1968 and 2004. Immunohistochemical studies for vimentin, carcinoembryonic antigen, estrogen receptor, progesterone receptor, and p16 were performed in 12 cases; HPV DNA/RNA analyses in 4 cases; and clonality studies in 9 cases. The patients' ages ranged from 42 to 81 years (mean: 62 y). Follow-up information was obtained in 11 patients. Histologic features varied between the tumors in the endometrium and the endocervix in 8 cases, and 5 of these cases had uniform, dilated glands having a microcystic appearance in the cervix. In 6 cases, the tumors in the endometrium and the endocervix had similar histologic features. The immunohistochemical studies showed some differences between the endometrial and endocervical adenocarcinomas in 8 of the 12 cases, independent of differing or similar histologic features. HPV testing in 4 of the cases (3 with similar and 1 with different histology) yielded similar results in the endometrium and endocervix: 2 cases were negative, 1 was positive and 1 was equivocal for HPV DNA/RNA analyses. Clonality studies showed differences between the adenocarcinoma in the endometrium and the endocervix in 7 cases, including 5 cases with different histologic appearances; 2 cases had similar loss of heterozygosity patterns. In conclusion, as suggested by clonality studies, coexisting endometrial and endocervical carcinomas with different histologic features are most likely independent neoplasms. Endometrial and endocervical carcinomas that have similar appearances can represent either the same neoplasm or independent primaries. Clonality tests may help determine their relationship. IHC studies may not be helpful for synchronous endometrial and endocervical tumors, especially those of endometrioid type. It is possible that IHC identifies cell differentiation, rather than site of origin. HPV studies are important to identify endocervical tumors associated with high-risk HPV. However, endometrial tumors involving the cervix and endocervical tumors unrelated to HPV are both negative for high-risk HPV.