title: Endocervical adenocarcinomas with prominent endometrial or endomyometrial involvement simulating primary endometrial carcinomas: utility of HPV DNA detection and immunohistochemical expression of p16 and hormone receptors to confirm the cervical origin of the corpus tumor.
abstract: Determining the primary site of a uterine adenocarcinoma can be problematic in hysterectomy specimens due to the overlapping morphology of endocervical adenocarcinomas and endometrial carcinomas, particularly when both the corpus (usually lower uterine segment) and endocervix are involved and precursor lesions are lacking or difficult to distinguish from intramucosal spread of carcinoma from one site to the other. Both preferential extension of endocervical adenocarcinomas into the endometrium (rather than deep cervical stroma) and myometrial invasion derived from the endometrial component are rarely encountered; to our knowledge, these unusual patterns of spread have not been detailed in prior reports. Clinicopathologic features of 10 endocervical adenocarcinomas (9 pure, 1 adenosquamous) with prominent endometrial or endomyometrial involvement were evaluated. Tumors were analyzed for the presence of human papillomavirus (HPV) DNA and by immunohistochemistry for expression of p16 and hormone receptors. Six cases had limited amounts of tumor in the cervix proper, with depths of invasion no greater than 5 mm in 4 and only adenocarcinoma in situ in 2. Four cases had cervical stromal invasion of more than 5 mm but all of these had greater amounts of horizontal extension into endometrium or endomyometrium. Four tumors extended into endometrium only and 6 had myoinvasion associated with the endometrial component. Five tumors were originally diagnosed as primary endometrial carcinoma with either cervical extension or concurrent endocervical adenocarcinoma in situ. HPV DNA was detected in both the cervical and corpus components in all tumors and all exhibited diffuse/strong p16 expression and decreased or absent expression of hormone receptors. These ancillary techniques are useful for clarifying the origin of uterine adenocarcinomas when morphologic features and tumor location are equivocal. These cases illustrate that dominant uterine corpus involvement (endometrial or endomyometrial) by primary endocervical adenocarcinoma can lead to misclassification as primary endometrial adenocarcinoma with cervical extension (Fédération Internationale de Gynécologie et d'Obstétrique stage II), especially when endometrial extension of endocervical adenocarcinoma simulates complex atypical hyperplasia. A subset of misclassified endocervical adenocarcinomas may account for some HPV-positive uterine carcinomas reported as primary endometrial carcinomas.
authors.affiliation: Department of Pathology, The Johns Hopkins University School of Medicine and Hospital, Baltimore, MD 21231, USA. ayemely1@jhmi.edu
authors.forename: Anna
authors.initials: A
authors.lastname: Yemelyanova
authors.forename: Russell
authors.initials: R
authors.lastname: Vang
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Seidman
authors.forename: Patti E
authors.initials: PE
authors.lastname: Gravitt
authors.forename: Brigitte M
authors.initials: BM
authors.lastname: Ronnett
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000378:metabolism / Q000821:virology; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis*; D004279:DNA, Viral / Q000032:analysis*; D003937:Diagnosis, Differential; D016889:Endometrial Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000821:virology; D004717:Endometrium / Q000378:metabolism / Q000473:pathology / Q000821:virology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008875:Middle Aged; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D011960:Receptors, Estrogen / Q000096:biosynthesis; D011980:Receptors, Progesterone / Q000096:biosynthesis; D011987:Receptors, Steroid / Q000096:biosynthesis*; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000821:virology
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D011987:Receptors, Steroid