title: Synchronous and metachronous endocervical and ovarian neoplasms: evidence supporting interpretation of the ovarian neoplasms as metastatic endocervical adenocarcinomas simulating primary ovarian surface epithelial neoplasms.
abstract: The vast majority of endocervical adenocarcinomas are high-risk human papillomavirus (HPV)-related neoplasms, characterized by p16 expression and frequent loss of hormone receptor expression, which infrequently metastasize to the ovaries. We report 10 cases of endocervical adenocarcinomas with ovarian metastases in which the ovarian tumors simulated primary ovarian surface epithelial neoplasms. The presence of HPV DNA was assessed to determine whether the ovarian neoplasms were metastases or independent neoplasms. Immunohistochemistry for hormone receptors and p16 was also performed. The ovarian metastases presented concurrently with the primary endocervical tumors in 5 cases, subsequent to the endocervical tumors in 3 cases, and prior to diagnosis of the endocervical tumors in 2 cases. The ovarian tumors ranged in size from 2 to 30 cm, with tumors in 7 cases measuring 10 cm or greater. The ovarian tumors were unilateral in 8 cases and bilateral in 2. In all cases, the ovarian tumors were initially diagnosed as or thought to represent independent primary ovarian surface epithelial tumors (atypical proliferative [borderline] tumors or well-differentiated carcinomas of endometrioid or mucinous type). The endocervical tumors ranged in size from microscopic foci to 3 cm, with depth of invasion ranging from 0.2 to 1.5 cm; in 2 cases, the invasive foci qualified as microinvasive according to Federation Internationale de Gynecologie et d'Obstetrique staging criteria for cervical carcinoma. Adenocarcinoma in situ was identified in all tumors. In all cases, the paired endocervical and ovarian tumors contained identical HPV types. All evaluable tumors were diffusely positive for p16; and in 8 cases, there was absent or only limited expression of hormone receptors. Two of the minimally invasive endocervical tumors were initially interpreted as adenocarcinoma in situ and not recognized as unequivocally invasive even when evaluated in conjunction with the histologically identical ovarian tumors. HPV DNA detection in the ovarian tumors of 2 patients without known cervical disease led to discovery of occult cervical adenocarcinomas in those patients. Endocervical adenocarcinomas, including some qualifying as microinvasive, can metastasize to the ovaries and simulate primary ovarian surface epithelial neoplasms. The presence of HPV DNA in these ovarian tumors confirms that they are metastatic endocervical adenocarcinomas.
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine and Hospital, Baltimore, MD 21231, USA.
authors.forename: Esther
authors.initials: E
authors.lastname: Elishaev
authors.forename: C Blake
authors.initials: CB
authors.lastname: Gilks
authors.forename: Dianne
authors.initials: D
authors.lastname: Miller
authors.forename: Monica
authors.initials: M
authors.lastname: Srodon
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Kurman
authors.forename: Brigitte M
authors.initials: BM
authors.lastname: Ronnett
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry / Q000556:secondary* / Q000821:virology; D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000473:pathology; D009378:Neoplasms, Multiple Primary / Q000737:chemistry / Q000473:pathology* / Q000821:virology; D010051:Ovarian Neoplasms / Q000737:chemistry / Q000556:secondary* / Q000821:virology; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification; D016133:Polymerase Chain Reaction; D002583:Uterine Cervical Neoplasms / Q000737:chemistry / Q000473:pathology* / Q000821:virology
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral