Synchronous Endometrioid Adenocarcinomas in the Ovary and Uterus Are Less Likely Two Independent Primaries
N Sherwood, JF Silverman, SD Finkelstein, MA Khalifa, N Ismiil, V Dube, S Nofech-Mozes, RS Saad. Allegheny General Hospital, Pittsburgh, PA; RedPath Integrated Pathology, Pittsburgh, PA; Sunnybrook Health Sciences Center/University of Toronto, Toronto, ON, Canada
Background: Histologic criteria have a limited role in determining whether synchronous endometrioid adenocarcinomas in the ovary and uterus represent two independent primaries or a metastatic event. Each of the two scenarios has its own staging and therapeutic implication. We carried out a molecular analysis of synchronous tumors to determine whether they are originating from a single (metastatic) or different clones (two primaries).
Design: We studied 28 patients with synchronous endometrioid tumors. The mutational profile for each neoplasm and time course of mutation acquisition was determined using PCR and quantitative genotyping for a broad panel of LOH markers targeting 1p,3p,5q,9p,10q,17p,17q,21q,22q and k-ras-2 sequencing. Extent of concordant mutational markers, specific alleles affected and temporal sequence of mutation acquisition was correlated, with clinical, pathologic and outcome features when available to validate relatedness determination. Cancers were considered to be one tumor with metastasis when over 50% of the mutational markers were concordant and temporal sequence of mutation acquisition was preserved. Independent primaries were determined to be present when these criteria were not met.
Results: Molecular analysis showed discordant mutations in 6/28 cases (21%), supporting the diagnosis of de novo primaries. All six cases showed low FIGO grade, no/superficial myometrial invasion and no cervical involvement, lymphovascular invasion (LVI) or lymph node metastasis. Both ovarian and endometrial endometrioid adenocarcinomas shared the same mutations, revealing a metastatic lesion in 22/28 cases (79%). These cases showed low FIGO grade in all cases (22/22, 100%), no/superficial invasion in 16/22 (73%), no LVI in 19/22 (86%), and negative lymph node metastases in 18/22 (82%). Ovarian tumors were grade 1 in 9/22 (41%); grade 2 in 10/22 (45%) and grade 3 in 3/22 (14%) cases.
Conclusions: In the majority of cases, clinicopathological features of synchronous ovarian and endometrial endometrioid adenocarcinomas are not helpful to differentiate between primary versus metastatic tumors. In this study, molecular testing shows that the majority of synchronous ovarian and endometrial endometrioid carcinomas represent metastatic events rather than independent primaries.
Category: Gynecologic & Obstetrics
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 161, Monday Morning