title: Morphologic Reproducibility, Genotyping, and Immunohistochemical Profiling Do Not Support a Category of Seromucinous Carcinoma of the Ovary.
abstract: The 2014 World Health Organization Classification of Tumors of Female Reproductive Organs endorsed the new category of seromucinous carcinoma, a neoplasm that exhibits morphologic and immunophenotypic overlap with other histotypes of ovarian carcinoma. The goal of this study was to determine whether seromucinous carcinoma was a distinct histotype by assessing its diagnostic reproducibility and comparing its molecular composition to the 5 major histotypes of ovarian carcinoma. Thirty-two tumors diagnosed as seromucinous carcinomas from 2 centers were studied. Eighteen cases were randomly selected for a review set comprising a total of 50 ovarian carcinomas of various histotypes. Morphologic histotype was independently assessed by 4 pathologists. For the 32 seromucinous carcinomas, a histotype-specific immunophenotype was assigned using a diagnostic immunohistochemical panel. Histotype-specific genotype was assigned using a combination of immunohistochemistry and targeted next-generation sequencing for somatic mutations, including genes recurrently mutated in ovarian carcinomas. There was low to modest agreement between pathologists with the reference diagnosis of seromucinous carcinoma, ranging from 39% to 56% for the 4 observers. The immunophenotype was not unique but overlapped predominantly with endometrioid and to a lesser extent with mucinous and low-grade serous carcinoma. Genomic and immunohistochemical alterations were detected in a number of target genes, including KRAS (70%), PIK3CA (37%), PTEN (19%), and ARID1A (16%); no CTNNB1 mutations were identified. Nine cases (30%) harbored concurrent KRAS/PIK3CA mutations. An endometrioid genotype was assigned to 19 cases, a low-grade serous genotype to 9, and a mucinous genotype to 1 and 3 cases were uninformative. Integrating morphology, immunophenotype, and genotyping resulted in reclassifying the seromucinous carcinomas to endometrioid 23/32 (72%), low-grade serous 8/32 (25%), and mucinous 1/32 (3%). The morphologic diagnosis of seromucinous carcinomas is not very reliable and it does not exhibit a distinct immunophenotype or genotype. The molecular features overlap mostly with endometrioid and low-grade serous carcinomas. Our data suggest the category of seromucinous carcinoma be discontinued as ancillary molecular tests can assign cases to one of the major histotypes.
authors.affiliation: Departments of *Pathology and Laboratory Medicine, Foothill Medical Center ‡Oncology, Translational Laboratory, Tom Baker Cancer Centre ∥Oncology, University of Calgary, Calgary, AB, Canada †Department of Pathology, Catholic University of Health and Allied Sciences, Mwanza, Tanzania §Department of Pathology, Belfast Health and Social Care Trust, Belfast, UK.
authors.forename: Peter F
authors.initials: PF
authors.lastname: Rambau
authors.forename: John B
authors.initials: JB
authors.lastname: McIntyre
authors.forename: Jennifer
authors.initials: J
authors.lastname: Taylor
authors.forename: Sandra
authors.initials: S
authors.lastname: Lee
authors.forename: Travis
authors.initials: T
authors.lastname: Ogilvie
authors.forename: Anna
authors.initials: A
authors.lastname: Sienko
authors.forename: Don
authors.initials: D
authors.lastname: Morris
authors.forename: Máire A
authors.initials: MA
authors.lastname: Duggan
authors.forename: W Glenn
authors.initials: WG
authors.lastname: McCluggage
authors.forename: Martin
authors.initials: M
authors.lastname: Köbel
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics*; D001706:Biopsy; D018269:Carcinoma, Endometrioid / Q000737:chemistry / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques; D009154:Mutation; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D018297:Neoplasms, Cystic, Mucinous, and Serous / Q000737:chemistry / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D015588:Observer Variation; D010051:Ovarian Neoplasms / Q000737:chemistry / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D010641:Phenotype; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D009626:Terminology as Topic; D046888:Tissue Array Analysis; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor