title: Low-grade ovarian serous neoplasms (low-grade serous carcinoma and serous borderline tumor) associated with high-grade serous carcinoma or undifferentiated carcinoma:  report of a series of cases of an unusual phenomenon.
abstract: Recent literature has suggested a dual pathway of ovarian serous carcinogenesis, with most serous carcinomas falling into 1 of 2 categories, low grade and high grade. These are considered to represent 2 distinct tumor types with a different underlying pathogenesis and associated with different molecular events, clinical behavior, and prognosis. Low-grade serous carcinoma is thought to evolve in many instances from a preexisting serous borderline tumor and cystadenoma. Given the distinct pathogenesis and different molecular events, it is expected that the coexistence of low-grade and high-grade serous carcinoma would be rare or may even be mutually exclusive; moreover, there are very few reported examples in the literature. We report a series of 7 cases in patients aged 34 to 78 years in whom ovarian low-grade serous carcinoma (4 cases, including 3 with associated serous borderline tumor), serous borderline tumor (2 cases), or seromucinous borderline tumor (1 case) was associated with a high-grade carcinoma, either high-grade serous (5 cases) or undifferentiated carcinoma (2 cases). The low-grade and high-grade components coexisted in the original neoplasm in 4 cases, and the high-grade component was present only in recurrence in 3 cases. In both instances, the undifferentiated carcinoma had a focal rhabdoid morphology, and alternative primary sites of tumor were excluded by a combination of clinical, radiologic, and pathologic parameters. We illustrate that low-grade serous carcinoma or serous borderline tumor ("low-grade" serous neoplasms) may rarely be associated with, and probably give rise to, a high-grade carcinoma, either high-grade serous or undifferentiated carcinoma. The coexistence of a low-grade serous neoplasm and undifferentiated carcinoma can be regarded as a form of dedifferentiation. p53 was diffusely positive in 4 of 6 high-grade carcinomas, which raises the possibility that secondary Tp53 mutation is important in high-grade transformation in some of these cases. WT1 was negative in the 2 undifferentiated carcinomas, and PAX8 was positive in 1, suggesting that the latter marker is more useful in helping to confirm a Mullerian origin in dedifferentiated low-grade serous neoplasms.
authors.affiliation: Department of Pathology, Belfast Health and Social Care Trust, Belfast, Northern Ireland.
authors.forename: Clinton
authors.initials: C
authors.lastname: Boyd
authors.forename: W Glenn
authors.initials: WG
authors.lastname: McCluggage
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D054337:Cell Dedifferentiation; D002454:Cell Differentiation; D018284:Cystadenocarcinoma, Serous / Q000737:chemistry / Q000401:mortality / Q000473:pathology* / Q000556:secondary / Q000628:therapy; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D060787:Neoplasm Grading; D010051:Ovarian Neoplasms / Q000737:chemistry / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors / Q000032:analysis; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D025721:WT1 Proteins / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; D000072636:PAX8 Transcription Factor; C083325:PAX8 protein, human; D051761:Paired Box Transcription Factors; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D025721:WT1 Proteins