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The growth pattern (confluent/expansile versus infiltrative) in primary ovarian mucinous carcinoma (OMC) is prognostically important, and the International Collaboration on Cancer Reporting (ICCR) currently recommends recording the percentage of infiltrative growth in this tumor type. Histologic grading of OMC is controversial with no single approach widely accepted or currently recognized by the World Health Organization Classification of Tumours. Since ovarian carcinoma grade is often considered in clinical decision-making, previous literature has recommended incorporating clinically relevant tumor parameters such as growth pattern into the OMC grade. We herein validate this approach, termed Growth-Based Grade (GBG), in an independent, well-annotated cohort from 2 institutions. OMCs with available histologic material underwent review and grading by Silverberg, International Federation of Obstetrics and Gynecology (FIGO), and GBG schema. GBG categorizes OMCs as low-grade (GBG-LG, confluent/expansile growth, or ≤10% infiltrative invasion) or high-grade (GBG-HG, infiltrative growth in >10% of tumor). The cohort consisted of 74 OMCs, 53 designated as GBG-LG, and 21 as GBG-HG. Using Silverberg grading, the cohort had 42 (57%) grade 1, 28 (38%) grade 2, and 4 (5%) grade 3 OMCs. Using FIGO grading, 50 (68%) OMCs were grade 1, 23 (31%) grade 2, and 1 (1%) grade 3. Follow-up data was available in 68 patients, of which 15 (22%) had cancer recurrence. GBG-HG tumors were far more likely to recur compared with GBG-LG tumors (57% vs. 6%; χ2P<0.0001). Silverberg and FIGO grading systems also correlated with progression-free survival in univariate analysis, but multivariate analysis showed only GBG to be significant (hazard ratio: 10.9; Cox proportional regression P=0.0004). Seven patients (10%) died of disease, all of whom had GBG-HG (log-rank P<0.0001). Multivariate analysis showed that the percentage of infiltrative growth was the only factor predictive of disease-specific survival (hazard ratio: 25.5, Cox P=0.02). Adding nuclear atypia to GBG categories did not improve prognostication. Our study validates the prognostic value of the GBG system for both disease-free survival and disease-specific survival in OMC, which outperformed Silverberg and FIGO grades in multivariate analysis. Thus, GBG should be the preferred method for tumor grading.

Patients with germline TP53mutations are characterized by the occurrence of multiple early-onset malignancies. The characteristic syndrome is Li-Fraumeni syndrome (OMIM # 151623), an autosomal dominant disorder typified by premenopausal breast carcinoma, adrenal cortical tumors, bone and soft tissue sarcomas, leukemias, and tumors of the brain and spinal cord. Gynecologic malignancies are uncommonly reported in families harboring TP53mutations, and the predominant tumor type reported is ovarian. Uterine carcinoma has been reported only a handful of times in patients with germline TP53mutations, none as a presenting tumor in a teenager. We report on an 18-year-old patient who presented with grade 3, high-stage endometrioid endometrial carcinoma. Sequencing detected a single-nucleotide substitution in the TP53gene (NM_000546.6:c.818G>A), encoding the missense substitution p.Arg273His (R273H) in both the tumor and normal tissue, consistent with a germline mutation. We discuss the biology of the TP53gene and p53 protein, with emphasis on the R273H mutation. We also review the literature on endometrial carcinoma in patients with germline TP53mutations.

An understanding of the radiologic and pathologic features of the multiple subtypes of ovarian neoplasms can help radiologists determine benign from borderline or malignant causes, and a diagnostic approach that considers epidemiologic, clinical, radiologic, and pathologic features is outlined.

Primary retroperitoneal neoplasms originating outside of the solid organs are rare, but they are often malignant and can grow to a substantial size at clinical presentation.

AimsMammary angiomatosis is a rare, benign vascular lesion that morphologically mimics low-grade angiosarcoma (LGAS). To date, only occasional reports of this entity have been published, none of which included analysis by immunohistochemistry. The purpose of this study was to further characterise mammary angiomatosis by clinical, histological, and immunohistochemical means while emphasising distinguishing features from LGAS.MethodsSeven cases of primary mammary angiomatosis were evaluated. For one patient, a subsequent recurrence was also evaluated.ResultsAll patients were female with a median age at presentation of 51 years (range: 19–58 years). The most common clinical presentation was that of a palpable abnormality or mass (5/8) and the median primary tumour size was 3.1 cm (range: 2–9 cm). Of the six patients with follow-up, one developed a recurrence 6 years after initial presentation. Histologically, all cases were composed of variably sized ectatic, thin-walled vessels lined by flat normochromic endothelium diffusely infiltrating mammary stroma. Where present, lesional vessels infiltrated between and around terminal duct lobular units but not into individual intralobular stroma. Most cases (6/8) showed a combination of lymphatic-appearing and haemangiomatous-appearing vessels. Lymphatic-appearing vessels were D2-40 positive in all but one case. D2-40 was negative or weak in haemangiomatous-appearing vessels. All lesional vessels were CD31 positive. Ki-67 indices were <1% in all but one case (5%).ConclusionsMammary angiomatosis is a rare vascular lesion that shares clinical, morphological and immunohistochemical features with LGAS; however, certain key traits make the distinction possible.

Mullerian clear cell carcinomas (CCC) are often aggressive, chemoresistant tumors. The prognostic significance of molecular subclassification of endometrioid carcinomas is well-established. However, less is known about the molecular landscape of CCC. The aim of this study was to better characterize the genetic landscape of a large cohort of CCC and correlate these findings with clinicopathologic features. CCC of the ovary (n=72), endometrium (n=24), and peritoneal/abdominal wall (n=5) were retrospectively identified. Tumors had undergone tumor-only targeted sequencing using a hybrid capture next-generation sequencing panel. Median tumor mutational burden (TMB) was 6.8 mutations/megabase (range 1.3-185, 21% were ≥10 mut/Mb). The most frequently mutated genes were ARID1A(48%), PIK3CA(45%), TP53(23%), and PTEN(10%). ERBB2amplification occurred in 4%. When classified according to the TCGA/ProMisE endometrial carcinoma molecular subgroups, 3 (3%) were POLE ultramutated, 5 (5%) were microsatellite unstable (MSI-H), 20 (20%) were TP53-mutant subgroup and 73 (72%) were no specific molecular profile (NSMP). Immunohistochemical expression of estrogen receptor, progesterone receptor, and programmed death-ligand 1 (PD-L1) were not associated with molecular subgroup. POLE and MSI-H tumors were characterized by an excellent prognosis, and the TP53-mutant subgroup had a worse disease-free survival than NSMP. NSMP tumors could be further substratified as high-risk NSMP if they lacked PIK3CA, PIK3R1, and ARID1Amutations, and/or harbored a TERTpromoter mutation. The overall TCGA and NSMP-specific stratifications were prognostic for both the entire cohort and the subset of stage 1 ovarian tumors. On multivariable analysis, stage, lymphovascular invasion, and TMB were prognostic for disease free survival, while advanced stage and TP53-mutant subgroup – but not a TP53mutation in isolation – were negative prognostic factors for overall survival. These data suggest that routine molecular profiling of Mullerian CCC may be warranted for both prognosis and identification of potential targeted treatment such as immunotherapy and anti-HER2 agents.

Pregnant women are at increased risk for severe outcomes from coronavirus disease 2019 (COVID-19), but the pathophysiology underlying this increased morbidity and its potential effect on the developing fetus is not well understood.