Small cell carcinoma of ovary, hypercalcemic type (SCCOHT) is a rare ovarian neoplasm that occurs in young women and has a poor prognosis. The histologic diagnosis of SCCOHT can be challenging due to its rarity and relatively non-specific histologic features, which range from the classic, first-described small cell morphology to a pattern in which there are large cells with abundant eosinophilic cytoplasm. Many entities can be in the differential diagnosis and to date, immunohistochemical stains have shown no distinctive profile and have been of limited aid. SMARCA4 (also known as BRG1) mutations have recently been reported at high frequency in these tumors. SMARCA4 is an important component of the SWI/SNF complex which regulates gene expression through alteration of nucleosome conformation. Studies to date have suggested that immunohistochemical loss of expression of SMARCA4 is associated with the presence of a SMARCA4 mutation in most cases. In this study, the sensitivity and specificity of the immunohistochemical loss of SMARCA4 expression for the diagnosis of SCCOHT is examined in the context of the differential diagnosis with other primary or metastatic ovarian tumors. All but one of the SCCOHT showed loss of SMARCA4 expression (16/17; 94%), while of 279 other tumors tested, only two tumors (one clear cell carcinoma and one ovarian melanoma) showed loss of SMARCA4 expression. We conclude that SMARCA4 immunohistochemistry is highly sensitive and specific for a diagnosis of SCCOHT and is of clinical utility in the differential diagnosis of poorly differentiated ovarian tumors.

Small cell carcinoma of the ovary, hypercalcemic type is an aggressive tumor generally affecting young women with limited treatment options. Mutations in SMARCA4, a catalytic subunit of the SWI/SNF chromatin remodeling complex, have recently been identified in nearly all small cell carcinoma of the ovary, hypercalcemic type cases and represent a signature molecular feature for this disease. Additional biological dependencies associated with small cell carcinoma of the ovary, hypercalcemic type have not been identified. SMARCA2, another catalytic subunit of the SWI/SNF complex mutually exclusive with SMARCA4, is thought to be post-translationally silenced in various cancer types. We analyzed 10 archival small cell carcinoma of the ovary, hypercalcemic type cases for SMARCA2 protein expression by immunohistochemistry and found that SMARCA2 expression was lost in all but one case. None of the 50 other tumors that primarily or secondarily involved the ovary demonstrated concomitant loss of SMARCA2 and SMARCA4. Deep sequencing revealed that this loss of SMARCA2 expression is not the result of mutational inactivation. In addition, we established a small cell carcinoma of the ovary, hypercalcemic type patient-derived xenograft and confirmed the loss of SMARCA2 in this in vitro model. This patient-derived xenograft model, established from a recurrent tumor, also had unexpected mutational features for this disease, including functional mutations in TP53 and POLE. Taken together, our data suggest that concomitant loss of SMARCA2 and SMARCA4 is another hallmark of small cell carcinoma of the ovary, hypercalcemic type—a finding that offers new opportunities for therapeutic interventions.

Use of an SLN algorithm in deeply invasive EEC does not impair oncologic outcomes. Survival is excellent in node-negative cases, irrespective of assessment method. Adjuvant chemotherapy in node-negative patients does not appear to impact outcome.

h i g h l i g h t s Overall survival in non-endometrioid endometrial carcinoma appears uncompromised using a sentinel lymph node algorithm. With negative nodes, recurrence-free survival is shorter with a sentinel node algorithm, but overall survival is similar. Lymphatic recurrences do not appear increased with sentinel lymph node assessment in non-endometrioid endometrial carcinoma.

Objective High-grade serous carcinoma (HGSC) generally presents at an advanced stage with poor long-term (LT) survival. Here we describe clinical features found in women surviving HGSC for ten or more years. Methods A multi-center research consortium was established between five participating academic centers. Patient selection criteria included high-grade serous ovarian, fallopian tube, or peritoneal carcinoma with at least ten years of follow up. Non-serous, borderline tumors and low-grade serous subtypes were excluded. Results The 203 identified LT ten-year survivors with HGSC were diagnosed at a median age of 57 years (range 37–84 years). The majority of patients had stage IIIC (72.4%) disease at presentation. Of those who underwent primary cytoreductive surgery, optimal cytoreduction was achieved in 143 (85.6%) patients. After a median follow up of 144 months, 88 (46.8%) patients did not develop recurrent disease after initial treatment. Unexpected findings from this survey of LT survivors includes 14% of patients having had suboptimal cytoreduction, 11% of patients having an initial platinum free interval of less than 12 months, and nearly 53% of patients having recurrent disease, yet still surviving more than ten years after diagnosis. Conclusions LT survivors of HGSC of the ovary generally have favorable clinical features including optimal surgical cytoreduction and primary platinum sensitive disease. The majority of patients will develop recurrent disease, however many remained disease free for more than 10 years. Future work will compare the clinical features of this unusual cohort of LT survivors with the characteristics of HGSC patients having less favorable outcomes.

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Objective-High-grade serous carcinoma (HGSC) generally presents at an advanced stage with poor long-term (LT) survival. Here we describe clinical features found in women surviving HGSC for ten or more years.Methods-A multi-center research consortium was established between five participating academic centers. Patient selection criteria included high-grade serous ovarian, fallopian tube, or peritoneal carcinoma with at least ten years of follow up. Non-serous, borderline tumors and lowgrade serous subtypes were excluded.Results-The 203 identified LT ten-year survivors with HGSC were diagnosed at a median age of 57 years (range 37-84 years). The majority of patients had stage IIIC (72.4%) disease at presentation. Of those who underwent primary cytoreductive surgery, optimal cytoreduction was achieved in 143 (85.6%) patients. After a median follow up of 144 months, 88 (46.8%) patients Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Disclosures/Conflicts of InterestThe authors declare no competing financial interests. HHS Public Access Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript did not develop recurrent disease after initial treatment. Unexpected findings from this survey of LT survivors includes 14% of patients having had suboptimal cytoreduction, 11% of patients having an initial platinum free interval of less than 12 months, and nearly 53% of patients having recurrent disease, yet still surviving more than ten years after diagnosis.Conclusions-LT survivors of HGSC of the ovary generally have favorable clinical features including optimal surgical cytoreduction and primary platinum sensitive disease. The majority of patients will develop recurrent disease, however many remained disease free for more than 10 years. Future work will compare the clinical features of this unusual cohort of LT survivors with the characteristics of HGSC patients having less favorable outcomes.

Our findings suggest that the assessment of mutations affecting TP53, KRAS, PIK3CA, ARID1A and POLE, and DNA MMR protein expression may be used to further aid the diagnosis and treatment decision-making of primary MOC.