Small Cell Carcinoma Of Ovary Research Articles

A dramatic response to checkpoint inhibitor in a woman with small cell carcinoma of the hypercalcemic type of the ovary

ObjectiveWe present the rare case of a 21 year old woman with small cell carcinoma of the right ovary of the hypercalcemic type with dramatic response to checkpoint inhibitor. MethodsCase report. Results and conclusionsOur patient, a 22-year old woman with small cell carcinoma of the hypercalcemic type with hepatic metastases, is currently 43 months under treatment with pembrolizumab. Last MRI revealed no viable liver metastases nor other signs of recurrence. This is the longest survival of a patient with small cell carcinoma of the ovary under therapy with checkpoint inhibitors reported in the literature so far.With this report we emphasize the importance of immunohistological testing for PD-L 1. Treating clinicians should keep off-label use of immune checkpoint blockade in mind when treating this highly aggressive tumor if all other treatment options fail.

Establishment and characterization of a novel cell line (SCCOHT-CH-1) and PDX models derived from Chinese patients of small cell ovarian carcinoma of the hypercalcemic type

Small cell carcinoma of the ovary hypercalcemic type (SCCOHT) is a rare and aggressive malignancy that poses a significant clinical challenge due to its grim prognosis. Unfortunately, only three SCCOHT cell lines are currently available for scientific research. In this study, we have successfully established a novel SCCOHT cell line from a recurrent lesion of a SCCOHT patient, named SCCOHT-CH-1. We comprehensively characterized the novel cell line by employing techniques such as morphological observation, CCK-8 assay, Transwell assay, clone formation assay, short tandem repeat sequence (STR) analysis, karyotype analysis, immunohistochemical staining, western blot assay, and xenograft tumor formation assay. SCCOHT-CH-1 cells were small circular and had a unique STR profile. The population-doubling time of SCCOHT-CH-1 was 33.02 h. The cell line showed potential migratory and invasive ability. Compared with another SCCOHT cell line COV434, SCCOHT-CH-1 exhibited higher expression of AKT, VIM, and CCND1. At the same time, SCCOHT-CH-1 has the ability of tumorigenesis in vivo. We also successfully constructed three patient-derived xenograft (PDX) models of SCCOHT, which were pathologically diagnosed to be consistent with the primary tumor, accompanied by loss of SAMRCA4 protein expression. The establishment of SCCOHT-CH-1 cell line and PDX models from Chinese people represent a pivotal step toward unraveling the molecular mechanism of SCCOHT and fostering the development of targeted interventions to tackle this challenging malignancy.

Abstract CT163: A phase II basket trial of dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART) SWOG S1609: the small cell carcinoma of the ovary, hypercalcemic type cohort

Abstract Background: Dual checkpoint inhibition with Anti-PD-1 and anti-CTLA4 checkpoint inhibitors have shown to be efficacious in many malignancies, but its potential role in various rare solid cancers is yet to be established. Small cell ovarian carcinoma, hypercalcemic type (SCCOHT) is a rare tumor characterized by loss of SMARC 2/4 function and so presents a novel paradigm for the treatment of SWI/SNF pathway deficient tumors (Petar Jelinic et al., 2018; Marc Tischkowitz et al., 2020). This study presents the first results of ipilimumab and nivolumab used in the SCCOHT cohort (#49) of the SWOG S1609 Dual Anti-CTLA-4 & Anti-PD-1 blockade in Rare Tumors (DART) trial. Methods: DART is a prospective, open-label, multicenter/multi-cohort phase 2 clinical trial of ipilimumab (1mg/kg intravenously every 6 weeks) plus nivolumab (240mg intravenously every 2 weeks). The primary endpoint includes objective response rate (ORR) (RECIST v1.1) (confirmed complete (CR) and partial responses (PR)). Secondary endpoints include progression-free survival (PFS), overall survival (OS), stable disease (SD) >6 months, and toxicity. Results: Five evaluable patients (median age 30) with SCCOHT were analyzed. Objective response rate was 20% (1 CR with 100% regression). The patient with CR has a duration of response (DoR) and OS of 35+ months. Another patient, showed unconfirmed PR with 81% regression (DoR 4 months), this patient went on to have confirmed iCR (CR confirmed by iRECIST) at around 24 months and has OS of 38+ months. At 12 months, 3 patients remain alive and 1 patient remains progression free; overall median PFS was 1.8 months (1.0-∞); median OS was 24 months (4.5-∞). The most common adverse events were fatigue, nausea, pruritus, dry mouth, maculo-papular rash and aspartate aminotransferase elevation (50%, n=2, respectively). There were two incidents (33.3%) of grade 3-4 adverse events. None of the adverse events led to discontinuation. There were no grade 5 adverse events. Conclusion: Ipilimumab plus nivolumab in five patients with the ultra-rare small cell ovarian carcinoma (hypercalcemic type) resulted in one CR durable at 35+ months and one unconfirmed PR with 81% regression. This is the first prospective study demonstrating efficacy of nivolumab and ipilimumab in this rare disease. Correlative studies to determine response and resistance markers are ongoing. Expanded prospective studies in small cell ovarian histologies are needed. Citation Format: Young Kwang Chae, Megan Othus, Sandip P. Patel, Raid Aljumaily, Khine Z. Win, Tanya Pejovic, Sajeve S. Thomas, William R. Robinson, Liam Il-Young Chung, Christine M. McLeod, Helen X. Chen, Elad Sharon, Howard Streicher, Christopher W. Ryan, Charles D. Blanke, Razelle Kurzrock. A phase II basket trial of dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART) SWOG S1609: the small cell carcinoma of the ovary, hypercalcemic type cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT163.

The Emerging Role of Chromatin Remodeling Complexes in Ovarian Cancer.

Ovarian cancer (OC) is the fifth leading cause of women's death from cancers. The high mortality rate is attributed to the late presence of the disease and the lack of modern diagnostic tools, including molecular biomarkers. Moreover, OC is a highly heterogeneous disease, which contributes to early treatment failure. Thus, exploring OC molecular mechanisms could significantly enhance our understanding of the disease and provide new treatment options. Chromatin remodeling complexes (CRCs) are ATP-dependent molecular machines responsible for chromatin reorganization and involved in many DNA-related processes, including transcriptional regulation, replication, and reparation. Dysregulation of chromatin remodeling machinery may be related to cancer development and chemoresistance in OC. Some forms of OC and other gynecologic diseases have been associated with mutations in specific CRC genes. Most notably, ARID1A in endometriosis-related OC, SMARCA4, and SMARCB1 in hypercalcemic type small cell ovarian carcinoma (SCCOHT), ACTL6A, CHRAC1, RSF1 amplification in high-grade serous OC. Here we review the available literature on CRCs' involvement in OC to improve our understanding of its development and investigate CRCs as possible biomarkers and treatment targets for OC.

Lymphadenectomy Benefits Small Cell Carcinoma of Ovary: A Population-Based Analysis.

Small cell carcinoma of the ovary (SCCO) is a rare type of ovarian cancer with high aggressiveness. The optimal treatment modality remains elusive. This study aims to comprehensively investigate the survival impact of clinical characteristics and treatments including lymphadenectomy in SCCO. A retrospective cohort study was performed and included patients from the Surveillance, Epidemiology, and End Results (SEER) database. Data collected included demographics, therapeutic details, and pathologic characteristics. Propensity-score matching analysis (PSM) was carried out to balance baseline variables between SCCO and non-SCCO. Cox regression, Kaplan–Meier, and stratified analyses were conducted before and after PSM. After filtering, 80 records on SCCO and 39,662 records on non-SSCO were obtained. Patients with SCCO were more prone to present unilateral tumor (57.6% and 85.0%, p < 0.001), larger tumor size (>15 cm: 9.5% and 32.5%; 10–15 cm: 13.2% vs. 22.5%, p < 0.001), younger age (59.1 ± 14.91 vs. 37.2 ± 19.05; p < 0.001), single status (17.0% vs. 45.0%; p < 0.001), single malignant tumor in a lifetime (76.1% vs. 87.5%; p = 0.0244), and pathologic grade IV diseases (14.5% vs. 40.0%; p < 0.001) compared with non-SCCO. After balancing the baseline clinical characteristics with a 1:4 ratio PSM, a total of matched 72 patients with SCCO and 254 patients with non-SCCO were identified. The survival rate of SCCO was distinctly inferior to non-SCCO, particularly in FIGO I, II, and III stages. Lymphadenectomy was performed in 37 (51.39%) SCCO patients, of whom 12 (32.43%) were found to have pathologically positive lymph nodes. Lymphadenectomy was linked to favorable overall survival in SCCO, particularly in the advanced stage, and was also an independent prognostic factor, whereas lymphadenectomy did not reveal an edge in matched non-SCCO. There was a pronounced survival benefit for SCCO when at least 10 or more nodes were resected. Lymphadenectomy in a non-stage-dependent way should be considered and deserves further clinical validation to promote the overall survival in SCCO.

Ovarian small cell carcinoma by ovarian torsion feature: A cytopathology challenging case.

Introduction and importanceOvarian small cell carcinomas are a rare type of ovarian cancer that is highly aggressive and consists of two distinct types the hypercalcemic type (SCCOHT) and pulmonary type (SCCOPT).Case presentationA 23 years old girl was admitted to the emergency room with the presentation of acute abdomen. The ultrasound and Magnetic resonance imaging revealed a right adnexal huge mass with adnexal torsion. In laparotomy, she underwent unilateral salpingo-oophorectomy due to ovarian torsion and possible malignancy. The histopathological evaluation was challenging and was finalized by a team of pathologists as hypercalcemic small cell carcinoma. She refused reoperation and unfortunately relapsed during chemotherapy and died 6 months after the initial diagnosis.Clinical discussionConclusion: We do not yet have comprehensive information on small cell ovarian cancer. Cytopathology diagnosis is still challenging and the treatments are not usually effective. Further clinical trials and studies are recommended to find appropriate treatments for these patients.

Cellular context determines DNA methylation profiles in SWI/SNF-deficient cancers of the gynecologic tract.

SWI/SNF (SWItch/Sucrose Non-Fermentable) complex deficiency has been reported in a wide variety of cancers and is often associated with an undifferentiated phenotype. In the gynecologic tract SWI/SNF-deficient cancers are diagnostically challenging and little is known about their cellular origins. Here we show that undifferentiated endometrial carcinoma (UDEC), SMARCA4-deficient uterine sarcoma (SDUS), and ovarian small cell carcinoma, hypercalcemic type (SCCOHT) harbor distinct DNA methylation signatures despite shared morphology and SWI/SNF inactivation. Our results indicate that the cellular context is an important determinant of the epigenetic landscape, even in the setting of core SWI/SNF deficiency, and therefore methylation profiling may represent a useful diagnostic tool in undifferentiated, SWI/SNF-deficient cancers. Furthermore, applying copy number analyses and group-wise differential methylation analyses including endometrioid endometrial carcinomas and extracranial malignant rhabdoid tumors, we uncover analogous molecular features in SDUS and SCCOHT in contrast to UDEC. These results suggest that SDUS and SCCOHT represent chromosomally stable SWI/SNF-deficient cancers of the gynecologic tract, which are within the broader spectrum of malignant rhabdoid tumors. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Non-Epithelial Ovarian Cancers: How Much Do We Really Know?

Non-epithelial ovarian cancers (NEOC) are a group of uncommon malignancies that mainly includes germ cell tumours (GCT), sex cord-stromal tumours (SCST), and some extremely rare tumours, such as small cell carcinomas and sarcomas. Each of these classifications encompasses multiple histologic subtypes. The aetiology and molecular origins of each sub-group of NEOC require further investigation, and our understanding on the genetic changes should be optimised. In this article, we provide an update on the clinical presentation, pathology, genetics, treatment and survival of the main histological subtypes of the GCT and the SCST, as well as of ovarian small cell carcinomas. We also discuss miRNA expression profiles of NEOC and report the currently active clinical trials that include NEOC.

Recent updates in thoracic SMARCA4-deficient undifferentiated tumor.

Germline inactivating mutations in SMARCA4 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4) gene encoding for BRG1 (Brahma related gene-1) are the molecular drivers in small cell carcinoma of ovary, hypercalcemic type (SCCOHT) and in malignant rhabdoid tumors (MRT) that occur in the context of rhabdoid tumor predisposition syndrome-type 2. Somatic SMARCA4 mutations and/or loss of BRG1 have been identified in a variety of adult-onset epithelial and mesenchymal neoplasms. Among thoracic tumors, these include subsets of smoking-related non-small cell lung carcinoma (NSCLC) and a relatively rare, newly recognised tumor entity: thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT). Less than 100 cases of SMARCA4-UT have been reported to date. They present as large compressive and infiltrative mediastinal, lung and/or pleural masses in middle-aged male smokers. They are undifferentiated tumors composed of sheets of small/epithelioid and/or rhabdoid tumor cells variably expressing epithelial markers and consistently showing loss of BRG1 and the closely related protein, Brahma (BRM). Frequent expression of stem cell markers (SOX2, CD34, SALL4) is noted. Despite gene expression profiles similar to MRTs and SCCOHT, they show striking genomic overlap with SMARCA4-mutant NSCLC with frequent TP53, STK11, KEAP1, and KRAS mutations, high tumor mutation burden (TMB), and presence of smoking related molecular signatures in tumor cells. SMARCA4-UT show uniformly poor survival and are irresponsive to conventional therapies. Immunotherapy responses are variable but promising, although PDL1 expression appears to be of poor predictive value. Drugs exploiting genetic and epigenetic mechanisms of SMARCA4 antagonism hold promise for future targeted therapies.

805P Clinically actionable alterations in adolescents and young adults (AYA) with gynaecological cancers

Gynecologic cancers in AYA are rare and research efforts to discover their distinct cancer biology are limited. Uncommon and aggressive subtypes of gynecologic cancer, such as mucinous and small cell ovarian carcinoma, are more frequent in AYA.

Hypercalcaemia due to ovarian small cell carcinoma of the hypercalcaemic type (SCCOHT)

Hypercalcaemia due to ovarian small cell carcinoma of the hypercalcaemic type (SCCOHT)

Ovarian small cell carcinoma, hypercalcemic type: rare and aggressive tumor

Small cell carcinoma of the ovary, hypercalcemic type, is a rare undifferentiated carcinoma which characteristically presents in women over 40 years of age with abdominal fullness, unilateral tumor, and hypercalcemia.[1][1]...

Re-expression of SMARCA4/BRG1 in small cell carcinoma of ovary, hypercalcemic type (SCCOHT) promotes an epithelial-like gene signature through an AP-1-dependent mechanism.

Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare and aggressive form of ovarian cancer. SCCOHT tumors have inactivating mutations in SMARCA4 (BRG1), one of the two mutually exclusive ATPases of the SWI/SNF chromatin remodeling complex. To address the role that BRG1 loss plays in SCCOHT tumorigenesis, we performed integrative multi-omic analyses in SCCOHT cell lines +/- BRG1 reexpression. BRG1 reexpression induced a gene and protein signature similar to an epithelial cell and gained chromatin accessibility sites correlated with other epithelial originating TCGA tumors. Gained chromatin accessibility and BRG1 recruited sites were strongly enriched for transcription-factor-binding motifs of AP-1 family members. Furthermore, AP-1 motifs were enriched at the promoters of highly upregulated epithelial genes. Using a dominant-negative AP-1 cell line, we found that both AP-1 DNA-binding activity and BRG1 reexpression are necessary for the gene and protein expression of epithelial genes. Our study demonstrates that BRG1 reexpression drives an epithelial-like gene and protein signature in SCCOHT cells that depends upon by AP-1 activity.

Update on SWI/SNF-related gynecologic mesenchymal neoplasms: SMARCA4-deficient uterine sarcoma and SMARCB1-deficient vulvar neoplasms.

Our knowledge regarding the role of genes encoding the chromatin remodeling switch/sucrose non-fermenting (SWI/SNF) complex in the initiation and progression of gynecologic malignancies continues to evolve. This review focuses on gynecologic tumors in which the sole or primary genetic alteration is in SMARCA4 or SMARCB1, two members of the SWI/SNF chromatin remodeling complex. In this review, we present a brief overview of the classical example of such tumors, ovarian small cell carcinoma of hypercalcemic type, and then a detailed review and update of SMARCB1-deficient and SMARCA4-deficient tumors of the uterus and vulva.

Small Cell Carcinoma of the Ovary: Clinicopathologic and Immunohistochemical Analysis of 7 New Cases of a Rare Malignancy

Small cell carcinoma of ovary (SCCO) is extremely rare. Two types of SCCO are recognized, the pulmonary type (SCCOPT) and the hypercalcemic type (SCCOHT). Establishing an accurate diagnosis is challenging, owing to its rarity and paucity of data describing the distinctive histopathologic and immunohistochemical (IHC) features. This was a retrospective study conducted over a period of 4 years. All cases reported as SCCO on histopathology were retrieved. All the available clinical, histopathological, and IHC features were studied in detail. A total of 7 cases of SCCO were diagnosed during the study period. There were 4 cases of SCCOPT and 3 cases of SCCOHT and with mean age of 57.25 and 22 years, respectively. All the cases presented as stage IV disease. Among the SCCOPT cases, 3 showed bilateral involvement with 1 showing concurrent uterine endometrioid adenocarcinoma. Microscopy revealed small hyperchromatic cells with brisk mitosis and multifocal necrosis. On IHC, these were consistently positive for chromogranin, CD56, and synaptophysin. All the SCCOHT cases showed unilateral involvement. Microscopically, in addition to small hyperchromatic cells, larger "rhabdoid" tumor cells were also seen. On IHC, chromogranin was negative, with positivity for vimentin and epithelial membrane antigen. The expression of SMARCA4/BRG1 was lost while SMARCB1/INI1 was retained in all cases. All of these patients developed recurrence and died due to disease progression despite treatment. SCCO is an extremely infrequent ovarian malignancy with poor prognosis. Knowledge about its characteristic features is important for accurate tissue diagnosis and appropriate management.

Abstract B25: SMARCA4/BRG1 and AP-1 co-regulate an epithelial-like signature in small-cell carcinoma of ovary, hypercalcemic type (SCCOHT)

Abstract Mutations in SMARCA4 (BRG1), one of the two mutually exclusive ATPases of the SWI/SNF chromatin remodeling complex, occur in &amp;gt;95% of small cell carcinomas of the ovary, hypercalcemic type (SCCOHT), a rare and aggressive form of ovarian cancer. Because of its apparent role as a driver for SCCOHT, we performed integrative multi-omic analyses in a SCCOHT cell line +/- BRG1 re-expression to identify its role in SCCOHT tumorigenesis. After re-expression, BRG1 was recruited to both distal and promoter regions. We also observed increased chromatin accessibility at distal sites enriched for transcription factor binding motifs for AP-1 family members. Of interest, BRG1 re-expression induced an epithelial-like gene and protein expression concomitant with enrichment of AP-1 motifs at the TSS of highly upregulated epithelial genes. To determine the biologic relevance of these changes at AP-1 binding sites, we used a dominant negative AP-1 cell line to demonstrate that the necessity of AP-1 DNA binding activity and BRG1 re-expression for the protein expression of epithelial genes. Our study demonstrates that BRG1 loss may drive SCCOHT tumorigenesis by diminishing an epithelial-like gene and protein signature of its cell of origin driven by altered AP-1 binding. Citation Format: Krystal A. Orlando, Jesse R. Raab, Amber K. Douglas, Aierken Abudu, Yemin Wang, Gian Luca Negri, Shane Colborne, Gregg B. Morin, Jessica D. Lang, William P.D. Hendricks, Elizabeth A. Raupach, Patrick Pirrotte, David G. Huntsman, Jeffrey M. Trent, Joel S. Parker, Bernard E. Weissman. SMARCA4/BRG1 and AP-1 co-regulate an epithelial-like signature in small-cell carcinoma of ovary, hypercalcemic type (SCCOHT) [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr B25.

Effect of high-dose chemotherapy with autologous stem cell rescue (HDC-aSCR) on outcome in ovarian small-cell carcinoma, hypercalcemic type (SCCOHT): Prospective series from the French Rare Gynecologic Malignant Tumors Network (TMRG).

6023 Background: Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT), is a rare and rapidly lethal disease affecting young women with over half dying within 2 years of diagnosis. We previously reported improved outcomes with cytoreductive surgery followed by HDC-aSCR in a prospective study, but these encouraging results needed to be confirmed in an independent and larger cohort. Methods: Between 2008 and 2019, out of 44 patients (pts) diagnosed with centrally confirmed SCCOHT in 16 referent centers of the TMRG network, 38 were treated prospectively according to the French recommendations of the network with complete surgery (primary or after neoadjuvant chemotherapy), 4 to 6 cycles of PAVEP chemotherapy (cisplatin, doxorubicin, vepeside, and cyclophosphamide), and for pts with complete response (CR), HDC-aSCR, followed by pelvic radiotherapy. The 6 patients who could not receive PAVEP (unfit or diagnostic delay) relapsed and died rapidly. The primary endpoint was the event-free survival (EFS) in the intention-to-treat cohort. Results: Median age at diagnosis was 33 years (14-76). 13 pts presented with FIGO stage I, 17 stage III and 6 stage IV, 2 unknown. Median follow-up was 55.5 months. 34 patients achieved CR with CT + surgery and 30 received HDC-aSCR (40%, 47% and 10% with stages I, III and IV diseases respectively) and 21 received also pelvic radiotherapy. Median overall and event-free survival was 36.4 and 15.9 months respectively, and 2-years event-free survival rate was 40% (CI95% 25-56). Median OS was respectively not reached, 18 and 9.6 months for FIGO I, III and IV patients. Among the pts (N = 14) who did not receive HDC-aSCR (rapid progression during or after PAVEP), the 2-yr EFS was 0% compared to 50.5% for the 30 patients receiving HDC. In multivariate analysis, HDC was significantly correlated with better outcomes (p &lt; 0.001). For the 21 patients receiving also pelvic radiotherapy, 57% (12/21) are free of recurrence at 4 years. Grades 3/4 adverse events were frequent (78%) but, in most cases, manageable, although one toxic death (3%) occurred during HDC (fungal septic shock). Conclusions: Treatment of SCCOHT, with intensive multimodal therapy, is associated with a 40% 2-yr event-free survival. However, this protocol is associated with significant toxicity and should be restricted to good performance status patient and expert centers.

A case of small cell neuroendocrine carcinoma of ovary

Objective Small cell neuroendocrine carcinoma of the ovary is a kind of ovarian cancer with a very low incidence.Its clinical manifestations are not obvious.The diagnosis should be based on the pathology and neuroendocrine indicators, and its primary nature should be determined.The main treatment is operation combined with platinum based chemotherapy.The survival period is related to clinical stage and treatment plan.The patient was hospitalized for 2 days because of the aggravation of abdominal distention and pain for half a year.The diagnosis of adnexal mass was confirmed by pathology.After three cycles of neoadjuvant chemotherapy (etoposide+ cisplatin), the patients underwent abdominal total hysterectomy+ greater omentum resection+ appendectomy+ right pelvic wall peritoneal biopsy+ mesenteric biopsy . After the operation, the patients received three cycles of EP chemotherapy, and they have been followed up for 15 months. Key words: Small cell carcinoma of ovary; Total hysterectomy with double appendages; omentum resection; Chemotherapy

SAT-231 A Case of Small Cell Ovarian Cancer, Hypercalcemic Type, in Pregnancy

Introduction Hypercalcemia in pregnancy is uncommon. Immediate evaluation and management is key to manage hypercalcemia in pregnancy to prevent maternal and fetal complications. Some common causes include primary hyperparathyroidism, vitamin D toxicity, and hyperthyroidism. An uncommon cause of hypercalcemia in pregnancy is small cell ovarian cancer, hypercalcemic type (SCCOHT). Case 26 year old woman, presented to the emergency department at 22 weeks of gestation with complaints of generalized weakness, fatigue, increased thirst, constipation, and intermittent right lower quadrant abdominal pain for 2 weeks. Past medical history was significant for polycystic ovarian syndrome. Labs revealed elevated albumin-corrected calcium: 17.5 mg/dl (8.7-10.5 mg/dl), low serum phosphorus: 2.1 mg/dl (2.7-4.5 mg/dl), low 25-OH vitamin D: 13 ng/ml (30-96 ng/ml), 1,25-OH Vitamin D: 44 pg/ml (20-79 pg/ml), and elevated PTHrP: 14 pmol/L (<2 pmol/L). The intact PTH was 12 pg/ml (9-77 pg/ml). TSH < 0.010 uIU/ml (0.4-4.0 uIU/ml) and free T4: 1.91 ng/dl (0.71-1.51 ng/dl). TSI & TPO levels were low. CA 125 was elevated: 135 U/ml (0-30 U/ml). Patient received IV hydration, IV furosemide, calcitonin, and pamidronate at the time of admission for management of hypercalcemia. MRI revealed large right adnexal mass measuring 19 cm; mostly solid but with cystic components. She underwent exploratory laparotomy with salpingo-oophorectomy. On post-op day 1 albumin corrected calcium decreased to 11.3 mg/dl. Repeat PTHrP on post-op day 3 decreased to 0.5 pmol/L. Pathology was notable for SCCOHT. At 27 weeks gestation, patient went into spontaneous labor and delivered. Following the delivery, she was started on chemotherapy with etoposide/cisplatin. After completion of one cycle of chemotherapy, her albumin corrected calcium level was 10.3 mg/dl. She was able to tolerate her first cycle of chemotherapy well and was in stable condition at the time of discharge. Discussion This case demonstrates an uncommon cause of hypercalcemia in pregnancy. Although rare (1% of all ovarian tumors), SCCOHT is an aggressive tumor with poor prognosis. SCCOHT should be considered as a differential in a young woman presenting with severe hypercalcemia. Majority of patients with SCCOHT have hypercalcemia, primarily mediated through the production of PTHrP, however our patient also had measurable calcitriol level possibly contributing to hypercalcemia. References Münstedt K, Estel R, Dreyer T, Kurata A, Benz A. Small Cell Ovarian Carcinomas - Characterisation of Two Rare Tumor Entities. Geburtshilfe Frauenheilkd. 2013;73(7):698-704.

Small cell ovarian carcinoma hypercalcemic type and endometrial adenocarcinoma in a 49-year-old patient: a very rare case

Background: Small cell ovarian carcinoma hypercalcemic type (SCCOHT) is a rare ovarian malignancy with less than 400 cases worldwide. However, it affects mainly young women and has poor prognosis. The incidence of concurrent endometrial and ovarian cancer is as low as 10%, and has not been described, to our knowledge, with SCCOHT. Case Report: This is a rare case of a 49-year-old female who presented with abdominal pain, constipation, asymptomatic hypercalcemia, a large palpable abdominal mass, and was diagnosed with SCCOHT with concurrent Grade I endometrial adenocarcinoma endometroid type. Conclusion: This is an interesting case due to the concurrent endometrial cancer, the size of the tumor, and the age of the patient and aims to increase clinical suspicion around SCCOHT. The importance of the MDT should be highlighted, especially for this type of tumors which can be a diagnostic and treatment challenge.