1. A Population-Based Study of Patients With Small Cell Carcinoma of the Ovary, Hypercalcemic Type, Encompassing a 30-Year Period
- Author
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Blatnik, Ana, Dragos, Vita Setrajcic, Blatnik, Olga, Stegel, Vida, Klancar, Gasper, Novakovic, Srdjan, Drev, Primoz, Zagar, Tina, Merlo, Sebastjan, Skof, Erik, Bojadziski, Mirjana Pavlova, Strojnik, Ksenija, and Krajc, Mateja
- Subjects
Medical research -- Analysis ,Medicine, Experimental -- Analysis ,Immunohistochemistry -- Analysis ,Ipilimumab -- Analysis ,Medical records -- Analysis ,Immunotherapy -- Analysis ,Ethylenediaminetetraacetic acid -- Analysis ,Carcinoma -- Analysis ,Cancer -- Analysis ,Genetic screening -- Analysis ,Health - Abstract
* Context.--Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare and lethal tumor, characterized by hypercalcemia and early onset and associated with germline and somatic SMARCA4 variants. Objective.--To identify all known cases of SCCOHT in the Slovenian population from 1991 to 2021 and present genetic testing results, histopathologic findings, and clinical data for these patients. We also estimate the incidence of SCCOHT. Design.--We conducted a retrospective analysis of hospital medical records and data from the Slovenian Cancer Registry in order to identify cases of SCCOHT and obtain relevant clinical data. Histopathologic review of tumor samples with assessment of immunohistochemical staining for SMARCA4/BRG1 was undertaken to confirm the diagnosis of SCCOHT. Germline and somatic genetic analyses were performed using targeted next-generation sequencing. Results.--Between 1991 and 2021, we identified 7 cases of SCCOHT in a population of 2 million. Genetic causes were determined in all cases. Two novel germline loss-of-function variants in SMARCA4 LRG_878t1:c.1423_1429delTACCTCA p.(Tyr475Ilefs*24) and LRG_878t1: c.3216-1G>T were identified. At diagnosis, patients were ages 21 to 41 and had International Federation of Gynecology and Obstetrics, or FIGO, stage IA-III disease. Outcomes were poor, with 6 of 7 patients dying of disease-related complications within 27 months from diagnosis. One patient had stable disease for 12 months while receiving immunotherapy. Conclusions.--We present genetic, histopathologic, and clinical characteristics for all cases of SCCOHT identified in the Slovenian population during a 30-year period. We report 2 novel germline SMARCA4 variants, possibly associated with high penetrance. We estimate the minimal incidence of SCCOHT to be 0.12 per 1 million per year., Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a very rare and devastatingly lethal tumor, first defined by Scully (1) in 1979 and described in more detail by [...]
- Published
- 2024
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