From the Departments of Clinical Cancer Genetics (A. Blatnik, Strojnik, Krajc).
Institute of Oncology Ljubljana, Ljubljana, Slovenia; and the Biotechnical Faculty (A. Blatnik, Dragoš).
Arch Pathol Lab Med. 2024 Mar 1;148(3):299-309. doi: 10.5858/arpa.2022-0297-OA.
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.
卵巢小细胞癌，高钙血症型（SCCOHT）是一种罕见且致命的肿瘤，其特征是高钙血症和早期发病，并与种系和体细胞 SMARCA4 变体相关。
从 1991 年到 2021 年，确定在斯洛文尼亚人群中所有已知的 SCCOHT 病例，并介绍这些患者的遗传检测结果、组织病理学发现和临床数据。我们还估计了 SCCOHT 的发病率。
我们对医院病历和斯洛文尼亚癌症登记处的数据进行了回顾性分析，以确定 SCCOHT 病例并获取相关临床数据。对肿瘤样本进行组织病理学复查，并评估 SMARCA4/BRG1 的免疫组织化学染色以确认 SCCOHT 的诊断。使用靶向下一代测序进行种系和体细胞基因分析。
在 1991 年至 2021 年间，我们在 200 万人口中发现了 7 例 SCCOHT。在所有病例中均确定了遗传原因。在 SMARCA4 基因中发现了 2 个新的种系功能丧失变体 LRG_878t1:c.1423_1429delTACCTCA p.(Tyr475Ilefs*24)和 LRG_878t1:c.3216-1G>T。诊断时，患者年龄为 21 岁至 41 岁，国际妇产科联合会（FIGO）分期为 IA-III 期疾病。结局较差，7 例患者中有 6 例在诊断后 27 个月内死于疾病相关并发症。1 例患者在接受免疫治疗时疾病稳定 12 个月。
我们介绍了在 30 年期间在斯洛文尼亚人群中发现的所有 SCCOHT 病例的遗传、组织病理学和临床特征。我们报告了 2 个新的种系 SMARCA4 变体，可能与高外显率相关。我们估计 SCCOHT 的最小发病率为每年每 100 万人 0.12 例。
