Small Cell Carcinoma of the Ovary, Hypercalcemic Type: Report of a Bilateral Case in a Teenager Associated with SMARCA4 Germline Mutation

Abstract

Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT), is a highly aggressive neoplasm that typically occurs in young females. Paraneoplastic hypercalcemia is associated in two thirds of the cases. Recent studies demonstrated that this rare tumor harbors the same molecular features of malignant rhabdoid tumor secondary to SMARCA4/BRG1 mutations. We illustrate herein a typical bilateral case of SCCOHT with comprehensive molecular characterization in a 14-year-old girl. We also discuss the value of SMARCA4 immunostaining in the diagnostic approach of undifferentiated ovarian and pelvic malignancies.

The influence of clinical and genetic factors on patient outcome in small cell carcinoma of the ovary, hypercalcemic type

“…Thus far, 96 unique SMARCA4 mutations have been described [5–8, 10–14, 25, 26]; the types of mutations have varied and include 21 splice mutations, 25 stop mutations, 41 frameshift mutations, 6 missense mutations, 2 in-frame deletions and 1 synonymous mutation (Supplementary Table S2). Regardless of the mutation type, however, almost all have led to loss of the SMARCA4 protein, with only 2 mutations leading to retained SMARCA4 protein: a missense mutation (p.Glu1080Asp) [7] and an in-frame deletion (Supplementary Table S2) [5].…”

An In-Depth Look at Small Cell Carcinoma of the Ovary, Hypercalcemic Type (SCCOHT): Clinical Implications from Recent Molecular Findings

“…The largest series showed that most tumors were unilateral (148/150, 99%) with a higher proportion in the right ovary (341/457, 66%) 16. Familial cases were often bilateral 17, 18. The tumors usually have a large size (average 15.3 cm, 6-26 cm in greatest dimension).…”

“…After these breakthrough works, a growing body of evidence unanimously provides an etiologic link between SMARCA4 mutations and SCCOHT 10, 17, 18, 26, 75, 76. A total of 118 (96 none-redundant) pathogenic SMARCA4 mutations have been describeed in 94 patients to date [Table 1] 10, 17, 18, 26, 75-79. These SMARCA4 mutations do not reveal the presence of hotspots yet.…”

Identification of novel hereditary cancer genes by whole exome sequencing

“…For example, identification of SMARCA4 mutations in hypercalcemic small cell carcinomas of the ovary led to a breakthrough in understanding of genetic basis of this disease [73][74][75][76]. Similarly, SMARCE1 mutations were revealed upon the study of multiple spinal meningiomas [82][83][84][85].…”