Abstract
BackgroundOvarian small cell carcinoma, hypercalcaemic type (SCCOHT) is a rare and lethal disease affecting young women. As histological diagnosis is challenging and urgent, there is a clear need for a robust diagnostic test. While mutations in the chromatin-remodelling gene, SMARCA4, appear to be typical, it may not be feasible routinely to be clinically relevant.MethodsPrevious studies have described the value of SMARCA4 IHC to differentiate SCCOHT from ovarian neoplasms (ON), with similar histologic appearances. We aimed to evaluate its clinical utility among a cohort of 44 SCCOHT and 94 rare ON frequently misdiagnosed as SCCOHT.ResultsForty-three percent (16/36) of SCCOHT had been classified locally as non-SCCOHT confirming the diagnosis challenge. Sensitivity and specificity of SMARCA4 IHC were excellent at 88% and 94%, respectively. In a community setting with a much lower prevalence of the disease, estimated PPV is 40% while NPV remained high at 99%. Finally, among the 16 SCCOHT misclassified locally, SMARCA4 IHC testing would have resulted in corrected diagnosis in 88% of cases.ConclusionsSMARCA4 IHC is a highly sensitive, and specific test for the diagnosis of SCCOHT and is of huge clinical utility in providing a timely and accurate diagnosis of this challenging disease.
Highlights
Ovarian small cell carcinoma, hypercalcaemic type (SCCOHT) is a rare and lethal disease affecting young women
We aimed to evaluate the clinical utility of SMARCA4 IHC testing among a large cohort of centrally reviewed SCCOHT (N = 44) and other rare ovarian tumours occurring in young women and frequently misdiagnosed as SCCOHT (N = 94)
Alterations in other SNI/SNF genes in SMARCA4-wildtype SCCOHT Given that 5/44 SCCOHT retained some degree of SMARCA4 expression, we explored whether these SMARCA4-positive tumours may demonstrate other SWItch/ Sucrose NonFermentable (SWI/SNF) alterations, in particular, loss of the other closely related catalytic domain, SMARCA2
Summary
Hypercalcaemic type (SCCOHT) is a rare and lethal disease affecting young women. Witkowski et al provided the largest and most up to date review of 293 patients with SCCOHT and collected information on stage, age and treatment modality.[2] The most significant prognostic factors were stage and treatment, with patients undergoing high dose chemotherapy followed by autologous stem cell transplant having significantly improved survival compared to those treated with conventional post-operative chemotherapy (5 year OS 71% vs 25%, p = 0.002) These tumours are usually composed of sheets of small closely packed cells with little cytoplasm arranged in follicle-like structures; a large cell variant has been described.[1,6] Despite well-established histological features, it is always challenging to distinguish SCCOHT from other rare ovarian neoplasms due to its non-specific morphology. SCCOHT tumours can be misdiagnosed in young women as others tumours such as sex-cord stromal, germ cell, sarcoma-like (PNET, peritoneal desmoplastic round cell tumour), blastemal tumours (neuroblastoma), lymphoma, melanoma or undifferentiated epithelial ovarian tumours with obvious critical prognostic and therapeutic implications
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call