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

Witkowski, Leora; Goudie, Catherine; Ramos, Pilar; Boshari, Talia; J, Brunet; Karnezis, Anthony N.; Longy, Michel; Knost, James A.; Saloustros, Emmanouil; McCluggage, W. Glenn; Stewart, Colin J.R.; Hendricks, William P.D.; Cunliffe, Heather E.; Huntsman, David G.; Pautier, Patricia; Levine, Douglas A.; Trent, Jeffrey M.; Berchuck, Andrew; Hasselblatt, Martin; Foulkes, William D.

doi:10.1016/j.ygyno.2016.03.013

Cited by 100 publications

(127 citation statements)

References 37 publications

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“…SMARCA4 female mutation carriers have a higher risk of developing small cell carcinoma of the ovary, hypercalcemic type (SCCOHT), which can be regarded as a special type of MRT and was found to be very similar to RTs in clinical, histologic, genomic, and epigenomic characteristics (40)(41)(42). Although these tumors represent a distinct clinical entity, the similarities to MRT have led some to suggest that SCCOHT be considered part of the rhabdoid tumor predisposition syndrome (RTPS) spectrum of tumors (Table 3).…”

Section: Genes Responsible For Rt Predispositionmentioning

confidence: 99%

“…The risk of SCCOHT and the decision to undergo prophylactic surgery will be individualized and informed by the family history, the age of the patient, the patient's reproductive plans, and by emerging data that will help with estimation of risk. SMARCA4-deficient SCCOHT has not been seen in women over age 60 (42), so screening recommendations can be altered in older women.…”

Section: Recommended Surveillance Protocols For Rtsmentioning

confidence: 99%

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Cancer Surveillance in Gorlin Syndrome and Rhabdoid Tumor Predisposition Syndrome

Foulkes

Kamihara

Evans

et al. 2017

Clinical Cancer Research

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Gorlin syndrome and rhabdoid tumor predisposition syndrome (RTPS) are autosomal dominant syndromes associated with an increased risk of childhood-onset brain tumors. Individuals with Gorlin syndrome can manifest a wide range of phenotypic abnormalities, with about 5% of family members developing medulloblastoma, usually occurring in the first 3 years of life. Gorlin syndrome is associated with germline mutations in components of the Sonic Hedgehog pathway, including Patched1 (PTCH1) and Suppressor of fused (SUFU). SUFU mutation carriers appear to have an especially high risk of early-onset medulloblastoma. Surveillance MRI in the first years of life in SUFU mutation carriers is, therefore, recommended. Given the risk of basal cell carcinomas, regular dermatologic examinations and sun protection are also recommended. Rhabdoid tumors (RT) are tumors initially defined by the descriptive “rhabdoid” term, implying a phenotypic similarity with rhabdomyoblasts at the microscopic level. RTs usually present before the age of 3 and can arise within the cranium as atypical teratoid/rhabdoid tumors or extracranially, especially in the kidney, as malignant rhabdoid tumors. However, RTs of both types share germline and somatic mutations in SMARCB1 or, more rarely, SMARCA4, each of which encodes a chromatin remodeling family member. SMARCA4 mutations are particularly associated with small cell carcinoma of the ovary, hypercalcemic type (SCCOHT). The outcome following a diagnosis of any of these tumors is often poor, and the value of surveillance is unknown. International efforts to determine surveillance protocols are underway, and preliminary recommendations are made for carriers of SMARCB1 and SMARCA4 mutations. Clin Cancer Res; 23(12); e62–e67. ©2017 AACR. See all articles in the online-only CCR Pediatric Oncology Series.

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Section: Genes Responsible For Rt Predispositionmentioning

confidence: 99%

Section: Recommended Surveillance Protocols For Rtsmentioning

confidence: 99%

Cancer Surveillance in Gorlin Syndrome and Rhabdoid Tumor Predisposition Syndrome

Foulkes

Kamihara

Evans

et al. 2017

Clinical Cancer Research

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153

113

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“…87 92 While the tumour cells in SCCOHT usually have scant cytoplasm resulting in a small cell appearance, some cases contain tumour cells with abundant eosinophilic cytoplasm, often resulting in a large cell appearance, sometimes with a rhabdoid morphology. As discussed below, SCCOHT is caused by mutations in the chromatin remodelling gene SMARCA4 90. These mutations are accompanied by loss of expression of the SMARCA4 (BRG1) protein in 97% of cases, and immunostaining for SMARCA4 has now been established as an extremely useful way to diagnose SCCOHT and distinguishes this entity from its mimics which almost always exhibit retention of nuclear immunoreactivity (figure 2).…”

Section: Small Cell Carcinoma Of the Ovary Of Hypercalcaemic Typementioning

confidence: 99%

“…While RTPS2-associated SMARCA4 mutations are largely loss of function variants, a handful of missense variants have been described 90. These variants have been found to occur across the length of the gene, with no predominant hotspot regions 90.…”

Section: Small Cell Carcinoma Of the Ovary Of Hypercalcaemic Typementioning

confidence: 99%

Paediatric ovarian tumours and their associated cancer susceptibility syndromes

et al. 2017

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Non-epithelial ovarian tumours are rare neoplasms that occasionally arise in childhood and adolescence. They can be associated with various cancer susceptibility syndromes. The morphological overlap seen across these tumours and their rarity can make the diagnosis challenging. In the case of an incorrect diagnosis, the underlying genetic susceptibility may be missed. In this review, we outline the genetic background of ovarian non-epithelial tumours arising in children, emphasizing the genes harbouring pathogenic germline variants associated with each tumour type. Specifically, juvenile granulosa cell tumours, Sertoli-Leydig cell tumours, sex cord tumours with annular tubules, Sertoli cell tumours, germ cell tumours and small cell carcinoma of the ovary of hypercalcaemic type are discussed in this review. For each tumour type, we detail the personal and family history features and the presenting characteristics of the ovarian tumour as well as the pathological features and molecular markers that point towards a cancer predisposition syndrome. Throughout, we stress the need for specialised pathological review in difficult cases.

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“…Optimal management of patients is not well defined; in literature several and different treatment strategies and chemotherapy are reported but in few cases due to the rareness of the disease, Harrison et al presented a review of the management of 17 cases in a Gynecological Cancer Intergroup (GCIG) study, with poor results showed [7]. In this context there are no evidence based recommendations nor guide lines (Table 2) [1,3,[8][9][10][11][12][13][14]. We present and discuss a case of SCCOHT in a young patient, as well a review of the literature about ovarian small cell tumors treatment.…”

Section: Introductionmentioning

confidence: 99%

Case 2 – Ovarian small cell carcinoma: a case report and review of the literature

Salutari¹

2017

CBN

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Ovarian small cell carcinoma is a rare tumor associated with poor prognosis. Although combination chemotherapy remains the cornerstone of treatment due to the rarity of these tumors, there is no evidencebased consensus for a standard treatment, although in the majority of cases platinum-based regimens are used. A case of small cell carcinoma of the ovary, hypercalcemic-type (SCCOHT), in a 22 year-old patient is reported.

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

Abstract: Stage at diagnosis is the most significant prognostic factor in SCCOHT and consolidation with HDC-aSCR may provide the best opportunity for long-term survival. The large fraction of SMARCA4 germline mutations carriers warrants genetic counseling for all patients.

Cited by 100 publications

References 37 publications

Cancer Surveillance in Gorlin Syndrome and Rhabdoid Tumor Predisposition Syndrome

Cancer Surveillance in Gorlin Syndrome and Rhabdoid Tumor Predisposition Syndrome

Paediatric ovarian tumours and their associated cancer susceptibility syndromes

Case 2 – Ovarian small cell carcinoma: a case report and review of the literature

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