A case of small cell carcinoma of the ovary hypercalcemic variant in a teenager.
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ABSTRACT:
SUBMITTER: Bakhru A
PROVIDER: S-EPMC3861231 | biostudies-literature | 2012
REPOSITORIES: biostudies-literature
Publications
A case of small cell carcinoma of the ovary hypercalcemic variant in a teenager.
Bakhru Arvind A Liu J Rebecca JR Lagstein Amir A
Gynecologic oncology case reports 20120919 4
► Young women with hypercalcemic type small cell ovarian cancer face a poor prognosis. ► Tumors respond to multi-agent chemotherapy, although rapid recurrence is typical. ► Using updated immunohistochemical staining patterns, this tumor can be identified. ...[more]
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Project description:A 12-yr-old normocalcemic female treated for a ruptured ovarian juvenile granulosa cell tumor at an outside hospital presented for exploratory laparotomy and gross surgical debulking of pelvic recurrence. Morphologically, the tumor was composed of sheets and nests of small blue cells forming cysts of various sizes and focal mucinous differentiation. Epithelial membrane antigen (EMA), patchy inhibin, and strong and diffuse p53 immunoreactivity were also observed. A revised diagnosis of mixed sex cord stromal tumor with heterologous elements was favored because of the inhibin immunoreactivity. Targeted next-generation sequencing of the tumor revealed a SMARCA4 c.1141C>T, p.Arg381Ter (NM_001128849.1) nonsense mutation and an in-frame 18-bp TP53 deletion (c.594_611del18, p.Gly199_Glu204del, NM_001126112.2). Cytogenetic analysis revealed a normal 46,XX karyotype, and OncoScan single-nucleotide polymorphism array analysis demonstrated copy-neutral loss of heterozygosity (CN-LOH) of 19p13.3-19p13.2 and mosaic CN-LOH of 17p13.3-p11.2 encompassing the SMARCA4 and TP53 loci, respectively. Subsequent germline SMARCA4 sequencing confirmed a heterozygous SMARCA4 p.Arg381Ter mutation. In lieu of the molecular findings, the diagnosis was amended to small cell carcinoma of the ovary, hypercalcemic type (SCCOHT). The patient was treated aggressively with paclitaxel, carboplatin, and bevacizumab. She received an autologous stem cell transplant but died 5 mo after SCCOHT diagnosis secondary to complications of the transplant. This case expands the morphologic, immunophenotypic, and genomic spectrum of SCCOHT and highlights how multimodal molecular analysis can assist with the diagnosis and clinical management of SCCOHT patients.
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Project description:Small cell carcinoma of the ovary hypercalcemic type (SCCOHT) is a rare and aggressive disease. While classically linked to mutations in SMARCA4, we describe a case in a patient with both SMARCA4 and BRCA2 germline mutations. We describe her disease presentation, histopathology and treatment with adjuvant systemic chemotherapy, interval hyperthermic intraperitoneal chemotherapy, high dose chemotherapy with stem cell rescue, and maintenance with a poly-ADP-ribose polymerase inhibitor (PARPi). Additionally, we share spatial transcriptomics completed on original tumor.
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