Doaa Atwi

Dedifferentiated Ovarian Carcinoma with ARID1A and ARID1B Mutations: A Clinicopathological Report and Literature Review

Dedifferentiated carcinoma of the female genital tract is a relatively recently recognized aggressive tumor affecting predominantly perimenopausal and postmenopausal women. In addition to having an undifferentiated component, dedifferentiated carcinoma includes a juxtaposed endometrioid adenocarcinoma, FIGO grade 1 or 2. Molecular characterization of these tumors has been a subject of discussion in multiple recent articles. We present a case of dedifferentiated carcinoma of the ovary in a 70-year-old female demonstrating concurrent inactivation of ARID1A and ARID1B. To the best of our knowledge, this is the second clinical report demonstrating dedifferentiated carcinoma of the ovary with concurrent inactivation of ARID1A and ARID1B. ARID1A and ARID1B inactivation seems to represent an alternate mechanism of switch/sucrose nonfermentable complex inactivation in the development of dedifferentiated carcinoma. Additional studies are warranted to precisely understand the molecular mechanism of cellular dedifferentiation in the dedifferentiated endometrial/ovarian carcinomas, thus guiding the development of targeted therapy.

Small Cell Carcinoma of the Ovary, Hypercalcemic Type, in a 12-Month-Old Girl

Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a highly aggressive malignant tumor affecting predominantly young adults and adolescents with an average age of 23.9 at time of diagnosis. Up to two thirds of patients have paraneoplastic hypercalcemia. The molecular signature of these tumors is SMARCA4 mutations, with somatic and germline pathogenic variants previously described. We report a case of a previously healthy one-year-old girl who was noticed to have mild anemia and an abdominal mass during a well-child visit. Further laboratory testing revealed hypercalcemia. A computerized tomography scan showed a left-sided ovarian mass (9.3 x 7.3 x 7 cm). The resection specimen showed a large ovarian tumor with solid tan-yellow cut surfaces and small foci of necrosis. Microscopically, the tumor was composed of sheets of small, hyperchromatic epithelioid cells with focal rhabdoid large cell morphology. The tumor cells were strongly and diffusely positive for WT1 (N-terminal antibodies) with focal EMA and Pan-keratin positivity. Absent SMARCA4 (BRG1) protein expression by immunohistochemistry ultimately established the diagnosis of small cell carcinoma of the ovary, hypercalcemic type. To our knowledge, this is the youngest patient reported in the literature.