Pediatric and Developmental Pathology

First Reported Histologically and Molecularly Confirmed Bilateral High-Grade Serous Ovarian Adenocarcinoma Metastasized to Placental Decidua of the Membranes

A 43-year-old female presented with blood loss and persistent abdominal pain at 14 weeks of gestation. Ultrasound examination and subsequent magnetic resonance imaging (MRI) revealed bilateral multicystic uterine adnexa. Exploratory laparotomy was performed at 17 weeks of gestation and bilateral serous ovarian adenocarcinoma FIGO stage IIIC was diagnosed. Complete cytoreductive surgery (CRS) was not feasible at that moment. Nine days after the exploratory laparotomy, immature rupture of membranes and contractions occurred and she delivered a premature boy after 19 weeks of gestation. Pathological examination of the placenta revealed that her ovarian cancer metastasized to the membranes. We describe the first case of ovarian cancer metastasized to the decidua of the placental membranes with histological, immunohistochemical, and molecular confirmation. This case highlights the importance of conscientious evaluation of placenta and membranes in pregnant women with ovarian cancer.

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.

Sex Cord-Stromal Tumours in Children: A Case Series

Sex cord-stromal tumours (SCSTs) in children are rare gonadal neoplasms exhibiting differentiation towards sex cord stromal elements. This case series explores paediatric SCSTs, presenting clinical, gross, histologic, and immunohistochemical findings, with a focus on limited information available about these tumours in African children. This retrospective study includes 9 cases of ovarian and testicular SCSTs (8 female and 1 male) in patients below 16 years of age. Female patients presented with various SCST subtypes, including juvenile granulosa cell tumours (JGCTs), fibroma, and mixed tumours. Precocious puberty was a common presentation. The male patient had a Leydig cell tumour. Tumour sizes varied, with the smallest in the testis and the largest in a 3-year-old girl. Histologically, most cases exhibited characteristic features of their respective subtypes. Paediatric SCSTs are rare but important considerations in children with gonadal masses. Their incidence in African children is largely unknown. JGCTs are the most prevalent ovarian subtype. Leydig cell tumours are rare in children and can present with virilisation. Mixed SCST-germ cell tumours, though extremely rare, warrant careful consideration and immunohistochemistry for accurate diagnosis.

Campomelic Dysplasia With Sex Reversal, Gonadal Dysgenesis, and Bilateral Gonadoblastoma

Campomelic dysplasia (CD) is a rare skeletal dysplasia typically associated with a high neonatal mortality rate due to respiratory insufficiency. The condition is due to mutations in the SOX9 gene, which affects skeletal and sexual development. Mutations further away from this gene result in a milder condition, and thus some of those affected live into adulthood. Due to SOX9’s effect on sexual development, there is sex reversal in approximately 75% of genotypic males (46XY). This report presents a unique case of a 1-year-old phenotypic female with a 46XY karyotype, diagnosed with CD, gonadal dysgenesis, and bilateral gonadoblastoma. The patient exhibited non-ambiguous female genitalia and a uterus but had undescended streak gonads. The streak gonads were surgically removed due to the increased risk of malignancy. Histological analysis revealed a right-sided streak gonad with multiple foci of dissecting gonadoblastoma and a left-sided streak gonad with classic gonadoblastoma. While the patients’ gene break point lies at the 17q23.1 locus, outside of the widely accepted SOX9 region, there may be reason to believe her mutation is affecting the SOX9 gene. This case shows the importance of early diagnosis and intervention with gonadectomy in patients with campomelic dysplasia or other sex reversal disorders.

Testicular Juvenile Granulosa Cell Tumor - a Rare Entity that May Have Mildly Elevated Serum Alpha Fetal Protein in Infants