Diagnosis
Diagnosis:
Sertoli-Leydig cell tumor
Discussion:
The histologic and IHC features are consistent with a Sertoli-Leydig cell tumor. The basophilic cell population with vague tubule formation are the Sertoli cells; the Leydig cells are the plump eosinophilic cells in the tumor.
This case was graded as having intermediate differentiation, due to the vague tubule formation and presence of the sarcomatous heterologous component.
Sertoli-Leydig cell tumors are rare sex cord stromal tumors of the ovary, accounting for <0.1% of all ovarian tumors. They can occur in a wide age range of patients, though the peak incidence is 25 years of age, and are almost always unilateral tumors.
Patients typically present with abdominal pain or swelling, and up to 50% can have androgenic manifestations (not seen in this patient). However, some cases are asymptomatic. Treatment is surgical resection. Chemotherapy is usually used only for high grade/stage tumors or recurrences. The stage and grade of the tumor are the most important prognostic factors.
Sertoli-Leydig cell tumors are graded with a three-tiered system:
- Well-differentiated: Sertoli cells form open/closed tubules, Leydig cells not difficult to find.
- Intermediately differentiated: Sertoli cells in lobules, slit-like tubules or nests.
- Poorly differentiated: Sarcomatoid sheets of cells, Leydig cells rare to absent.
Heterologous elements, when present, are typically seen in intermediate or poorly differentiated tumors. They can have a variety of appearances, including intestinal (most common), hepatic, carcinoid, rhabdomyoblastic, sarcomatous, or cartilaginous. The presence of heterologous elements negatively impacts the prognosis.
Grossly, well-differentiated tumors are well-circumscribed, with solid yellow lobulated cut surfaces. Higher grade tumors can be cystic, hemorrhagic, or even necrotic, depending on the presence of heterologous elements.
Both the Sertoli and Leydig cells are typically positive for inhibin, calretinin, and WT-1. The Leydig cells with also be positive for Melan-A. Other stains like CD99, cytokeratins, NSE, CD56, and synaptophysin are frequently positive in these tumors as well. EMA is almost always negative, which along with inhibin positivity can help distinguish Sertoli-Leydig cell tumor from other similar-appearing entities, such as endometrioid carcinoma or carcinoid.
Recent studies have shown that up to 50% of Sertoli-Leydig cell tumors have mutations in DICER1, a microRNA maturation pathway gene. These mutations have also been observed in cervical embryonal rhabdomyosarcoma and thyroid carcinoma.
References:
Oliva, E. Sertoli-Leydig cell tumor. Expertpath. https://app.expertpath.com/ document/sertoli-leydig-cell-tumor/ 6949af98-5eb1-49e0-b124-12624840f016
Schneider DT et al. Ovarian sertoli-leydig cell tumors in children and adolescents: an analysis of the European Cooperative Study Group on Pediatric Rare Tumors (EXPeRT). European Journal of Cancer. (2015) 51(4): 543-550.
Witkowski L et al. DICER1 hotspot mutations in non-epithelial gonadal tumors. British Journal of Cancer. (2013) 109(10): 2744-2750.