August 2022 – Genitourinary Pathology

Sex cord-stromal tumor consistent with Sertoli cell tumor.

Sertoli cell tumor (SCT) is a sex cord-stromal tumor of the testis, accounting for less than 1% of all testicular tumors. It is the second most common pure sex cord-stromal tumor, representing approximately one-third of sex cord-stromal tumors. It occurs most frequently in middle-aged Caucasian males, with a median age of approximately 40 years. Clinically, SCTs are detected incidentally on imaging or present with a combination of unilateral testicular mass, swelling, discomfort, and/or pain. Hormonal manifestations such as gynecomastia are relatively infrequent. Most cases are benign; however, approximately 5%-10% of tumors are malignant. Rarely, SCTs can initially manifest with a distant metastasis.^1,2

Per the 2022 Word Health Classification, SCT, not otherwise specified (NOS) and large cell calcifying SCT, represent two major categories of SCTs.¹ On histopathologic examination, SCT, NOS is characterized by an admixture of tubular, sheet-like, cord-like, and trabecular architecture. The neoplastic cells have round to ovoid nuclei with occasional nucleoli. These cells have clear to pale eosinophilic cytoplasm that is moderate to abundant.³ Necrosis, increased mitotic activity, cytological atypia, lymphovascular invasion, and infiltrative growth are typically absent. The presence of any of these features, along with large tumor size, is suggestive of a malignant SCT.¹

The sclerosing variant of the SCT, NOS deserves further mention. This variant is characterized by a dense fibrocollagenous background, occupying more than 50% of the lesion. The architectural and cytomorphologic features of the sclerosing variant are essentially similar to conventional SCT, NOS; however, the cords, tubules, and clusters of cells appear embedded within and partially entrapped by the hypocellular stroma. Originally, the sclerosing variant was conceptualized as a distinctive variant separate from SCT, NOS, but it is currently considered under the umbrella of SCT, NOS due to overlapping CTNNB1 gene mutation and nuclear immunoreactivity for beta-catenin.^1,4,5 Most of the cases of SCT, NOS, sclerosing variant follow a benign course.^1-3 The case presented herein bears morphologic resemblance to the sclerosing variant; however, it was not classified as a sclerosing variant of the SCT, NOS because the sclerotic stroma represented less than 50% of the entire tumor.

On immunohistochemical examination, the majority of cases are positive for SF1, while nuclear β-catenin immunoreactivity is present in approximately two-thirds of the cases. Inhibin is positive in about half of the tumors. The absence of germ cell neoplasia in situ and negative staining for OCT 3/4 are helpful in ruling out a GCNIS-derived lesion.

References

1. WHO Classification of Tumours Editorial Board. Urinary and male genital tumours [Internet]. Lyon (France): International Agency for Research on Cancer; 2022. (WHO classification of tumours series, 5th ed.; vol. 8). Available from: https://tumourclassification.iarc.who.int/chapters/36.
2. Al-Obaidy KI, Idrees MT. Testicular tumors: A contemporary update on morphologic, immunohistochemical and molecular features. Adv Anat Pathol. 2021;28:258-75.
3. Kao CS, Kum JB, Idrees MT, Ulbright TM. Sclerosing Sertoli cell tumor of the testis: a clinicopathologic study of 20 cases. Am J Surg Pathol. 2014;38:510-7.
4. Perrone F, Bertolotti A, Montemurro G, Paolini B, Pierotti MA, Colecchia M. Frequent mutation and nuclear localization of β-catenin in sertoli cell tumors of the testis. Am J Surg Pathol. 2014;38:66-71.
5. Zhang C, Ulbright TM. Nuclear localization of β-catenin in Sertoli cell tumors and other sex cord-stromal tumors of the testis: An immunohistochemical study of 87 cases. Am J Surg Pathol. 2015;39:1390-4.