August 2022 – Genitourinary Pathology

A man in his 70s presented with a slowly enlarging, painless testicular swelling and was found to have a 1.6 cm mass confined to the left testicle on imaging. Microscopic images and selected immunohistochemical stains are shown in Figures 1 and 2, respectively. Histologic sections showed a relatively well-circumscribed neoplasm, comprised of cords and tubules, without infiltrative growth. Interspersed spindled stromal elements and collagenous material (less than 50% of the lesion) were identified. The cytomorphology of the cord-like structures was significant for cells exhibiting clear, moderate to abundant cytoplasm and ovoid nuclei without atypia or increased mitotic activity. No germ cell neoplasia in situ (GCNIS) was identified in the background seminiferous tubules. The cells of interest showed nuclear localization of beta-catenin (Figures 2A and B) and steroidogenic factor 1 (SF1) (Figures 2C and D). In addition, these cells expressed pankeratin, vimentin, and inhibin (focal), and were negative for alpha fetoprotein, CD30, glypican 3, OCT 3/4, PLAP, SALL4, and WT1.

Figure 1: Multipanel
Figure 2: Multipanel

What would be the most likely diagnosis?

  • Seminoma
  • Sex cord-stromal tumor consistent with Sertoli cell tumor
  • Metastatic tumor
  • Adenomatoid tumor

The correct answer is ...

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.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.


  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:
  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.
Photo of Burak Tekin, M.D.

Burak Tekin, M.D.

Resident, Anatomic and Clinical Pathology
Mayo Clinic

Sounak Gupta, M.B.B.S., Ph.D.

Consultant, Anatomic Pathology
Mayo Clinic
Associate Professor of Laboratory Medicine and Pathology
Assistant Professor of Pathology
Mayo Clinic College of Medicine and Science

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