COW-2022-10

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Large cell calcifying Sertoli cell tumor

Large cell calcifying Sertoli cell tumor (LCCSCT)is a neoplasm of Sertoli cells with abundant eosinophilic cytoplasm and coarse calcifications. Al-Obaidy and colleagues recently reviewed 115 cases reported in English literature: 84/115 (73%) were sporadic, 23/115 (20%) associated with Carney ́s complex, 6/115 (5%) associated with Peutz-Jeghers syndrome and 2/115 (1.7%) with neurofibromatosis type I. Most patients of LCCSCT present with painless testicular mass while tumors associated with Carney complex usually present in teenagers and are more frequently manifest as gynecomastia and isosexual pseudoprecocity. It is estimated that about 75% of males with Carney ́s complex may develop LCCSCTs. Overall, most cases present in teenagers or adults in the early 20s. In our case, the nodule was first noted when the patient was in his early 20s. Patients with syndromic association usually show germline mutations of PRKAR1A gene in patients with Carney ́s complex and STK11(LKB1)gene in patients with Peutz-Jeghers syndrome.

Grossly, LCCSCT are well demarcated, firm with coarse calcifications. At microscopy, the tumor shows large Sertoli cells with pale or granular cytoplasm with oval nuclei and prominent nucleoli. These cells area arranged in nests and cords within a myxoid or fibrous stroma. Cytoplasmic vacuolization in tumor cells is a common feature, at least focally. A neutrophilic infiltrate and perinodular aggregates of lymphocytes(see Figure 1C) are common. About half of cases show prominent calcifications(typically aggregated psamomomatous and multi berry-like or dystrophic calcifications)and some cases may even show ossification(Figures 1D and 2A). An intratubular component may be seen. Neoplastic cells are immunoreactive for vimentin, inhibin, calretinin, SF1, S100, NSE, desmin, EMA, and may show focal cytokeratin expression.

The presence of two or more of the following features are predictive of aggressive behavior: necrosis, size greater than 40 mm, extra-testicular growth, severe atypia, vascular invasion, or mitotic rate in excess of 3 mitotic figures per 10 high-power fields. None of them were observed in the present case. In their recent review, Al-Obaidy and colleagues suggested that all LCCSCTs in patients older than 25 years should be considered as potentially malignant since 2/19 (11%) of patients with no adverse features proved to be clinically aggressive. Unfortunately, some of the pathological criteria weremissing in the malignant reported cases (lymphovascular invasion in one; mitotic count and necrosis in the other).

A distinctive neoplasm that should be distinguished from LCCSCT is Intratubular large cell hyalinizing Sertoli cell neoplasia (ILHSCN). ILHSCN is invariably associated with Peutz-Jeghers syndrome. It presents gynecomastia and advanced bone age because of excess of circulating estrogen due to conversion of androgens into estrogens by aromatase in tumor cells. It may cause bilateral testicular enlargement without a distinctive mass. These tumors are predominantly intratubular showing patchily distributed expanded seminiferous tubules surrounded by prominent thickened basement membrane. Basement membrane protrudes into the lumen as globular eosinophilic deposits. The tubules contain large Sertoli cells. Rarely, neoplastic cells may invade the stroma with or without foci of calcification and may resemble large cell calcifying Sertoli cell tumors (LCCST).LCCST however, has a prominent invasive component, cells with dense eosinophilic cytoplasm, neutrophilic infiltrate and prominent calcification. ILHSCNs are benign. Our case did not show any intratubular component.

Al-Obaidy KI, Idrees MT, Abdulfatah E, Kunju LP, Wu A, Ulbright TM. Large Cell Calcifying Sertoli Cell Tumor: A Clinicopathologic Study of 18 Cases With Comprehensive Review of the Literature and Reappraisal of Prognostic Features. Am J Surg Pathol. 2021 Dec 16.

Kratzer SS, Ulbright TM, Talerman A, Srigley JR, Roth LM, Wahle GR, Moussa M, Stephens JK, Millos A, Young RH. Large cell calcifying Sertoli cell tumor of the testis: contrasting features of six malignant and six benign tumors and a review of the literature. Am J Surg Pathol. 1997 Nov;21(11):1271-80.

Petersson F, Bulimbasic S, Sima R, Michal M, Hora M, Malagon HD, Matoska J, Hes O. Large cell calcifying Sertoli cell tumor: a clinicopathologic study of 1 malignant and 3 benign tumors using histomorphology, immunohistochemistry, ultrastructure, comparative genomic hybridization, and polymerase chain reaction analysis of the PRKAR1A gene. Hum Pathol. 2010 Apr;41(4):552-9.

Daniel Athanazio
Imagepat, Laboratory of Pathology
Federal University of Bahia / Hospital Universitário Professor Edgard Santos Salvador, Bahia, Brazil

Maiara Ferreira de Souza
Imagepat, Laboratory of Pathology Salvador, Bahia, Brazil

George Depra Ferrari
Hospital da Bahia Salvador, Bahia, Brazil

Testis

Testis; Testicular Neoplasms; Sertoli Cell Tumor; Sertoli Cells