Sertoli cell (SC) and sertoliform tumors of the testis are very uncommon; for this reason their differential diagnosis and classification can be challenging. We applied an extensive immunophenotypic panel that included androgenic hormones, enzymes and receptors, neuroendocrine, lineage and genitourinary markers to a series of these lesions to determine if and which immunostains can aid in their diagnostic workup. Study cases included: 2 androgen insensitivity syndrome associated SC-adenomas, 3 SC tumors not otherwise specified (SCT-NOS), 3 sclerosing-SCT, 2 large cell calcifying-SCT, 1 SCT with heterologous-sarcomatous elements, 1 malignant SCT, and 1 sertoliform rete testis adenoma (sertoliform-RTA). We found that SCT-NOS and variants with sclerosis showed a phenotype akin to atrophic seminiferous tubules characterized by gain of expression of pankeratin, calretinin, CD56, which are negative in normal SC. Distinctive phenotypes were identified in: sclerosing-SCT: androgen receptors(AR)+(strong) / PAX2/PAX8+ (subset) / S100+/ inhibin-; large cell calcifying-SCT: calretinin+(strong) / S100+ / AR-; Sertoliform-RTA: PAX2/PAX8+ / pankeratin+ /inhibin-. Androgenic hormones and enzymes did not show diagnostic utility. A panel of calretinin, inhibin, pankeratin, S100, PAX2/PAX8 and AR consistently allowed distinction between variants of Sertoli and sertoliform tumors.
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