Elsevier

Human Pathology

Volume 61, March 2017, Pages 181-189
Human Pathology

Original contribution
Comparative immunomorphology of testicular Sertoli and sertoliform tumors

https://doi.org/10.1016/j.humpath.2016.11.004Get rights and content

Highlights

  • Sertoli cell and sertoliform tumors of the testis are very uncommon

  • Some Sertoli cell tumors resemble atrophic tubules by morphology and phenotype

  • Sclerosing Sertoli cell tumor variant shows a markedly different phenotype

  • Sertoliform rete testis adenoma mimics Sertoli tumors but stains like rete testis

  • Immunohistochemistry is useful in the subclassification of Sertoli tumors

Summary

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 (SCT) 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.

Introduction

Tubular structures of the testis include the seminiferous tubules, rete testis and epididymis. Sertoli cells (SC), the main constituent of the tubules, originate from the adrenogenital primordium; the rete testis and epididymis originate from intratesticular and extratesticular mesonephric ducts, respectively [1], [2], [3]. Tumors arising from the tubular structures of the testis comprise a minority of testicular neoplasms (<1%), and most originate from SC [4], [5], [6]. Given their rarity and overlapping morphology tumors arising from testicular tubular structures can pose diagnostic challenges. The goal of our study was to determine if, and which, immunostains can contribute in the diagnosis and classification of these lesions. We used a large panel of antibodies that included endocrine, neuroendocrine, lineage and genitourinary markers and compared the results among the tumors and their normal counterparts.

Section snippets

Materials and methods

The pathology databases from seven hospitals affiliated with the University of Minnesota Medical School were searched for testicular non–germ cell tumors and lesions. Confirmed cases with available paraffin-embedded blocks were included in the study. Immature/dysgenetic tubules (Pick adenomas/tubular congeries) and non−Sertoli/sertoliform neoplasms were excluded.

The lesions were classified according to current World Health Organization and Armed Forces Institute of Pathology classifications.

Results

Thirteen lesions from 12 patients met the inclusion criteria (Table 1): 2 androgen insensitivity syndrome–associated SC-hyperplasia/adenomas (SCH-AIS); 3 SCT not otherwise specified (SCT-NOS); 3 sclerosing SCT; 2 large cell calcifying SCT; 1 SCT-heterologous sarcomatous-UMP; 1 malignant-SCT, and 1 sertoliform rete testis adenoma (sertoliform RTA). Representative images of each diagnostic category are shown in Fig. 1. The mean age at diagnosis for the neoplastic lesions was 31 (range, 19-59),

Discussion

The epidemiologic findings in our cohort were concordant with the existing literature [4], [5], [6]: most SCT occurred in the 3rd decade, were discovered incidentally or presented with pain. Syndromic cases presented at an earlier age (2nd decade) and the sertoliform RTA much later (7th decade). Most cases pursued a benign course, except for the tumor with all the histologic features associated with aggressive behavior: infiltrative margins, high mitotic activity (20/10 HPF), necrosis and

Conclusions

We found consistent immunophenotypic differences among SCT variants that support their use in the workup of these lesions (Table 4). SCT associated with sclerosis or deposition of basement membrane material resembles the phenotype of SC from atrophic seminiferous tubules, which differs from normal SC by gain of expression of several proteins (pankeratin, CD56, calretinin, nestin). Partial or complete loss of the androgen receptor expression occurs in most SCT suggesting that it represents a

References (11)

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All authors acknowledge substantial participation and responsibility for this work. The authors do not have conflicts of interest to declare. The institutional review board of the Minneapolis VA Health Care System (IRB# 4615B) approved this project on 11/12/15. There are no funding sources to disclose.

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