Sertoli Cell Tumours of the Testis (WHO 2022): NOS, Large Cell Calcifying, Sertoli Cell Nodule, IHC, Virtual Slides and MCQs

Sertoli cell tumours

Subtitle: Sertoli cell tumours of the testis (WHO 2022): Sertoli cell tumour NOS and CTNNB1, large cell calcifying Sertoli cell tumour (PRKAR1A, Carney complex), sclerosing pattern, Sertoli cell nodules, IHC panel, malignancy criteria, mimics, virtual slides and 8 MCQs.

Author: PathologyMCQ Editorial Board

Category: Urological Pathology

Last Updated: October 2026

Read Time: 6 minutes

At-a-Glance

  • Sertoli cell tumour NOS: tubules, cords and sheets in a fibrous or hyalinised stroma; CTNNB1 mutation with nuclear beta-catenin in most; about 10% malignant.
  • Large cell calcifying SCT: young patients, large eosinophilic cells, laminated calcification, S100+; 40% syndromic (Carney complex, Peutzโ€“Jeghers).
  • Sertoli cell nodule: non-neoplastic, incidental, in cryptorchid and Klinefelter testes.
  • Sex cord markers (SF1, SOX9, WT1, inhibin, calretinin) positive; germ cell markers negative.

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Sertoli cell tumours are rare sex cord-stromal tumours of the testis. WHO 2022 recognises Sertoli cell tumour NOS (which includes the sclerosing pattern) and large cell calcifying Sertoli cell tumour. The non-neoplastic Sertoli cell nodule is a common mimic that must not be called a tumour.

Sertoli Cell Tumour NOS

  • Age: adults, mean about 45 years; usually a painless mass, rarely hormonal symptoms.
  • Histology: well-formed tubules, cords and solid nests of cells with pale to eosinophilic or lipid-rich cytoplasm, in a fibrous, hyalinised or oedematous stroma. The sclerosing pattern (formerly sclerosing Sertoli cell tumour) shows small tubules and cords in dense hyalinised stroma and behaves indolently.
  • Molecular: CTNNB1 exon 3 mutation in 60โ€“70%, with nuclear beta-catenin on IHC.
  • Behaviour: about 10% metastasise, usually to retroperitoneal nodes.

Large Cell Calcifying Sertoli Cell Tumour

  • Age: usually under 20; 40% syndromic (Carney complex with PRKAR1A mutation, Peutzโ€“Jeghers syndrome), then often bilateral and multifocal.
  • Histology: large polygonal cells with abundant eosinophilic to amphophilic cytoplasm in cords, trabeculae and nests; myxoid to sclerotic stroma; laminated calcification; a neutrophil-rich infiltrate.
  • IHC: strong diffuse S100, calretinin and inhibin; androgen receptor negative in tumour cells.
  • Behaviour: usually benign; malignant cases are sporadic, unilateral, in older patients, with size >4 cm, atypia, necrosis, vascular invasion and mitoses >3/10 HPF.

Sertoli Cell Nodule (Not a Tumour)

  • Incidental, usually microscopic aggregates of hypoplastic tubules lined by immature Sertoli cells with thick basement membranes and often laminated calcospherites, in cryptorchid, infertile or Klinefelter testes.
  • Tubules may contain scattered germ cells; the nodule lacks a mass, atypia and mitoses.
  • Report as “Sertoli cell nodule” to avoid an unnecessary diagnosis of tumour.

Criteria for Malignancy in Sertoli Cell Tumour NOS

Features predicting malignant behaviour (two or more)
FeatureThreshold
Size>5 cm
NecrosisPresent
Vascular invasionPresent
Nuclear atypiaModerate to severe
Mitoses>5 per 10 HPF
GrowthInfiltrative margins

Metastasis is the only certain proof of malignancy; the tumour may show only focal tubular differentiation, with gain of cytokeratin and neuroendocrine markers and loss of androgen receptor.

IHC and Mimics

Sertoli cell tumours and their mimics
TumourKey histologyIHC
Sertoli cell tumour NOSTubules and cords, hyalinised stromaSF1, SOX9, WT1, calretinin, inhibin (variable), nuclear beta-catenin; OCT4โˆ’, SALL4โˆ’
Large cell calcifying SCTLarge eosinophilic cells, laminated calcification, neutrophilsS100 strong, inhibin, calretinin; ARโˆ’
Leydig cell tumourPolygonal eosinophilic cells, lipofuscin, Reinke crystalsInhibin, calretinin, Melan-A; beta-catenin membranous
Seminoma (tubular pattern)Clear cells, fibrous septa, lymphocytesOCT4, SALL4, CD117, PLAP; sex cord markers negative
Adenomatoid tumourVacuolated cells in tubules and cords, paratesticularCalretinin, WT1, D2-40, cytokeratin; inhibinโˆ’
Adult granulosa cell tumourMicrofollicles, Callโ€“Exner bodies, grooved nucleiInhibin, calretinin, FOXL2 mutation

Virtual Slides

Normal Sertoli cells within seminiferous tubules, and an adenomatoid tumour, the commonest paratesticular mimic of a tubular sex cord tumour.

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Test Yourself: 8 MCQs

Sertoli cell tumours: 8 MCQs

Subtypes, nodules, IHC, molecular and malignancy criteria, with instant explanations.

Score: 0 / 8

More practice: the question banks โ†’

Exam Pearls

  • SCT NOS: CTNNB1, nuclear beta-catenin; 10% malignant.
  • LCCSCT: young, calcified, S100+, Carney/PJS.
  • Sertoli cell nodule = cryptorchid testis, not a tumour.
  • Reinke crystals = Leydig. OCT4 = germ cell.
  • Malignancy: >5 cm, necrosis, LVI, atypia, >5 mitoses.

For tips, pitfalls, notes, reporting templates and worksheets, join the approach-based course in histopathology and cytology โ†’, and see the Histopathology Notes, volumes 1 and 2 โ†’

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References

  • WHO Classification of Tumours Editorial Board. Urinary and Male Genital Tumours. 5th ed. IARC; 2022.
  • Young RH, Koelliker DD, Scully RE. Sertoli cell tumors of the testis, not otherwise specified: a clinicopathologic analysis of 60 cases. Am J Surg Pathol. 1998;22:709โ€“21.
  • Perrone F, et al. Frequent mutation and nuclear localization of beta-catenin in Sertoli cell tumors of the testis. Am J Surg Pathol. 2014;38:66โ€“71.

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