Testis & paratestis
Sex cord stromal tumors
Intratubular large cell hyalinizing Sertoli cell neoplasia
Editor-in-Chief: Debra L. Zynger, M.D.
Last author update: 18 November 2019
Last staff update: 3 August 2023 (update in progress)
Copyright: 2019-2023, PathologyOutlines.com, Inc.
PubMed Search: Intratubular large cell Sertoli
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Pathophysiology | Etiology | Clinical features | Diagnosis | Laboratory | Radiology description | Prognostic factors | Case reports | Treatment | Gross description | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Negative stains | Molecular / cytogenetics description | Sample pathology report | Differential diagnosis | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Vormittag-Nocito E, Kajdacsy-Balla A. Intratubular large cell hyalinizing Sertoli cell neoplasia. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/testisitlchscn.html. Accessed September 26th, 2023.
Definition / general
- A sex cord stromal tumor of the testis that is composed of an intratubular neoplastic proliferation of large Sertoli cells and prominent basement membrane deposits occurring almost exclusively in patients with Peutz-Jeghers syndrome (Moch: WHO Classification of Tumours of the Urinary System and Male Genital Organs, 4th Edition, 2016)
Essential features
- Benign, multifocal and often bilateral testicular lesion
- Found in prepubertal males, usually associated with gynecomastia
- Associated with Peutz-Jeghers syndrome
Terminology
- Accepted: intratubular large cell hyalinizing Sertoli cell neoplasia or intratubular large cell hyalinizing Sertoli cell tumor
- Historically: sex cord tumor with annular tubules (not recommended)
ICD coding
Epidemiology
- Males
- Age: most are prepubertal
- Associated with Peutz-Jeghers syndrome (Moch: WHO Classification of Tumours of the Urinary System and Male Genital Organs, 4th Edition, 2016)
Sites
- Seminiferous tubules
Pathophysiology
- Unknown
Etiology
- STK11 mutations seen in Peutz-Jeghers syndrome predispose to proliferation
Clinical features
- Estrogenic clinical manifestations (Am J Surg Pathol 2007;31:827):
- Gynecomastia
- Advanced bone age
- Increased growth velocity
- Other clinical manifestations of Peutz-Jeghers syndrome
Diagnosis
- Testis biopsy or orchiectomy; microscopic diagnosis (Am J Surg Pathol 2007;31:827)
Laboratory
- Increased estradiol level
Radiology description
- In situ disease not identified by imaging, except sometimes by ultrasound (Semin Diagn Pathol 2014;31:323)
- Can be followed by ultrasound for invasion (Am J Surg Pathol 2007;31:827)
Prognostic factors
- Considered a benign condition, unknown what makes rare cases invasive
Case reports
- 4 year old boy with gynecomastia, increased serum estrogens and advanced bone age (N Engl J Med 1991;324:317)
- 4 year old Native American boy with increased serum estrogens, gynecomastia and advanced bone age (J Pediatr Hematol Oncol 2015;37:e184)
- 6 year old boy with increased serum estrogen (first recorded case) (Cancer 1980;46:223)
- 8 year old boy with gynecomastia, advanced bone age, increased growth velocity and increased testicular volume (Acta Clin Belg 2017;72:254)
Treatment
- Aromatase inhibitor therapy initial treatment
- Orchiectomy for nonresponders with continued / progressive clinical estrogen symptoms (Am J Surg Pathol 2007;31:827)
Gross description
- May feel areas of firmness up to a few millimeters but tubules have normal gross morphology (Moch: WHO Classification of Tumours of the Urinary System and Male Genital Organs, 4th Edition, 2016)
Microscopic (histologic) description
- Scattered expanded seminiferous tubules 4 - 5x normal diameter (Am J Surg Pathol 2007;31:827, Moch: WHO Classification of Tumours of the Urinary System and Male Genital Organs, 4th Edition, 2016)
- Large Sertoli cells (Am J Surg Pathol 2007;31:827)
- Pale to eosinophilic cytoplasm
- Uniform nuclei
- Fine chromatin
- Thickened basement membrane (Am J Surg Pathol 2007;31:827)
- Projections of basement membrane into lumen forming eosinophilic deposits
- No mitotic figures
- Rare calcification in basement membrane deposits only (Am J Surg Pathol 2007;31:827)
Microscopic (histologic) images
Contributed by Vikas Mehta, M.D.
Seminiferous tubules
Basement membrane deposition
Calretinin
Inhibin A
Collagen IV
PAS
Positive stains
- Inhibin A
- Aromatase
- Calretinin: patchy positivity
- Cytokeratin AE1 / AE3
- MelanA
- Collagen IV and PAS stains highlight basement membrane deposition (Moch: WHO Classification of Tumours of the Urinary System and Male Genital Organs, 4th Edition, 2016)
Negative stains
- Not well studied in literature
Molecular / cytogenetics description
- STK11 mutations in nearly 100% of cases (Am J Surg Pathol 2007;31:827)
Sample pathology report
- Testis, right, core needle biopsy:
- Intratubular large cell hyalinizing Sertoli cell neoplasia
Differential diagnosis
- Large cell calcifying Sertoli cell tumor:
- Associated with Carney complex
- Invasive malignancy
- Larger and more readily identifiable calcium deposits
- Sertoli cell nodules / adenoma:
- Associated with cryptorchid testes
- Small, fetal type Sertoli cells
- Spermatogonia present
- Can have basement membrane deposition
- Gonadoblastoma:
- Prominent deposits of basement membrane
- Tubular-like arrangement
- Associated with intersex disorder
- Morphology of small sex cord cells and large seminoma-like cells
Board review style question #1
What diagnosis is associated with a 4 year old patient who presents with pigmented macules around the lips and oral mucosa, gynecomastia and the following findings on testis biopsy?
- Gonadoblastoma
- Intratubular large cell hyalinizing Sertoli cell neoplasia
- Large cell calcifying Sertoli cell neoplasm
- Sertoli cell nodule
Board review style answer #1
B. Intratubular large cell hyalinizing Sertoli cell neoplasia. The patient has Peutz-Jeghers syndrome and the testicle shows intratubular large cell hyalinizing Sertoli cell neoplasia. The image shows a tubule composed of large Sertoli cells without normal spermatogonia and spherules of basement membrane-like material characteristic of this entity.
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Board review style question #2
Which of the following symptoms is most associated with intratubular large cell hyalinizing Sertoli cell neoplasia?
- Gynecomastia
- Mucosal ulcers
- Normal age of puberty
- Short stature
Board review style answer #2
A. Gynecomastia. This is a symptom seen due to the elevated serum estradiol level in these patients.
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