Testis & paratestis
Nonneoplastic lesions
Sertoli cell nodule
Author: Swapnil U. Rane, M.D.
Last author update: 1 October 2013
Last staff update: 7 September 2023 (update in progress)
Copyright: 2002-2023, PathologyOutlines.com, Inc.
PubMed Search: Sertoli cell nodule pathology
Table of Contents
Definition / general | Terminology | Epidemiology | Pathophysiology | Clinical features | Laboratory | Prognostic factors | Case reports | Treatment | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Negative stains | Electron microscopy images | Differential diagnosisCite this page: Rane SU. Sertoli cell nodule. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/testissertolihyperplasia.html. Accessed September 30th, 2023.
Definition / general
- Nonneoplastic proliferation of Sertoli cells within seminiferous tubules, without any identifiable germ cells
Terminology
- Synonyms:
- Picks adenoma
- Sertoli cell nodule
- Intratubular Sertoli Cell Proliferations (ISCP)
- Testicular tubular adenoma
- Tubular adenoma of testis
- Nodules of immature tubules
- Though termed "adenoma," are not clonal (Diagnostic Criteria Handbook in Histopathology: A Surgical Pathology Vade Mecum)
Epidemiology
- Ages 4 to 35 years (mean / median: 22 years) (J Clin Pathol 2004;57:802)
- Common in undescended testis (~60%) but also present in otherwise normally descended testis
- Associated with
- McCune-Albright syndrome (MAS) (J Clin Endocrinol Metab 2001;86:1778)
- Complete Androgen Insensitivity Syndrome / Testicular feminization syndrome (Eur J Obstet Gynecol Reprod Biol 2004;114:104, Int J Gynecol Pathol 2001;20:196, Pathol Res Pract 1984;178:403, J Pediatr Urol 2013;9:e31)
- Peutz-Jeghers syndrome (Am J Surg Pathol 2001;25:1237)
Pathophysiology
- Associated with McCune-Albright, Peutz-Jeghers and Androgen insensitivity syndromes but no molecular cause has been identified
Clinical features
- Usually incidental finding in enlarged testis excised for suspicion of malignancy or orchidectomy performed in patient with Androgen Insensitivity Syndrome or cryptorchidism
- Androgen insensitivity syndrome: phenotypically female
- Peutz-Jeghers syndrome: multiple testicular nodules; may have gynecomastia and other signs of estradiol excess
Laboratory
- Commonly elevated serum estradiol, low androgen levels
- Serum levels of anti-Müllerian hormone and inhibin B may be elevated in some cases and can be used to monitor the evolution of this lesion
- Serum AFP, β HCG and LDH are not elevated and are useful negative biomarkers to rule out germ cell tumors, which are more common
Prognostic factors
- Most cases are nonneoplastic, with no potential for malignant transformation or metastases; prognosis is based on associated condition
- Isolated case reports of development of Intratubular Large cell Sertoli cell neoplasia within otherwise classical ISCP or an associated invasive Sertoli cell tumor but no reports of progression for up to 10 years, even without orchidectomy (Am J Surg Pathol 2001;25:1237)
Case reports
- Associated with Androgen Insensitivity Syndromes:
- 16 year old girl with complete androgen insensitivity syndrome associated with bilateral Sertoli cell adenomas and paratesticular leiomyomas (J Pediatr Urol 2013;9:e31)
- 22 year old woman with androgen receptor gene mutation associated with complete androgen insensitivity syndrome and Sertoli cell adenoma (Int J Gynecol Pathol 2001;20:196)
- 30 year old woman with bilateral Sertoli cell adenoma and serous cyst and androgen insensitivity syndrome (Eur J Obstet Gynecol Reprod Biol 2004;114:104)
- Testicular feminization syndrome with Sertoli cell adenoma (Pathol Res Pract 1984;178:403)
- Associated with McCune-Albright Syndrome:
- 3 year old boy with macroorchidism due to autonomous hyperfunction of Sertoli cells and G(s)alpha gene mutation (J Clin Endocrinol Metab 2001;86:1778)
- Associated with Peutz-Jeghers syndrome:
- Sertoli cell proliferations of the infantile testis (Am J Surg Pathol 2001;25:1237)
- Intratubular large cell hyalinizing Sertoli cell neoplasia of the testis (Am J Surg Pathol 2007;31:827)
Treatment
- Not needed (conservative approach), since nonneoplastic, and usually an incidental finding
Gross description
- Sertoli cell nodules are usually microscopic but larger nodules may be identified grossly
- Rarely Sertoli cell hyperplasia replaces entire testis
- Presence of multiple nodules giving rise to a nodular testis has been reported with Peutz-Jeghers syndrome
Gross images
Images hosted on other servers:
Demarcated bulging pale yellowish nodules
Sharply demarcated yellowish white nodule
Microscopic (histologic) description
- Unencapsulated nodules composed of Sertoli cells arranged in well formed tubules that vaguely resemble immature Sertoli cells
- Bland hyperchromatic oval / round nuclei that are stratified with variable eosinophilic (hyaline) blob in lumen
- Tubules have thickened basement membrane, which invaginates within lumen, so that basement membrane-like material appears to be within the lumen and may be mistaken for a Call-Exner body
- No / rare germ cells admixed with immature Sertoli cells
- Adjacent testis commonly shows atrophy with hypospermatogenesis or total absence of spermatogenesis
- Usually clusters of Leydig cells between the tubules, at least focally; rarely Leydig cell hyperplasia (which confirms a nonneoplastic process)
Microscopic (histologic) images
Contributed by Jian-Hua Qiao, M.D.
Hyperplastic Sertoli cells
Atrophic seminiferous tubules
Persistent immature tubules
Hyalinization of basement membrane
Atrophic seminiferous tubules
Images hosted on other servers:
Sertoli cell nodule
Sertoli cell nodule
Boundary with normal testis
Round to elongated nuclei
Thickened basement membrane
Positive stains
- Anti-Müllerian hormone (Am J Surg Pathol 2001;25:1237), inhibin A
- CK8, CK18 (immature Sertoli cells only); AE1 / AE3
Negative stains
- Useful negative markers include α fetoprotein, β hCG, p53
Electron microscopy images
Images hosted on other servers:
Thickened multilamellar basement membranes
Hyaline core
Differential diagnosis
- Gonadoblastoma
- Nested arrangement of large atypical germ cells, similar to seminoma cells with small cells resembling immature Sertoli cells and granulosa cells
- Associated with mixed gonadal dysgenesis
- Large cell calcifying Sertoli cell tumor
- Polygonal cells with abundant eosinophilic cytoplasm
- Relatively large nuclei with prominent nucleoli
- Myxoid to fibrous stroma with scattered, large, irregularly shaped islands of calcification
- Sclerosing Sertoli cell tumor
- Prominent collagenous background
- May contain focal entrapped nonneoplastic tubules, lined by immature Sertoli cells and germ cells but is a focal finding
- Sclerotic stroma and not an accumulation of basal membrane substance
- Sertoli cell tumor NOS
- Lacks fetal phenotype
- No prominent internalized basement membrane component
- May have interspersed germ cells, secondary to incorporation of nonneoplastic elements, typically at periphery
- Occurs in clusters that usually lack intratubular arrangement
