Testis & paratestis
Sex cord stromal tumors
Sex cord stromal tumors-general
Editorial Board Member: Debra L. Zynger, M.D.
Deputy Editor-in-Chief: Maria Tretiakova, M.D., Ph.D.
Last author update: 25 April 2023
Last staff update: 25 April 2023
Copyright: 2002-2023, PathologyOutlines.com, Inc.
PubMed Search: Sex cord stromal tumors
Table of Contents
Definition / general | Essential features | Terminology | Epidemiology | Sites | Pathophysiology | Etiology | Clinical features | Diagnosis | Prognostic factors | Case reports | Treatment | Immunohistochemistry & special stains | Molecular / cytogenetics descriptionCite this page: Gupta P, Mehta V. Sex cord stromal tumors-general. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/testissexcordgeneral.html. Accessed September 21st, 2023.
Definition / general
- Includes neoplasms of pure sex cord and pure stromal type as well as those with admixtures of both components in various proportions and degree of differentiation, each strikingly different in clinical features and biology
- Sex cord elements are usually positive for steroid producing immunohistochemical cell markers (e.g., inhibin, SF1); in addition, the presence of stromal elements is easily confirmed by a reticulin stain that shows the framework surrounding individual tumor cells
- Some arise in the setting of androgen insensitivity syndrome (AIS) or adrenogenital syndrome (AGS), designated as tumor-like lesion occurring in specific syndrome
Essential features
- Includes neoplasms of pure sex cord and pure stromal type as well as those with admixtures of both components
- Uncommon testicular tumors with a greater proportion in children (25%)
- Typically show indolent behavior; only 5% are malignant
- Usually positive for steroid producing immunohistochemical cell markers (e.g., inhibin, SF1)
Terminology
- Terminology is analogous to ovarian sex cord stromal tumors but some tumors occur almost exclusively in testis (large cell calcifying Sertoli cell tumor and sclerosing Sertoli cell tumor), while others are extremely uncommon in testis (lipid rich Sertoli cell tumor) (Korean J Pathol 2014;48:50, Mod Pathol 2005;18:S81)
- Broadly divided as pure (only 1 type) or mixed (2+ types)
- Classification
- Pure tumors
- Leydig cell tumor
- Sertoli cell tumors
- Granulosa cell tumors
- Fibroma thecoma group
- Mixed and other sex cord stromal tumors
- Mixed sex cord stromal tumor
- Signet ring stromal carcinoma
- Myoid gonadal stromal tumor
- Sex cord stromal tumor, NOS
- Pure tumors
Epidemiology
- Uncommon; accounts for ≤ 5% of all testicular tumors, with a greater proportion (~25%) seen in children (Can Urol Assoc J 2017;11:E344, Urology 2009;73:1165)
- Of these, Leydig cell tumors constitute about 75% and Sertoli cell tumors are the next most common
- Wide age range in general but
- Juvenile granulosa cell tumor is the most common congenital testicular tumor; more common in neonates and infants, associated with ambiguous genitalia or abnormalities of sex chromosomes
- Sertoli cell tumors are common before age 1; associated with Peutz-Jeghers syndrome and Carney complex
- Leydig cell tumors are most common in the third to fifth decade of life
Sites
- Testis
Pathophysiology
- Poor gonadal development may lead to testicular cancer; this follows the hypothesis of testicular dysgenesis syndrome
- Various histologic studies show dysgenetic features such as undifferentiated tubules, immature Sertoli cells, etc. in testicular cancer
- Altered functioning of somatic cells (Leydig and Sertoli) due to mutations / polymorphism, along with environmental and lifestyle factors, act during early development; these dysfunctioning somatic cells lead to disturbed hormone balance leading to altered germ cell differentiation (Semin Cell Dev Biol 2015;45:124)
Etiology
- Usually unknown
- Not associated with undescended testicle (Arch Pathol Lab Med 2007;131:311)
Clinical features
- Usually presents as testicular mass
- Functional tumors are generally uncommon, except for Leydig cell tumors (unlike ovarian sex cord stromal tumors)
Diagnosis
- Tumor histology and immunohistochemistry
Prognostic factors
- Usually indolent behavior; 5% are malignant
- Morphologic prognostic factors include size, mitotic rate, necrosis, cellular atypia, infiltrative borders and vascular invasion
- Stage is the most important prognostic factor
- Stage with TNM for malignant tumors
Case reports
- 7 year old boy with malignant large cell calcifying Sertoli cell tumor (Urology 2018;117:145)
- 22 year old man with adult granulosa cell tumor (Am J Case Rep 2014;15:471)
- 27 year old man with large mixed sex cord stromal tumor (Pan Afr Med J 2017;27:51)
- 45 year old man with testicular adult granulosa cell tumor (Urol Case Rep 2021;41:101972)
- 62 year old man with large cell calcifying Sertoli cell tumor (J Clin Diagn Res 2016;10:ED03)
Treatment
- High inguinal orchidectomy is treatment of choice
- Testicular sparing surgery may be attempted in small tumors
- Retroperitoneal lymph node dissection if clinical / radiological evidence of metastatic disease
Immunohistochemistry & special stains
- Vimentin is typically positive but not specific
- Keratin is frequently positive in Sertoli cell tumors, while staining is focal / absent in Leydig cell tumors and granulosa cell tumors and typically negative in fibromas
- EMA is typically negative
- Inhibin positivity has been shown in juvenile granulosa cell tumors and Leydig cell tumors even at metastatic sites but Sertoli cell tumors are not uniformly positive (25 - 90%)
- Calretinin in postpuberal testis is expressed in Leydig cells but less commonly in Sertoli cells
- SF1 is highly specific (negative in germ cell tumors)
- FOXL2 positivity and mutations have been detected in granulosa cell tumors
- MelanA is often positive in Leydig cell tumors
- CD99 is expressed in normal Sertoli and granulosa cells and in testicular sex cord stromal tumors but it is not a reliable marker for sex cord stromal tumors
- S100 may stain normal Sertoli and Leydig cells and rete testis, as well as Sertoli cell tumors (including large cell variant), Leydig cell tumors and sex cord stromal tumors - unclassified
- Fibrothecomas are often positive for inhibin (patchy to diffuse), calretinin and keratin; they can also stain for MelanA, BCL2, CD34, S100, muscle specific actin and desmin
- PAX2 and PAX8 are typically negative
- SALL4 is negative (positive in germ cell tumors)
| Immunohistochemistry of sex cord stromal tumors | |||||||||
| Calretinin | Inhibin | S100 | Keratin | SF1 | Vimentin | SMA | FOXL2 | MelanA | |
| Sertoli cell tumor | + / - | + / - | + / - | + | + | + | - / + | - | |
| Large cell calcifying Sertoli cell tumor | + | + | + / - | + / - | + | + | + | ||
| Leydig cell tumor | + | + | + / - | + / - | + | + / - | - | + | |
| Adult granulosa cell tumor | + | + | + / - | - / + | + | + | - / + | + / - | - |
| Juvenile granulosa cell tumor | + | + | + | + | |||||
| Fibroma thecoma tumors | + | + / - | + / - | + | + | ||||
| Mixed and unclassified sex cord stromal tumors | + | + | + | + | |||||
| Sex cord stromal tumor, NOS | + / - | + / - | + | - / + | + | + | + | + | + / - |
| Myoid stromal tumor | + / - | + | + | + | |||||
- Reference: Adv Anat Pathol 2021;28:258
Molecular / cytogenetics description
- No pathognomonic findings established
- Lack hotspot mutations in DICER1 (in contrast to ovarian sex cord stromal tumors) (Mod Pathol 2015;28:1603)
