Table of Contents
Definition / general | Terminology | Epidemiology | Clinical features | Prognostic factors | Case reports | Treatment | Gross description | Immunohistochemistry & special stains | Molecular / cytogenetics description | Sertoli cell tumor (SCT) | Leydig cell tumor (LCT) | Sertoli-Leydig cell tumor (SLCT) | Adult granulosa cell tumor (AGCT) | Juvenile granulosa cell tumor (JGCT) | Fibroma-thecomaCite this page: Mehta V. Sex cord stromal tumors-general. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/testissexcordgeneral.html. Accessed April 1st, 2023.
Definition / general
- Includes neoplasms of pure sex cord and pure stromal type and also those with admixtures of both components in various proportions and degree of differentiation; each strikingly different in clinical features and biology
- Leydig cell tumor is the most common pure testicular sex cord stromal neoplasm (91 - 93% of testicular sex cord stromal neoplasms)
- Some arise in setting of androgen insensitivity syndrome (AIS) or adrenogenital syndrome (AGS); designate as tumor-like lesion occurring in specific syndrome
Terminology
- Terminology 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 tumors
- Malignant Leydig cell tumor
- Sertoli cell tumor
- Malignant Sertoli cell tumor
- Large cell calcifying Sertoli cell tumor
- Intratubular large cell hyalinizing Sertoli cell neoplasia
- Granulosa cell tumor
- Leydig cell tumors
- Tumors of fibroma-thecoma group
- Mixed and unclassified sex cord stromal tumors
- Mixed sex cord stromal tumor
- Unclassified sex cord stromal tumor
- Tumors containing both germ cell and sex cord / gonadal stromal tumor
- Pure tumors
Epidemiology
- Uncommon; 2 - 5% of adult testicular tumors but ~25% of testicular tumors in infants and children
- 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
Clinical features
- Usually presents as testicular mass
- Functional tumors are generally uncommon except for Leydig cell tumors (unlike ovarian sex cord stromal tumors)
Prognostic factors
- 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 or Children's Oncology Group (COG) staging system for germ cell 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)
- 62 year old man with large cell calcifying Sertoli cell tumor (J Clin Diagn Res 2016;10:ED03)
- 78 year old man with adult granulosa cell tumor with a heterologous sarcomatous component (Diagn Pathol 2014;9:107)
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
Gross description
- Sertoli cell tumor (SCT)
- Typically unilateral (exceptions: if associated with Peutz-Jeghers syndrome or some large calcifying SCTs) with a mean diameter of 3.5 cm (typically smaller if associated with Peutz-Jeghers syndrome)
- Well circumscribed, frequently with a lobulated, yellow, tan or white cut surface
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 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 | Vimentin | Actin SM | MelanA | |
Sertoli cell tumor, NOS | + / - | + / - | + / - | + | + | - / + | - |
Leydig cell tumor | + | + | - / + | - / + | + | - | + |
Granulosa cell tumor | + | + | + / - | - / + | + | - / + | - |
Sex cord stromal tumor, NOS | + / - | + / - | + | - / + | + | + | + / - |
Molecular / cytogenetics description
- No pathognomonic findings established
- Lack hotspot mutations inĀ DICER1 (in contrast to ovarian sex cord stromal tumors) (Mod Pathol 2015;28:1603)
Sertoli cell tumor (SCT)
Definition / general
Gross description
Microscopic (histologic) description
Microscopic (histologic) images
Contributed by Vikas Mehta, M.D.
Molecular / cytogenetics description
- See also Sertoli cell tumors
- ≤ 1% of all testicular neoplasms and are rare in children
- Occasionally, they may develop in patients with androgen insensitivity syndrome or in association with Peutz-Jeghers syndrome
Gross description
- Typically unilateral (exceptions: if associated with Peutz-Jeghers syndrome or some large calcifying SCTs) with a mean diameter of 3.5 cm (typically smaller if associated with Peutz-Jeghers syndrome)
- Tumors are well circumscribed, frequently with a lobulated, yellow, tan or white cut surface
Microscopic (histologic) description
- Nodular or diffuse growths with round or elongated hollow, solid (sometimes irregular in size and shape) or retiform tubules
- Cord-like or solid growths may predominate
- Tubules are lined by a single layer of cuboidal to columnar cells with moderate to abundant eosinophilic to pale (lipid accumulation, sometimes forming large vacuoles) cytoplasm
- Stroma may be scanty or abundant with edema or hyalinization; marked sclerosis can occur
Microscopic (histologic) images
Contributed by Vikas Mehta, M.D.
Molecular / cytogenetics description
- Most common changes include gains of chromosomes X and loss of the entirety or part of chromosomes 2 and 19 (Oncol Rep 2007;17:585)
- Both the NOS type as well as sclerosing subtype demonstrate CTNNB1 gene mutations (Am J Surg Pathol 2014;38:1160, Am J Surg Pathol 2014;38:66)
Leydig cell tumor (LCT)
Definition / general
Gross description
Microscopic (histologic) description
Microscopic (histologic) images
Contributed by Vikas Mehta, M.D.
Molecular / cytogenetics description
- See also Leydig cell tumor
- Most common sex cord stromal tumor (2 - 3% of all testicular neoplasms) but only 25% diagnosed beyond age 50
- 15 - 30% of patients develop gynecomastia and children almost always present with isosexual pseudoprecocity
- Approximately 10% of patients have undescended testis or rarely Klinefelter or Turner syndrome
- Only about 3% are bilateral and 10% are malignant (the latter only in adults) (Anal Quant Cytol Histol 2007;29:139, Am J Surg Pathol 1985;9:177)
Gross description
- Usually well circumscribed ranging from 3 to 5 cm with a uniform solid, yellow to tan cut surface
- Lobulation may be grossly seen; areas of hemorrhage or necrosis are seen in approximately 30% of cases
Microscopic (histologic) description
- Often diffuse or nodular growths; in the latter, the stroma may be prominent and extensively hyalinized forming broad bands
- Cells are typically large and polygonal with abundant, slightly granular, eosinophilic cytoplasm but occasionally it is clear (abundant lipid)
- Nuclei are typically round and contain a single prominent nucleolus
- Crystals of Reinke and lipochrome pigment identified in one - third and 10 - 15% of cases respectively (Am J Surg Pathol 2002;26:1424)
Microscopic (histologic) images
Contributed by Vikas Mehta, M.D.
Molecular / cytogenetics description
- Most common changes include gains of chromosomes X, 19 and 19p and losses of chromosomes 8 and 16 (Oncol Rep 2007;17:585)
- Some childhood LCTs have acquired missense mutations in codon 578 of the gene for the luteininzing hormone / choriogonadotropin receptor (LHCGR)
- Rarely LCTs are found to have mutations in the FH gene, either sporadically or as part of the hereditary leiomyomatosis and renal cell carcinoma syndrome (J Clin Endocrinol Metab 2006;91:3071)
Sertoli-Leydig cell tumor (SLCT)
Definition / general
Gross description
Microscopic (histologic) description
- These tumors are rare and their histologic appearance is similar to that seen in their ovarian counterpart
Gross description
- They typically have a solid, yellow and often lobulated cut surface
Microscopic (histologic) description
- Most tumors have tubules, cords and trabeculae in a haphazard arrangement embedded in a stroma that frequently contains Leydig cells
- Most tumors are of intermediate differentiation
- Cellular, neoplastic stroma, sometimes with a Leydig cell component, is diagnostic of SLCT
Adult granulosa cell tumor (AGCT)
Definition / general
Gross description
Microscopic (histologic) description
Microscopic (histologic) images
Contributed by Vikas Mehta, M.D.
Molecular / cytogenetics description
- See also Adult granulosa cell tumor
- This rare tumor occurs in adult males with an average age of 42
- Patients may have a testicular mass for several years or gynecomastia (Clinics (Sao Paulo) 2006;61:77, Hum Pathol 1993;24:1120, Arch Pathol Lab Med 2000;124:1525)
Gross description
- Tumors may be as large as 13 cm and typically they have a homogeneous, yellow-gray or white, firm and lobulated cut surface and cysts may be present
Microscopic (histologic) description
- Appearance is similar to ovarian adult granulosa cell tumors; more common patterns include diffuse or microfollicular with Call-Exner bodies
- Cells typically have scant cytoplasm and elongated nuclei with frequent grooves; mitotic rate is generally low
- Tumors may have a prominent fibromatous or fibrothecomatous background as seen in the ovary (Clinics (Sao Paulo) 2006;61:77, Hum Pathol 1993;24:1120, Arch Pathol Lab Med 2000;124:1525)
- Gross or microscopic features associated with aggressive behavior include size > 7 cm, vascular or lymphatic invasion and hemorrhage or necrosis (Hum Pathol 2008;39:701)
Microscopic (histologic) images
Contributed by Vikas Mehta, M.D.
Molecular / cytogenetics description
- Acquired FOXL2 mutations have been identified in a smaller proportion of these tumors than in their ovarian counterpart (Arch Pathol Lab Med 2012;136:825)
Juvenile granulosa cell tumor (JGCT)
Definition / general
Gross description
Microscopic (histologic) description
- See also Juvenile granulosa cell tumor
- Most common neoplasm of the testis during the first 6 months; almost all tumors are diagnosed during the first year of life and only occasionally seen in older children or adults
- Approximately 20% of tumors occur in neonates with sex chromosome abnormalities affecting the Y chromosome and ambiguous genitalia (Drash syndrome) and nearly 40% occur in cryptorchid testes; no malignant cases reported (Am J Surg Pathol 1985;9:87, Am J Surg Pathol 1996;20:72, Am J Surg Pathol 1986;10:577, Am J Surg Pathol 1985;9:737)
Gross description
- Tumors measure up to 6.5 cm in largest dimension
- May be solid (yellow-orange or tan-white), cystic or both
Microscopic (histologic) description
- Solid, nodular or follicular patterns are the most common and sometimes alternate
- Follicles vary from large and round / oval to small and irregular containing basophilic or eosinophilic secretion (mucicarmine+)
- In solid or nodular areas, the cells grow in sheets or irregular clusters
- Cells have moderate to large amounts of pale to eosinophilic cytoplasm, round to oval hyperchromatic nuclei, some of which contain nucleoli
- Mitoses are common in contrast to AGCT
- Extensive hyalinization (forming nodules) and prominent myxoid background may be seen (Am J Surg Pathol 1985;9:87, Am J Surg Pathol 1996;20:72, Am J Surg Pathol 1986;10:577, Am J Surg Pathol 1985;9:737)
Fibroma-thecoma
Definition / general
Gross description
Microscopic (histologic) description
- See also Fibromas
- Uncommon tumors in contrast to their ovarian counterpart
- Thecomas are truly exceptional
- Patients present with symptoms and signs related to a testicular mass (Am J Surg Pathol 2013;37:1208)
Gross description
- Variable sized, typically well circumscribed but not encapsulated with a firm, white-tan to yellow cut surface
Microscopic (histologic) description
- Spindle shaped fibroblasts growing in a storiform pattern with variable amounts of collagen or edema but they can also grow in short fascicles
- They may be cellular and also have ≤ 2 mitoses/10 HPFs
- They may entrap seminiferous tubules (Am J Surg Pathol 2013;37:1208)