Testis and epididymis
Sex cord stromal tumors
General

Author: Vikas Mehta, M.D.

Revised: 13 November 2018, last major update September 2018

Copyright: (c) 2002-2018, PathologyOutlines.com, Inc.

PubMed Search: Testis sex cord stromal tumors [TIAB]

Cite this page: Mehta, V. Sex cord stromal tumors - general. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/testissexcordgeneral.html. Accessed December 11th, 2018.
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
Epidemiology
  • Uncommon; 2 - 5% of adult testicular tumors but ~25% of testicular tumors in infants and children
  • Wide age range in general but:
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
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
  • 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
  • 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

Images hosted on PathOut server:

Contributed by Vikas Mehta, M.D.

Diffuse and trabecular growth



Molecular / cytogenetics description
Leydig cell tumor (LCT)
Definition / general
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

Images hosted on PathOut server:

Contributed by Vikas Mehta, M.D.

Solid sheets of tumor cells

Significant cytologic atypia



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
  • See also Sertoli-Leydig cell tumor
  • 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
  • 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

Images hosted on PathOut server:

Contributed by Vikas Mehta, M.D.

Diffuse growth pattern



Molecular / cytogenetics description
Juvenile granulosa cell tumor (JGCT)
Definition / general
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
  • 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)