Testis and epididymis
Sex cord stromal tumors
General

Author: Vikas Mehta, M.D.

Revised: 4 September 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 September 26th, 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 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:
WHO classification
Clinical features
  • Usually presents as testicular mass
  • Unlike ovarian sex cord stromal tumors, functional tumors are generally uncommon except for Leydig cell tumors
Prognostic factors
  • Indolent behavior (unlike germ cell tumors); 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 but only if clinical / radiological evidence of metastatic disease
Immunohistochemistry
  • Vimentin is typically positive but not specific
  • Keratin is frequently positive in Sertoli cell tumors (SCTs), while staining is focal / absent in Leydig cell tumors (LCTs) and granulosa cell tumors (GCTs) and typically negative in fibromas
  • EMA is typically negative (except rare LCTs / SCTs)
  • Inhibin positivity has been shown in juvenile GCTs and LCTs even at metastatic sites but SCTs 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, especially in the differential diagnosis of germ cell tumors
  • FOXL2 positivity and mutations have been detected in GCTs
  • MelanA is often positive in LCTs
  • 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 SCTs (including large cell variant), LCTs 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
  • Sex cord stromal tumors of the testis are typically negative for PAX2 and PAX8

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
  • Testicular sex cord stromal tumors 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)