Sex Cord-Stromal Tumors of the Testis - Departments of Pathology ...

Sex Cord-Stromal Tumors of the Testis 

Charles Zaloudek, M.D. 

Professor, Department of Pathology 

University of California, San Francisco 

505 Parnassus Ave., M563 

San Francisco, CA 94143 

Charles.zaloudek@ucsf.edu 

Sex cord stromal neoplasms are uncommon testicular tumors, accounting for only a 

few percent of all testicular tumors. These tumors occur over a wide age range, from children 

to the elderly. The clinical presentation is generally due to discovery of a testicular mass. 

Functional tumors are uncommon. The classification of testicular sex cord-stromal tumors is 

somewhat reminiscent of the classification of ovarian sex cord-stromal tumors, which are 

considerably more common. Thus, most pathologists are familiar with the terminology even 

though they may have little experience with these tumor types in the testis. We use the WHO 

classification, which is given below. 

Sex Cord-Gonadal Stromal Tumors of the Testis 

Leydig cell tumor 

Malignant Leydig cell tumor 

Sertoli cell tumor 

Lipid rich Sertoli cell tumor 

Sclerosing Sertoli cell tumor 

Large cell calcifying Sertoli cell tumor 

Malignant Sertoli cell tumor 

Granulosa cell tumor 

Juvenile granulosa cell tumor 

Adult type granulosa cell tumor 

Tumors of fibroma/thecoma group 

Thecoma 

Fibroma 

Unclassified sex cord-gonadal stromal tumor 

Leydig Cell Tumor 

The Leydig cell tumor is the most common testicular sex cord-stromal tumor. (Al- 

Agha and Axiotis 2007) There are two age peaks, one in children and one in adults, although 

the ages of adults with these tumors vary over a wide age range from 20 to 60 years. Children 

present with small tumors and almost always have isosexual precocity caused by androgen 

(usually testosterone) secreted by the tumor. About 10% have gynecomastia due to estrogen 

production by the tumor. Adults usually present with a testicular mass. About 30% have 

gynecomastia, which tends to be detected before the testicular tumor. A majority of adult 

Zaloudek Testis Sex Cord‐Stromal Tumors Page 1

patients have abnormal serum levels of steroid hormones, with about a third of patients 

having increased serum androgens and a third, particularly those with gynecomastia, having 

elevated serum estrogen levels. (Suardi, Strada et al. 2009) Leydig cell tumors are more 

common in patients with cryptorchidism, testicular atrophy, and infertility. Some Leydig cell 

tumors occur in patients with germline fumarate hydratase mutations; (Carvajal-Carmona, 

Alam et al. 2006) these patients are also predisposed to hereditary leiomyomatosis and renal 

cell carcinoma. 

Grossly, Leydig cell tumors are generally in the 2-5 cm range, with an average 

diameter of 3 cm. (Kim, Young et al. 1985) A few are larger, measuring up to 10 cm. On cut 

section, the testis contains a yellow, brown, or tan solid nodule. Many tumors have a 

characteristic yellow-brown color due to the presence of lipofuscin in the tumor cells. 

Hemorrhage and necrosis can be present. As would be anticipated, Leydig cell tumors are 

smaller in children. Leydig cell tumors are occasionally extratesticular. Gross features that 

are suggestive of malignancy include large size, an infiltrative edge, necrosis, and 

extratesticular extension. (Al-Agha and Axiotis 2007) 

Microscopically, the tumor cells grow mainly in sheets, but other patterns include 

pseudoglandular, trabecular, and nodular growth. (Kim, Young et al. 1985) The nodules are 

separated by fibrous stroma. At low magnification, some tumors appear circumscribed, 

others push into the surrounding testicular parenchyma, and others infiltrate the surrounding 

testis. Rare patterns include growth in cords and trabeculae, formation of vague follicles, 

microcystic growth, (Billings, Roth et al. 1999) which can be confused with yolk sac tumor, 

and a spindle cell pattern, which can be either focal or be present extensively. (Ulbright, 

Srigley et al. 2002) In most tumors the cells are large and polygonal with abundant 

eosinophilic cytoplasm and round nuclei with prominent nucleoli. Some tumors contain large 

cells with abundant foamy pale cytoplasm and smaller nuclei resulting in an adrenal cortical 

like appearance, and in others the cells have round hyperchromatic nuclei and less abundant 

cytoplasm. The nuclei tend to be relatively uniform and mitotic figures are usually 

infrequent. Finely granular yellow brown lipofuscin pigment is present in the tumor cell 

cytoplasm in some cases. Lipofuscin has a red purple granular appearance in sections stained 

with a PAS stain. Crystalloids of Reinke are eosinophilic rod-shaped cytoplasmic structures 

that are the most definitive light microscopic marker of Leydig cell differentiation. 

Unfortunately, they can be identified in only about 40% of Leydig cell tumors. Rare Leydig 

cell tumors have clear cytoplasm, potentially leading to confusion with seminoma. Fat, 

calcifications, and osseous metaplasia sometimes present. (Ulbright, Srigley et al. 2002) 

Often, the fat appears to result from accumulation of lipid in the tumor cells. 

Immunohistochemistry is useful in the diagnosis of Leydig cell tumors. Positive 

markers include inhibin, calretinin, and melan-A. (Busam, Iversen et al. 1998; Iczkowski, 

Bostwick et al. 1998; McCluggage, Shanks et al. 1998; Augusto, Leteurtre et al. 2002) We 

have had good luck staining Leydig cell tumors with steroidogenic factor-1. CD99 is 

positive, with staining of tumor cell membranes in about 2/3 of cases. Most Leydig cell 

tumors show positive staining for vimentin. Other staining reactions that have been reported 

include staining for chromogranin (>90%), synaptophysin (70%), S100 (8% in one study, 

62% in another) and cytokeratin (~ 40%). (Iczkowski, Bostwick et al. 1998) 


UCSF Immunostain Panel for Leydig Cell Tumor 

Stain Anticipated Result 

Inhibin Positive, cytoplasmic 

Steroidogenic factor-1 Positive, nuclear 

Melan-A Positive, cytoplasmic, granular 

Cytokeratin cocktail Negative (but 30-40% positive) 

Epithelial Membrane Antigen Negative 

Malignant Leydig cell tumors are most common in older patients. (Cheville, Sebo et 

al. 1998) Tumors that occur in patients with gynecomastia are more likely to be benign. No 

clinically malignant Leydig cell tumors have occurred in prepuberal children, although one 

tumor in a 1-year-old boy appeared histologically malignant. (Drut, Wludarski et al. 2006) 

Pathologic features that are suspicious for malignancy include large tumor size (> 5cm), 

frequent mitotic figures (> 3/10 hpf), atypical mitotic figures, vascular space invasion, 

nuclear atypia, necrosis, invasive borders, and invasion of the rete testis or beyond. (Kim, 

Young et al. 1985; Cheville, Sebo et al. 1998) Clinicopathological studies based on 

consultation cases seem to have a higher percentage of malignant tumors than actually occur 

in practice. Several recent clinical series have found tumor related deaths to be uncommon (1 

of 52 patients in one study; 0 of 37patients in another). (Di Tonno, Tavolini et al. 2009; 

Suardi, Strada et al. 2009) Testis sparing surgery appears safe and effective, provided that the 

diagnosis can be made at frozen section and the tumor is small with no gross or histologic 

features of suggestive of malignancy. (Giannarini, Mogorovich et al. 2007; Suardi, Strada et 

al. 2009) No effective chemotherapy protocols have been identified nor does radiation 

therapy appear helpful. It is unclear whether retroperitoneal lymph node dissection is 

beneficial. 

Features Suggestive of Malignancy in Leydig Cell Tumors 

Old age (never malignant in young children) 

Large size, tumor diameter > 5 cm 

Mitotic activity (> 3 mf per 10 hpf) 

Atypical mitotic figures 

Lymphovascular space invasion 

Nuclear atypia 

Necrosis 

Invasive growth 

The differential diagnosis of a Leydig cell tumor includes a number of non-neoplastic 

hyperplasias as well as several types of neoplasms. 

-Leydig cell hyperplasia, nodular type. Hyperplastic Leydig cell nodules exhibit nondestructive 

growth of Leydig cells in an interstitial location between the tubules. The nodules 

tend to be multiple, and they can be bilateral. They are usually small (< 0.5 cm). Leydig cell 

hyperplasia can occur in patients with elevated gonadotropin levels. 


-Testicular tumor of the adrenogenital syndrome (TTAGS). Patients with adrenogenital 

syndrome, usually of the salt loosing type caused by a 21-hydroxylase deficiency, or 

Nelson’s syndrome (ACTH secreting pituitary adenoma in patients treated by bilateral 

adrenalectomy for Cushing’s syndrome) can have multifocal and bilateral nodules that can 

mimic a Leydig cell tumor. (Rutgers, Young et al. 1988) TTAGS are hyperplastic nodules 

caused by elevated levels of ACTH. Often, the history is known, which facilitates the correct 

diagnosis, but occasionally the testicular tumors are discovered prior to diagnosis of the 

adrenogenital syndrome. Grossly, the tumors can be large, measuring up to 5-10 cm, or they 

can be small and impalpable. Small tumors are often centered in the hilum of the testis. In 

general, tumors in children are small and those that are detected in older patients are larger. 

The cut surfaces are brown with confluent nodules separated by broad bands of fibrous 

tissue. The tumor cells are large and polygonal with uniform round nuclei with nucleoli and 

abundant eosinophilic or pale cytoplasm. Some nodules contain cells with clear vacuolated 

cytoplasm. The cytoplasm contains lipofuscin but no Reinke crystalloids are present. Fibrous 

bands that are generally broader and more extensive than occur in Leydig cell tumors 

separate nests of cells. Sometimes, when the nodules are hilar, rete tubules are present 

between them. These “tumors” are not true neoplasms, but nodular hyperplasias that regress 

with treatment that lowers adrenocorticotrophin levels. 

-Large cell calcifying Sertoli cell tumor. Many examples of this tumor occur in patients with 

the Carney syndrome, as discussed below. These tumors can be confused with Leydig cell 

tumors because the tumor cells are polygonal and have abundant eosinophilic cytoplasm. No 

Reinke crystalloids are identified. This type of Sertoli cell tumor characteristically contains 

calcifications, can grow in tubules, and has a more myxoid stroma that often contains 

neutrophils. 

-Seminoma. A Leydig cell tumor with clear cytoplasm can be confused with a seminoma, but 

in the case of the Leydig cell tumor the clear cytoplasm due to the presence of lipids, not 

glycogen. Findings that are present in association with seminoma, but not a Leydig cell 

tumor, include intratubular germ cell neoplasia, lymphocytes, typically in fibrous septae and 

sometimes forming germinal centers, and granulomas. Of course, the immunohistochemical 

features of a seminoma are totally different than those of a Leydig cell tumor. 

Sertoli Cell Tumor 

A variety of types of Sertoli cell tumor have been described, with interesting 

histologic patterns or unusual clinical associations, or both. Sertoli cell tumors, nos are the 

most common, and a tumor designated simply as a “Sertoli cell tumor” is generally taken to 

be a Sertoli cell tumor, nos. 

Sertoli Cell Tumors of the Testis 

Sertoli cell tumor, nos 

Sclerosing Sertoli cell tumor 

Large cell calcifying Sertoli cell tumor 

Sertoli cell tumor associated with Peutz-Jeghers syndrome 


Sertoli cell tumors occur in patients of all ages. About a third of them occur in 

children less than 10 years old, (Harms and Kock 1997) but they are most common in 

middle-aged men. The average age is about 45. (Young, Koelliker et al. 1998) The typical 

presentation is with a slowly enlarging testicular mass. They are almost always unilateral. 

Most tumors are nonfunctional. Tumors that secret estrogens are unusual, but these can cause 

gynecomastia or impotence. 

Gynecomastia in Sertoli Cell Tumors 

Sertoli cell tumor, nos Rare 

Sclerosing Sertoli cell tumor Never 

Large cell calcifying Sertoli cell tumor Rare 

Grossly, Sertoli cell tumors are solid gray, white or tan masses, usually less than 4 cm 

in diameter. Cystic change can be present. 

Microscopically, a nodular pattern is often prominent at low magnification, with the 

nodules separated by broad bands of fibrous tissue. A variety of growth patterns are 

recognized, including growth of tumor cells in sheets, nests, trabeculae and cords. However, 

these patterns are not specific and for a definitive diagnosis tubules must be identified. The 

tubules can be solid or hollow and rarely elongated branching rete like tubules lined by 

cuboidal cells are present. The tubules are often poorly formed and sometimes it requires 

some imagination to recognize them. The background tends to be fibrous but it can be 

hyalinized or myxoid. The tumor cells are cuboidal to columnar and have scant to moderate 

pale or clear cytoplasm. Some tumors are composed mainly of polygonal cells with abundant 

eosinophilic cytoplasm. Zones composed of spindle cells are occasionally present in a Sertoli 

cell tumor. A variant with abundant clear foamy cytoplasm, the lipid rich variant, has been 

described. Cytoplasmic vacuoles are common and prominent cytoplasmic vacuolization can 

result in a microcystic appearance. The tumor cell nuclei are uniform and round to oval with 

small nucleoli. 

Immunohistochemical stains for inhibin, cytokeratin, and vimentin are positive. 

(Iczkowski, Bostwick et al. 1998; McCluggage, Shanks et al. 1998; Kommoss, Oliva et al. 

2000; Kato, Fukase et al. 2001; Comperat, Tissier et al. 2004) About half stain for calretinin. 

Other sex cord-stromal markers, such as WT-1, CD99 and melan-A can be positive. Many 

Sertoli cell tumors show positive staining for S100. Chromogranin and synaptophysin have 

been reported as positive in some studies. Sertoli cells are usually negative for EMA, but 

malignant Sertoli cell tumors can be positive. 

About 10% of Sertoli cell tumors are malignant. Malignant Sertoli cell tumors occur 

in children as well as in adults. Gynecomastia is more common in malignant cases. 

Malignant Sertoli cell tumors do not respond to chemotherapy or radiotherapy, so surgery is 

the mainstay of treatment and retroperitoneal lymph node dissection is generally advised. 

Metastatic spread is to the retroperitoneal lymph nodes and lungs. Pathologic features that 

suggest malignancy include marked nuclear atypia and pleomorphism, frequent mitotic 

figures (> 5mf/10hpf), vascular invasion, necrosis, large size (>5 cm), and predominance of a 

diffuse growth pattern. 


Several benign pseudotumors must be considered in the differential diagnosis, along 

with other neoplasms. The differential diagnosis is mainly with the following: 

-Hamartomatous Sertoli cell nodules of the androgen insensitivity syndrome. Patients with 

the AIS (“testicular feminization”) have multiple testicular hamartomatous nodules 

composed of tubules lined by Sertoli cells. Leydig cells are often present in the stroma 

between the tubules, in contrast to Sertoli cell tumors, where Leydig cells are pushed aside. 

About 25% of patients with the AIS develop multifocal bilateral Sertoli cell adenomas 

composed of pure proliferations of Sertoli cells lining tubules. It is unclear whether these are 

hyperplastic nodules, or autonomous neoplastic nodules but in any event malignant behavior 

has never been observed. The adenomas often contain eosinophilic waxy basement 

membrane deposits. 

-Small Sertoli cell nodules. Small nodules of Sertoli cells are a common incidental 

microscopic finding common in orchiectomy specimens from cryptorchid patients. These 

nodules are not grossly visible, in contrast to Sertoli cell tumors, which are usually > 1 cm in 

diameter. The nodules often contain central accumulations of basement membrane material. 

-Seminoma. In some malignant Sertoli cell tumors the tumor cells have clear cytoplasm and 

grow in sheets. Lymphocytes are scattered among the tumor cells, but plasma cells, which 

are uncommon in seminoma, are often numerous as well. This results in a histologic picture 

that can lead to a misdiagnosis as seminoma. (Henley, Young et al. 2002; Ulbright 2008) 

Unlike seminoma cells, the Sertoli cells often contain cytoplasmic vacuoles, have smaller 

round nuclei, and do not have conspicuous nucleoli. Mitotic figures are usually more 

numerous in seminoma. The presence of granulomas or intratubular germ cell neoplasia 

would favor a diagnosis of seminoma. The immunohistochemical findings permit a clear 

distinction between Sertoli cell tumor and seminoma. Many seminoma-like Sertoli cell 

tumors occur in older men at an age when seminoma is uncommon (> 55 years old). 

Variants of Sertoli Cell Tumor 

Several variants of Sertoli cell tumor have been described. These have distinctive 

histologic or clinical features, or both. The most important of these are sclerosing Sertoli cell 

tumor, large cell calcifying Sertoli cell tumor and Sertoli cell tumors in patients with the 

Peutz-Jeghers syndrome. 

Sclerosing Sertoli Cell Tumor 

Sclerosing Sertoli cell tumors occur predominantly in young men with an average age 

of 35 years. (Zukerberg, Young et al. 1991) They either present as a painless slowly 

enlarging testicular mass without any associated hormonal symptoms or the tumor is 

incidental finding.Grossly, sclerosing Sertoli cell tumors are small hard solid nodules with a 

white to yellow tan cut surface. Most are < 1.5 cm in diameter, although rare larger tumors 

have been reported. Microscopically, the tumor cells grow in cords, solid or hollow tubules, 

or as nests of cells. The key finding in this variant of Sertoli cell tumor is the densely 

collagenous background stroma that dominates the histologic picture and compresses the 

tubules, prompting the name “sclerosing” Sertoli cell tumor. (Zukerberg, Young et al. 1991) 

The sclerosis should be present throughout the tumor, not just focally, for classification as a 

sclerosing Sertoli cell tumor. The tumor cells nuclei vary from large and vesicular to small 

and hyperchromatic. They are usually columnar or cuboidal and have pale, sometimes 


vacuolated cytoplasm. Mitotic activity and nuclear atypia have only een reported in one case. 

All reported sclerosing Sertoli cell tumors have had a benign evolution. 

Large Cell Calcifying Sertoli Cell Tumor 

Patients with this type of Sertoli cell tumor tend to be young, with an average age of 

16, although tumors occur over a wide age range from children to older adults. (Proppe and 

Scully 1980) The usual presentation is with a slowly enlarging painless testicular mass. 

Hormones may be produced by the tumor or by hyperplastic Leydig cells in the surrounding 

testis, and some patients accordingly present with endocrine associated symptoms such as 

gynecomastia or isosexual precocity. About 40% of large cell calcifying Sertoli cell tumors 

occur in patients with Carney’s syndrome or another genetic syndrome such as Peutz-Jeghers 

syndrome. (Kratzer, Ulbright et al. 1997) Tumors in Carney’s patients are small, bilateral and 

multifocal and they are usually detected in childhood or adolescence. Other findings 

associated with the Carney syndrome include lentigines of the face, myxomas of the heart, 

skin and soft tissue, myxoid fibroadenomas of the breast, blue nevi of skin, pigmented 

nodules of the adrenal cortex with Cushing’s syndrome, human growth hormone producing 

adenomas of pituitary and psammomatous melanotic schwannomas. Pathologists should 

always bring up the possibility that the patient might have the Carney syndrome if a large cell 

calcifying Sertoli cell tumor is diagnosed, particularly if it is bilateral and multifocal. 

Grossly, the tumor is tan or yellow and contains gritty areas of calcification. Most measure 

less than 4 cm in diameter. Large cell calcifying Sertoli cell tumors are unusual in that they 

can be multifocal and about 40% are bilateral. 

Microscopically, the tumor consists of nests, cords, trabeculae and solid tubules of 

polygonal cells with abundant eosinophilic cytoplasm. The tumor cell nuclei are round and 

vesicular with prominent nucleoli. Mitotic figures are rare. Intratubular growth and 

calcifications are common. The tumor cells grow in myxoid to collagenous stroma that is 

calcified or ossified in about half the cases. A neutrophilic stromal infiltrate is characteristic. 

The tumor cells stain for vimentin and are inhibin and melan-A positive. (Petersson, 

Bulimbasic et al. 2010) They are usually cytokeratin negative although infrequently there is 

minimal focal staining. (Kratzer, Ulbright et al. 1997) The tumor cells are EMA negative. 

Given the appearance of the tumor cells, it is worth noting that they usually stain for S100, 

which could potentially lead to confusion with metastatic melanoma. 

The differential diagnosis includes Leydig cell tumor because of the polygonal cell 

shape and abundant eosinophilic cytoplasm, but Leydig cell tumors generally lack a 

neutrophilic infiltrate and calcifications, do not exhibit tubular growth and do not grow 

within tubules. Large cell calcifiying Sertoli cell tumors do not contain crystalloids of Reinke 

or lipofuscin. 

Malignant large cell calcifying Sertoli cell tumors are rare, but some have been 

reported. (Kratzer, Ulbright et al. 1997) Patients with malignant tumors are older than those 

with malignant tumors (average age 39 vs 17) and malignant tumors generally do not occur 

in patients with the Carney syndrome. Features suggestive of malignancy include large size 

(>4 cm), extratesticular growth, tumor cell necrosis, high-grade nuclear atypia, frequent 

mitotic figures (mitotic rate > 3 mf/10 hpf) and vascular invasion. It has been suggested that 

if one of these features is present the possibility of malignancy should be mentioned, and if 

two or more are present the tumor should be classified as malignant. (Kratzer, Ulbright et al. 

1997) Invasion of the rete testis has been noted in a few benign cases. (Plata, Algaba et al. 


1995) Occasional tumors with none of these features, such as one with minimal atypia and no 

mitotic activity but with invasion of the rete testis, prove to be malignant. (De Raeve, 

Schoonooghe et al. 2003) 

Sertoli Cell Proliferations in Peutz Jeghers Syndrome 

Patients with the Peutz-Jeghers syndrome develop multifocal bilateral intratubular 

proliferations of Sertoli cells that occur in lobular clusters through out the parenchyma. 

(Venara, Rey et al. 2001; Ulbright, Amin et al. 2007) Most patients are children; they all 

have gynecomastia and some have isosexual precocity depending on the hormone or 

hormones produced. Many patients have other features of Peutz-Jeghers syndrome, such as 

pigmented macules around the mouth and on the lips. The testes are generally bilaterally 

enlarged with echogenic foci on ultrasound examination, but a palpable mass is not present; 

rare patients have unilateral testicular enlargement. The diagnosis is generally made by 

testicular biopsy, usually performed bilaterally. The involved tubules are expanded and 

contain cells similar to those in a large cell calcifying Sertoli tumor. They are polygonal with 

abundant eosinophilic cytoplasm. There is abundant eosinophilic hyalinized basement 

membrane material in the expanded tubules. Sometimes the growth pattern is annular and 

with the prominent hyaline material it is reminiscent of the sex cord tumor with annular 

tubules (SCTAT) that occurs in the ovaries of women with the Peutz-Jeghers syndrome. 

Usually, calcifications are not present. In most cases the proliferation is entirely intratubular, 

but in a minority of patients an invasive Sertoli cell tumor is also present. (Young, 

Gooneratne et al. 1995; Venara, Rey et al. 2001) The invasive tumors are usually small and 

their classification is problematic. Some resemble large cell calcifying Sertoli cell tumors but 

they lack calcifications and do not have the prominent fibromyxoid stroma with neutrophils. 

Others have a more tubular pattern. Followup has not revealed progression in patients who 

have only intratubular proliferations at diagnosis, so the nature of these proliferations 

remains unsettled. Ulbright et al favor interpreting them as intratubular neoplasms because of 

the occasional association with an invasive neoplasm. 

Granulosa Cell Tumor 

Granulosa cell tumors are rare types of testicular tumors. There are two variants, 

similar to the situation in the ovary. One type occurs mainly in adults, and is termed the adult 

type granulosa cell tumor. The other type occurs predominantly in young children, and is 

termed the juvenile type of granulosa cell tumor. 

Adult Granulosa Cell Tumor 

Adult type granulosa cell tumors are very rare. (Nistal, L†zaro et al. 1992; Jimenez- 

Quintero, Ro et al. 1993) In the only series reported, 7 granulosa cell tumors were found in a 

review of 52 sex cord stromal tumors at MD Anderson. (Jimenez-Quintero, Ro et al. 1993) 

Six cases were pathology consultations and one was a patient treated at MD Anderson. They 

occur over a wide age range, from 16-76 years. The average age is in the mid 40’s. The 

presentation is with a painless testicular mass. A significant number of tumors have been 

asymptomatic and detected during routine physical examinations. Many tumors are 

nonfunctional, but others secrete estrogen and cause gynecomastia. 


Grossly, adult type granulosa cell tumors can be solid, cystic, or solid and cystic. 

They form well-circumscribed nodules with cut surfaces that are yellow to gray. The average 

size is about 5 cm. 

The same microscopic patterns that are seen in ovarian granulosa cell tumors occur in 

testicular granulosa cell tumors. These include microfollicular, trabecular, gyriform, insular, 

and diffuse patterns of growth. The diffuse pattern is the most common one. The tumor cells 

have scant pale cytoplasm. The nuclei are pale and round to oval with small nucleoli and, 

sometimes, nuclear grooves. Mitotic figures are usually uncommon, but they are occasionally 

numerous and readily identified. 

Granulosa cell tumors of the testis show positive immunohistochemical staining for 

inhibin, vimentin, and, in some tumors, cytokeratin. Staining for EMA is negative. 

Most of the reported cases have been clinically benign. The largest series included 

only seven patients, but 2 of the 5 patients included in that series developed metastases, 

(Jimenez-Quintero, Ro et al. 1993) and other patients with malignant tumors have been 

reported. The diagnosis in some reported cases is questionable; for example, Hammerich et al 

reported a tumor as a granulosa cell tumor, but their illustrations show a tumor that contains 

closed and open tubules, more suggestive of a Sertoli cell tumor. (Hammerich, Hille et al. 

2008) Features that are worrisome for malignancy include large tumor size, vascular 

invasion, hemorrhage, and necrosis. 

Juvenile Granulosa Cell Tumor 

Juvenile granulosa cell tumors of the testis occur almost exclusively in young 

children. In the Kiel pediatric tumor registry sex cord-stromal tumors accounted for 17.7% of 

all testicular tumors, with juvenile granulosa cell tumors constituting 31.4% of the total. 

(Harms and Kock 1997) A majority of these tumors are diagnosed during the first days or 

weeks of life, (Lawrence, Young et al. 1985) and presumably are congenital tumors. More 

than 95% are diagnosed before the patient has reached the age of 1 year. As might be 

anticipated, some cases are diagnosed antenatally. (Peterson and Skoog 2008) Almost all 

patients present with a painless scrotal mass, but a few present because of testicular torsion. 

(Nistal, Redondo et al. 1988) A few tumors have been reported to occur in undescended 

testicles. Hormonal symptoms almost never occur. Most patients have a normal 46XY 

karyotype. 

On gross exam, the testis contains a solid to cystic gray or yellow nodule that usually 

occupies most of the testis, often leaving only a thin rim of normal testicular parenchyma. 

The cut surface can be nodular or microcystic, with small cysts only 1-2 mm in diameter, or 

larger cysts may be present. The tumor size ranges from less than a cm to about 5 cm, with 

an average diameter of about 2 cm. (Lawrence, Young et al. 1985; Harms and Kock 1997) 

Microscopically, solid cellular areas are intermixed with follicle like structures filled 

with mucoid material. The follicle contents are often basophilic and stain lightly with 

mucicarmine. The follicles tend to be large and somewhat irregular, and can be termed 

macrofollicles. The follicles are lined by several layers of stratified tumor cells and 

surrounded by a spindle cell stroma or by neoplastic granulosa cells. Solid areas may contain 

abundant hyalinized stroma. The tumor cells have abundant pale to eosinophilic cytoplasm 

and in some tumors they are focally or diffusely luteinized. The nuclei are round and 

hyperchromatic and often contain conspicuous nucleoli. Mitotic figures are generally readily 


identified and they can be numerous. The degree of atypia is typically less than is seen in 

ovarian juvenile granulosa cell tumors. 

Immunohistochemical studies of these tumors are limited, but they have been shown 

to be positive for inhibin, vimentin and CD99 and to stain focally for cytokeratin. As has 

been observed in ovarian granulosa cell tumors, the cells can stain for S100 and SMA. 

(Alexiev, Alaish et al. 2007) The results of staining for other antigens have not been reported, 

but positive staining for sex cord-stromal markers such as calretinin and steroidogenic factor- 

1 is likely to be present. 

Malignant behavior has not reported. Follow-up studies are limited, but all patients 

have been well after orchiectomy or enucleation. In view of the favorable outcome, fertility 

sparing enucleation has been advocated in patients who have a normal serum AFP 

(presumably excluding yolk sac tumor). (Shukla, Huff et al. 2004) 

The histogenesis is controversial. In one series of 14 juvenile granulosa cell tumors 

one example showed intratubular growth adjacent to the main tumor mass. This has led to 

speculation that the tumors may be derived from Sertoli cells. 

The differential diagnosis includes other types of sex cord stromal tumors, but the 

main differential diagnosis is with yolk sac tumor. Yolk sac tumor exhibits a number of 

distinctive growth patterns that are not seen in juvenile granulosa cell tumor, so adequate 

histologic study usually resolves the issue. In addition, there are significant 

immunohistochemical differences between the two, with juvenile granulosa cell tumor being 

positive for inhibin, calretinin, and steroidogenic factor-1, and yolk sac tumor showing 

positive staining for cytokeratin, alpha-fetoprotein, SALL4, and glypican-3. 

Fibroma Thecoma Group 

Tumors that resemble fibromas or thecomas of the ovary are extremely rare. (Jones, 

Young et al. 1997) They are generally small and circumscribed with a yellow or white cut 

surface. Microscopically, they consist of bundles of bland spindle cells with oval nuclei and 

scanty cytoplasm. A variable amount of collagen is present in the background. Several 

cellular fibromas, similar in appearance to the corresponding ovarian tumors, have been 

reported. Several tumors with minor aggregates of sex cord elements have been reported. (De 

Pinieux, Glaser et al. 1999) The presence of more than a minor amount of sex cord cells 

excludes a tumor from the fibroma category, and requires its placement in the mixed or 

unclassified category, discussed below, since such tumors have metastatic potential that is 

lacking in fibroma. 

Mixed and Unclassified Sex Cord Stromal Tumors 

This category contains tumors that cannot be accurately placed into one of the defined 

categories of sex cord stromal tumors. They usually present as a painless testicular mass. 

About a third of these tumors occur in children, in whom 2/3 of sex cord stromal tumors fall 

into this category. About 15% of patients have gynecomastia. 

Grossly, they are gray, tan or yellow solid nodules. Microscopically, they often 

contain a mixture of sex cord and stromal elements. A combination of epithelioid and 

spindled tumor cells is typical, although in some tumors spindled cells predominate. 

(Renshaw, Gordon et al. 1997; Magro, Gurrera et al. 2007) In some tumors there are focal 

Sertoli tubules or aggregates of granulosa like cells, but the tumor does not fit well into either 

category. In tumors that contain a mixture of well defined types of sex cord and stromal 


elements, all should be listed in the report; the behavior is likely to be determined by a 

combination of the percentage of each type and its malignant potential. 

These tumors have all been benign in children less than 10 years of age but about 20% of 

those that occur in older patients are malignant. Worrisome findings include cellular atypia 

and pleomorphism, a high mitotic rate, necrosis, vascular invasion, an invasive margin and 

large tumor size. 

References 

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