Case 4 -
Sex Cord Stromal Tumor, Most Likely Sertoli Cell Tumor, with Fibroma-like Stroma
Victor E. Reuter
Memorial Sloan-Kattering Cancer Center
Click on each slide thumbnail image for an enlarged view
Unilateral testicular tumor in a 15
Case 4 - Slide 1
Case 4 - Figure 1
Gross appearance of the 2.0 cm enucleated testicular mass.
Case 4 - Figure 2
Low magnification view of the lesion.
Case 4 - Figure 3
Two views of the mesenchymal component of the lesion. The image on the left contains primitive-appearing stromal cells and the image on the left appears more fibrous.
Sex Cord Stromal Tumor, most likely Sertoli cell tumor, with
This is a very unusual case for which I requested input
from my pathology colleagues at Memorial, particularly the GYN folks. I also asked Esther Oliva form MGH
to take a look at the case and she was kind enough to share it with Dr. Robert Scully. It was
reassuring to me that even he found it to be an unusual tumor. So, why did I chose to share something
so rare with you? Well, because it allows me to review the differential diagnosis of testicular tumors
in very young patients, which I will do at the end of the case discussion.
This 15 month child was found to have a unilateral testicular mass by his mother. Apparently it was
not painful. On physical examination the child was found to be normally developed, the testes were
descended and the penis was normal. There was no family history of note and no gynecomastia. The
scrotum was explored surgically and a 2 cm mass was enucleated and submitted for a frozen section. We
rendered a diagnosis of "tumor" so a completion orchiectomy was performed. The slide you have reviewed
in entirely, representative of the lesion. The remaining testis and adnexa were unremarkable.
The first look at the microscopic features of the this tumor allows us to rule out a secondary lesion
(lymphoma/leukemia) and mesenchymal lesion (sarcoma) and germ cell tumor (yolk sac tumor). The tumor
cell are arranged in cords and nests. Rarely collections of single cells are evident. These cells are
small, primitive-appearing and fusiform. The nuclear chromatin is fine and nucleoli are absent. These
cells were immunoreactive for Inhibin and CD99 but negative for Oct 3/4. In areas these cells are
present within tubular stuctures and sometimes associated with germinal cells. These germinal cells were
negative for all these markers. We interpreted the germ cells as entrapped germ cells with features of
spermatogonia. Alternatively you could interpret them as distorted seminiferous tubules involved by
"intratubular" tumor. Some of these tubular structures had densely eosinophilic hyaline bodies
reminiscent of Call-Exner bodies. No cysts were present. A surprising finding was the fibroma-like
stroma within the lesion. This component was variably cellular and focally it was reminiscent of
ovarian-like stroma. In fact, this component was immunoreactive for estrogen receptor. While this
finding is not terribly unusual in association with ovaian sex cord stromal tumors, it is very rare in
testicular tumors. Obviously, when confronted with this finding we immediately thought of the
possibility of a "syndrome" (androgen insensitivity, etc) but given the clinical and overall pathologic
features, this possibility was discarded. The possibility of Gonadoblastoma was discarded for similar
Putting everything together, we concluded that we were dealing with an unusual morphologic
manifestation of a sex cord stromal tumor in a child. In a child of this age the most common type would
be a Juvenile Granulosa Cell Tumor, but none of the usual morphologic or clinical features were present.
The best fit is a Sertoli cell tumor with entrapped germinal cells and fibroma-like stroma. The child is
doing well 4 months after surgery. Unusual indeed!
Sex cord-stromal (gonadal stromal) tumors are rare, comprising approximately 4.0% of testicular
neoplasms. Similar tumors may arise in the female gonads. The term refers to neoplasms containing
Leydig (interstitial) cells, Sertoli cells, granulosa cells, or theca cells. Tumors may be made up of
one or a combination of these cell types in varying degrees of differentiation. The terminology used to
describe these tumors is confusing and controversial but it is best to adhere to the classification set
forth by the World Health Organization. Among the entities I considered in the differential diagnosis I
will highlight a few.
Leydig (Interstitial) Cell Tumor:
Leydig cell tumors (LCT) are the most common pure testicular sex cord-stromal neoplasm and account for
1% to 3% of testicular neoplasms. They may occur at any age, though most common between the third and
sixth decades of life
Fifteen to twenty percent of cases will present in prepubertal
children. Approximately 10% will metastasize with metastasis occurring at an older age. LCTs usually
arise in normally descended testes although they have been described in cryptorchid gonads as well as in
testes which have undergone orchiopexy. Most, if not all, children with LCT present with isosexual
precocity, which is characterized by deepening of the voice, appearance of body hair, penile enlargement
and advanced bone age. Often these physical changes are accompanied by excessive aggression or shyness.
LCT must be considered in the differential diagnosis in all prepubertal patients with a testicular mass
and precocious puberty.
Grossly, LCT is a well-circumscribed, yellow-tan or brown-gray lobulated mass occasionally containing
fibrous septae. Macroscopic evidence of hemorrhage or necrosis is rare. Microscopically, the tumor is
made up of large polyclonal cells with abundant eosinophilic and granular cytoplasm. Less frequently,
the cytoplasm may be clear or vacuolated or microcystic
Nuclei are round or vesicular
with delicate chromatin and a single prominent nucleolus. The cells usually exhibit a solid pattern of
infiltration although fibrous septae may give them a pseudotubular or trabecular appearance.
Crystalloids of Reinke are present in 25% to 40% of cases and may require electron microscopic
examination for their identification. On light microscopy they appear as densely eosinophilic
needle-like or rhomboid structures within the cytoplasm. LCT are likely to be immunoreactive with
inhibin and vimentin but not cytokeratins, CD-30, Oct 3/4, or PLAP.
Sertoli Cell Tumor
Sertoli cell tumors (SCT) are rare, comprising less than 1% of testicular neoplasms
They were first described in the testis by Teilum who recognized their histologic similarity
to Sertoli cell tumors of the canine testis. They may occur at any age and approximately 15% develop in
children. Patients characteristically present with a painless mass in a normally descended testis.
Gynecomastia is evident in one third of patients. Hormonal alterations in patients with SCT have been
poorly documented. Nevertheless, SCT should be in the differential diagnosis of all prepubertal patients
presenting with a testicular mass and gynecomastia. Cases have been reported in boys with Peutz-Jeghers
Grossly, SCT are well circumscribed, solid and yellow-white or tan. The lesions may be lobulated and
may contain small areas of hemorrhage. Microscopic examination reveals mostly tubules but also cords,
nests, and masses of tumor cells in a fibrous stroma. The neoplastic cells may contain abundant
intracytoplasmic lipid giving them a clear or vacuolated appearance. Electron microscopy may reveal
Charol-Bottcher filaments within the cytoplasm, which are characteristic of Sertoli cells. The
classification of SCT should be reserved for tumors composed entirely of Sertoli cells. Those neoplasms
composed only partially of these cells should be classified as mixed or incompletely differentiated sex
cord-stromal tumors. SCT are immunoreactive for inhibin, vimentin and cytokeratins.  Markers
typically seen in GCT are negative. 
Juvenile Granulosa Cell Tumor
Granulosa cell tumors analogous to juvenile granulosa cell tumors of the ovary are the most common sex
cord-stromal tumor of the infantile testis
They are usually present in the first
six months of life, the oldest reported case being in a 21-month-old. Two cases have developed in
undescended testes. Juvenile granulosa cell tumors may arise in patients with an abnormal karyotype and
ambiguous genitalia. Tumors may be solid, cystic or both and the cysts frequently contain a gelatinous
material. Microscopically, the tumor exhibits either a follicular or solid pattern and the cells are
characterized by a moderate to large amount of eosinophilic cytoplasm and hyperchromatic nuclei. Stromal
hyalinization is often extensive. Although mitoses may be plentiful, no testicular tumor of this type
Sex Cord-gonadal Stromal Tumors, Mixed or Incompletely Differentiated Forms
As you might expect, these two categories include tumors with more than one identifiable sex
cord-stromal element, as well as tumors in which the exact gonadal stromal cell of origin cannot be
established with certainty
These neoplasms may occur at any age although more than
half of the patients are either children or infants. Painless testicular enlargement is the most common
presenting symptom that is infrequently associated with gynecomastia. Grossly, these tumors are similar
to other sex cord-stromal neoplasms and their microscopic appearance is quite variable, ranging from
predominantly epithelioid to predominantly stromal growth patterns. Frequently the cells are
undifferentiated making precise classification impossible. Approximately 30% of tumors presenting in
patients older than 10 years of age are malignant whereas tumors presenting in younger patients follow a
benign course. Histologic predictors of aggressive clinical behavior have not been established. Radical
orchiectomy is the treatment of choice; however, retroperitoneal lymph node dissection should be given
serious consideration in patients older than 10 years of age.
Gonadoblastomas are rare neoplasms composed of sex cord elements intimately admixed with germ
These tumors generally arise in chromosomally abnormal individuals with
dysgenetic gonads; 20% of cases occur in phenotypic males. Patients usually present with cryptorchidism,
hypospadia, and internal female genitalia, although two cases have been reported arising in a scrotal
testis. One third of cases are bilateral and 60% are associated with malignant germ cell elements that
are usually seminoma, but may be yolk sac tumor of embryonal carcinoma. While gonadoblastomas do not
metastasize, metastasis from the associated germ cell tumor may occur.
The microscopic appearance is distinctive and consists of tumor nests surrounded by connective
tissue. The nests contain germ cells with clear cytoplasm and sex cord elements resembling Sertoli
cells, granulosa cells or both. The nests may contain hyalinized eosinophilic structures resembling
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