A 40-year-old man presented for elective sterilization and was found on physical
examination to have a previously undetected, rock-hard right testicular mass. Ultrasound demonstrated a
3 cm. heterogeneous, partially calcified, solid mass in his right testicle. A right orchiectomy was
performed with prosthesis insertion.
Case 5 - Figure 1 - Much of the lesion consists of calcified and ossified islands in a hypocellular, sclerotic stroma.
Case 5 - Figure 2 - Strands and cords of uniform eosinophilic cells, a minor component of the tumor in terms of surface area, are the characteristic feature of this neoplasm.
Case 5 - Figure 3 - At higher magnification, the eosinophilic cells have uniform nuclei with prominent nucleoli. Occasional cells have cytoplasmic vacuoles.
The microscopic sections for review consist
primarily of large amounts of dystrophic calcification, ossification, and unusual, psammoma-like
calcifications. Between the areas of calcification are variably apparent cords and small islands of
epithelioid cells with very prominent eosinophilic cytoplasm, closely resembling Leydig cells. On
higher power magnification, many of the cells contain one or more small to coalescent cytoplasmic
vacuoles. In a few foci, cells containing yellow, lipochrome-type pigment are noted. The material
submitted for your review contains little or no adjacent normal testis, but initial sections from the
mass showed only atrophic changes in the adjacent seminiferous tubules, with no evidence of an
intratubular component. On careful examination, no crystals of Reinke are identified. The nuclei are
uniform and vesicular with a single medium-sized to more prominent nucleolus. Mitotic figures are
vanishingly rare. There is no evidence of tissue necrosis. Initial sections showed rare cells within
apparent lymphovascular spaces but these may represent an artifact of sectioning, as they are not
identified on subsequent sections.
The neoplastic cells show focal reactivity for
cytokeratin and S100 protein, with strong reactivity for inhibin, calretinin, and vimentin. The cells
are non-reactive for CD117 (KIT), CD30, CD99, ER, and PR.
Diagnosis: Large cell calcifying Sertoli cell tumor (LCCSCT) of the testis
The patient subsequently underwent a partial retroperitoneal
lymph node dissection. The nodes were negative. He is currently free of disease more than 1 year after
According to current nosology, Sertoli cell tumors of the testis come in three types.
Most common is the classic Sertoli cell tumor, sometimes referred to as Sertoli cell tumor, not otherwise
specified (NOS). There are two less common Sertoli variants, the large cell calcifying variant (LCCSCT)
as typified by the current case and the sclerosing variant. The remainder of this brief discussion
will focus on LCCSCT.
Although considerably fewer than 100 LCCSCT have been reported, the unusual clinical
features of these tumors have sparked considerable interest among urologists, pathologists and
geneticists. Some male patients with Peutz-Jeghers syndrome have Sertoli cell tumors with features of
LCCSCT, although often the testicular tumors of Peutz-Jeghers have unusual or mixed appearances,
resembling LCCSCT without the calcifications in some instances, and in other cases resembling ovarian sex
cord tumors with annular tubules.
It was recognized early in the history of LCCSCT that some tumors were associated with a
constellation of clinical findings including pituitary neoplasms, adrenal hyperactivity, atrial myxomas,
and spotty cutaneous pigmentation. Subsequently it was determined that these features fit well into the
spectrum of Carney's Complex, a condition originally described as, "the complex of myxomas, spotty
pigmentation, and endocrine overactivity". This definition has been progressively refined, and the
condition is now known to be due to a specific autosomal dominant trait with well-described genetics and
associated clinical features including cardiac and extracardiac mxomas, pituitary adenomas, nodular
adrenal hyperplasia, psammomatous melanotic Schwannomas, and LCCSCT's.
About 38% of LCCSCT's occur in patients with Carney's Complex or other less common
syndromes. In this setting, the tumors are usually multifocal and bilateral, and occur in younger
patients with a mean age of approximately 17 years. Only one LCCSCT in this group has been reported to
have behaved in a malignant fashion.
In contrast, about 62% of LCCSCT's occur as solitary lesions in patients without other
reproduceable stigmata of disease. These solitary lesions typically occur in older individuals with a
mean age of 39 years. Importantly, it has been reported that up to 25% of these isolated tumors may
behave in a malignant fashion. Microscopic features associated with malignancy have included
extratesticular extension, size greater than 4 cm, mitotic rate greater than 3 per 10 HPF, prominent
nuclear atypia, necrosis, and vascular invasion. Metastases typically involve retroperitoneal lymph
nodes and response to chemotherapy regimens has been variable in this group.
LCCSCT's are usually easy to distinguish from
classic Sertoli cell tumors or non-neoplastic Sertoli cell nodules. Occasional classic Sertoli cell
tumors may contain cords of cells with prominent eosinophilic cytoplasm, but these cells usually lack the
large nuclei and prominent nucleoli of LCCSCT, as well as the abundant calcifications.
It is clear that prior to the description of LCCSCT, these tumors were misdiagnosed as
Leydig cell tumors because of their prominent eosinophilic cytoplasm and sparse or absent tubule
formation. Because the malignancy rate of true Leydig cell tumors is low (malignant cases are
proportionally over reported) and that of isolated LCCSCT is approximately 25%, some purported malignant
Leydig cell tumors in the older literature may represent misdiagnosed LCCSCT. Light microscopic features
found in LCCSCT that are helpful in this distinction include focal tubule formation, growth within
seminiferous tubules, lack of Reinke crystals, and prominent calcifications.
The key "take home" point for this case is that irmmunohistochemical stains may add to
the confusion of LCCSCT with Leydig cell tumor. Inhibin and calretinin are strongly positive in both
Leydig cell tumors and LCCSCT, but are weakly positive or negative in conventional SCT. Conversely, CD99
is typically positive in conventional SCT, but is negative or very weakly positive in Leydig cell tumors
and LCCSCT. These findings suggest that LCCSCT has at least partially assumed a Leydig-like
immunophenotype to match its Leydig-like appearance in H&E stains. The presence of intratubular
growth and other clinical as well as ultrastructural features still suggest that these are fundamentally
Sertoli cell lesions. Ultimately, the cell of origin of LCCSCT is of considerably less importance than
its potential for confusion with Leydig cell tumor. As noted above, this an important distinction
because of the apparently higher rate of malignant behavior in isolated LCCSCT, as well as their
association with other syndromes when occuring multifocally in younger patients.
Seminomas are far more common than LCCSCT and may occasionally exhibit a prominent
fibrous stroma. LCCSCT lack the diffuse lymphoplasmacytic infiltrate often accompanying seminomas and
have distinctly different nuclear features with a much lower mitotic rate. Immunohistochemistry for
placental alkaline phosphatase and KIT (CD117) will strongly label seminoma cells, but will be
non-reactive in LCCSCT.
Adenomatoid tumors of the testis usually involve the epididymis, but may occasionally be
located within the tunica. Most adenomatoid tumors are composed of highly vacuolated cells with
endothelial-like spaces and are unlikely to be confused with LCCSCT. However, some adenomatoid tumors
consist of more epithelioid cells with prominent eosinophilic cytoplasm growing in cords and small
clusters with only minimal cytoplasmic vacuolization. This pattern can closely mimic LCCSCT.
Adenomatoid tumors, being of mesothelial differentiation, will show strong positivity for cytokeratin in
contrast to the more focal cytokeratin positivity typically seen in LCCSCT. Adenomatoid tumors lack
staining for inhibin, but are often strongly positive for calretinin, as are Leydig cell tumors and
Rests of cortical adrenal cells may be encountered in the region of the epididymis,
spermatic cord and rete testis and may be found in up to 10% of newborn males, if carefully sought.
Occasional adrenal rests may involve the tunica. These nests of cortical cells are typically sharply
demarcated or encapsulated and because of their small size, are unlikely to cause diagnositic problems.
However, at higher magnification these cells may mimic Leydig or LCCSCT cells. Reactivity for inhibin
could potentially add to the diagnostic confusion.
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