Moderators: Dr. Gregor Mikuz and Dr. Victor E. Reuter
Section 5 -
Tumors of the Testicular Adnexa and Paratesticular Tissues
Victor E. Reuter
Memorial Sloan Kettering Cancer Center
The majority of testicular tumors are of germ cell origin, followed by gonadal-stromal neoplasms.
Nevertheless, other neoplasms do occur and, due to their rarity, often present diagnostic dilemmas.
is beyond the scope of this presentation to discuss all intrascrotal lesions, but rather we will focus on
selected lesions that may present as intrascrotal masses and cause diagnostic challenges.
Lesions of the Rete Testis: Hyperplasia, Adenoma and Adenocarcinoma:
Hyperplasia of the rete testis is a common, usually incidental finding and may be associated with many
conditions, including testicular atrophy and as a reaction to adjacent intragonadal neoplasms such as
germ cell tumors.
It has been associated with other conditions such as chronic hepatic
insufficiency and renal dysplasia. Microscopically it is characterized by proliferation of the rete
epithelium which forms exaggerated tubulopapillary channels which are interconnecting. The lining
epithelium is composed of cuboidal to low columnar cells with banal nuclear cytology. The
interanastomosing channels may become cystically dilated but usually merge with normal appearing rete
testis. It is important to recognize hyperplasia of the rete when it is associated with germ cell
tumors. For example, hyperplastic rete may be confused with a nonseminomatous component in cases of pure
seminoma, leading to not only an inaccurate diagnosis but also to improper therapy. Clues to the correct
diagnosis lie in the benign nuclear cytology of the hyperplastic rete epithelium and its close
association to normal rete testis. Hyperplasia of the rete may also be seen in association to pagetoid
spread of in situ germ cell neoplasia. Once again this phenomenon should not be confused with a
nonseminomatous germ cell tumor. In other circumstances the hyperplasic rete testis epithelium
associated with an invasive germ cell tumor may exhibit intracytoplasmic eosinophilic hyaline globules
which likely represent absorbed proteinaceous material. In these cases one should not mistake this
finding with yolk sac tumor.
Benign tumors of the rete testis have been described rarely and these have run the spectrum of
adenoma, cystadenoma and cystadenofibroma, depending on their cellular components.  A
distinctive variant has been called Sertoliform Cystadenoma. These circumscribed lesions have measured
up to 3 cm in greatest diameter and contain benign appearing columnar tumor cells with basally located
nuclei and prominent, regular nucleoli. If associated with a sclerotic stroma the tumor cells may be
seen as cords or thin trabeculae. It should be blatantly apparent that this particular lesion may be
very difficult to differentiate from a sertoli cell tumor, this observation being more acute since at
least one case of sertoliform cystadenoma of the rete testis has been shown to be immunoreactive for
inhibin.  The correct diagnosis can be made if transition with hyperplastic or normal rete
epithelium is present.
Carcinoma of the rete testis is extremely rare with less than 40 bona fide cases described in the
In fact, many of the cases may well represent other tumors confused with
carcinoma arising in the rete. Lesions that must be considered in the differential diagnosis include a).
metastatic carcinoma, b). mesothelioma, and c). ovarian-type carcinoma. Before accepting a tumor as a
primary carcinoma of the rete testis, the following conditions must be met.
Rete testis carcinoma has been described in all ages but it is classically a tumor of adults with a
peak incidence in the seventh decade of life. Most patients present with unilateral painful testicular
swelling, with or without an associated hydrocele. Survival is poor with most patients dying within a
year of diagnosis.
- Tumor centered in the hilum of the testis. This may be difficult to asses in masses of considerable
- Transition from normal to neoplastic rete epithelium. Once again, this may be difficult to ascertain in
large lesions that have destroyed the normal anatomy of the testicular hilum. One must also be cognizant
of the fact that other tumors such as those of germ cell and mesothelial origin may involve the rete
- Absence of a primary elsewhere with similar histology.
- Morphology incompatible with any other intratesticular, adnexal or scrotal primary.
- Proper immunohistochemical panel excluding other primaries.
Grossly these tumors are usually solid but may be at least partially cystic. Microscopically they
may exhibit variable patterns of growth, although a tubulopapillary architecture usually predominates.
Other histologies include reteform (elongated and compressed tubules), sertoliform (tubular), solid, and
biphasic with both epithelial and spindle cell areas. The tumor cells range from cuboidal-to-columnar
with eosinophilic-to- basophilic cytoplasm and moderate to marked nuclear atypia.
As previously mentioned rete testis carcinomas are very rare and this diagnosis should be made only
after other entities have been excluded. Malignant mesothelioma may have a very similar morphology
although it is usually centered along the tunica and is immunoreactive for mesothelial-associated markers
such as calretinin and WT-1 rather than those markers associated with adenocarcinoma such as CEA, CD-15
AND B72.3. Testicular Müllerian type tumors may also mimic adenocarcinoma of the rete testis
morphologically, but they a more commonly cystic and associated with psammoma bodies. Immunoreactivity
for WT-1 and CA-125 is characteristic. Another diagnosis that must be excluded is metastatic carcinoma.
Metastases are more commonly bilateral but may occasionally be unilateral. It is usually a manifestation
of advanced disease and seen in patients with an established diagnosis of metastatic carcinoma, most
commonly from the prostate, lung or gastrointestinal tract.
Tumors of the epididymis are fleetingly rare and will not be discussed, with the exception of clear
cell papillary cystadenoma. These lesions may occur sporadically but are usually associated with von
Microscopically the lesions exhibit cystic spaces filled with
papillary structures lined by cuboidal-to-columnar cells which contain clear cytoplasm, uniform nuclei
with occasional inconspicuous nucleoli. Given these morphologic features, it is easy to see why the
tumor may be confused with metastatic clear cell carcinoma, particularly of the kidney. A recent study
demonstrated that the tumor cells of clear cell papillary cystadenoma are immunoreactive for CK7 but not
RCC. Only one of five cases was immunoreactive for CD10. Clear cell renal cell carcinomas should not be
immunoreactive for CK7 and CD10 should be positive in a distinct cytoplasmic membranous distribution. At
the morphologic level one should remember that clear cell renal cell carcinomas, particularly low grade
lesions, will rarely, if ever, have an associated papillary architecture.
Müllerian-Type Epithelial Tumors:
These rare tumors exhibit the full morphologic spectrum seen in their ovarian counterparts; for this
reason most authors have used similar nomenclature to describe them.
mucinous tumors are most common and the histology may range from a simple cystadenoma to borderline tumor
to frank adenocarcinoma. Endometrioid, clear cell and Brenner tumors have also been described as single
case reports. The histogenesis of these tumors is a matter of speculation with some authors suggesting
Müllerian metaplasia of the tunica vaginalis and others originate from Müllerian rests in the
paratesticular soft tissue. Some authors have raised the possibility of these tumors arising from the
appendix testis. Interestingly, we have observed striking Müllerian-type metaplasia in this location in
a significant number of orchiectomy specimens removed for various reasons. Some have even demonstrated a
small amount of ovarian-type stroma undermining the Müllerian epithelium.
Müllerian-type serous tumors have been described in children and adults with a peak incidence in the
sixth decade of life. They usually present with painful testicular swelling. While borderline lesions
are commonly cystic, frankly malignant tumors may be predominantly solid. In the latter cases the tumors
invariably are infiltrative and these tumors are capable of local recurrence and metastasis. The
morphology of these tumors may exhibit the entire spectrum seen in the ovary. We have observed rare
examples of borderline tumors with an associated ovarian-type stroma.
Müllerian-type mucinous tumors are rarer than their serous counterparts. They have a similar age
distribution and, once again, exhibit the same morphologic spectrum seen in their ovarian counterparts.
Some cases have been described as having an intratesticular rather than a paratesticular location. In
these cases extreme care should be taken to rule out the possibility of teratoma primarily, but also
metastatic carcinoma. Mucinous cystadenomas and borderline tumors are benign while carcinomas may recur
Lesions of Mesothelial origin; Hyperplasia, Adenomatoid tumor and Mesothelioma:
Mesothelial hyperplasia occurs as a result of chronic injury as seen in cases of chronic inflammation
of adjacent tissues, hydrocele, hematocele, inguinal hernia and underlying tumors, whether benign or
Microscopically one sees exophytic papillary projections in
continuity with the mesothelial lining. Importantly, small tubular structures as well as nests and cords
of cells may be present in the superficial submesothelial connective tissue, at times associated with
submesothelial fibrosis. Extension into the underlying connective tissue is always superficial with a
"horizontal" rather than "vertical" pattern of infiltration. The mesothelial cells will exhibit typical
reactive features including binucleation, moderate increase in the nuclear to cytoplasmic ratio, mild
hyperchromasia and pleomorphism and minimal mitotic activity. Features characteristic of mesothelioma
such as extensive infiltration, solid growth and marked atypia are absent. It has been stated that
reactive mesothelium is immunoreactive for Desmin whereas mesothelioma is not. In addition, reactive
mesothelial cells are less likely to be immnoreactive for p53. Both will express Calretinin and WT-1.
Nevertheless, close examination to the gross and microscopic features of the lesion are likely to lead to
the correct diagnosis without the need of immunohistochemistry.
Adenomatoid tumors are a common benign tumor of mesothelial origin.
asymptomatic and associated with the head of the epididymis, although some may appear to arise within the
testis. They may be large; up to 7 cm but are invariably well circumscribed and round-to-oval in shape.
The neoplastic cells may be arranged in nests, tubules, cords and even solid sheets or lining small
cystic cavities. The cells may be cuboidal, columnar or flattened. The cytoplasm is usually abundant
and eosinophilic and may be vacuolated. The associated stroma may be sparse or abundant and can take on
a rather fibrous, myoid and even hyalinized appearance. Rarely these tumors may become infarcted in
which case they may be associated with severe pain.  Microscopically there may be a marked
fibroblastic/myofibroblastic proliferation, mimicking a malignant mesenchymal tumor. In these cases the
lesion appears to be infiltrative rather than circumscribed. Because of the diverse cytologic and
architectural features which may be encountered in adenomatoid tumors, the differential diagnosis is
quite extensive. Depending on the case, one may consider metastatic carcinoma (signet ring cells and
tubules), liposarcoma (vacuolated cells), yolk sac tumor (vacuolated cells), mesothelioma (infarction
with atypical reactive stroma), Sertoli cell tumor (tubules), and Leydig cell tumor (large eosinophilic
cells). Taking note of the localization of the lesion, knowledge of the morphologic diversity which may
be encountered and prudent use of immunohistochemistry is useful in establishing a correct diagnosis. As
expected, these lesions are likely to be immunoreactive for calretinin and WT-1.
Malignant mesotheliomas arise from the tunica vaginalis and are most commonly seen in the sixth and
seventh decades of life.
Rare examples have been described in young adults and
children. Asbestos exposure has been documented in up to 40% of cases and remains the only established
risk factor. A similar relationship with adenomatoid tumor has not been established. Patients usually
present with unilateral painful testicular swelling and hydrocele. Gross examination reveals significant
thickening of the tunica vaginalis which may also exhibit multiple nodules or masses along its surface.
The tunica may be adherent to the underlying testicular tunica albuginea and the tumor mass may extend
into the underlying testicular parenchyma. Microscopically the tumor cells have the same features seen
in their pleural counterparts, although almost two thirds of cases are pure epithelial with the remaining
exhibiting the classic biphasic histology. Rarely will one encounter a pure spindle cell mesothelioma at
this site. The tumor cells may take on a complex tubulopapillary architecture superficially, while the
invasive component may be composed of tubular structures or solid nest and cords. The tumor cells
commonly will exhibit a high nuclear-to-cytoplasmic ratio with moderate-to-marked nuclear atypia and
mitotic activity. Necrosis may be present as well as extensive stromal fibrosis. As previously
mentioned tumor cells may infiltrate into the testicular hilum and testicular parenchyma, even with
intratubular growth. In the former the tumor may mimic a rete testis primary, whereas in the latter the
differential diagnosis will include metastatic carcinoma and a germ cell neoplasm such as yolk sac tumor.
Mesotheliomas of the tunica vaginalis have a poor prognosis with almost 50% of patients dying of
disease within 2 years of diagnosis. If incompletely excised, they will recur and these inevitably will
lead to disease progression and death. Recurrences may be as late as 10 years from diagnosis and for
this reason long term clinical follow-up is mandatory.
The literature describes several mesothelial tumors that are solitary, cytologically banal and well
circumscribed under the rubric of "well differentiated mesothelioma".
similar features but cystic have been called "benign cystic mesothelioma".  Great caution
must be exercised in making these diagnoses since follow-up have shown the potential for recurrence and
progression. While we make a note that mesothelial tumors with these features may be associated with
indolent behavior, close clinical follow-up is still warranted. Personally I am very reluctant to make
the diagnosis of "benign" mesothelioma.
As previously discussed, metastatic tumors to the testis, testicular adnexa and paratesticular tissues
may mimic primary tumors arising at these sites.
The incidence in resected
specimens is low, only because metastases to the gonads usually present in a setting of advanced disease
where orchiectomy is unwarranted. Nevertheless orchiectomy containing metastatic disease may be
encountered in cases of occult primary, intractable pain or unusual clinical presentation such as
Of the epithelial tumors, the most common to metastasize to the gonad include prostate, lung,
gastrointestinal tract (including appendix, stomach and colon), and kidney, although tumors from
virtually any site may be encountered. While not an epithelial tumor, it is important to be aware that
metastases from malignant melanoma to the gonad (8%) are not rare.
Desmoplastic Small Round Cell Tumor:
Rare cases of this entity have been described in the scrotum in association with the paratesticular
As in other sites, patients tend to be young and present with a scrotal
mass which grossly is tan and firm. Microscopically one encounters the typical "small blue cells" with
scant cytoplasm, arranged in tight tubules or solid nests and associated with a dense fibrotic stroma. A
tumor-related microvascular proliferation is commonly encountered. Most cases have the typical
immunohistochemical profile of cytokeratin, vimentin and desmin positivity with negative staining for
S-100 protein, and CD-99. These are aggressive tumors which are likely to have positive regional lymph
node or systemic involvement at diagnosis. Despite recent successes with aggressive systemic therapy,
prognosis remains poor.  The differential diagnosis includes other tumors with "small blue
cells" such as lymphoma, rhabdomyosarcoma, and primitive neuroectodermal tumor (PNET). In the rare cases
with a tubular architecture, it is conceivable that other tumors such as mesothelioma or sertoli cell
tumor may enter in the differential diagnosis.
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