Case 4 -
Testicular/Scrotal Mass: Adenomatoid Tumor
Esther Oliva, Mass General Hospital, Boston, MA
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A 76-year-old male was incidentally found to have a firm left testicular/scrotal mass of approximately 2 cm on physical exam. The patient had no known significant past clinical history. He underwent resection of the mass. On gross examination, the tumor measured 1.7 x 1.6 x 1.5 cm and was relatively well circumscribed with a white to tan, rubbery and homogeneous cut surface.
Case 4 - Figure 1
individual and interanastomosing tubules are present in a collagenous background.
Case 4 - Figure 2
interanastomosing cords and trabeculae are part of the tumor.
Case 4 - Figure 3
small tubules show prominent vacuoles within the tumor cells.
Case 4 - Figure 4
some tubules are lined by flattened cells and others are reminiscent of vascular spaces.
Case 4 - Figure 5
some tubules are reminiscent of true glands.
Case 4 - Figure 6
many cells have a signet-ring cell-like morphology.
Case 4 - Figure 7
close up shows round to oval nuclei with homogeneous chromatin and small nucleoli.
Case 4 - Figure 8
the tumor is associated at the periphery with a prominent lymphoid infiltrate forming lymphoid aggregates.
Pathological/Microscopic Findings and any Immunohistochemical or Other Studies:
On gross examination, the tumor measured 1.7 x 1.6 x 1.5 cm and was relatively well circumscribed with
a white to tan, rubbery, and homogeneous cut surface. On microscopic examination, the tumor was well
circumscribed but not encapsulated. It had a wide morphologic spectrum with tubules (some of them with a
gland-like appearance), cords and trabeculae and thread- like bridging strands. Tubules were most
prominent and either hollow or solid, simple or complex, and some were interanastomosing. The cells
lining the tubules were flattened or cuboidal, but many cells had abundant eosinophilic cytoplasm and
some may contain one or several small intracytoplasmic vacuoles (signet-ring-like). The nuclei were
round to oval with a small nucleolus and finely dispersed chromatin, and mitotic figures were lacking.
The stroma associated with the tumor was scant and hyalinized and had lymphoid aggregates at the
In this case no immunohistochemistry was performed.
The presence of a prominent adenomatoid growth, tubules, cords and trabeculae, and signet-ring-like
cells, are microscopic features that may cause concern for malignant mesothelioma, adenocarcinoma, sex
cord stromal tumor, and vascular tumor in this particular case.
Testicular/scrotal mass: Adenomatoid tumor
Adenomatoid tumor was initially coined as "benign mesothelioma of the genital tract" by Masson in 1942
but renamed as "adenomatoid tumor" by Golden and Ash in 1945 to convey the distinctive benign nature of
the neoplasm which has a mesothelial origin. It can be seen in both females and males. In the latter,
it accounts for approximately 30% of all testicular masses, and it is most commonly seen in the
epididymis (more often the head), followed by the spermatic cord arising typically from the tunica
albuginea and in some cases secondarily involving the testicular parenchyma. Rarely, adenomatoid tumors
can occur in other locations (liver, pancreas, mesocolon and omentum). Adenomatoid tumors are the most
common mesothelial neoplasms of the paratesticular region. Clinically, they often occur between the
third and fifth decades, and they are palpated or asymptomatic and rarely may cause acute scrotal pain
(especially when infarcted). On clinical examination, scrotal enlargement may be noticed. On
ultrasound, adenomatoid tumor appears hyperechoic and homogenous.
On gross examination, these benign neoplasms are usually solitary (but rarely can be multiple),
between 3 to 5 cm (although they can be up to 7.5 cm) in larger dimension with a solid, firm, white, gray
to tan cut surface. They are unencapsulated but well demarcated and often they have a crescent shape.
If massive infarction occurs, their consistency is soft, and they typically have a reddish cut surface.
On microscopic examination, adenomatoid tumors show a wide morphologic spectrum that mostly includes
tubular (gland- like), nested and corded, stranded (thread-like bridging strands) patterns, or commonly
admixture thereof. The tubules can be hollow or solid or cystically dilated with irregular outlines,
simple or complex, and/or interanastomosing (angiomatoid pattern). The tubules, nests, or cords can be
compacted, imparting a solid appearance. The cells lining the tubules are frequently flattened or
cuboidal, but cells often have abundant eosinophilic (some with oncocytic appearance) or amphophilic
cytoplasm, and some may contain one or several small intracytoplasmic vacuoles (signet-ring-like)
(present in all cases in one study). The nuclei are round to oval with a small nucleolus and finely
dispersed chromatin, and mitotic figures are scant. The stroma is typically minimal in amount, but it
may be abundant and hyalinized, may be associated with myxoid background, and may contain a lymphoid
infiltrate (sometimes forming lymphoid aggregates, being more common in tumors from males than females),
the latter more prevalent at the periphery of the tumor. Rarely, smooth muscle may be seen. Even though
adenomatoid tumors are grossly and microscopically well demarcated, the neoplastic cells may infiltrate
the testicular parenchyma. When associated with infarction, the central portion of the tumor appears
necrotic with pale mummified tumor cells identified at least focally. Often, necrosis is associated with
either exuberant granulation tissue with marked acute inflammatory infiltrate, edema, vascular
proliferation, and loose stroma (acute phase) or a prominent fibroblastic/myofibroblastic reaction that
show plump nuclei, prominent nucleoli, and some mitotic activity associated with collagen deposition
(chronic phase) that may impart a pseudoinfiltrative appearance. Viable tumor, however, is always seen
at the periphery of the tumor. Rarely, if the tumor is present close to the rete testis, the latter may
show hyperplastic changes.
Immunohistochemical profile of these tumors is as follows: Pankeratin (strong cytoplasmic and
membranous staining), EMA, calretinin (nuclear +/- accompanying cytoplasmic staining), D2-40 (membranous)
and WT1 (nuclear staining) typically positive, while CK5/6 is rarely positive (typically focal and weak
staining) and h-caldesmon appears to be consistently negative at least in one study of 12 testicular
adenomatoid tumors (Sangoi AR, et al, Modern Pathol 2009, 22:1228-1235). PAX2, PAX8, ER, PR, and AR are
also negative in adenomatoid tumors. These tumors have been reported to stain for GLUT-1. It is
important to keep in mind that WT1 staining can also be seen in epididymal epithelium and Sertoli and
Leydig cells while calretinin staining can be seen in Leydig cells but not in epididymal epithelium.
By electron microscopy, the tumor cells have slender microvilli, intracellular canaliculi, desmosomes,
and basal lamina.
The presence of a solid white growth, prominent adenomatoid growth, signet-ring-like cells, necrosis,
cytologic atypia (associated usually with necrosis) and pseudoinfiltration are microscopic features that
may cause concern for malignancy in these benign mesothelial tumors. Entities considered in the
differential diagnosis include: malignant mesothelioma, adenocarcinoma, malignant germ cell tumor, sex
cord stromal tumor, and vascular tumors.
Malignant mesothelioma is not an incidental finding but presents typically as multiple plaques,
nodules, or masses that may have a papillary growth coating the tunica albuginea/vaginalis. Although
both neoplasms share some histologic features, characteristics favoring malignant mesothelioma include
lack of circumscription, more rigid, rounded and hollow tubules, absent "adenomatoid" appearance with
irregular contours, striking papillary growth, and at least some degree of cytologic atypia. Prominent
cytoplasmic vacuoles are not a common feature of malignant mesothelioma. Immunohistochemistry is not
helpful in this differential diagnosis except for GLUT-1 that appears to stain both tumor types but with
a different staining pattern (strong linear membranous in malignant mesothelioma), but there is only very
limited experience, and caution should be used when interpreting this marker.
Primary or metastatic adenocarcinoma may be in the differential diagnosis if the adenomatoid tumor has
a large component of signet-ring-like cells or a prominent tubular growth. Absence of a prior malignant
process, absence of disease at other locations and lack of positivity for CD15, BerEp4, and CEA favor the
diagnosis of adenomatoid tumor. Primary rete testis carcinoma and tumors of Müllerian derivation also
are PAX2 and PAX 8 positive (nuclear staining) while these markers are negative in adenomatoid tumors.
Sex cord stromal tumors may be in the differential diagnosis as both neoplasms show overlapping
histologic and immunohistochemical features including the finding of cords and tubules, oxyphilic, and
vacuolated cells as well as positive staining for calretinin and WT1. However, sex cord stromal tumors
are typically centered in the testicular parenchyma; they lack other characteristic histologic patterns
seen in adenomatoid tumors which in turn are typically negative for inhibin.
The gross appearance of an adenomatoid tumor may overlap with that seen in seminoma, and confusion can
occur especially if the tumor is present within the testicular parenchyma. Both tumors have a prominent
inflammatory infiltrate mainly composed of lymphocytes. However, seminoma is typically composed of large
irregular nests or sheets of large primitive cells with cytologic atypia associated with brick mitotic
activity. The thread-like bridging strands or anastomosing tubules with flat to cuboidal cells may mimic
the growth patterns seen in yolk sac tumor, but the overall morphologic appearance is quite different
facilitating the diagnosis.
Vascular tumors that may enter in the differential diagnosis include epithelioid hemangioendothelioma
as these tumors may also have cells with abundant cytoplasm, intracytoplasmic vacuoles and
interanastomosing spaces. However, these tumors are typically positive for CD31, CD34, and other
As mentioned earlier, when a tumor is extensively infarcted it may be associated with a prominent
fibroblastic reaction. In these cases, the differential diagnosis includes inflammatory pseudotumor.
The latter is typically located in the spermatic cord, it is solitary, and it is composed of spindle cell
proliferation associated with a myxoid background. It also has striking vascularity and a variable
inflammatory infiltrate. Necrosis is uncommon in these fibroblastic proliferations, and no epithelial
elements appear admixed with it.
Adenomatoid tumors are associated with an excellent prognosis as they are benign neoplasms. It is
especially important to recognize these tumors in the frozen section as this can avoid more aggressive
It is important to be aware of this benign subtype of mesothelial tumor in order to avoid unnecesary
treatment as typically it occurs in young patients.
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