Testicular Adenomatoid Tumor Pathology 

An adenomatoid tumor is a benign neoplasm of mesothelial origin that can be found in both female and male genital tracts, but it is more commonly found in the male adnexa, where it is the most common benign neoplasm.

Adenomatoid tumors represent 30% of the tumors of the testicular adnexa and 60% of benign tumors of these structures. Beccia et al studied 314 epididymis tumors, of which 75% were benign and 73% of those were diagnosed as adenomatoid tumors, followed by leiomyomas (11%), and papillary cystoadenomas of the epididymis (9%).[1] These tumors are commonly incidental findings, most often seen in patients in the third through fifth decades, although one case in a 70-year-old patient has been reported[2] and another in boy younger than 5 years.[3]

The mesothelial origin of adenomatoid tumors is currently accepted based on ultrastructural and immunohistochemical analyses.[4, 5, 6, 7, 8] It was first suggested by Evans in 1943[9] but refuted by Golden and Ash,[10] who proposed the term "adenomatoid tumor" that is now accepted and in widespread use.

Adenomatoid tumors are most commonly located in the male genital tract, in the lower pole of the epididymis, followed by the tunica vaginalis and spermatic cord. Extragenital tumors have also been described[11] in places such as the adrenal gland,[12, 13] lymph nodes,[14] mediastinum,[15] heart, pancreas,[16] and pleura.[17] The involvement of the mesocolon and omentum has also been reported.[18, 19]

These tumors usually present clinically as a solid, hyperechoic, well-circumscribed mass, between 1 and 5 cm, although a 6-cm adenomatoid tumor has been reported.[4] Adenomatoid tumors typically have no distinct growth pattern. In the epididymis and testicle, these lesions can cause pain and demonstrate a palpable mass. Dell'atti reports a case diagnosed with testicular ultrasound.[20]

Grossly, adenomatoid tumors appear as small, solid, firm, grayish white nodules; they are usually well circumscribed and occasionally contain small cysts.

Microscopically, the adenomatoid lesion is unencapsulated, and on rare occasions, it may extend to the testicular parenchyma (most often tumors of the upper pole). There is a proliferation of cells ranging from cuboidal to flattened, which form solid cords with an epithelial appearance alternating with tubular and angiomatoid spaces (see the following images). These cells have weakly acidophil and markedly vacuolated cytoplasm, without prominent nucleoli and little to no mitotic activity. The surrounding stroma is fibrous, sometimes hyalinized, and may contain abundant smooth muscle and elastic fibers, with inner lymphoid aggregates.

Low magnification of adenomatoid tumor showing cords of cells in parallel and haphazard orientation.

Medium magnification showing cords of bland cells with abundant pink cytoplasm and focal vacuolization.

In this example, the vacuoles are more numerous with coalescence. Scattered inflammatory cells are also seen.

Cords of adenomatoid tumor cells with focal lymphoid infiltrate.

The 3 patterns of adenomatoid tumors recognized by Taxy et al are plexiform, tubular, and canalicular, with most cases showing a mixture of multiple patterns.[5] Tiltman subsequently used the same classification for tumors of the female genital tract.[21] Quigley and Hart described 4 other histologic patterns that were similar to the ones described by Taxy[22] :

• Adenomatoid (tubular): Characterized by glandular structures, irregularly lined by cuboidal cells, some of which have vacuolated cytoplasm, resembling signet ring cells (see the images below)

  There are cords of tumor cells with focal vacuolization and also glandlike structures (center).

  Cytologic features of adenomatoid tumor cells. They have abundant pink cytoplasm, eccentric nuclei, with central and small nucleoli. Lymphocytes are common. Intervening hyalinization of stroma is common, a well as smooth muscle hyperplasia (not shown).

• Angiomatoid (canalicular): Consist of wide pseudovascular spaces, composed of flattened cells, scant cytoplasm, with an endothelial appearance

• Solid (plexiform): Formed by solid cords of cells with abundant, eosinophilic cytoplasm, with an epithelial-like appearance

• Cystic (mixed): A rare form, characterized by big, cystic cavities separated by fibrous septa, and lined by flattened to cuboidal cells

Other histologic findings include tumors with infarcted areas, abundant fibroblastic and myofibroblastic proliferation, and also increased mitotic activity, which can occasionally make the diagnosis difficult.

The mesothelial origin of adenomatoid tumors is proved by its positivity for calretinin and epithelial markers, such as AE1AE3, epithelial membrane antigen (EMA), Cam5.2, CK5/6, and CK7 (see the following images). The latter 2 markers (CK5/6, CK7) may be only focally positive. Endothelial markers such as CD31 and CD34 are negative. In difficult cases, in which the differential diagnosis is metastatic adenocarcinoma, a panel to include markers that are positive in carcinoma and not in mesothelial proliferation may include carcinoembryonic antigen (CEA), factor VIII-related antigen, HBME-1,MOC31, BER-EP4, B72.3, and CD15.

High-power image of calretinin immunohistochemical study showing both cytoplasmic and nuclear positivity.

Low-power image showing strong and diffuse positivity for pan-cytokeratin.

Adenomatoid tumors are negative for germ cell tumor markers such as OCT3/4, Nanog, Sox-2, alpha-fetoprotein (AFP), placental alkaline phosphatase (PLAP), CD117, and CD30, in the rare occasions in which the hematoxylin and eosin (H&E) evaluation alone does not readily render a diagnosis of the tumor.

No specific genetic abnormalities have been found in adenomatoid tumors.

Adenomatoid tumors are uniformly benign neoplasms. In selected cases, these tumors can encroach the testicular adnexal structures and mimic a malignant proliferation on imaging. Frozen section diagnosis can readily establish the diagnosis in typical cases and allow for testicle-sparing surgery.[23, 24]

Mesothelioma, Malignant

Metastatic Adenocarcinoma

Papillary Cystadenoma of the Epididymis