COW-2020-03

1. b
2. c

1. Adenomatoid tumor
2. Calretinin

The lesion arises in the paratesticular region. The testis showed normal spermatogenesis (not shown). On low power the lesion is circumscribed, non-encapsulated with lymphoid aggregates at the periphery. The lesion has a varied growth pattern consisting of glands, tubules, cords, small nests and occasional single cells. The stroma is fibrous with lymphocytes dispersed throughout. On higher magnification the tubes, chords and cysts are formed and lined by cuboidal to flat epithelial cells with eosinophilic cytoplasm and cytoplasmic vacuoles. Some single cells with small cytoplasmic vacuoles resemble signet ring cells. Many cells lining the tubules and glands have vacuoles of considerable sizes, imparting a microcystic appearance. The nuclei are round and bland, lacking nucleoli; mitosis and necrosis are absent. Immunostains for epithelial markers (AE1/3 and 34betaE12, not shown) and mesothelial marker (calretinin) are positive, confirming the diagnosis of adenomatoid tumor.
Adenomatoid tumors are rare, yet account for 30% of all paratesticular tumors. They are benign tumors of mesothelial origin. It may be intratesticular infiltrating between testicular tubules, which should not be interpreted as evidence of malignancy. Key histological features including circumscribed lesion, varied growth pattern, prominent lymphoid aggregates, vacuolated cytoplasm, lack of mitosis and positivity for epithelial (AE1/3, 34betaE12) and mesothelial markers (WT-1, D2-40, calretinin) support the diagnosis.
Due to the wide spectrum of morphological patterns, the differential diagnosis for adenomatoid tumors is broad and includes primary and metastatic adenocarcinoma of testis, vascular tumors, malignant mesothelioma, germ cell tumor especially yolk sac tumor, and other sex cord stroma tumors such as Leydig cell tumor and Sertoli cell tumor.
Rarely malignant mesothelioma of the paratestis enters the differential diagnosis when the lesion is florid and extends into the testis. Presence of flank cytological atypia, increased mitosis, presence of tumor necrosis and vascular invasion should raise the concern for mesothelioma. Homozygous deletion of p16 supports the diagnosis of a mesothelioma.
When an adenomatoid tumor exhibits extensive cytoplasmic vacuolation, a yolk sac tumor may be suspected. Yolk sac tumors have a higher degree of nuclear pleomorphism and lack the desmoplastic stroma seen in adenomatoid tumors. Additionally, yolk sac tumors stain positive for AFP and glypican-3, unlike adenomatoid tumors.
The dilated cystic and tubular spaces in adenomatoid tumors may be mistaken for a vascular lesion. However immunohistochemistry for vacular markers (CD34 and factor VIII) will be negative in adenomatoid tumors.
Adenocarcinomas, both primary and metastatic, will stain positive for CEA, MOC3 and Ber-ep4 (4), which are negative in adenomatoid tumors.

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Stephanie J. Conrad, Ming Zhou
Tufts Medical Center
sconrad@tuftsmedicalcenter.org

Testis

Adenomatoid, mesothelial, paratestis