Case 4 -

Testicular/Scrotal Mass: Adenomatoid Tumor Esther Oliva, Mass General Hospital, Boston, MA

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Clinical History 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 periphery. In this case no immunohistochemistry was performed. Differential Diagnoses: 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. Final Diagnosis: Testicular/scrotal mass: Adenomatoid tumor Discussion: 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 vascular markers. 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 surgery. Conclusion(s): 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. References: Alexiev, B. A., L. F. Xu, et al. (2011). "Adenomatoid Tumor of the Testis With Intratesticular Growth: A Case Report and Review of the Literature." Int J Surg Pathol. Amin, M. B. (2005). "Selected other problematic testicular and paratesticular lesions: rete testis neoplasms and pseudotumors, mesothelial lesions and secondary tumors." Mod Pathol 18 Suppl 2: S131-145. Amin, W. and A. V. Parwani (2009). "Adenomatoid tumor of testis." Clin Med Pathol 2: 17-22. Banks, E. R. and S. E. Mills (1990). "Histiocytoid (epithelioid) hemangioma of the testis. The so-called vascular variant of "adenomatoid tumor"." Am J Surg Pathol 14: 584-589. Cao, D., J. Li, et al. (2009). "SALL4 is a novel diagnostic marker for testicular germ cell tumors." Am J Surg Pathol 33: 1065-1077. Cheng, C. L. and A. Wee (2003). "Diffuse uterine adenomatoid tumor in an immunosuppressed renal transplant recipient." Int J Gynecol Pathol 22: 198-201. Churg, A. (2003). "Paratesticular mesothelial proliferations." Semin Diagn Pathol 20: 272-278. Delahunt, B., J. N. Eble, et al. (2000). "Immunohistochemical evidence for mesothelial origin of paratesticular adenomatoid tumour." Histopathology 36: 109-115. Evans, K. (2004). "Rapidly growing adenomatoid tumor extending into testicular parenchyma mimics testicular carcinoma." Urology 64: 589. Garg, K., P. Lee, et al. (2005). "Adenomatoid tumor of the adrenal gland: a clinicopathologic study of 3 cases." Ann Diagn Pathol 9: 11-15. Gupta, R., R. S. Howell, et al. (2009). "Paratesticular paraganglioma: a rare cause of an intrascrotal mass." Arch Pathol Lab Med 133: 811-813. Isotalo, P. A., G. L. Keeney, et al. (2003). "Adenomatoid tumor of the adrenal gland: a clinicopathologic study of five cases and review of the literature." Am J Surg Pathol 27: 969-977. Jones, T. D., T. M. Ulbright, et al. (2004). "OCT4 staining in testicular tumors: a sensitive and specific marker for seminoma and embryonal carcinoma." Am J Surg Pathol 28: 935-940. Lugli, A., Y. Forster, et al. (2003). "Calretinin expression in human normal and neoplastic tissues: a tissue microarray analysis on 5233 tissue samples." Hum Pathol 34: 994-1000. Manson, A. L. (1988). "Adenomatoid tumor of testicular tunica albuginea mimicking testicular carcinoma." J Urol 139: 819-820. Moch, H., H. Ohnacker, et al. (1994). "A new case of malignant mesothelioma of the tunica vaginalis testis. Immunohistochemistry in comparison with an adenomatoid tumor of the testis." Pathol Res Pract 190: 400-404; discussion 404-408. Monappa, V., A. C. Rao, et al. (2009). "Adenomatoid tumor of tunica albuginea mimicking seminoma on fine needle aspiration cytology: a case report." Acta Cytol 53: 349-352. Nagata, S., S. Aishima, et al. (2008). "Adenomatoid tumour of the liver." J Clin Pathol 61: 777-780. Ordonez, N. G. (2003). "Application of mesothelin immunostaining in tumor diagnosis." Am J Surg Pathol 27: 1418-1428. Passman, C., D. Urban, et al. (2009). "Testicular lesions other than germ cell tumours: feasibility of testis-sparing surgery." BJU Int 103: 488-491. Perez-Ordonez, B. and J. R. Srigley (2000). "Mesothelial lesions of the paratesticular region." Semin Diagn Pathol 17: 294-306. Sangoi, A. R., J. K. McKenney, et al. (2009). "Adenomatoid tumors of the female and male genital tracts: a clinicopathological and immunohistochemical study of 44 cases." Mod Pathol 22: 1228-1235. Schwartz, E. J. and T. A. Longacre (2004). "Adenomatoid tumors of the female and male genital tracts express WT1." Int J Gynecol Pathol 23: 123- 128. Skinnider, B. F. and R. H. Young (2004). "Infarcted adenomatoid tumor: a report of five cases of a facet of a benign neoplasm that may cause diagnostic difficulty." Am J Surg Pathol 28: 77-83. Soini, Y. and A. Talvensaari-Mattila (2006). "Expression of claudins 1, 4, 5, and 7 in ovarian tumors of diverse types." Int J Gynecol Pathol 25: 330-335. Tong, G. X., L. Memeo, et al. (2011). "PAX8 and PAX2 immunostaining facilitates the diagnosis of primary epithelial neoplasms of the male genital tract." Am J Surg Pathol 35: 1473-1483. Wachter, D. L., P. H. Wunsch, et al. (2011). "Adenomatoid tumors of the female and male genital tract. A comparative clinicopathologic and immunohistochemical analysis of 47 cases emphasizing their site-specific morphologic diversity." Virchows Arch 458: 593-602. Weissferdt, A., N. Kalhor, et al. (2011). "Malignant mesothelioma with prominent adenomatoid features: a clinicopathologic and immunohistochemical study of 10 cases." Ann Diagn Pathol 15: 25-29. Young, R. H. (2008). "Testicular tumors--some new and a few perennial problems." Arch Pathol Lab Med 132: 548-564.