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Adenomatoid Tumors of the Testis: Report of a Case with a Focus on Histogenesis, Clinico-Pathologic Characteristics and Differential Diagnoses of These Rare Neoplasms

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Adenomatoid Tumors of the Testis: Report of a Case with a Focus on Histogenesis, Clinico-Pathologic Characteristics and Differential Diagnoses of These Rare Neoplasms WCRJ 2015; 2 (4): e606 ADENOMATOID TUMORS OF THE TESTIS: REPORT OF A CASE WITH A FOCUS ON HISTOGENESIS, CLINICO-PATHOLOGIC CHARACTERISTICS AND DIFFERENTIAL DIAGNOSES OF THESE RARE NEOPLASMS L. ALESSANDRINI1 , F. ITALIA3, T. PERIN1,2, A. LLESHI4, V. CANZONIERI1,2 1Division of Pathology, CRO Aviano National Cancer Institute, Aviano (PN) Italy; 2CRO-Biobank, CRO Aviano National Cancer Institute, Pordenone, Italy. 3Oncopath Lab, Floridia, SR, Italy. 4Medical Oncology A, CRO Aviano National Cancer Institute, Aviano (PN), Italy. ABSTRACT – Adenomatoid tumors (ATs) are relatively uncommon benign tumors usually arising in the paratesticular area. Among different theories proposed for its histogenesis, the most favored one seems to be the mesothelial origin, supported by different immunohistochemical and ultrastructural studies. As a consequence of the variety of morphologic patterns observed for ATs, the differential di- agnosis of these tumors is quite extensive, ranging from benign to malignant tumors of both epithe- lial and stromal origin. These tumors represent a diagnostic challenge due to their clinical signs similar to those of other testicular neoplasms and ultrasonography nonspecific findings. The importance of a correct diagnosis implies avoidance of unnecessary orchiectomy, thereby maintaining endogenous testosterone production and fertility potential at its fullest. Clinical outcome is excellent in all cases, with no published relapses, and follow-up by postoperative ultrasound is sufficient. We report a case of AT occurring in the tunica albuginea of the right testis in a 48-year-old man, referred to our Institute for a diagnostic revision. A brief review of the literature is also addressed, with a focus on histogenesis, clinico-pathologic characteristics and differential diagnoses of these rare neoplasms. INTRODUCTION ticular parenchyma4,5. Pediatric cases are considered very rare with only few reported cases5,6. The Au- ATs are relatively uncommon benign tumors usu- thors present a case of AT occurring in the tunica al- ally occurring in the male and female genital tracts. buginea of a 48-year-old man, referred to our The term adenomatoid tumor was first introduced Institute for a diagnostic revision. A brief review of by Golden and Ash in 19451 to describe a group of the current literature is also addressed, with a focus benign tumors of the urogenital tract, with a glan- on clinico-pathologic specific characteristic, histo- dular pattern and unknown histogenesis. Adenoma- genesis and differential diagnoses of these tumors. toid tumors are the most common paratesticular neoplasms and account for approximately 30% of all paratesticular masses2. The great majority of tu- CASE REPORT mors in men arise in the epididymis (about 77%), the testis sheath or tunica albuginea (about 22%), A 48-year-old man with a diagnosis of adenoma- and rarely in the spermatic cord (about 1%). Extra- toid tumor of the testis was referred in September genital adenomatoid tumors are rare and have been 2015 to our Institute for a second diagnostic opin- found in the adrenal glands, heart, mesentery, lymph ion. His clinical history started 5 months before, nodes, and pleura3. Occasionally, they grow into tes- when he presented a gradual increase in size of the Corresponding Author: Vincenzo Canzonieri, MD; e-mail: [email protected] 1 scrotum unassociated with pain or other symp- posed by Masson et al9 and subsequently supported toms. His physical examination was unremarkable, by reported cases of ATs at extragenital sites covered except for an approximately 1.5 cm nontender in- by serosal membrane3. Mesothelial origin of ATs has tratesticular mass. Scrotal ultrasonography re- been confirmed by ultrastructural and immunohisto- vealed a hypoechoic mass of the right testis, chemical studies of both male and female genital tract measuring 1.5 x 1 x 0.8 cm. However, serum tumor tumors. On transmission electron microscopy, this markers including alpha-fetoprotein and beta- tumor typically shows features in common with human chorionic gonadotropin were within normal mesothelial cells, that is prominent desmosomes, and limits. The patient subsequently underwent testis- long microvilli on the luminal surface of tumor acini sparing surgery, as preoperative imaging and clin- and on the surface of intercellular canaliculi10. The ical data were suggestive of a bening lesion. ultrastructural similarity between adenomatoid tu- Formalin-fixed, paraffin-embedded tissue samples mour, mesothelial cells and epithelioid mesothelioma were obtained, and 4-micron sections were stained has been observed and confirmed in several stud- with hematoxylin and eosin. 2.5-micron sections ies11,12. The similarity of ultrastructural features of were cut and immunohistochemical analysis was adenomatoid tumour and epididymal duct cells has performed in an automated system (Benchmark- also been noted and it has been suggested that ade- XT/Benchmark-ULTRA, Ventana, Tucson, AZ, nomatoid tumour is derived from coelomic cells as USA). The following primary antibodies were they differentiate towards genital epithelium13. For used: Pankeratin (AE1/AE3/pCk26, pre-diluted, what concerns immunohistochemistry, AT, as well as Ventana, Tucson, AZ, USA), Calretinin (SP65, mesothelial cells, universally express vimentin and prediluted, Ventana), vimentin (V9, prediluted, cytokeratin AE1/AE3, while cytokeratin 34βE12 ex- Ventana). Color was developed with 3.3’-di- pression is seen in 25% of cases14. Epithelial mem- aminobenzidine (DAB) and slides were counter- brane antigen is present in both the cytoplasm and stained with Meyer’s hematoxylin. Appropriate cell membrane of tumor cells 14. Thrombomodulin is positive and negative controls run concurrently. all expressed on the surface of microvilli of the aci- Postoperative histopathologic examination of nar component of the tumor, while staining is seen in the mass demonstrated a well-demarcated vaguely occasional cells in the cords of the solid component. nodular lesion measuring 1 cm in maximum di- Both solid and acinar areas are strongly positive for ameter, composed of irregularly arranged tubules calretinin15,16. Markers expressed in a variety of car- and gland-like structures with eosinophilic cells, cinomas such as Leu M1, AUA-1, CA19.9, Ber-EP4, embedded in a fibrous stroma containing lymphoid CEA, HEA-125, B72.3, MOC-31, and LEA.135 are aggregates (Figure 1 A,B). Immunohistochemical all negative, as are markers of endothelial cells staining showed a diffuse and strong positivity in (CD34 and factor VIII). Negative expression of p53 neoplastic cells for Calretinin, Pancytokeratins and is consistent with the benign nature of these tumors14. Vimentin (Figure 2 A-C). In the present case, tumor cells were positive Two pathologists revised the case in our Insti- for Calretinin, Cytokeratins and Vimentin, accord- tute and diagnosis was confirmed. ing to literature data. There was no history of testicular tumor or any Macro and microscopic features of ATs could be other tumor in the family. At 3 months follow-up of help to identify the lesion. During gross examina- examination, the patient was asymptomatic, and tion, it is usually clear that the neoplasm is parates- scrotal ultrasound scan showed no evidence of ticular or juxtatesticular. Very rarely the testicular local recurrence. parenchymal involvement is so extensive to give the gross impression of a “bona fide” testicular neoplasm. Their size is up to about 7 cm with the majority being DISCUSSION in the range of 3-5 cm. The tumor is grossly well cir- cumscribed and oval to crescent-shaped. It is typi- Adenomatoid tumors are rare and benign tumors of cally white and firm on cut surface. ATs have a the male and female genital tract, whose histogenesis plethora of microscopic appearances represented by has been a source of controversy for years. In early three basic patterns: tubules, cords, and small nests studies AT was thought to be derived from lined by or formed of cells that are cuboidal with mesonephric (Wolffian) remnants due to its apparent moderate to occasionally abundant eosinophilic, am- localization exclusively within the genital tract7. Con- phophilic or vacuolated cytoplasm. Severe atypia and versely a paramesonephric (Mullerian) origin has also mitoses are usually absent17-19. An irregular disposi- been proposed for ATs because of an observed conti- tion of tubules, cords and nests within a prominent nuity of Fallopian tube or appendix testis epithelium fibrous stroma may suggest infiltration and bring into with adjacent tumour acini8. The first hypothesis of a consideration diverse entities such as malignant mesothelial origin for adenomatoid tumour was pro- mesothelioma and secondary carcinoma20. AT, al- 2 ADENOMATOID TUMOR, TESTIS, MESOTHELIAL CELLS Figure 1. A, Vaguely nodular lesion composed of haphazardly arranged tubules and gland-like structures (Hematoxylin & eosin, 25x original magnification). B, The lesion displays distorted tubules and glands in a fibrous stroma; a small lymphocyte aggre- gate is identifiable on top left corner (Hematoxylin& eosin, 100x original magnification). C, Higher magnification shows gland- like structures lined by bland cells. Mitoses are absent (Hematoxylin& eosin, 400x original magnification). though grossly circumscribed, often infiltrates mi- greater degree of nuclear pleomorphism. The ab- croscopically between the testicular tubules, a finding sence of staining of epithelial markers is of utility that should not be misinterpreted
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