CASE OF THE WEEK
66-year-old male with past medical history of prostate cancer presented with an increasing size of a chronic hydrocele causing progressive urination difficulty. CT revealed a large 14 cm left hydrocele causing mass effect on the testis with vascularized nodularity surrounding the testis and extending along the wall of scrotum. He subsequently underwent radical orchiectomy of the left testis and hydrocelectomy. Male patient in his 60s with chronic hydrocele causing urination difficulty Contributors :
Li Li, MD, PhD. Pathology Sciences Medical Group (PSMG), EVMS, Sentara Health System, Norfolk, Virginia
Morgan Rouse, student. Virginia.
What is the correct diagnosis?
Adenocarcinoma of the epididymis
Adenocarcinoma of the rete testis
Papillary serous carcinoma
Yolk sac tumor
Well-differentiated papillary mesothelial tumor
1: Well-differentiated papillary mesothelial tumor
Paratesticular Mesothelioma
Mesotheliomas of the testis are rare neoplasms, accounting for < 1% of all mesotheliomas. (1) Known potential risk factors include asbestos exposure, trauma, herniorrhaphy and longstanding hydrocele. On histologic examination, testicular mesotheliomas resemble mesothelial tumors found in other locations, displaying subtypes such as epithelial, sarcomatoid, and biphasic morphologies with varying degrees of differentiation. In epithelial neoplasms, epithelioid cells with characteristic pale, elongated nuclei arise from epithelial linings such as the tunica vaginalis. In the biphasic type, clusters of spindle cells accompany the epithelioid cells. The sarcomatoid subtype is characterized by a predominance of spindle cell morphology. Other features include papillary or tubular architecture. Tumor morphology is also associated with stromal desmoplasia, moderate pleomorphism, and mitoses.
The major prognostic factors include the presence of metastasis and tumor grade. The differential for tumors arising from the tunica vaginalis include adenomatoid, well-differentiated papillary mesothelial, germ cell tumor, pleomorphic sarcoma, serous papillary tumor, and metastatic malignancy. On immunostaining, testicular mesotheliomas show positivity for AE1/AE3, EMA, calretinin, D2-40, CK5/6, WT-1, CK7, thrombomodulin, and vimentin. They are typically negative for CEA, CK20, CD15 (LeuM1), and BerEP4.
In our case, gross examination revealed a 14 cm intracystic growth tumor exhibiting papillary, tubulopapillary, and micropapillary growth patterns. The tumor cells were characterized by epithelioid appearance with abundant eosinophilic cytoplasm and large, round nuclei with vesicular chromatin and prominent features (Fig. 1, H&E stain). Focal infiltration into the underlying fibroid stroma of the tunica vaginalis was present, but there was no invasion into the testicular parenchyma, rete testis, or epididymis (Fig. 1a). Immunohistochemistry staining was performed (Figure 2). The tumor cells were positive for AE1/AE3, CK7, WT-1, and D2-40, but negative for CK20 and BerEP4. Interestingly, EMA and CK5/6 were also negative in this tumor. Additionally, Glypican 3, Claudin 4, and SALL4, markers for yolk sac tumors, adenocarcinomas, and germ cell tumors respectively, were negative in this case. (2-4)
Given the infrequency of testicular mesotheliomas, it is important to evaluate individual presentations and compare them to available data. A recent case series noted infiltration of testicular parenchyma in just 5 of 13 malignant mesothelioma cases. (5) This study also found that BAP1 and MTAP were each lost in just ~20% of mesothelioma of the tunica vaginalis. Interestingly, loss of Merlin, a tumor suppressor and gene product of NF2, in conjunction with BAP1 and MTAP, has been used to distinguish mesotheliomas with high sensitivity. (6) Our patient’s tumor showed normal retained expression of BAP1, MTAP (heterogenous staining pattern), and Merlin.
While rare, understanding important correlates between the clinical presentation and the histological and molecular phenotype of testicular mesotheliomas will aid in diagnosis and broaden differentials in the work-up of related cases. Furthermore, improved understanding of this unique pathology is gained through detailed analysis of each case.
1. Gordetsky J, Rane S. Mesothelioma. PathologyOutlines.com website. Accessed April 24, 2024.
2. Esheba GE, Pate LL, Longacre TA. Oncofetal protein glypican-3 distinguishes yolk sac tumor from clear cell carcinoma of the ovary. Am J Surg Pathol, 2008.
3. Jo VY, Cibas ES, Pinkus GS. Claudin-4 immunohistochemistry is highly effective in distinguishing adenocarcinoma from malignant mesothelioma in effusion cytology. Cancer Cytopathol, 2014.
4. Miettinen M, Wang Z, McCue PA, Sarlomo-Rikala M, Rys J, Biernat W, Lasota J, Lee YS. SALL4 expression in germ cell and non-germ cell tumors: a systematic immunohistochemical study of 3215 cases. Am J Surg Pathol, 2014.
5. Anderson WJ, Sholl LM, Fletcher CDM, Schulte S, Wang LJ, Maclean FM, Hirsch MS. Molecular and immunohistochemical characterisation of mesothelioma of the tunica vaginalis. Histopathology, 2022.
6. Chapel DB, Hornick JL, Barlow J, Bueno R, Sholl LM. Clinical and molecular validation of BAP1, MTAP, P53, and Merlin immunohistochemistry in diagnosis of pleural mesothelioma. Mod Pathol, 2022.
Li Li, MD, PhD. Pathology Sciences Medical Group (PSMG), EVMS, Sentara Health System, Norfolk, Virginia
Morgan Rouse, student. Virginia.
Testicle
paratesticular mesothelioma, BAP1, MTAP