Dermatology: Practical and Conceptual Letter to the Editor | Dermatol Pract Concept. 2023;13(4):e2023213 1 Merkel Cell Carcinoma: Mind the Genital Metastatic Sites! Giacomo Santandrea1,4, Stefania Borsari2, Angelina Filice3, Simonetta Piana1 1 Pathology Unit, Arcispedale Santa Maria Nuova, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy 2 Centro Oncologico ad Alta Tecnologia Diagnostica-Skin Cancer Center, Azienda USL– IRCCS di Reggio Emilia, Reggio Emilia, Italy 3 Nuclear Medicine Unit, Arcispedale Santa Maria Nuova, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy 4 Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, Modena, Italy Citation: Santandrea G, Borsari S, Filice A, Piana S. Merkel Cell Carcinoma: Mind The Genital Metastatic Sites! Dermatol Pract Concept. 2023;13(4):e2023213. DOI: https://doi.org/10.5826/dpc.1304a213 Accepted: April 26, 2023; Published: October 2023 Copyright: ©2023 Santandrea et al. This is an open-access article distributed under the terms of the Creative Commons Attribution- NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited. Funding: None. Competing Interests: None. Authorship: All authors have contributed significantly to this publication. Corresponding Author: Dr. Simonetta Piana, Pathology Unit, Azienda USL-IRCCS Reggio Emilia, Viale Risorgimento 80, Reggio Emilia, Italy. TEL +39 0522 295919 FAX +39 0522 296945 E-mail: Simonetta.Piana@ausl.re.it To the Editor, Merkel cell carcinoma (MCC) is a rare neuroendocrine tumor of the skin, presenting mostly in sun-exposed site of Caucasian elderly patients. The median age is 75 years, with less than 5% of patients younger than 50 years. MCC is associated with immunosuppression and its incidence is increasing worldwide. Merkel cell polyomavirus (MCPyV), demonstrated either immunohistochemically or by PCR in a subset of MCC, and the UV damage are probably inter- related etiopathogenetic agents. Even if, in the past, it was considered almost indolent, now it is classified as a high- grade malignancy, especially because it often disseminates distantly. After lymph nodes, the most common sites of dis- tant metastases are skin/soft tissue (25%), liver (23%), bone (21%), pancreas (8%), lung (7%) and brain (5%) [1]. As a result, during staging procedures, the aforementioned body sites must be evaluated carefully as regional lymph nodes. However, rare metastatic sites may occur, and they can be overlooked; genitourinary tract and specifically testes can represent a neglected metastatic localization. A man, aged 50 years, was diagnosed with a skin MCC of left knee. The lesion was located in the deep dermis and measured 1 cm in the greatest axis. As expected, MCC re- sulted immunohistochemically positive with chromogranin and keratin 20, but it was also immunoreactive with MCPyV antibody. He underwent a tumor excision, followed by a negative sentinel lymph node procedure and a Computed Tomography (CT) scan, which ruled out any metastases. Nine months later, on the Positron Emission Tomography– Computed Tomography scan with 2-deoxy-2-[ 18F] fluoro-D-glucose (2-[ 18F]FDG PET/CT), performed for rou- tine follow-up, a 4-centimeter solid mass with a high uptake ( SUVmax 10), was found in the right testis (Figure 1). A right radical orchiectomy was performed, with the suspicion of a germ cell tumor. At histology, the mass was composed 2 Letter to the Editor | Dermatol Pract Concept. 2023;13(4):e2023213 Figure 1. (A) [18F]F-FDG PET/CT transaxial images with low-dose CT. (B) PET. (C) Image fused PET/CT. (D) Maximum intensity projection (MIP). The red arrows in images B, C and D, shows a focal uptake (SUVmax 10) in the right testis. of neoplastic epithelial cells with fine granular chromatin and nuclear molding (Figure 2A), immunohistochemically positive with keratin 20 (Figure 2B) and chromogranin. Anti MCPyV antibody was positive as well (Figure 2C). Overall, morphological findings were suggestive of a metastasis from a MCC. A subsequent total body CT scan excluded any fur- ther localization. Testis is a very rare metastatic site from MCC [2-6]. In a recent review [6], only eleven cases of testicular MCC metas- tases are reported in literature. At variance with the present cases, most patients presented with already advanced or lo- cally advanced stage at diagnosis. According to the authors, single testis metastasis does not necessarily mean a systemic disease as the patients without other extra-testicular local- ization experimented a survival longer than 1 year [6]. In MCC, the main prognostic factors are regional and distant metastases. If localized, MCC carries the best prog- nosis (50.6% 5-year overall survival [OS] rate ). In regional and distant disease, 5-year OS was estimated to be 35.4% and 13.5%, respectively [1]. The surveillance strategies during follow up are therefore crucial. As examination of the genitals is not usually included in routine follow-up of MCC, dermatologists should at least advice patients on self-examination. Letter to the Editor | Dermatol Pract Concept. 2023;13(4):e2023213 3 References 1. Gauci ML, Aristei C, Becker JC, et al. Diagnosis and treatment of  Merkel  cell  carcinoma: European consensus-based inter- disciplinary guideline - Update 2022. Eur J Cancer. 2022;171: 203-231. DOI: 10.1016/j.ejca.2022.03.043. PMID: 35732101. 2. Tummala MK, Hausner PF, McGuire WP, Gipson T, Berk- man A. Case 1. Testis: a sanctuary site in Merkel cell carci- noma. J Clin Oncol. 2006;24(6):1008–1009. DOI: 10.1200 /JCO.2005.01.7103. PMID: 16484705. 3. Whitman EJ, Brassell SA, Rosner IL, Moncur JT. Merkel cell carcinoma as a solitary metastasis to the testis. J Clin Oncol. 2007;25(24):3785–3786. DOI: 10.1200/JCO.2007.12.3091. PMID: 17704430. 4. Mweempwa A, Tan A, Dray M. Recurrent Merkel cell carcinoma of the testis with unknown primary site: a case report. J Med Case Rep. 2016 10(1):314. DOI: 10.1186/s13256-016-1102-5 .PMID: 27814751. PMCID: PMC5097413. 5. Gigliano D, Lobo J, Lopes P, et al. Merkel cell carcinoma met- astatic to the  testis: report of a rare diagnosis and review of the literature. Autops Case Rep. 2020;11:e2020198. DOI: 10.4322/acr.2020.198. PMID:  34277480. PMCID: PMC8101657. 6. Laffi A, Cozzi G, Spada F, et al. Metachronous testicular me- tastases from Merkel cell Carcinoma (MCC): a case report and literature review. Am J Case Rep. 2022;23:e936552. DOI: 10.12659/AJCR.936552. PMID:  36031755. PMCID: PMC9438938. Figure 2. (A) MCC growing through the seminiferous tubules of the testicular parenchyma. (B) MCC immunohistochemical positivity with cytokeratin 20. (C) MCPyV is detected in neoplastic cells.