Merkel cell polyomavirus (MCPyV) is a DNA virus whose pathogenic mechanisms

Merkel cell polyomavirus (MCPyV) is a DNA virus whose pathogenic mechanisms in Merkel cell carcinoma (MCC) are still being unraveled. this context we discuss the differential diagnostic considerations especially with cutaneous Richter transformation (diffuse large B-cell lymphoma). We also assessed for the presence of MCPyV in both the patient’s MCC and the CLL. Finally we provide a large meta-analysis of patients with CLL and MCC. Patients with both MCC and CLL have a dismal prognosis with greater than 50% overall mortality within the first year and a half after MCC diagnosis. Keywords: Merkel cell polyomavirus Merkel cell carcinoma chronic lymphocytic lymphoma Richter transformation Introduction Merkel cell carcinoma (MCC) is an aggressive neuroendocrine tumor occurring most often in the skin of elderly patients some of which are immunocompromised.(1) Merkel cell polyomavirus (MCPyV) is a non-enveloped double stranded human DNA virus detected and implicated in the pathogenesis of MCC.(2-7) Because patients with chronic lymphocytic lymphoma GSK2801 (CLL) have altered immunologic status related to their disease burden they are at higher risk for developing a range of secondary malignancies with MCC Cntn6 being one of the more potentially aggressive.(8 9 In fact a GSK2801 possible pathogenic link between MCC and CLL is usually suggested by the respective increased incidence of either cancer (MCC or CLL) occurring in patients with one or the other cancer types.(10-12) We present a case of primary cutaneous MCC mimicking a large B-cell transformation in a patient with CLL assess for the presence of MCPyV and perform a metanalysis of comparable reported cases. Case Report A 65 year old male with a 7 year history of CLL presented with a single 2.0 cm subcutaneous nodule near the medial epicondyle. At this time he was being evaluated for treatment of his CLL as he had developed thrombocytopenia splenomegaly and fatigue related to his disease. The initial impression was that the lesion was felt to be most likely adenopathy related to progressive CLL. He underwent 2 cycles of treatment with fludarabine/cyclophosphamide/rituximab (FCR) at which point the upper extremity lesion was noted to progress rapidly in size without progression of CLL elsewhere. Due to the location of the lesion clinical progression and lack of overlying epidermal change the differential diagnosis was expanded to include an enlarged trochlear lymph node a deeply infiltrative tumor or an abscess. An excisional biopsy exhibited a deep atypical homogeneous infiltrate of medium to large cells with regular round nuclear contours and vesicular to granular chromatin (fig. 1A). Overt nuclear molding was not readily identified. While no superficial dermal or epidermal involvement was noted no definitive capsular nodal tissue was identified either. Due to the clinical picture and lack of more definitive epidermal involvement the differential diagnosis included a transformed CLL (ie Richter transformation in the form of deep dermal/subcutaneous diffuse large B-cell lymphoma). The cells were unfavorable for CD3/CD5/CD23 and CD20 by IHC. Because the patient was treated with rituximab (a humanized anti-CD20 antibody) the unfavorable CD20 finding was not unexpected and additional hematolymphoid and B-cell markers were employed. The tumor cells were PAX5 positive (fig. 1B) and TdT was also positive in 10% of the tumor nuclei (fig. 1C). Due to the granular chromatin pattern and lack of prominent nucleoli tumor cells were stained with and positive for pancytokeratin CK20 (fig. 2A) chromagranin GSK2801 (fig. 2B) and CK8/18. CK7 was unfavorable. The diagnosis of a deep dermal MCC with subcutaneous involvement was made. The lesion recurred locally after 1 month. At five months metastatic disease was noted in the skin axillary lymph node and lung. The patient was dead of disease at 10 months. Physique 1 A) Merkel cell carcinoma with granular chromatin pattern (H&E 200x). B) Diffuse staining for PAX-5 (200x) and C) partial nuclear staining for TdT (200x). Physique 2 A) Merkel cell carcinoma cells staining diffusely positive for CK20 GSK2801 (with distinctive paranuclear dot-like pattern characteristic of MCC) and B) chromogranin (both 200x) In order to investigate for the presence of MCPyV we performed PCR amplification of a ~350 bp segment of the MCPyV large-T antigen from the primary and relapse MCC GSK2801 specimens GSK2801 as well as CLL-involved bone marrow and normal fat tissue (Physique 3). This was accomplished by extracting total DNA and de-crosslinking followed by PCR and Sanger.