Merkel cell carcinoma in a patient with B-cell chronic lymphocytic leukemia treated with cladribine and rituximab

Abstract

Merkel cell carcinoma (MCC) is an uncommon, neuroendocrine skin tumor with an aggressive clinical course. The etiology of the disease is unknown, although sun exposure and immunosuppression may play a role in its development. Coexistence of MCC with chronic lymphocytic leukemia (CLL) is extremely rare and to our knowledge it has been previously described in only 8 patients. We report a 51-year-old woman who presented with a red lump on the right cheek diagnosed as MCC. She had been diagnosed as having CLL 3 years earlier and was treated with 4 courses of cladribine (2-CdA) and subsequently with 4 courses of 2-CdA combined with rituximab. MCC was diagnosed on the basis of histological and immunohistochemical evaluation 2 months after the last course of 2-CdA and rituximab. Surgical excision with tumor-free margins was performed and local adjuvant radiotherapy was applied. Histopathological and immunohistochemical evaluation of the cervical lymph node specimens showed monotonous and diffuse infiltrate of small CD5+, CD20+, CD23+ lymphocytes and no MCC cells were present. To our knowledge, this is the first reported case of MCC occurring in CLL patients soon after treatment with 2-CdA and/or rituximab. The development of MCC in our patient may suggest that this complication rarely observed in CLL patients may have a link with strongly immunosuppressive therapy with 2-CdA and rituximab.

Merkel Cell Carcinomas Arising in Autoimmune Disease Affected Patients Treated with Biologic Drugs, Including Anti-TNF

“…To the best of our knowledge, in the current literature, there are only anecdotal reports of MCC occurrence in patients treated with biologic drugs, for a total number of 7 patients: 4 patients treated with rituximab, respectively, for acquired factor VIII inhibitor (46), B-cell chronic lymphocytic leukemia (47), relapsing follicular lymphoma (48), and chronic lymphocytic lymphoma (49). The remaining 3 cases are of patients affected by rheumatic diseases, one with long-standing rheumatoid arthritis treated with adalimumab (16), one with etanercept (18), and the last one affected by psoriatic arthritis treated with etanercept (17).…”

“…Other immunosuppressive drugs used in the treatment of acquired factor VIII inhibitor (46), B-cell chronic lymphocytic leukemia (47), relapsing follicular and chronic lymphocytic lymphomas (48,49) have been found to be associated with MCC.…”

Merkel cell carcinoma expresses K homology domain–containing protein overexpressed in cancer similar to other high-grade neuroendocrine carcinomas

“…Risk factors for developing MCC include immunosuppression [1][2][3][4][5][6][7][8][9] and exposure to ultraviolet radiation [1,2,[10][11][12]. The incidence is approximately 1200 per year with a 3-fold increase over the past 3 decades that is likely to increase as the population ages [1,13].…”

Concurrent Chronic Lymphocytic Leukemia and Merkel Cell Carcinoma in Primary Skin Tumor and Metastatic Lymph Node

“…In case of our patient diagnosis was established when she was 45 years old. Although there are many publications that report coexistence of CLL and MCC [3,[5][6][7][8][9][10][11]] the case of our patient was unique due to two reasons. The first was that CLL infiltrate coexisted within the primary skin tumor (MCC).…”