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  • Although second malignancies are increasingly observed after

    2019-05-14

    Although second malignancies are increasingly observed after NHL, the incidence of CLL and RCC in the same patient is exceptional [4,5]. Nishikubo et al. [4] reported a case series of 8 patients with lymphoid malignancies and RCC. In 2 of 8 patients, CLL and T-cell CLL were diagnosed 1 year and 8 months prior to RCC, respectively. More recently, in a series of 9 patients with lymphoma and RCC, only 1 patient had CLL [5]. This patient had carried a diagnosis of CLL for 15 years without any treatment. Finally, a case series of 5 patients with concomitant lymphoid malignancies and RCC were reported by Serefhanoglu et al. [6] Three of 5 patients had CLL. In 2 of 3 patients, the CLL was diagnosed prior (13 months and 5 years, respectively) to their RCC; while in 1 patient coincidence of CLL and RCC was reported. Our patient developed RCC after 5 years in the setting of NHL, and he had been treated with multiple courses of chemotherapy including both alkylating agents (12 cycles of cyclophosphamide) and purine analogues (12 cycles of fludarabine). Although he did not receive radiotherapy, he had multiple CT scans during his follow-up. Certain chemotherapeutic regimens have been shown to increase both the risk of NHL and RCC. Additionally, this increased risk was also attributed to radiotherapy that the patients received for NHL [2]. The actuarial risk of developing a second cancer 3–20 years after diagnosis of NHL was 21%, compared with a order (S)-Crizotinib expected cumulative risk of 15%. NHL patients whom underwent treatment for lymphoma are at increased risk for developing RCC, especially <1 year and >10 years after treatment [2]. In contrast, some authors [3,4,7] identified patients with simultaneous NHL and RCC whom did not receive any treatment at the time of presentation, and they have suggested that this association could not be attributed to treatment modalities alone. Recently, Dutcher et al. [8] have reviewed the current data about the existence of RCC and hematologic malignancies in the same patient. Among these 186 patients, the most common sequence of diagnosis was a hematologic malignancy (twelve with CLL) followed by RCC (43%), secondly, synchronous (33%), and the least common pattern was RCC first and hematologic malignancy developed later (22%). The authors have also reported that these patients have common clinical characteristics, including a male predominance (2.25:1), having a hematological malignancy of B-cell origin (94%), and showing an evident risk of extranodal lymphoma (32%). The immune dysregulation via a breakdown in tumor surveillance as a result of lymphoma predisposes the patient to the development of RCC [3]. Proliferating cell nuclear antigen positivity (≥10%) but not p53 or human papillomavirus (HPV) DNA correlated with worse clinical prognosis such as invasion or metastasis of RCC [9]. However, the role of HPV in RCC is controversial [10]. Sakai et al. [11] suggested that RCC related interleukin 6 synthesis might stimulate the proliferation of the myeloma cells. Growing evidence supports the idea that a common genetic mutation can explain the elevated incidence of second malignancies in patients with NHL. Deletions of 3p have been described in 95–98% of sporadic clear cell type RCC [12,13]. In addition, abnormalities in 11p, chromosome 13, and deletions in 17p in 11–33% of patients with advanced stage RCC have been reported [12]. Cytogenetic analysis of NHL cells by more accurate fluorescence in-situ hybridization methods such as ratio-painting and comparative genomic hybridization have enabled to identify further unsuspected chromosomal abnormalities including 17p deletions, trisomy of chromosome 7, amplification of 3(p12) and mutations in p53 [14]. The persistently increased risk of second malignancies in the clinical setting of CLL, particularly those treated with intense courses of chemotherapy, should alert clinicians to the importance of continued medical surveillance. Future studies are needed to better clarify if this association is a causal relationship or coincidental occurrence.