Occurrence of renal cell carcinoma and hematologic malignancies (predominantly lymphoid) in individuals and in families

Abstract

The relationship between renal cell cancer (RCC) and hematologic malignancy (HM) in the same individual has been reported for more than 20 years, and is noted in SEER database studies. Family histories suggest a familial association as well. This study evaluates the occurrence of renal cell cancer and hematologic malignancies in individual patients and families, and the occurrence of age-of-onset anticipation among generations. Family history data from our familial patient registry, including more than 700 pedigrees of familial hematologic malignancies, and 700 patients with renal cell cancer, were reviewed. Twenty-six patients with a personal history of both RCC and HM are reported. Seventy four patients with RCC are noted to have 95 family members with HM. Consistent with past reports, there was male predominance among the patients with both diseases (71 %), and among the RCC patients' relatives with HM (57 %). Also consistent was a predominance of lymphoid malignancies in those with both diseases (92 %) and in the HMs among family members of RCC patients (79 %). The majority (95 %) of HM relatives were first or second degree relatives of the patient with RCC. Thirty of 34 parent/child pairs demonstrated age of onset anticipation in which the child developed either disease at a younger age than the parent. The co-occurrence of RCC and HM in the same patient has been shown to be significantly greater than expected. Families also appear to have an increased association. The appearance of anticipation suggests that genetic factors may be significant in this association of RCC and HM.

Concurrent renal cell carcinoma and hematologic malignancies: Nine case reports

“…The phenomenon of concurrent RCC and HM has been reported in the literature, with a focus on gender, timing of the diagnosis of RCC and HM, and most common HM (Table 2 )[ 1 - 5 , 8 , 10 , 11 ]. All except one of the studies in Table 2 documented a higher number of men with both conditions.…”

“…NHL was the most common HM in the majority of these studies. In Dutcher and colleagues’ review of 199 cases of RCC and HM in the same patient identified in the literature ( n = 173) and in their registry ( n = 26) between 1991 and 2016, an association between RCC and HM within families was observed, exemplified by 74 patients with RCC who had 95 family members with HM[ 8 ]. These authors suggested a genetic correlation between RCC and B-cell malignancies.…”

“…A host of mechanisms has been reported as playing a role in developing concurrent RCC and HM. As the greatest number of patients with these combined conditions involves diagnosis of HM first[ 8 , 11 ], it has been proposed that immune dysregulation or breakdown of tumor surveillance associated with the lymphoma may lead to RCC[ 3 , 10 ]. An abnormal immune response may either precipitate lymphoma in patients whose RCC was diagnosed first or predispose a patient to developing both malignancies simultaneously[ 1 , 9 , 10 ].…”

“…Furthermore, it has been reported that patients with the diagnosis of NHL have an increased incidence of RCC, bladder carcinoma, lung carcinoma, brain tumors, and melanoma as well as other HM such as acute myeloid leukemia and HL[ 6 , 7 ]. Three predominant features have been described in these patients: (1) Greater number of males; (2) The majority of HM are lymphoid; and (3) The HM are usually diagnosed prior to or simultaneously with the RCC[ 8 ].…”

“…Several mechanisms have been proposed to account for concurrent RCC and HM, including genetic mutations common to both RCC and HM, hormonal or environmental factors, viral infections, prior cytotoxic chemotherapy or radiation for malignancy, and immune dysregulation[ 2 , 3 , 5 , 8 - 12 ]. It has been suggested that the first malignancy predisposes to the second through an immunomodulatory effect[ 1 - 4 ].…”