To the Editor: With the increase of long-term survivors of childhood cancer, second malignancies caused by chemo/radiotherapy have become a source of concern [1]. Renal cell carcinoma (RCC) as a second malignant neoplasm has received little attention. We incidentally found an RCC in an autopsied patient who died from interstitial pneumonia 12 years after initial diagnosis of neuroblastoma (NBL).
The patient (a 2-year-old boy) was admitted to our hospital because of left upper abdominal tumor in 1976. The resected tumor originated from the left adrenal gland and was diagnosed as Evans stage II NBL. The patient received multiagent chemotherapy (vincristine, cyclophosphamide, and doxorubicin) and local irradiation (total dose: 31.3 Gy). The left kidney was partially blocked, where the radiation dose was 7.0 Gy. No recurrences were observed during the subsequent 12 years, but the patient developed interstitial pneumonia due to cyclophosphamide and expired in 1989 at the age of 14 years. Autopsy revealed no residual NBL but extensive lung fibrosis. The left kidney showed a 11 Γ 1-cm solid, cystic lesion at the upper pole (Fig. 1A). Histology was clear cell-type RCC with Grade I nuclear atypia (Fig. 1B).
A literature review revealed nine NBL patients who developed RCC from childhood to early adulthood. Their ages at diagnosis for NBL and RCC were 2-24 months and 3-35 years, respectively. The interval between the two tumors ranged from 3 to 35 years, with a median of 15 years [2][3][4]. All cases, including the present one, had received chemotherapy and/or radiotherapy for the NBL. Although a recent report referred to a possible association between RCC and radiation therapy [2], the literature review showed two patients with RCC who had received no irradiation to the kidney. Chemotherapy alone might be a predisposing factor for RCC. An accumulation of cases is necessary to clarify the relationship between RCC and treatments for NBL.
Six out of the nine previously reported patients were asymptomatic at the time of diagnosis for RCC. Four out of these six patients were alive without tumor, one was alive with tumor, and one was lost to follow-up. In contrast, among the three patients with symptoms, one died of RCC, one was alive with tumor, and one was alive without tumor.
Incidentally detected RCCs generally have a more favorable prognosis than those with clinical signs. Careful follow-up for possible occurrence of RCC is desirable in NBL patients who have undergone chemotherapy and/or radiation therapy.