A multiple myeloma (MM) is a malignant disease of plasma cells, which manifests as one or more of lytic bone lesions, monoclonal protein in the blood and/or urine and disease in the bone marrow (1). The diagnosis of a secondary solid neoplasm in patients with a MM is uncommon, and it is debatable whether the MM itself is a risk factor for the incidence of a secondary solid neoplasm (2~5). Although the development of a second primary cancer generally results from carcinogenic agents, such as chemotherapy or radiation therapy (6), the pathogenesis of second primary cancer in a MM, or vice versa has not definitely been associated with alkylating therapy (3). It has been suggested that myeloma patients may have an immunologic tolerance for developing solid tumors, since these patients have an impaired immune system. A second solid tumor in patients with a MM has rarely been reported in Korea, with all reported solid tumors being stomach cancers (7~9). In our hospital, three cases of the synchronous occurrence of a MM and solid tumors, namely, small cell carcinoma of the lung, adenocarcinoma of the colon and squamous carcinoma of the pyriform sinus were experienced. Thus, herein these 3 cases, which simultaneously presented with a MM, are reported and their clinical courses and treatment results described.

With increases in routine health screening, MM is now diagnosed earlier, and those patients with typical symptoms related to a MM reduced (10). Our cases of a MM with solid tumors had no initial typical symptoms of a MM, such as bone pain, fatigue, weight loss or infection. All were incidentally diagnosed with a MM during the initial work-up or follow-up evaluation of known solid tumors. All three patients had Salmon-Durie stage I, with beta-2 microglobulin levels below 4 mg/L. Patients with a smoldering or stage I MM require no primary therapy as they can do well for many months or years before the disease progresses (4). These patients should initially be observed until progression of the MM, which is defined as a sustained 25% or greater increase in the M-protein in the serum or urine, and the development of new sites of a lytic disease or hypercalcemia. Because the prognosis of advanced solid tumors is generally poorer than that of an early stage MM, it was decided to treat the solid tumors as a primary disease. Although the response to chemotherapy seemed to be similar to that in patients without a MM, all three patients frequently showed grade 3~4 neutropenia and/or thrombocytopenia during the course of chemotherapy, despite having normal blood cell counts before the first chemotherapy. An initial BM exam showed normocellular (two patients) or hypercellular (one patient) bone marrow for their ages, but their cellularities might have been overestimated due to the packed dysplastic plasma cells in the BM. Therefore, the doses of chemotherapeutic agents were reduced and the cycle intervals frequently delayed, which might have resulted in the suboptimal response of the chemotherapy. Therefore, these patients should be monitored frequently during chemotherapy, with the use of CSF (Colony-stimulating factor) considered to maintain the dose intensity. None of the three patients experienced serious infection or hemorrhagic episodes during the chemotherapy.

In general, it is unclear whether a MM itself is a risk factor for the incidence of secondary solid neoplasms (2~5). The use of alkylating agents and an immunologic tolerance have been suggested as a possible mechanism accounting for the development of a second primary tumor in patients with a MM or vice versa; however, this has not been conclusively proved (3). Six large MM group studies have been reviewed for this study, which are summarized in Table 1 (2,3,5,11~13).

According to the most recent national surveys of cancer patients in the United States (14) and Korea (15), the cumulative probability of developing any type of malignancy, with the exception of in-situ neoplasms, in patients aged 60 years has been shown to be approximately 1.5% per year. Since the median survival of patients with a MM is 33 months (13), the age-specific risk of developing any cancer for MM patients can be speculated to be approximately 4.5% during their survival duration. Six studies have shown that a MM was associated with an increased risk of secondary malignancies, including hematologic malignancies and solid cancers. However, a MM was not clearly correlated with an increased risk for developing a secondary solid malignancy. Two small series have shown an increased risk for secondary solid cancer, whereas two larger series failed to demonstrate any correlation. Therefore, it is suggested that a MM may be associated with an increased risk of secondary malignancies, including hematologic and non-hematologic malignancies, although the correlation between a MM and secondary solid cancer is unclear.