Incidence Patterns of Patients with Two or More Lymphoid Malignancies in a Patient with a Prior History of Lymphoid Malignancy: A Population-Based Cancer Registry Study in Nagasaki, Japan

Background: The occurrence of second or more lymphoid malignancies in a patient with a prior history of lymphoid malignancy or a combination of two different subtypes of lymphoid malignancies at the same time in a patient have been sporadically reported. However, the incidence pattern of such cases in a large number setting has been rarely reported. Therefore, we investigated patients with two or more lymphoid malignancies in a population-based cancer registry.

Methods: After approval of the institutional review board, we obtained a dataset of cases with lymphoid malignancies during the periods of 1985-2012 from the Nagasaki Prefectural Cancer Registry (NPCR), which was established in 1974, covers a population of approximately 1.56 million people in Nagasaki, Japan, and is known to be one of the highest data quality of the registry (the death certification only 9% and the proportion of morphological verification 79%). The overall age-adjusted incidence rate of lymphoid malignancies during 1985-2012 was already reported to be 20.5 for men and 12.9 for women (per 100,000 population). In the dataset, the lymphoid malignancies were coded according to the ICD-O-1, -2 and -3 systems. In case those were coded according to the ICD-O-1 and -2 systems, we substituted the corresponding ICD-O-3 code. For cases with undetermined codes, we reviewed the cancer registry sheets or pathological reports as much as possible. Finally, we confirmed all the lymphoid malignancies by ICD-O-3 histology codes 9650-9667, 9670-9699, 9700-9719, 9724-9729, 9731-9734, and 9760-9769. We then extracted cases having two or more histopathologically distinct lymphoid malignancies. We eliminated cases that were apparently considered to be recurrence cases of the first lymphoma. We analyzed the age- and sex-specific frequencies of multiple lymphomas among whole lymphoid malignancies, and characterized the combination pattern.

Results: A total of 11,124 cases (male 5,981 cases and female 5,143 cases) of lymphoid malignancies were registered in the NPCR during 1985-2012. Among those, we identified 45 cases (male 27 and female 18) who had two or more different subtypes of lymphoid malignancies at same diagnosed date or at different diagnosed date. The median age at diagnosis of the first lymphoma of the 45 cases was 65.2 years (ranges from 26.6 years to 91.5 years). The overall prevalence of patients having multiple lymphoma among all patients with lymphoid malignancies during the periods of 1985-2012 was 0.40% (95%CI, 0.30-0.54%) for all, 0.45% (95%CI, 0.31-0.65%) for male, and 0.35% (95%CI, 0.21-0.55%) for female. There was no statistically significant difference in the prevalence by sex (Odds ratio, 1.29, P=0.40). Among the 45 cases, a patient was diagnosed as having two subtypes at same date, follicular lymphoma on spleen and Waldenstrom's macroglobulinemia. Another patient had three subtypes of lymphomas at different year; MALT on spleen in 2006, DLBCL on nasal in 2009, and Multiple Myeloma on bone marrow. The rest of the 43 patients developed two subtypes of lymphomas at different date. Median duration between date of the first lymphoid malignancy and date of the second one was 4.0 years (ranges from 0.1 years to 22 years). Among 45 cases, 23 (51.1%) had different cell lineage lymphomas between first and second lymphoma. The frequencies of the major combination pattern of first/second subtypes were as follows; MALT/DLBCL (n=4), MALT/mature T-lymphoma (n=4), DLBCL/ATL (n=3), DLBCL/ mature T-lymphoma (n=3), AILD/mature B-cell lymphoma (n=2), and others. From four patients with first Hodgkin's lymphoma, DLBCL (n=2), MALT (n=1), and ATL (n=1) developed as the second lymphoid malignancies.

Conclusion: In the era of improved survival of patients with lymphoid malignancies, hematologists should be aware of the potential development of secondary or more lymphoid malignancies after treatment for first lymphoid malignancies.