Clonal identification and homology differentiate primary central nervous system lymphoma from non-central nervous...

Lymphoplasmacytic lymphoma/Waldenström macroglobulinemia rarely transforms into diffuse large B-cell lymphoma, and there have been no reports of cases proving clonal identity when presenting as primary central nervous system lymphoma. There are many unclear aspects regarding the mechanism by which lymphoplasmacytic lymphoma/Waldenström macroglobulinemia infiltrates the central nervous system and transforms, as well as the treatment methods for the transformed lymphoma.

A 49-year-old Asian Japanese male was emergently transported due to loss of consciousness, revealing a tumorous lesion in the brain. He was diagnosed with primary central nervous system lymphoma following an endoscopic biopsy and treated with immunochemotherapy included high-dose methotrexate. During the second course of immunochemotherapy, a computed tomography scan conducted to investigate bilateral lower leg edema revealed tumorous lesions in both lower legs. A biopsy of the thigh node specimen was diagnosed as lymphoplasmacytic lymphoma. When high-dose methotrexate including immunochemotherapies was finished, the lymphoma lesions in central nervous system had disappeared. However, the symptoms of bilateral lower leg edema were prominent because of remaining the bilateral thigh nodes, so additional immunochemotherapy for lymphoplasmacytic lymphoma/Waldenström macroglobulinemia was administered, resulting in complete remission of the lymphoplasmacytic lymphoma/Waldenström macroglobulinemia as well. primary central nervous system lymphoma, and he has maintained both lymphomas for 4 years. The myeloid differentiation factor 88 (MYD88) gene mutation was detected in primary central nervous system lymphoma and lymphoplasmacytic lymphoma/Waldenström macroglobulinemia lymphoma cells. The same clonal origin of primary central nervous system lymphoma and lymphoplasmacytic lymphoma/Waldenström macroglobulinemia was confirmed according to homology in a region of the immunoglobulin heavy chain V (IGHV) gene. On the basis of the characteristics of primary central nervous system lymphoma and lymphoplasmacytic lymphoma/Waldenström macroglobulinemia, we speculated that the lymphoplasmacytic lymphoma/Waldenström macroglobulinemia lymphoma cells had already invaded the central nervous system, a condition called Bing-Neel syndrome, and transformed into primary central nervous system lymphoma cells after a certain period.

It was revealed that the lymphoma cells of both lymphoplasmacytic lymphoma/Waldenström macroglobulinemia and primary central nervous system lymphoma derived from a common cell possessing MYD88. The utility of adding chemotherapy for low-grade lymphoma in addition to therapy for primary central nervous system lymphoma is not clear. While lymphoplasmacytic lymphoma is a low-grade lymphoma that does not always require chemotherapy, combining treatment for lymphoplasmacytic lymphoma and primary central nervous system lymphoma may contribute to the effectiveness of both treatments.