LAUSR

Dear Editor, Testicular plasmacytoma, a rare extramedullary plasmacytoma (EMP), presents with distinct clinical and prognostic features and might occur concurrently with, prior to, or after a diagnosis of multiple myeloma (MM). Differences in the cell origins and evolution of testicular plasmacytoma and myeloma are not well understood. Here, we present a rare case of MM that initially presented as testicular plasmacytoma and progressed for 27 months after diagnosis, providing a unique framework to investigate sequential genomic evolution. A 49-year-old male was admitted for a mass in his testes that gradually increased for 2 months. Testicular mass resection was performed, and a plasmacytoma was confirmed by pathological examination. Bone marrow aspiration demonstrated 16.4% malignant clonal plasma cell infiltration. Serum protein immunofixation electrophoresis showed a monoclonal IgD/λ protein. No damage to common target organs (e.g., anemia, hypercalcemia, renal failure, or bone lesions) was detected. He was diagnosed with the IgD/λ type of MM involving both testes. The plasmacytoma specimen was subjected to single-nucleotide polymorphism (SNP) array karyotyping, and a series of copy number variations (CNVs), including loss of whole chromosome 13, 17q11.2, 17q12q21.2, and 17q23.2q24.1 and gain of 17q22, were identified (Fig. 1A). Del(13) was confirmed by FISH in both plasmacytoma specimens and bone marrow plasma cells (Fig. 1C1, D1). However, the 17q12q21.2 deletion was verified in only testicular tumor tissue and not in bone marrow plasma cells (Fig. 1C2, D2), suggesting that the plasmacytoma cells might have migrated from the bone marrow to the testes since they shared the same chromosome 13 deletion and that alterations in chromosome 17q might play a role in malignant transformation and migration. This result is in accordance with the fact that chromosome 13 deletion is an early-stage marker of progression from monoclonal gammopathy of undetermined significance (MGUS) to MM [1]. The patient sequentially received systematic chemotherapy and testicular radiotherapy but developed a spontaneous rib fracture 27 months after the initial diagnosis. The bone marrow was shown to comprise 47.2% plasma cells. The bone marrow cell SNP array showed that a series of CNVs, including gain of 1q21q44 and 11p15.2p15.1, and loss of 19 were newly acquired in addit ion to those observed in plasmacytomas (Fig. 1B). FISH further confirmed the newly acquired 1q21+ (Fig. 1 C1, D1, and E1), chromosome 19 loss (Fig. 1 C3, D3, and E3), and − 13 (Fig. 1E1) and 17q (Fig. 1E2) abnormalities, suggesting that the bone marrow myeloma cells probably originated from the same clone as the plasma testes cells and that they gained more complex chromosomal abnormalities upon disease progression. To our knowledge, this is the first case demonstrating evolution between the testes and bone marrow at the wholegenome level and supports the speculation that testicular plasmacytoma is a systematic myeloma subset. It also provides evidence of clonal evolution from an indolent myeloma to a plasmacytoma and aggressive myeloma. It may also be representative of linear clonal evolution or the “static progression model” [2]. * Rui Zhang [email protected]