Myeloid transformation of plasma cell myeloma: molecular evidence of clonal evolution revealed by next generation sequen
- PDF / 1,716,136 Bytes
- 8 Pages / 595.276 x 790.866 pts Page_size
- 51 Downloads / 158 Views
CASE REPORT
Open Access
Myeloid transformation of plasma cell myeloma: molecular evidence of clonal evolution revealed by next generation sequencing Jonathon H. Gralewski1, Ginell R. Post1, Frits van Rhee2 and Youzhong Yuan1*
Abstract Background: Plasma cell myeloma (PCM) is a neoplasm of terminally differentiated B lymphocytes with molecular heterogeneity. Although therapy-related myeloid neoplasms are common in plasma cell myeloma patients after chemotherapy, transdifferentiation of plasma cell myeloma into myeloid neoplasms has not been reported in literature. Here we report a very rare case of myeloid neoplasm transformed from plasma cell myeloma. Case presentation: A 60-year-old man with a history of plasma cell myeloma with IGH-MAF gene rearrangement and RAS/RAF mutations developed multiple soft tissue lesions one year following melphalan-based chemotherapy and autologous stem cell transplant. Morphological and immunohistochemical characterization of the extramedullary disease demonstrated that the tumor cells were derived from the monocyte-macrophage lineage. Next generation sequencing (NGS) studies detected similar clonal aberrations in the diagnostic plasma cell population and post-therapy neoplastic cells, including IGH-MAF rearrangement, multiple genetic mutations in RAS signaling pathway proteins, and loss of tumor suppressor genes. Molecular genetic analysis also revealed unique genomic alterations in the transformed tumor cells, including gain of NF1 and loss of TRAF3. Conclusion: To our knowledge, this is the first case of myeloid sarcoma transdifferentiated from plasma cell neoplasm. Our findings in this unique case suggest clonal evolution of plasma cell myeloma to myeloma neoplasm and the potential roles of abnormal RAS/RAF signaling pathway in lineage switch or transdifferentiation. Keywords: Clonal evolution, Myeloid sarcoma, Molecular profiling, Next generation sequencing, Transdifferentiation, Plasma cell myeloma, RAS/RAF signaling pathway
Background Plasma cell myeloma (PCM) is a neoplasm of terminally differentiated B lymphocytes and most often involves the bone marrow. Malignant plasma cells are defined immunophenotypically by diminished or increased expression of at least two antigens not present on non-neoplastic plasma cells. For example, malignant plasma cells show decreased or loss of CD45 and/or CD19 expression and may aberrantly express CD56, CD117, and/or CD20 [1]. Immunohistochemical stains performed on diagnostic * Correspondence: [email protected] 1 Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR 72205-7199, USA Full list of author information is available at the end of the article
biopsies demonstrate retained expression of nonneoplastic plasma cell antigens (e.g. CD138 and MUM1) and cytoplasmic light chain restriction. PCM is characterized by molecular heterogeneity, including balanced translocations involving the immunoglobulin heavy chain locus, complex karyotypes, and mutations in the RAS signaling cascade [2–4]. For example, KRAS, NRA
Data Loading...
