TY - JOUR
T1 - Peripheral T-cell lymphoma emerging in a patient with aggressive polymyositis
T2 - Molecular evidence for neoplastic transformation of an oligoclonal T-cell infiltrate
AU - Tsankova, Nadejda M.
AU - Bevan, Carolyn
AU - Jobanputra, Vaidehi
AU - Ko, Yen Chen Kevin
AU - Mayer, Elizabeth W.
AU - Lefkowitch, Jay H.
AU - Mansukhani, Mahesh
AU - Rowland, Lewis P.
AU - Bhagat, Govind
AU - Tanji, Kurenai
PY - 2013/10
Y1 - 2013/10
N2 - We report a rare case of peripheral T-cell lymphoma arising in a 52-year-old man with biopsy-proven aggressive polymyositis, who had cardiac involvement, progressive bulbar symptoms, and died 11 months post diagnosis due to multiorgan failure. Using a multimodality approach including immunohistochemistry, genome-wide single nucleotide polymorphism (SNP)-array analysis, and high-throughput sequencing of the complementary determining region 3 (CDR3) of T-cell receptor beta (TCRβ) genes, our study demonstrates a molecular link between polymyositis and T-cell lymphoma, and provides evidence of the rapid and possibly late occurrence of genomic instability during neoplastic transformation of an oligoclonal T-cell population. Immunohistochemical analysis revealed loss of CD5, CD7, and CD8 antigen expression in autopsy tissue samples, as well as the occurrence of aberrant CD56 expression, not seen in pre-mortem biopsies, supporting the emergence of a neoplastic T-cell population. Multiplex polymerase chain reaction and next-generation sequencing of the TCRβ CDR3 region displayed two unique T-cell clones in both the diagnostic biopsy confirming polymyositis and the autopsy muscle tissue exhibiting T-cell lymphoma, linking the two pathological processes. SNP-array analysis revealed complex genomic abnormalities at autopsy but not in the pre-mortem muscle biopsies displaying polymyositis, confirming malignant transformation of the oligoclonal T-cell infiltrate. Our findings raise the possibility that clinically aggressive polymyositis might represent a preneoplastic condition in some instances, similar to certain other autoimmune and inflammatory disorders.
AB - We report a rare case of peripheral T-cell lymphoma arising in a 52-year-old man with biopsy-proven aggressive polymyositis, who had cardiac involvement, progressive bulbar symptoms, and died 11 months post diagnosis due to multiorgan failure. Using a multimodality approach including immunohistochemistry, genome-wide single nucleotide polymorphism (SNP)-array analysis, and high-throughput sequencing of the complementary determining region 3 (CDR3) of T-cell receptor beta (TCRβ) genes, our study demonstrates a molecular link between polymyositis and T-cell lymphoma, and provides evidence of the rapid and possibly late occurrence of genomic instability during neoplastic transformation of an oligoclonal T-cell population. Immunohistochemical analysis revealed loss of CD5, CD7, and CD8 antigen expression in autopsy tissue samples, as well as the occurrence of aberrant CD56 expression, not seen in pre-mortem biopsies, supporting the emergence of a neoplastic T-cell population. Multiplex polymerase chain reaction and next-generation sequencing of the TCRβ CDR3 region displayed two unique T-cell clones in both the diagnostic biopsy confirming polymyositis and the autopsy muscle tissue exhibiting T-cell lymphoma, linking the two pathological processes. SNP-array analysis revealed complex genomic abnormalities at autopsy but not in the pre-mortem muscle biopsies displaying polymyositis, confirming malignant transformation of the oligoclonal T-cell infiltrate. Our findings raise the possibility that clinically aggressive polymyositis might represent a preneoplastic condition in some instances, similar to certain other autoimmune and inflammatory disorders.
KW - Inflammatory myopathy
KW - Oligoclonal
KW - Polymyositis
KW - SNP-array
KW - T-cell lymphoma
KW - TCR next-generation sequencing
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U2 - 10.1007/s00401-013-1164-z
DO - 10.1007/s00401-013-1164-z
M3 - Article
C2 - 23942639
AN - SCOPUS:84885471401
VL - 126
SP - 595
EP - 601
JO - Acta Neuropathologica
JF - Acta Neuropathologica
SN - 0001-6322
IS - 4
ER -