Peripheral T-cell lymphoma emerging in a patient with aggressive polymyositis: molecular evidence for neoplastic transformation of an oligoclonal T-cell infiltrate.
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.
Division of Neuropathology, Department of Pathology and Cell Biology, Columbia University Medical Center and New York Presbyterian Hospital, 630 W. 168th Street, PH15-124, New York, 10032, USA, nmt2111@columbia.edu.
Nadejda M
NM
Tsankova
Carolyn
C
Bevan
Vaidehi
V
Jobanputra
Yen Chen Kevin
YC
Ko
Elizabeth W
EW
Mayer
Jay H
JH
Lefkowitch
Mahesh
M
Mansukhani
Lewis P
LP
Rowland
Govind
G
Bhagat
Kurenai
K
Tanji
D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics; D001344:Autopsy; D001483:Base Sequence; D001921:Brain / Q000473:pathology; D006332:Cardiomegaly / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D017809:Fatal Outcome; D006801:Humans; D007150:Immunohistochemistry; D016411:Lymphoma, T-Cell, Peripheral / Q000150:complications* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D018908:Muscle Weakness / Q000209:etiology; D018482:Muscle, Skeletal / Q000473:pathology; D009133:Muscular Atrophy / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D017285:Polymyositis / Q000150:complications* / Q000473:pathology; D017422:Sequence Analysis, DNA; D013601:T-Lymphocytes / Q000473:pathology*
D015703:Antigens, CD