title: T-cell prolymphocytic leukemia frequently shows cutaneous involvement and is associated with gains of MYC, loss of ATM, and TCL1A rearrangement.
abstract: T-cell prolymphocytic leukemia (T-PLL) is a rare aggressive mature T-cell leukemia with frequent cutaneous presentation, which has not been well characterized. Among the 25 T-PLLs diagnosed between 1990 and 2013 at our institution, 32% (8/25) showed cutaneous manifestations, presenting as rash, purpura, papules, and ulcers. The skin biopsies showed leukemia cutis with perivascular and periadnexal irregular, small to medium-sized lymphoid infiltrates without epidermotropism. The lymphoid infiltrates were composed of mature CD4+ T cells expressing other T-cell antigens, and a subset (48%) showed dual CD4+/CD8+ coexpression. Higher median absolute peripheral blood lymphocyte count (43.0 vs. 13.0 k/mm; P=0.031) and elevated lactate dehydrogenase levels (P=0.00018) at the time of diagnosis were significantly associated with T-PLLs with skin involvement compared with those without. The extent of bone marrow involvement (P=0.849) and overall survival (P=0.144) was similar in the 2 groups. Fluorescence in situ hybridization or karyotype revealed frequent gains of MYC (67%; n=9), loss of ATM (64%; n=11), and TCL1A rearrangement or inversion 14q (75%; n=12). Gains of TCL1A was also seen (78%; n=9), including in some cases that had concurrent TCL1A rearrangement, whereas TP53 loss was less common (30%; n=10). No correlation was seen between the immunophenotype and morphology versus the presence or absence of skin involvement. These data suggest that cutaneous involvement by T-PLL is relatively common and often associated with significant peripheral blood involvement. The frequent MYC, ATM, and TCL1A alterations identified support that these genes are integral to the pathogenesis of T-PLL.
authors.affiliation: Departments of *Pathology †Biostatistics, Washington University School of Medicine, Saint Louis, MO.
authors.forename: Andy C
authors.initials: AC
authors.lastname: Hsi
authors.forename: Diane H
authors.initials: DH
authors.lastname: Robirds
authors.forename: Jingqin
authors.initials: J
authors.lastname: Luo
authors.forename: Friederike H
authors.initials: FH
authors.lastname: Kreisel
authors.forename: John L
authors.initials: JL
authors.lastname: Frater
authors.forename: TuDung T
authors.initials: TT
authors.lastname: Nguyen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D001706:Biopsy; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015321:Gene Rearrangement; D020022:Genetic Predisposition to Disease; D006801:Humans; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D007621:Karyotyping; D015461:Leukemia, Prolymphocytic, T-Cell / Q000235:genetics* / Q000276:immunology / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008923:Missouri; D010641:Phenotype; D011237:Predictive Value of Tests; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000235:genetics* / Q000276:immunology / Q000401:mortality / Q000473:pathology; D013997:Time Factors
chemical_list: D014408:Biomarkers, Tumor; C489427:MYC protein, human; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; C090851:TCL1A protein, human; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins