title: Methotrexate-associated B-cell lymphoproliferative disorders presenting in the skin: A clinicopathologic and immunophenotypical study of 10 cases.
abstract: Methotrexate (MTX)-associated B-cell lymphoproliferative disorders (B-LPD) may first present in the skin, but their clinicopathologic features are still ill defined. Differentiation from primary cutaneous follicle center lymphoma and primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL-LT) is important, as MTX-associated B-LPD may show spontaneous regression after withdrawal of MTX therapy. In the present study, the clinicopathologic and phenotypical features of 10 patients with MTX-associated B-LPD first presenting in the skin, including 5 EBV(+) and 5 EBV(-) cases, were investigated. Six patients had skin-limited disease. Clinically, abrogation of MTX therapy resulted in a complete response in 4 cases and a partial response in another 2. The 5-year disease-specific survival was 90%. MTX-associated B-LPD differed from primary cutaneous follicle center lymphoma by the presence of ulcerating and/or generalized skin lesions, an infiltrate composed of centroblasts/immunoblasts rather than large centrocytes, reduced staining for CD79a, and expression of BCL2, IRF4, and FOXP1 in most cases. EBV(+) MTX-associated B-LPD differed from PCLBCL-LT by the presence ulcerative skin lesions, marked tumor cell polymorphism, reduced staining for CD79a, and expression of CD30 and EBV. EBV(-) cases showed morphologic and immunophenotypical similarities to PCLBCL-LT but differed by presentation with generalized skin lesions in 4 of 5 cases. The results of this study, showing a relatively good clinical outcome and spontaneous disease regression after only withdrawal of MTX in a considerable proportion of patients, underscores the importance of a careful wait-and-see policy before considering more aggressive therapies in patients with MTX-associated B-LPD of the skin.
authors.affiliation: Departments of *Pathology †Dermatology, Leiden University Medical Center, Leiden ‡Department of Dermatology, Saint Lucas Andreas Hospital, Amsterdam, The Netherlands.
authors.forename: Lianne
authors.initials: L
authors.lastname: Koens
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Senff
authors.forename: Maarten H
authors.initials: MH
authors.lastname: Vermeer
authors.forename: Rein
authors.initials: R
authors.lastname: Willemze
authors.forename: Patty M
authors.initials: PM
authors.lastname: Jansen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000473:pathology / Q000821:virology; D014408:Biomarkers, Tumor / Q000032:analysis; D049109:Cell Proliferation / Q000187:drug effects*; D004279:DNA, Viral / Q000302:isolation & purification; D003937:Diagnosis, Differential; D020031:Epstein-Barr Virus Infections / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology / Q000821:virology; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D016393:Lymphoma, B-Cell / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology / Q000821:virology; D008297:Male; D008727:Methotrexate / Q000009:adverse effects*; D008875:Middle Aged; D010641:Phenotype; D011237:Predictive Value of Tests; D012307:Risk Factors; D012867:Skin / Q000187:drug effects* / Q000276:immunology / Q000473:pathology / Q000821:virology; D012878:Skin Neoplasms / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology / Q000821:virology; D013997:Time Factors
chemical_list: D014408:Biomarkers, Tumor; D004279:DNA, Viral; D007166:Immunosuppressive Agents; D008727:Methotrexate