title: Primary cutaneous marginal zone B-cell lymphoma: a molecular and clinicopathological study of cases from Asia, Germany, and the United States.
abstract: Primary cutaneous marginal zone B-cell lymphoma is considered the cutaneous counterpart of extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue. Although its molecular pathogenesis is currently unknown, an etiological link with Borrelia burgdorferi infection has been identified in European, but not in American or Asian cases. To better understand the pathogenesis and the geographical differences of cutaneous marginal zone B-cell lymphoma, 60 cases from the East Asia, Germany, and the United States at their initial presentation were subjected to the following analyses; (1) clinicopathological comparison between the geographical regions, (2) detection of B. burgdorferi DNA, (3) detection of the API2-MALT1 fusion transcript, a gene alteration specific to mucosa-associated lymphoid tissue lymphoma, and (4) inactivation of tumor suppressor genes (death-associated protein kinase (DAPK), p16(INK4a), p14(ARF), MGMT, TIMP3, CDH1, and RARB) by hypermethylation of the CpG islands. Cases from the three geographical regions showed similar clinicopathological features. However, moderate/marked tissue eosinophilia was found in 9/25 Asian cases, but only 1/23 German cases (P=0.011) and 0/12 American cases (P=0.015). All 60 cases were negative for either Borrelia DNA or API2-MALT1 fusion. Tumors from the three regions were highly methylated for DAPK (38-50% of the cases, mean 43%) and p16(INK4a) (42-70%, mean 49%), and the positivities were significantly higher than those of nonneoplastic skin (8%, P=0.0010 and 14%, P=0.0032, respectively). Methylation of these genes had no significant association with progressive features of the tumor. Primary cutaneous marginal zone B-cell lymphomas from the three geographical regions have common clinicopathological features, however, moderate/marked tissue eosinophilia is a feature found almost exclusively in Asian cases. Borrelia infection and API2-MALT1 fusion are not significant in this tumor. Methylation of DAPK and p16(INK4a) genes is a frequent event in this lymphoma at its initial presentation, but may not be associated with tumor progression.
authors.affiliation: Department of Pathology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Takino
authors.forename: Chunmei
authors.initials: C
authors.lastname: Li
authors.forename: Sindy
authors.initials: S
authors.lastname: Hu
authors.forename: Tseng-Tong
authors.initials: TT
authors.lastname: Kuo
authors.forename: Eva
authors.initials: E
authors.lastname: Geissinger
authors.forename: Hans Konrad
authors.initials: HK
authors.lastname: Muller-Hermelink
authors.forename: Bong
authors.initials: B
authors.lastname: Kim
authors.forename: Steven H
authors.initials: SH
authors.lastname: Swerdlow
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Inagaki
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001208:Asia; D001899:Borrelia Infections / Q000453:epidemiology; D025065:Borrelia burgdorferi; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D005260:Female; D016147:Genes, Tumor Suppressor; D005858:Germany; D006801:Humans; D018442:Lymphoma, B-Cell, Marginal Zone / Q000235:genetics* / Q000382:microbiology* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D016133:Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000235:genetics* / Q000382:microbiology* / Q000473:pathology*; D014481:United States
chemical_list: C415943:API2-MALT1 fusion protein, human; D015514:Oncogene Proteins, Fusion