title: ALK+, CD30-, CD20- large B-cell lymphoma containing anaplastic lymphoma kinase (ALK) fused to clathrin heavy chain gene (CLTC).
abstract: Pathological features and genomic basis of a rare case of ALK(+), CD30(-), CD20(-) large B-cell lymphoma were analyzed. A 36-year-old Japanese female was admitted because of lumbago and constitutional symptoms. Physical examination and laboratory tests showed anemia (hemoglobin, 7.5 g/dL), mild hepatosplenomegaly, and immunoglobin G (IgG) lambda-type monoclonal gammopathy (IgG, 2782 mg/dL). The lymphoma spread exclusively in extranodal sites such as bone marrow, liver, spleen, ovary, and muscle. Biopsy specimens obtained from the ovary showed monomorphic proliferation of large immunoblastic cells with basophilic cytoplasm, round-shaped nuclei with a high nuclear to cytoplasmic ratio, and prominent single nucleolus. Immunostaining with anti-anaplastic lymphoma kinase (ALK) antibody, ALK1, showed finely granular cytoplasmic staining pattern. These cells were also positive for epithelial membrane antigen, CD4, CD19, CD38, CD138, cytoplasmic IgG, and lambda chain, but negative for CD30 (Ber-H2), CD56, CD57, and other T- and B-cell markers. Southern blot analyses revealed that Ig heavy and lambda light chain genes, but not T-cell receptor (TCR) beta gene, were clonally rearranged. Chromosomal analyses by conventional G-banding, spectral karyotyping, and fluorescence in situ hybridization showed complex abnormality involving 2p23, and chromosome 2 was translocated to chromosome 17. As 2;17 translocation resulting in the fusion of clathrin heavy chain (CLTC) gene with ALK was previously reported in inflammatory myofibroblastic tumor, we performed reverse transcriptase-polymerase chain reaction and demonstrated that the lymphoma cells contained CLTC-ALK fusion transcript. Under the diagnosis of ALK(+), CD30(-), CD20(-) large B-cell lymphoma, she was treated with conventional combination chemotherapies. However, the lymphoma was primarily chemotherapy resistant, and the patient died 11 months after admission. We consider that this case confirms the existence of ALK(+), CD30(-), CD20(-) large B-cell lymphomas proposed by Delsol et al. (16) and further provides relevant information regarding their clinicopathological features and cytogenetics.
authors.affiliation: Department of Internal Medicine, Hitachi General Hospital, Hitachi, Ibaraki, USA.
authors.forename: Norio
authors.initials: N
authors.lastname: Chikatsu
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kojima
authors.forename: Kazumi
authors.initials: K
authors.lastname: Suzukawa
authors.forename: Atsushi
authors.initials: A
authors.lastname: Shinagawa
authors.forename: Toshiro
authors.initials: T
authors.lastname: Nagasawa
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ozawa
authors.forename: Yoriko
authors.initials: Y
authors.lastname: Yamashita
authors.forename: Naoyoshi
authors.initials: N
authors.lastname: Mori
mesh_terms: D000328:Adult; D000077548:Anaplastic Lymphoma Kinase; D018951:Antigens, CD20 / Q000378:metabolism; D015139:Blotting, Southern; D002869:Chromosome Aberrations; D033922:Clathrin Heavy Chains / Q000235:genetics*; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D017730:Ki-1 Antigen / Q000378:metabolism; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015514:Oncogene Proteins, Fusion; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D020794:Receptor Protein-Tyrosine Kinases; D020133:Reverse Transcriptase Polymerase Chain Reaction; D032681:Spectral Karyotyping
chemical_list: D018951:Antigens, CD20; D017730:Ki-1 Antigen; D015514:Oncogene Proteins, Fusion; D033922:Clathrin Heavy Chains; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases