1. ¹Department of Internal Medicine, Hitachi General Hospital, Hitachi, Ibaraki, Japan
2. ²Division of Hematology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
3. ³Pathology of Biological Response, Nagoya University School of Medicine, Nagoya, Aichi, Japan

Correspondence: Hiroshi Kojima, M.D., Ph.D., Division of Hematology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki, 305-8575, Japan. fax: 0298-53-3127; e-mail: hkojima@md.tsukuba.ac.jp.

Accepted 1 May 2003.

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) -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 chain, but negative for CD30 (Ber-H2), CD56, CD57, and other T- and B-cell markers. Southern blot analyses revealed that Ig heavy and light chain genes, but not T-cell receptor (TCR) 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.