Chikatsu Norio, Kojima Hiroshi, Suzukawa Kazumi, Shinagawa Atsushi, Nagasawa Toshiro, Ozawa Hiroaki, Yamashita Yoriko, Mori Naoyoshi
Department of Internal Medicine, Hitachi General Hospital, Hitachi, Ibaraki, USA.
Mod Pathol. 2003 Aug;16(8):828-32. doi: 10.1097/01.MP.0000081729.40230.1F.
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.
分析了1例罕见的ALK(+)、CD30(-)、CD20(-)大B细胞淋巴瘤的病理特征和基因组基础。一名36岁的日本女性因腰痛和全身症状入院。体格检查和实验室检查显示贫血（血红蛋白，7.5 g/dL）、轻度肝脾肿大以及免疫球蛋白G（IgG）λ型单克隆丙种球蛋白病（IgG，2782 mg/dL）。淋巴瘤仅在骨髓、肝脏、脾脏、卵巢和肌肉等结外部位扩散。取自卵巢的活检标本显示大免疫母细胞呈单形性增殖，胞质嗜碱性，核圆形，核质比高，有明显的单个核仁。用抗间变性淋巴瘤激酶（ALK）抗体ALK1进行免疫染色，显示细颗粒状胞质染色模式。这些细胞上皮膜抗原、CD4、CD19、CD38、CD138、胞质IgG和λ链也呈阳性，但CD30（Ber-H2）、CD56、CD57以及其他T和B细胞标志物呈阴性。Southern印迹分析显示Ig重链和λ轻链基因发生克隆性重排，但T细胞受体（TCR）β基因未发生重排。通过传统G显带、光谱核型分析和荧光原位杂交进行的染色体分析显示涉及2p23的复杂异常，且2号染色体易位至17号染色体。由于先前在炎性肌纤维母细胞瘤中报道过导致网格蛋白重链（CLTC）基因与ALK融合的2;17易位，我们进行了逆转录聚合酶链反应，并证明淋巴瘤细胞含有CLTC-ALK融合转录本。在诊断为ALK(+)、CD30(-)、CD20(-)大B细胞淋巴瘤后，她接受了传统联合化疗。然而，该淋巴瘤对化疗原发性耐药，患者在入院11个月后死亡。我们认为该病例证实了Delsol等人（16）提出的ALK(+)、CD30(-)、CD20(-)大B细胞淋巴瘤的存在，并进一步提供了有关其临床病理特征和细胞遗传学的相关信息。
