Oncogenesis and clinicopathologic characteristics of MALT lymphoma

AP12-MALT1融合基因是黏膜相关淋巴组织(MALT)淋巴瘤的特异性基因。我们最近描述了一种可用于石蜡切片的多重RT-PCR方法。利用这一方法，我们阐明了肺、皮肤、眼附件、结肠和胃的MALT淋巴瘤的临床病理意义。在41%的肺MALT淋巴瘤中检测到融合基因。融合基因阳性的肿瘤患者很少有自身免疫性疾病，其LDH水平通常正常。在组织学上，融合阳性肿瘤是典型的MALT淋巴瘤，并且与核Bcl10的表达有关(Am J Pathol，2003)。24例亚洲皮肤MALT淋巴瘤API2-MALT1融合和疏螺旋体感染均为阴性。然而，核Bcl10的表达与融合基因密切相关，在肿瘤中经常被检测到，并与肉眼可见的结节病变相关(Am J Surg Pathol，2003)。麦芽莱姆…眼附属器多瘤显示API2-MALT1融合者占13%。这些阳性病例通常表现为其他染色体异常，提示一些融合阳性的眼MALT淋巴瘤可能进展为高度恶性淋巴瘤(Mod Pathol，2003)。15%的结肠MALT淋巴瘤表现为API2-MALT1融合。融合基因多见于男性患者，且与晚期临床分期有关。后一项观察表明，可能需要对融合阳性的结肠MALT淋巴瘤进行密切随访(Mod Pathol，2003)。对累及多个器官的胃MALT淋巴瘤的分析表明，这些病例经常是API2-MALT1融合阳性，幽门螺杆菌感染阴性，对根除幽门螺杆菌治疗耐药(J Gasterenterol，2004)。一项对胃MALT淋巴瘤的大规模分析表明，API2-MALT1融合阳性肿瘤对根除幽门螺杆菌治疗完全耐药。因此，我们将胃MALT淋巴瘤分为三组：(A)根除敏感，(B)根除耐药，融合基因阴性，和(C)根除耐药，融合基因阳性。每一组都表现出独特的临床病理特征(Am J Surg Pathol，2004)。报告1例API2-MALT1融合阴性肺MALT淋巴瘤，发生于1例HIV阴性的年轻男性(Leuk淋巴瘤，2004年)。较少

AP12-MALT1 fusion gene is specific to mucosa-associated lymphoid tissue (MALT) lymphoma. We recently described a multiplex RT-PCR assay for this fission gene that can be applicable to paraffin sections. Using this assay, we clarified clinicopathological significances in MALT lymphomas of the lung, skin, ocular adnexa, colon, and stomach. The fusion gene was detected in 41% of pulmonary MALT lymphoma cases. The patients with fusion gene-positive tumors rarely had autoimmune disease, and their LDH level was often normal. Histologically the fusion-positive tumors were typical for MALT lymphoma, and were associated with nuclear BCL10 expression (Am J Pathol, 2003). Twenty-four Asian cases of cutaneous MALT lymphomas were negative for API2-MALT1 fusion and Borrelia infection. However, nuclear BCL10 expression, which is closely associated with the fusion gene, was frequently detected in the tumor calls, and was associated with macroscopically nodular lesion (Am J Surg Pathol, 2003). MALT lym … More phoma of the ocular adnexa showed the API2-MALT1 fusion in 13% of the cases analyzed. These positive cases often showed other chromosomal abnormalities, suggesting that some cases of the fusion-positive ocular MALT lymphoma might progress to high-grade lymphoma (Mod Pathol, 2003). MALT lymphoma of the colon showed the API2-MALT1 fusion in 15% of the cases analyzed. The fusion gene was often found in male patients, and was associated with advanced clinical stage. The latter observation suggests that a close follow-up may be needed for fusion-positive MALT lymphomas of the colon (Mod Pathol, 2003). An analysis of gastric MALT lymphomas involving multiple organs showed that these cases were frequently positive for API2-MALT1 fusion, negative for H. pylon infection, and resistant to H. pylori eradication therapy (J Gastroenterol, 2004). A large-scale analysis of gastric MALT lymphoma showed that API2-MALT1 fusion-positive tumors were totally resistant to H. pylori eradication therapy. Consequently, we divided gastric MALT lymphomas into three groups: (A) eradication-sensitive, (B) eradication-resistant, fusion gene-negative, and (C) eradication-resistant, fusion gene-positive. Each group showed unique clinicopathological features (Am J Surg Pathol, 2004). An API2-MALT1 fusion-negative pulmonary MALT lymphoma case which was developed in a HIV negative young man was reported (Leuk Lymphoma, 2004). Less