Department of Pathology, San Bortolo Hospital, Vicenza, Italy.
Am J Surg Pathol. 2013 May;37(5):780-6. doi: 10.1097/PAS.0b013e318287791f.
ALK-positive large B-cell lymphomas usually harbor clathrin (CLTC)-ALK rearrangement or, more rarely, nucleophosmin (NPM)-ALK fusion gene. Here we report a large B-cell lymphoma with a peculiar pattern of diffuse and cytoplasmic immunohistochemical staining and carrying sequestosome 1 (SQSTM1)-ALK rearrangement, identified by reverse transcription polymerase chain reaction analysis and Rapid Amplification of cDNA Ends analysis and confirmed by fluorescence in situ hybridization with specific dual-color fusion probes. The gene fusion product and the transcription factor STAT3 are both phosphorylated, and thereby the pathogenetic mechanism of this case shows important analogies with that of NPM-ALK and CLTC-ALK lymphomas, in which STAT3 plays a central role in the lymphomagenesis. Consequently, STAT3 inhibition provides a possible therapeutic target also for lymphomas with SQSTM1-ALK variant translocation.
ALK 阳性大 B 细胞淋巴瘤通常存在网格蛋白（CLTC）-ALK 重排，或更罕见的核仁磷酸蛋白（NPM）-ALK 融合基因。我们在此报告一例大 B 细胞淋巴瘤，其免疫组化染色呈弥漫性和细胞质模式，具有独特的形态，携带自噬相关蛋白 1（SQSTM1）-ALK 重排，通过逆转录聚合酶链反应分析和快速扩增 cDNA 末端分析鉴定，并通过特异性双色融合探针的荧光原位杂交证实。该基因融合产物和转录因子 STAT3 均被磷酸化，因此该病例的发病机制与 NPM-ALK 和 CLTC-ALK 淋巴瘤具有重要的相似性，在这些淋巴瘤中，STAT3 在淋巴瘤发生中起核心作用。因此，STAT3 抑制也为具有 SQSTM1-ALK 变体易位的淋巴瘤提供了一个可能的治疗靶点。
