Sukov William R, Cheville John C, Carlson Austin W, Shearer Brandon M, Piatigorsky Eli J, Grogg Karen L, Sebo Thomas J, Sinnwell Jason P, Ketterling Rhett P
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55902, USA.
Mod Pathol. 2007 May;20(5):592-603. doi: 10.1038/modpathol.3800776. Epub 2007 Mar 30.
Inflammatory myofibroblastic tumor of the urinary bladder is an unusual spindle cell neoplasm that displays cytologic atypia, infiltrative growth and mitotic activity mimicking malignant tumors, such as leiomyosarcoma, rhabdomyosarcoma and sarcomatoid carcinoma. The objective of this study was to determine if anaplastic lymphoma kinase (ALK-1) protein expression detected by immunohistochemistry and ALK rearrangements detected by fluorescence in situ hybridization (FISH) were useful in distinguishing inflammatory myofibroblastic tumor from malignant spindle cell tumors of the urinary bladder. In inflammatory myofibroblastic tumor, ALK-1 expression was identified in 13 of 21 cases (62%) and ALK rearrangements in 14 of 21 cases (67%). All cases of inflammatory myofibroblastic tumor demonstrating ALK-1 expression, carried ALK rearrangements. One case negative for ALK-1 expression exhibited ALK rearrangement. ALK rearrangements were more common in women (P=0.0032). Leiomyosarcoma, sarcomatoid carcinoma, embryonal rhabdomyosarcoma and reactive myofibroblastic proliferations were negative for ALK-1 protein and ALK rearrangements. Immunohistochemistry using markers of muscle, epithelial, neural, and follicular dendritic cell differentiation showed overlap between inflammatory myofibroblastic tumor with and without ALK gene rearrangements, and between inflammatory myofibroblastic tumor and spindle cell malignancies. However, coexpression of cytokeratin and muscle-specific antigens was unique to inflammatory myofibroblastic tumor, observed in approximately half the tumors. This study indicates that detection of ALK protein and ALK gene rearrangements are useful in distinguishing inflammatory myofibroblastic tumor from spindle cell malignancies in the urinary bladder. Additionally, our findings suggest that ALK rearrangement is the primary mechanism for ALK activation and that inflammatory myofibroblastic tumor likely represents a heterogeneous group of spindle cell proliferations with the majority associated with ALK translocations, and the remaining associated with other etiologies.
膀胱炎性肌纤维母细胞瘤是一种不常见的梭形细胞肿瘤，其表现出细胞学异型性、浸润性生长以及有丝分裂活性，可模仿恶性肿瘤，如平滑肌肉瘤、横纹肌肉瘤和肉瘤样癌。本研究的目的是确定通过免疫组织化学检测的间变性淋巴瘤激酶（ALK-1）蛋白表达以及通过荧光原位杂交（FISH）检测的ALK重排是否有助于将炎性肌纤维母细胞瘤与膀胱恶性梭形细胞肿瘤区分开来。在炎性肌纤维母细胞瘤中，21例中有13例（62%）检测到ALK-1表达，21例中有14例（67%）检测到ALK重排。所有显示ALK-1表达的炎性肌纤维母细胞瘤病例均有ALK重排。1例ALK-1表达阴性的病例表现出ALK重排。ALK重排在女性中更常见（P=0.0032）。平滑肌肉瘤、肉瘤样癌、胚胎性横纹肌肉瘤和反应性肌纤维母细胞增生的ALK-1蛋白和ALK重排均为阴性。使用肌肉、上皮、神经和滤泡树突状细胞分化标志物的免疫组织化学显示，有和没有ALK基因重排的炎性肌纤维母细胞瘤之间，以及炎性肌纤维母细胞瘤与梭形细胞恶性肿瘤之间存在重叠。然而，细胞角蛋白和肌肉特异性抗原的共表达是炎性肌纤维母细胞瘤所特有的，在大约一半的肿瘤中观察到。本研究表明，检测ALK蛋白和ALK基因重排有助于将炎性肌纤维母细胞瘤与膀胱梭形细胞恶性肿瘤区分开来。此外，我们的研究结果表明，ALK重排是ALK激活的主要机制，炎性肌纤维母细胞瘤可能代表一组异质性的梭形细胞增殖，大多数与ALK易位相关，其余与其他病因相关。
