Expression of ALK1 and p80 in Inflammatory Myofibroblastic Tumor and Its Mesenchymal Mimics: A Study of 135 Cases

Abstract

Inflammatory myofibroblastic tumor (IMT), a tumor of myofibroblastic spindle cells accompanied by a lymphoplasmacytic and eosinophilic inflammatory infiltrate, and anaplastic large cell lymphoma share clonal aberrations involving the short arm of chromosome 2 in region p21-p23 (1-5). Chromosome 2p23 is the site of the human ALK gene, which codes for anaplastic lymphoma kinase, a tyrosine kinase receptor and member of the insulin growth factor receptor superfamily. Antibodies to the protein product of the ALK gene detect both ALK expression associated with 2p23 rearrangements and other abnormalities in ALK deregulation. ALK rearrangements and/or ALK1 and p80 immunoreactivity have been reported in 36 -60% of IMTs and 8 -33% of "inflammatory pseudotumors" (3, 5, 6 -9). Fusion oncogenes have been identified in a small proportion of IMTs with ALK rearrangements and include TPM3-ALK and TPM4-ALK (4). In anaplastic large cell lymphoma, the clonal abnormalities of ALK include a characteristic translocation t(2, 5)(p23;q35), variant translocations, and a TPM3-ALK fusion oncogene in some cases (2, 10 -15). Various investigators have shown that ALK gene rearrangements and ALK expression are found

Utility of ALK-1 protein expression and ALK rearrangements in distinguishing inflammatory myofibroblastic tumor from malignant spindle cell lesions of the urinary bladder

“…6,7,11,13 This study confirms the utility of the detection of ALK-1 protein by immunoperoxidase methods and ALK rearrangements by FISH and the limited value of immunohistochemical markers for epithelial, myogenic and follicular dendritic differentiation in the separation of inflammatory myofibroblastic tumors from malignant spindle cell tumors of the urinary bladder. Originally identified as a protein overexpressed in anaplastic large-cell lymphoma, ALK-1 has subsequently been shown to be overexpressed in a substantial proportion of inflammatory myofibroblastic tumors of various anatomic locations, [1][2][3][4][5][6][7][8][9]15 including the urinary bladder. 3,7,[10][11][12][13][14]16,19,25 Several studies have demonstrated a variable degree of cytoplasmic immunohistochemical staining for ALK-1.…”

“…[1][2][3][4][5][6][7][8][9] The vast majority of these tumors behave in a benign fashion, although occasionally tumors can recur following surgical excision. Histologically, inflammatory myofibroblastic tumor is characterized by a proliferation of spindled cells arranged in loose, variably cellular fascicles admixed with inflammatory cells including plasma cells, and lymphocytes.…”

“…2,4,9,15,18,19 ALK, located on chromosome 2p23, encodes the ALK protein, a tyrosine kinase receptor, originally shown to be overexpressed in anaplastic large cell lymphoma. Rearrangements of ALK with various gene partners have been identified in inflammatory myofibroblastic tumor from a number of anatomic sites.…”

Low-grade Sarcomas with CD34-Positive Fibroblasts and Low-Grade Myofibroblastic Sarcomas

“…Immunohistochemically, most cases are positive for smooth muscle and muscle-specific actins, and a smaller number for desmin; some cases (especially those in a submesothelial location) express cytokeratins. ALK immunostaining is positive in 36 to 60% [132][133][134] of cases, with a granular pattern in cytoplasm or nucleus, and sometimes cell and nuclear membranous accentuation; the variant patterns possibly relating to different fusion genes. ALK expression, found predominantly in abdominal and pulmonary IMT in childhood, might be associated with an improved outcome.…”

Inflammatory Myofibroblastic Tumor of the Larynx: Report of a Rare Case and Literature Review

“…The tumor is histopathologically characterized by intense proliferation of myoblastic spindle cells wiyh chronic lymphocytic infiltration of the stratum [1,2] The tumor resembles laryngeal papillomatosis [13], squamous cell carcinoma, leiomyosarcoma, malignant histiocytoma, embryonic rhabdomyosarcoma and lymphoma and requires complete immunohistichemical tests (Vimentin, Muscle specific actin (SMA), ALK-1, Desmin, Caldesmon, Calponin, Cytokeratin, CD 68) [14]. Genetic rearrangements involving the 2p23 chromosome in which the ALK18 receptor tyrosine kinase gene has been mapped have also been observed [7,15].…”