Inflammatory myofibroblastic tumor and low-grade myofibroblastic sarcoma: a comparative study of clinicopathologic features and further observations on the immunohistochemical profile of myofibroblasts

Abstract

Inflammatory myofibroblastic tumor (IMT) and low-grade myofibroblastic sarcoma (LGMS) are intermediate- or low-grade malignant myofibroblastic neoplasms. In this study, the clinicopathologic profiles of 24 IMTs and 10 LGMS were compared with a focus on the immunohistochemical profiles of the neoplastic myofibroblasts. The primary antibodies used in this study were specific for the ultrastructural subcellular components: (1) *-smooth muscle actin (*-SMA), muscle-specific actin (MSA), calponin, and h-caldesmon for myofilaments; (2) fibronectin for fibronexus; (3) laminin for basal lamina; (4) desmin and cytokeratin for intermediate filaments. Anaplastic lymphoma kinase (ALK) alterations were examined by immunohistochemical means, with selective fluorescence in situ hybridization analysis. Histologically, IMT had inhomogeneous microscopic features with multi-component and multi-patterned architecture, whereas LGMS tended to be more uniform in appearance with a higher cellularity, more prominent nuclear hyperchromasia, and a more widely infiltrative growth pattern than IMT. Immunohistochemically, firstly, more than 90% of the cases of both IMT and LGMS expressed calponin, *-SMA, MSA, and fibronectin, almost all with a high expression level, and no cases were positive for h-caldesmon. Secondly, 33.3% (7/21) of IMTs and 40% (4/10) of LGMS were positive for desmin with a low expression level. The positive percentage for laminin was 81.8% (18/22) in IMT, but was 42.9% (3/7) in LGMS with a low expression level. Thirdly, 13.6% (3/22) of IMTs were positive for cytokeratin, but no expression was found in LGMS. ALK staining was found in 40.9% (9/22) of IMTs, and the presence of ALK gene rearrangements was confirmed by fluorescence in situ hybridization in 5 of 6 IMTs examined. However, neither ALK gene rearrangements nor ALK protein labeling was detected in LGMS (0/9). In summary, IMT and LGMS are both composed of cells displaying well-developed myofibroblastic differentiation, which frequently and extensively express actin-associated proteins (*-SMA, MSA, and calponin) and fibronectin, consistent with the ultrastructure markers (myofilaments and fibronectin fibrils). Laminin expression does not exclude a diagnosis of myofibroblastic neoplasms. ALK and cytokeratin, when positive, can be helpful in differentiating IMT from LGMS. LGMS is not a member of the family of ALK-positive tumors.