[566] Smoothelin Is a Specific Marker for Smooth Muscle Neoplasms of the Gastrointestinal Tract

DP Coco, MS Hirsch, JL Hornick. Brigham & Women's Hospital, Harvard Medical School, Boston, MA

Background: Smoothelin is a smooth muscle (SM)-specific cytoskeletal protein exclusively found in differentiated SM cells, unlike other SM proteins (e.g., h-caldesmon, -smooth muscle actin, desmin, smooth muscle myosin), which are expressed in proliferative (early) stages of SM development and occasionally in other cell types (striated muscle, myofibroblasts, myoepithelial cells, pericytes). Smoothelin has been shown to be expressed predominantly in visceral SM and to a lesser extent in vascular SM. Smoothelin expression in mesenchymal tumors of the gastrointestinal (GI) tract has not previously been evaluated. The purpose of this study was to determine whether immunostaining for smoothelin could help distinguish SM neoplasms from their morphologic mimics, particularly KIT-negative gastrointestinal stromal tumors (GISTs), desmin-positive GISTs, and desmoid fibromatosis.
Design: In total, 107 spindle cell tumors of the GI tract, abdominal cavity, and retroperitoneum were retrieved from consult and surgical pathology archives, including 36 GISTs (6 KIT-negative; 9 desmin-positive), 12 GI leiomyosarcomas (LMS), 9 GI mural leiomyomas, 13 colorectal leiomyomas of the muscularis mucosae, 9 gastric schwannomas, 12 inflammatory myofibroblastic tumors (IMT), 7 cases of mesenteric desmoid fibromatosis, and 9 dedifferentiated liposarcomas (DDLPS). Immunostaining for smoothelin (Chemicon; clone R4A; 1:800 dilution) was performed on all cases. Cytoplasmic and nuclear staining was recorded.
Results: Diffuse, predominantly cytoplasmic expression of smoothelin (>75% of tumor cells) was present in all 22 (100%) benign GI SM tumors. In contrast, only 2 (17%) GI LMS showed cytoplasmic staining for smoothelin. None of the GISTs, desmoid tumors, IMTs, schwannomas, or DDLPS showed cytoplasmic reactivity for smoothelin. Interestingly, 7 (58%) GI LMS and 6 (17%) GISTs (all with an epithelioid component) showed multifocal, exclusively nuclear staining for smoothelin. Nuclear expression of smoothelin was not detected in any of the other tumor types examined.
Conclusions: Diffuse cytoplasmic staining for smoothelin is highly sensitive and specific for benign leiomyomas of the GI tract. Aberrant nuclear only expression is common in GI LMS and may also be seen in epithelioid and mixed-type GISTs. These findings suggest that the extent and pattern of smoothelin expression may help differentiate between benign and malignant SM tumors of the GI tract, and may also be useful in distinguishing GI leiomyomas from KIT-negative and/or desmin-positive GISTs.
Category: Gastrointestinal

Wednesday, March 11, 2009 9:30 AM

Poster Session V # 86, Wednesday Morning