Epithelioid inflammatory myofibroblastic sarcoma: a clinicopathological, immunohistochemical and molecular cytogenetic analysis of five additional cases and review of the literature

BACKGROUND: To explore the clinical characteristics and pathological features of epithelioid inflammatory myofibroblastic sarcoma (EIMS) with emphasis on the diagnostic spectrum. METHODS: The clinical data and histological features in 5 additional cases of EIMS were retrospectively reviewed. Immunohistochemical study and interphase fluorescence in situ hybridization (FISH) analysis were carried out. RESULTS: There were 2 males and 3 females with age at presentation ranging from 15 to 58 years (mean, 37 years). All 5 tumors were intra-abdominal with 2 arising in the mesentery and 1 each in the omentum, rectum and transverse colon. The tumor size ranged from 5 to 20 cm in maximum diameter (mean, 10.7 cm). Histologically, all 5 tumors were composed predominantly of large epithelioid cells possessing vesicular nuclei, prominent nucleoli, and amphophilic cytoplasm. Mitotic figures were easily identified (mean, 20/10HPF). Tumor cells were arranged in clusters or sheets embedded in a myxoid stroma containing prominent neutrophils. A minor component of spindle cells was present in focal areas. By immunohistochemistry, all 5 cases were positive for anaplastic lymphoma kinase (ALK) with a nuclear membrane pattern in 4 and cytoplasmic staining with perinuclear accentuation in 1. Besides ALK, tumor cells stained variably for desmin (4/5), alpha smooth muscle actin (2/5), muscle-specific actin (1/2) and pan-cytokeratin (1/4). FISH analysis demonstrated the presence of ALK rearrangement in all 5 cases. Of 5 patients, 3 developed local recurrence, 1 died of disease 8 months after surgery. CONCLUSION: EIMS represents a highly aggressive variant of inflammatory myofibroblastic tumor characterized by epithelioid morphology, prominent neutrophilic infiltrate, and nuclear membrane staining of ALK with ALK rearrangement. As patients with ALK-rearrangement tumors may benefit from targeted therapy, accurate diagnosis of EIMS is very important. Familiar with the characteristic features of EIMS will help pathologists avoid misdiagnosing the tumor as other malignancies.