Round Cell Inflammatory Myofibroblastic Tumor with Nuclear Membrane or Perinuclear ALK: An Aggressive Intra-Abdominal Variant
JL Hornick, WL Wang, A Roy, D Lopez-Terrada, AJ Lazar, CM Coffin. Brigham and Women's Hospital, Boston; UT-MD Anderson Cancer Center, Houston; Baylor College of Medicine, Houston; Vanderbilt University School of Medicine, Nashville
Background: Inflammatory myofibroblastic tumor (IMT) is a mesenchymal neoplasm of intermediate biologic potential that may recur and rarely metastasize. Pathologic features do not correlate well with behavior. Approximately 50% of IMTs harbor ALK gene rearrangement and overexpress ALK, most demonstrating diffuse cytoplasmic staining. Rare IMTs with a distinct nuclear membrane or perinuclear pattern of ALK and round cell morphology have been reported. These cases showed an aggressive clinical course, suggesting that such patterns may predict malignant behavior.
Design: IMTs from 4 institutions were screened to identify tumors showing nuclear membrane or perinuclear ALK. Clinicopathologic features were evaluated, and follow-up was obtained. FISH and RT-PCR were performed on a subset of cases.
Results: 8 cases were identified. All patients were male (mean age 35 yr; range 7 mo – 59 yr), and all tumors were intra-abdominal (mesentery or omentum). Mean size was 16 cm (range 8–26 cm); 3 were multifocal. The tumors were composed predominantly of sheets of round to epithelioid cells with vesicular nuclei, large nucleoli, and amphophilic cytoplasm. In all cases, a minor spindle cell component was present; 5 had abundant myxoid stroma. In 4 cases neutrophils were prominent, in 3 cases lymphocytes. Median mitotic rate was 6 per 10 HPF; 5 had necrosis. All were positive for ALK (6 nuclear membrane pattern; 2 perinuclear), 7 desmin, 3 focal SMA, and 5 focal CD30. All were negative for myf4, keratins, EMA, and S-100. Thus far, FISH was positive for ALK rearrangement in 2 cases, and in 1 case a RANBP2-ALK fusion was detected by RT-PCR. Follow-up ranged from 3 mo - 3 yr (median 13 mo). Seven patients underwent surgical resection; in 1 case, tumor was inoperable. All patients had rapid local recurrence (within 8 mo); 4 had multiple recurrences. Seven had post-operative chemotherapy; 2 had XRT. Two patients also developed metastases (1 liver; 1 lung). Thus far, 3 patients died of disease, 4 are alive with disease, and 1 has no evidence of disease.
Conclusions: Round cell IMT with nuclear membrane or perinuclear ALK is a distinctive variant with an intra-abdominal predilection. Unlike conventional IMT, abundant myxoid stroma and prominent neutrophils are common. These tumors pursue an aggressive course with rapid local recurrences.
Category: Bone & Soft Tissue
Monday, March 22, 2010 9:15 AM
Platform Session: Section F, Monday Morning