Ossifying fibromyxoid tumor of soft parts: a clinicopathologic study of 70 cases with emphasis on atypical and malignant variants.

The ossifying fibromyxoid tumor of soft parts (OFMT) is an uncommon soft tissue neoplasm of uncertain lineage. Approximately 100 cases of OFMT have been reported. Although the majority behave in a benign fashion, very rare tumors with histologic and clinical evidence of malignancy have been reported. Criteria for malignancy in OFMT have not as yet been defined. Seventy cases of OFMT were retrieved from our consultation archives and studied with respect to patient age and sex, tumor site and size, growth pattern, percentage of typical OFMT, cellularity and nuclear grade, mitotic figures (MF)/50 high power fields (HPF), atypical mitoses, necrosis, vascular invasion, and the presence of bone. Immunohistochemistry for pancytokeratin, S-100 protein, smooth muscle actin, desmin, and collagen II was performed on a subset of cases. Follow-up information was obtained from the submitting pathologists and clinicians. The Fisher exact test was used for statistical analysis. Patients (39 male, 31 female) ranged in age from 14 to 83 years (median 49 years). The tumors occurred primarily as subcutaneous or deeply seated masses in the trunk and proximal extremities and ranged from 1 to 14 cm (median 4.0 cm). The percentage of typical OFMT present in each case ranged from 0% to 100% (median 70%), and bone was present in 44 cases (63%). Mitotic activity ranged from 0 to 40 MF/50 HPF (median 2 MF/50 HPF), necrosis was present in 12 cases (17%), and vascular invasion was seen in 8 cases (11%). High cellularity or high nuclear grade was seen in 14 and 13 cases, respectively. Immunohistochemical results were as follows: S-100 protein (33 of 55, 60%), pancytokeratin (5 of 48, 10%), smooth muscle actin (2 of 44, 5%), desmin (5 of 39, 13%), and collagen II (1 of 26, 4%). Follow-up (51 cases, mean 54 months, median 36 months, range 5-151 months) showed local recurrences in nine patients and metastases in eight patients. Currently, 41 patients are disease free, 6 are alive with disease, 4 are dead of disease, and 1 died of other causes. The presence of high cellularity (p = 0.002), high nuclear grade (p = 0.001), or >2 MF/50 HPF (p = 0.004) were significantly associated with the development of metastatic disease and local recurrence. Infiltrative growth was also associated with increased risk of local recurrence (p = 0.03). We conclude that the histologic spectrum of OFMT is broader than previously appreciated, as many clinically benign cases display moderate cellularity, nuclear enlargement, or have identifiable mitotic figures. Our results strongly suggest that OFMT with 1) high nuclear grade or 2) high cellularity and mitotic activity of >2 MF/50 HPF should be regarded as sarcomas with significant potential for metastasis and untoward outcome ("malignant OFMT"). The remainder can be considered within the spectrum of OFMT, recognizing that even these lesions possess a risk, albeit very low, of metastasis. Consequently, OFMT should be considered tumors of intermediate malignancy. Their line of differentiation remains unclear, although we suggest they may belong to the category of translocation-associated sarcomas, not all of which recapitulate a normal line of differentiation.