Ossifying Fibromyxoid Tumor

American Joint Committee on Cancer (AJCC) or Union for International Cancer Control (UICC) TNM staging can be applied to the malignant subtype.

At least 85% of OFMTs, including typical, atypical, and malignant lesions, display a gene fusion, most commonly (in ~50% of cases) involving the PHF1 gene; the most prevalent variants are EP400-PHF1, MEAF6-PHF1, EPC1-PHF1, and PHF1-TFE3. In addition, rare fusions involving BCOR, BCORL1, CREBBP, and/or KDM2A have been described, especially in malignant OFMT; the proteins encoded by these genes share with PHF1 direct or indirect involvement in processes affecting histone modification. Little is known about other genetic changes affecting the clinical behavior of OFMT, but FISH studies have suggested that loss of chromosome 22 material might be more common in the malignant subgroup.

Grossly, lesions range from 0.5 to 21 cm in greatest diameter, with a median of about 4 cm. OFMTs are usually well circumscribed and nodular or multinodular, and they are generally covered by a thick fibrous pseudocapsule with or without a shell of bone. The cut surface of the tumor is often glistening; white to tan in color; and firm, hard, or rubbery in texture.

Microscopically, OFMTs are generally well circumscribed, with a thick fibrous capsule or pseudocapsule. Dense fibrous septa often extend into the tumor, producing a multinodular appearance. A complete or incomplete peripheral shell of metaplastic woven or lamellar bone is present in many cases. Bone may also be present in fibrous septa. Despite apparent circumscription at low power, the tumor may invade through the capsule and form extracapsular nodules in adjacent tissue. The tumor is composed of lobules of uniform, round to spindle-shaped cells with bland round to ovoid nuclei and scant, pale eosinophilic cytoplasm. Tumor cells are usually arranged in cords, nests, or sheets, surrounded by variably fibrous or myxoid stroma. Cellularity varies from low to moderate to high. Mitotic activity is usually low in typical OFMTs. About two-thirds of OFMTs are positive for S100, although immunoreactivity is rarely diffuse. Desmin expression is observed in almost half of OFMTs. The lesions may also express MUC4, EMA, keratins, and SMA. SMARCB1 (INI1) expression is lost in a mosaic pattern in about three-quarters of OFMTs. A malignant subtype has been proposed by some, as defined by cases with high nuclear grade or high cellularity and > 2 mitoses per 10 mm². In clinically malignant lesions, bone or osteoid deposition within tumor cell nodules may also be identified. OFMTs with histological findings deviating a little from typical OFMT, but not fulfilling these criteria for the malignant subtype, can be classified pragmatically as atypical OFMT.

Not clinically relevant

Follow-up data indicate that even typical OFMT has the unpredictable potential for recurrence and metastasis. This is often delayed and may occur 10–20 years or more after the primary excision. The local recurrence rates for typical, atypical, and malignant OFMTs, respectively, are reported as 0–12%, 0–13%, and 0–60%. The common metastatic sites are lung and soft tissue. The metastasis rates for typical, atypical, and malignant OFMTs, respectively, are reported as 0–4%, 0–6%, and 20–60%.

Demonstration of PHF1 and/or TFE3 gene rearrangement can be helpful.

Essential: lobulated growth pattern with frequent capsular ossification; usually very bland cytology with uniform round to ovoid nuclei; frequent (but not invariable) positivity for S100 and/or desmin.

Desirable: PHF1 gene rearrangement (in selected cases).