February 2019

Final Diagnosis and Discussion

A 56-year-old male with a subcutaneous mass

Final Diagnosis:  Ossifying fibromyxoid tumor

Discussion:

Ossifying fibromyxoid tumor (OFMT) is a rare soft tissue neoplasm that typically involves the subcutaneous tissues and rarely extends into the dermis.  It is seen equally in both males and females and the median age at presentation has been reported as 49-55 years with a range of 14-88.^1-3 It is most commonly found on the trunk and proximal extremities, with rare cases reported in other subcutaneous locations such as the scalp or lower lip.^1,3 The typical histologic appearance is that of a well circumscribed and encapsulated mass with an incomplete peripheral shell of bone.  Occasionally, cases lack this rim of bone or contain bone spicules more centrally within the tumor.  The tumor itself is made up of sheets, cords, and nests of round to oval spindled cells in a fibromyxoid, mucoid, or fibrous stroma.  The stroma is typically highly vascular.

OFMT is considered a neoplasm of intermediate malignancy and complete excision is recommended.  While most cases behave in a benign fashion, cases with high cellularity, high nuclear grade, and increased mitotic activity (>2/50 HPF) have been associated with increased local recurrence and metastasis.^1-2 Additionally, infiltrative growth has been shown to be associated with increased local recurrence.¹

While these tumors have been theorized to be either schwannian or chondroid in origin, a clear cell of origin has not been identified.¹  Immunohistochemical staining with S100 (highest proportion of tumors staining), GFAP, desmin, SMA, cytokeratin, and EMA have all been reported, but none of these markers or combination of markers are sensitive or specific.^1-4 Graham et al.⁴ reported expression of neural, schwannian, and chondroid markers as well as gene expression that is distinctly different from other schwannian tumors. While a single genetic profile has not been identified, Gebre-Mehdin et al. identified PHF1 gene rearrangements by FISH in 7 of 13 (54%) of cases of OFMT, with the rearrangement seen in typical, atypical, and malignant variants.⁵ These results were supported on a larger scale by Graham et al. who detected the rearrangement by FISH in 20 of 41 cases studied.⁶  While this does not encompass the origin of all tumors classified histologically as OFMT, it confirms classification as a translocation associated tumor, as originally projected by Folpe and Weiss in 2003.¹

References:

1. Folpe AL and Weiss SW. Ossifying Fibromyxoid Tumor of Soft Parts. Am J Surg Pathol. 2003; 27(4): 421-431.

2. Mesinkovska NA, Buehler D, McClain CM, Rubin BP, Goldblum JR, and Billings SD. Ossifying Fibromyxoid Tumor: a clinicopathologic analysis of 26 subcutaneous tumors with emphasis on differential diagnosis and prognostic factors. J Cutan Pathol. 2015; 42: 622-631.

3. Miettinen M, Finnell V, and Fetsch JF. Ossifying Fibromyxoid Tumor of Soft Parts—A Clinicopathologic and Immunohistochemical Study of 104 Cases with Long-term Follow-up and a Critical Review of the Literature. Am J Surg Pathol. 2008; 32: 996-1005.

4. Graham RPD, Dry S, Li X, Binder S, Bahrami A, Raimondi SC, Dogan A, Chakraborty S, Souchek JJ, and Folpe AL. Ossifying Fibromyxoid Tumor of Soft Parts: A Clinicopathologic, Proteomic, and Genomic Study. Am J Surg Pathol 2011; 35(11): 1615-1625.

5. Gebre-Medhin S, Nord KH, Möller E, Mandahl N, Magnusson L, Nilsson J, Jo VY, Steyern FV, Brosjö O, Larsson O, Domanski HA, Sciot R, Debiec-Rychter M, Fletcher CDM, and Mertens F. Recurrent Rearrangement of the PHF1 Gene in Ossifying Fibromyxoid Tumors. Am J Pathol. 2012; 181(3): 1069-1077.

6. Graham RP, Weiss SW, Sukov WR, Goldblum JR, Billings SD, Dotlic S, and Folpe AL. PHF1 Rearrangements in Ossifying Fibromyxoid Tumors of Soft Parts. Am J Surg Pathol. 2013; 37: 1751-1755.