PHF1 Rearrangements in Ossifying Fibromyxoid Tumors (OFMT), with Emphasis on the Malignant Variant
Rondell P Graham, Sharon W Weiss, John Goldblum, Steven Billings, Snjezana Dotlic, Andrew L Folpe. Mayo Clinic, Rochester, MN; Cleveland Clinic, Cleveland, OH; University Hospital Center, Zagreb, Croatia; Emory University, Atlanta, GA
Background: OFMT is a rare borderline malignant mesenchymal tumor of uncertain lineage. Very recently, Gebre-Medhin and colleagues have reported rearrangements of the endometrial stromal sarcoma-associated gene PHF1 in subsets of OFMT, including typical, atypical and malignant variants (Am J Pathol 2012; 181; 1069). We sought to confirm and extend these findings, in particular with regards to malignant OFMT, the existence of which has been debated.
Design: All available slides from 11 OFMT were retrieved from our archives and classifed according to the Folpe and Weiss (2003) OFMT classification scheme. Interphase FISH was performed on paraffin-embedded sections using a clinically validated, laboratory developed break apart probe for detection of rearrangements of the PHF1 gene according to an established protocol.
Results: The tumors involved 7 men and 4 women, with a median age of 54 years (20-83 years), and arose in the soft tissues of the head and neck (n=2), trunk (n=1), upper (n=2) and lower limbs (n=6). OFMT were classified as typical (3 cases), atypical (1 case) and malignant (7 cases). PHF1 rearrangements were identified in 6/11 (55%) cases including 1/3 (33%) typical, 1/1 (100%) atypical and 4/6 (66%) malignant cases.
Conclusions: We have confirmed PHF1 rearrangements as frequent molecular cytogenetic findings in OFMT of all types. We conclude that the frequency of PHF1 gene rearrangements in OFMT; 1) imply a pathogenetic role, 2) emphatically confirm the existence of malignant OFMT as part of the histologic spectrum of a single entity, and 3) and underscore the utilitiy of molecular genetic analysis in the diagnosis of malignant or a histologically ambiguous cases of OFMT. On-going molecular genetic study of a larger number of OFMT of all types should help to clarify the relative frequency of PHF1 rearrangements in these rare mesenchymal tumors.
Category: Bone & Soft Tissue
Monday, March 4, 2013 1:00 PM
Poster Session II # 10, Monday Afternoon