Rearrangement of DDIT3 (CHOP) in Perivascular Epithelioid Tumors (PEComas): A Novel Finding
Karen E Schoedel, Carol Sherer, Kathleen Cieply, Andrew L Folpe. University of Pittsburgh Medical Center, Pittsburgh, PA; Mayo Clinic, Rochester, MN
Background: The genetic events underlying the development of soft tissue perivascular epithelioid tumors (PEComas) have not been fully elucidated. A prior comparative genomic hybridization study has shown genetic gains and losses on several chromosomes including gains involving X, 12q, 3q, 5 and 2q. Loss of expression of the tumor suppressor genes TSC1 and TSC2 has also been shown in some PEComas. Prompted by a recent case of PEComa found during routine pathological evaluation to have rearrangement of DDIT3, we evaluated a larger series of well-characterized PEComas of soft tissue, gynecologic and cutaneous origin for evidence of DDIT3 rearrangement.
Design: Inclusive of the index case, 13 morphologically and immunophenotypically classical PEComas were retrieved from our institutional and consultation archives. In each case, H&E stained slides were reviewed and tumor areas marked. Three corresponding unstained slides were submitted for FISH analysis using the Vysis LSI DDIT3 dual color break apart probe. Approximately 60 cells were evaluated in each case and the cutoff value for positivity was 15.5%.
Results: The tumors occurred in 4 male and 9 female patients, ranging in age from 28 to 72 years (mean 49 years). Tumors involved soft tissue/viscera (N=7), skin (N=4), and uterus (N=2). Cases were classified as histologically benign (N=8), of uncertain malignant potential (N=1) and histologically malignant (N=4). Rearrangements of the DDIT3 locus were identified in 3/13 cases (23%), all of soft tissue origin (1 malignant, 1 uncertain, 1 benign).
Conclusions: This represents, to the best of our knowledge, the first report of DDIT3 rearrangements in PEComas. This finding suggests the presence of a DDIT3-containing translocation in at least a subset of PEComas, although the fusion partner(s) is (are) currently unknown. It is unlikely that DDIT3 rearrangement will prove to be related to clinical behavior in PEComas, given its presence in tumors both with and without morphological features of malignancy. DDIT3 is known to be involved in adipocyte differentiation, cell cycle progression and malignant transformation, and may prove to be important in the pathogenesis of PEComas.
Category: Bone & Soft Tissue
Monday, March 19, 2012 1:00 PM
Poster Session II # 13, Monday Afternoon