Translocation-positive low-grade fibromyxoid sarcoma: clinicopathologic and molecular analysis of a series expanding the morphologic spectrum and suggesting potential relationship to sclerosing epithelioid fibrosarcoma: a study from the French Sarcoma Group

Am J Surg Pathol. 2007 Sep;31(9):1387-402. doi: 10.1097/PAS.0b013e3180321959.

Abstract

Low-grade fibromyxoid sarcomas (LGFMS) bear either the t(7,16) (q32-34;p11) or t(11,16) (p11;p11) translocations, resulting in FUS-CREB3L2 or FUS-CREB3L1 fusions, respectively. Heretofore, fusion transcripts were mainly detected in frozen tissues, using reverse transcription-polymerase chain reaction. In this study, we aimed to develop a reliable method to detect these in paraffin-embedded tissues, and to examine the clinicopathologic characteristics of a series of translocation-positive LGFMS. Sixty-three neoplasms with typical morphologic features of LGFMS and 66 non-LGFMS tumors selected for their resemblance to LGFMS (LGFMS-like tumors) were examined. RNA of sufficient quality could be extracted from 111/129 (86%) cases (59 LGFMS, 52 non-LGFMS). Of all, 48/59 (sensitivity, 81%) LGFMS contained detectable transcripts (45 FUS-CREB3L2, 3 FUS-CREB3L1). Most relevant clinicopathologic features of fusion-positive LGFMS included predominance in lower extremities (22/48; thigh: 13/48), deep situation (46/48), and occasional presence of unusual histologic features, for example, hypercellular areas (16/48), foci of epithelioid cells (13/48), and giant rosettes (6/48). Most tumors expressed EMA (41/45), at least focally, CD99 (38/41) and bcl-2 (36/41) while being essentially negative for CD34 (2/45), mdm2 (1/41), smooth muscle actin (1/45), S100 protein (0/46), desmin (0/44), h-caldesmon (0/42), keratins (0/44), and CD117 (0/40). Eleven presumed LGFMS were fusion negative. Of all, 7/52 non-LGMFS neoplasms contained FUS-CREB3L2 transcripts, of which 4 had been diagnosed as sclerosing epithelioid fibrosarcoma. In conclusion, FUS-CREB3L1/L2 fusion transcripts can be detected in paraffin-embedded LGFMS in a sensitive manner, using reverse transcription-polymerase chain reaction. Most fusion-positive LGFMS are EMA-positive and CD34/S100/smooth muscle actin negative. The presence of epithelioid cells and fusion transcripts in both LGFMS and a subset of sclerosing epithelioid fibrosarcoma suggest that these neoplasms might be related.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Base Sequence
  • Basic-Leucine Zipper Transcription Factors / genetics*
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / genetics*
  • Child
  • Cyclic AMP Response Element-Binding Protein / genetics*
  • Epithelioid Cells / pathology*
  • Female
  • Fibroma / chemistry
  • Fibroma / diagnosis*
  • Fibroma / genetics
  • Fibroma / pathology
  • Fibrosarcoma / chemistry
  • Fibrosarcoma / diagnosis*
  • Fibrosarcoma / genetics
  • Fibrosarcoma / pathology
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • In Situ Hybridization, Fluorescence
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Neoplasm Invasiveness
  • Nerve Tissue Proteins / genetics*
  • Paraffin Embedding
  • Predictive Value of Tests
  • RNA, Messenger / analysis
  • RNA-Binding Protein FUS / genetics*
  • Reproducibility of Results
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sensitivity and Specificity
  • Translocation, Genetic*

Substances

  • Basic-Leucine Zipper Transcription Factors
  • Biomarkers, Tumor
  • CREB3L1 protein, human
  • CREB3L2 protein, human
  • Cyclic AMP Response Element-Binding Protein
  • Nerve Tissue Proteins
  • RNA, Messenger
  • RNA-Binding Protein FUS