Molecular Characterization of Dermatofibrosarcoma Protuberans The Clinicopathologic Significance of Uncommon Fusion Gene Rearrangements and Their Diagnostic Importance in the Exclusively Subcutaneous and Circumscribed Lesions

Pei Hang Lee, Shih Chiang Huang, Pao Shu Wu, Hui Chun Tai, Chih Hung Lee, Jen Chieh Lee, Yu Chien Kao, Jen Wei Tsai, Tsung Han Hsieh, Chien Feng Li, Wan Shan Li, Ting Ting Liu, Yu Li Su, Shih Chen Yu, Hsuan Ying Huang

Research output: Contribution to journalArticlepeer-review

Abstract

The clinicopathologic relevance of various gene rearrangements underlying dermatofibrosarcoma protuberans (DFSP) remains insufficiently characterized. In 188 DFSPs, we determined PDGFB, COL1A1, PDGFD, COL6A3, and EMILIN2 rearrangements by fluorescence in situ hybridization (FISH). The clinicopathologic significance of rearrangement types and factors related to recurrence and metastasis were statistically analyzed. In all, classic PDGFB rearrangement, cryptic COL1A1-PDGFB fusion, and PDGFD rearrangement were identified in 172 (91.4%), 8 (4.3%), and 8 (4.3%: 4 COL6A3-PDFGD, 4 EMILIN2-PDGFD) cases, respectively. In an index DFSP harboring the cryptic fusion, the COL1A1-PDGFB transcript was confirmed by both RNA sequencing and reverse transcription-polymerase chain reaction. In comparison with cases harboring classic PDGFB rearrangement, cryptic PDGFB-rearranged DFSPs usually exhibited higher 5′-COL1A1 copy numbers. In a combined reappraisal of published and current cases, COL6A3-PDGFD-positive DFSPs (n=16) predominated in females (n=14, 88%) and torso (n=14, 88%), especially the breast (n=7, 44%); EMILIN2-PDGFD-positive DFSPs (n=6) preferentially demonstrated near exclusively subcutaneous growth (n=5, 83%) and fibrosarcomatous transformation (n=5, 83%). In our cohort, local recurrence was related to fibrosarcomatous variant (P=0.029, odds ratio=3.478) and head and neck location (P=0.046, odds ratio=3.508). Distant metastasis only occurred in the fibrosarcomatous variant (9/73, 12.3%) but not in other cases. In conclusion, 8.6% of DFSPs are negative for PDGFB break-apart FISH, which, especially those with challenging subcutaneous and circumscribed manifestation, require complementary diagnosis by FISH assays targeting COL1A1 and PDGFD. The types of fusion gene rearrangements, head and neck location, and fibrosarcomatous transformation may account for clinicopathologic and prognostic variations in DFSPs and warrant future independent validation.

Original languageEnglish
JournalAmerican Journal of Surgical Pathology
DOIs
Publication statusAccepted/In press - 2022

ASJC Scopus subject areas

  • Anatomy
  • Surgery
  • Pathology and Forensic Medicine

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