PDGFB, 22q13, for Dermatofibrosarcoma Protuberans/Giant Cell Fibroblastoma, FISH
Confirming the diagnosis of dermatofibrosarcoma protuberans (DFSP)/giant cell fibroblastoma (GCF) and excluding other spindle neoplasms that closely simulate the DFSP histology, including dermatofibroma (benign fibrous histiocytoma), neurofibroma, spindle cell lipoma, and a variety of other benign and malignant spindle cell neoplasms.
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Dermatofibrosarcoma protuberans (DFSP) is a superficial, low-grade sarcoma genetically characterized by the unbalanced chromosomal translocation t(17;22)(q21;q13), usually in the form of a supernumerary ring chromosome. The product of this chromosomal translocation is the chimeric gene COL1A1-PDGFB. Rearrangements of this gene have been detected in approximately 90% of DFSP and its related infantile form, giant cell fibroblastoma, but not in other tumors.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
0-9% rearranged cells
An interpretative report will be provided.
A neoplastic clone is detected when the percent of cells with an abnormality exceeds the normal reference range for the PDGFB FISH probe.
A positive result is consistent with rearrangement/amplification of the PDGFB gene locus on 22q13 and supports the diagnosis of dermatofibrosarcoma protuberans (DFSP) or giant cell fibroblastoma (GCF). A negative result is consistent with no rearrangement/amplification of the PDGFB gene locus on 22q13. However, this result does not exclude the diagnosis of DFSP or GCF.
The degree of PDGFB copy gain/amplification/rearrangement varies in individual tumors and among different cells in the same tumor. It is not currently known if patients with different levels of rearrangement/amplification have the same prognosis and response to therapy.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Reliable results are dependent on adequate specimen collection and processing. This test has been validated on formalin-fixed, paraffin-embedded tissues; other types of fixatives are discouraged. Improper treatment of tissues, such as decalcification, may cause FISH failure.
Clinical diagnosis and/or therapy should not be based solely on this assay. The results should be considered in conjunction with clinical information, histologic analysis, and/or additional diagnostic tests.
A blinded investigation was performed on 49 formalin-fixed, paraffin-embedded tissues including 24 dermatofibrosarcoma protuberans (DFSP) tumors, 5 giant cell fibroblastoma (GCF) tumors, and 20 non-DFSP/GCF tumors. Each specimen had been previously characterized by 2 experienced, soft tissue pathologists. Two technologists scored 100 interphase nuclei for each specimen (200 total cells/case). Results showed that 20 of the 24 DFSP tumors had amplification of PDGFB, 1 had a rearrangement, and 3 were negative for both amplification and rearrangement. Each of the 20 non-DFSP/GCF tumors yielded normal results (ie, negative for both rearrangement and amplification). The 5 of the 5 GCF cases were also identified as abnormal.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Abbott JJ, Erickson-Johnson M, Wang X, et al: Gains of COL1A1-PDGFB genomic copies occur in fibrosarcomatous transformation of dermatofibrosarcoma protuberans. Mod Pathol 2006 Nov;19(11):1512-1518
2. Labropoulos SV, Fletcher JA, Oliveira AM, et al: Sustained complete remission of metastatic dermatofibrosarcoma protuberans with imatinib mesylate. Anticancer Drugs 2005 April;16(4):461-466
3. Macarenco RS, Zamolyi R, Franco MF, et al: Genomic gains of COL1A1-PDGFB occur in the evolution of giant cell fibroblastoma into dermatofibrosarcoma protuberans. Genes Chromosomes Cancer 2008 Mar;47(3):260-265