Materiały źródłowe

• #1 Dermatofibrosarcoma Protuberans – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK513305/

  Dermatofibrosarcoma protuberans (DFSP) stands as a rare soft tissue sarcoma that emerges in the dermis and is often found on the trunk and proximal extremities. […] The chromosomal translocation t(17;22)(q22;q13) leads to the formation of the abnormal fusion protein COL1A1-PDGFB, contributing to its pathogenesis. […] Ninety percent of patients with DFSP, including those who develop the fibrosarcomatous variant (DFSP-FS), have the t(17;22)(q22;q13) translocation. […] The t(17;22)(q22;q13) translocation results in the formation of supernumerary ring chromosomes from chromosome 22 and contains low-level amplified sequences from 17q22-qter and 22q10-q13.1. […] The ring chromosomes and the translocated linear derivative of chromosome 22 harbor a fusion gene where PDGFB merges with the collagen type 1A1 (COL1A1) gene. […] This genetic rearrangement induces PDGFB upregulation, resulting in excessive platelet-derived growth factor (PDGF) production, continuous activation of the tyrosine kinase PDGFRB receptor, cellular proliferation, and tumor development.

• #2 Dermatofibrosarcoma Protuberans: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1100203-overview

  Dermatofibrosarcoma protuberans (DFSP) is a cutaneous malignancy that arises from the dermis and invades deeper tissue (eg, fat, fascia, muscle, bone). […] The cellular origin of DFSP is not clear. Evidence supports the cellular origin being fibroblastic, histiocytic, or neuroectodermal. DFSP manifests partial features of each. Therefore, many authorities suggest pluripotential progenitor cells, such as undifferentiated mesenchymal cells, may be the origin of DFSP, because they have the capacity to differentiate into all 3 cell types. […] Cultured DFSP tumor cells have increased growth in response to platelet-derived growth factor (PDGF)beta. Cytogenetic studies reveal specific abnormalities in DFSP tumor cells, such as reciprocal translocations of chromosomes 17 and 22, t(17;22), and supernumerary ring chromosomes composed of interspersed sequences from bands 17(17q22) and 22(22q12). These rearrangements fuse the collagen type I alpha 1 (COL1A1) and the PDGF-beta chain (PDGFB, c-sis proto-oncogene) genes. The collagen promoter drives COL1A1 and PDGFB fusion protein production. The fusion protein is then processed into functional PDGF-B and subsequently interacts with the PDGF receptor on the cell surface of DFSP tumor cells. The activation of the PDGF receptor tyrosine kinase triggers the proliferation of DFSP tumor cells. […] Laboratory studies have shown that chromosomal aberrations may contribute to the pathogenesis of DFSP; however, no evidence of hereditary or familial predisposition exists.

• #3 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Dermatofibrosarcoma-Protuberans-(DFSP)-Pathophysiology.aspx

  Dermatofibrosarcoma protuberans (DFSP) is the result of a mutation in one of the cells that make up the body, which then proliferates to produce a tumor. It is not inherited, but occurs as a sporadic translocation between chromosomes 17 and 22 (t:17;22). […] The specific genes involved are the COL1A1 on the 17th chromosome with the PDGFB gene on the 22nd chromosome, and the translocated material forms an extra chromosome. This is either linear or circular in shape. […] The abnormal circular piece of genetic material formed by the fusion of these two genes (in part) encodes the translation of an abnormal or fusion protein, which has functions similar to the PDGFB protein, but is produced in massive excess. This leads to the hyperstimulation of proliferative processes relating to the involved cells, causing tumor production.

• #4 Pathogenesis of Dermatofibrosarcoma Protuberans | SpringerLink

  https://link.springer.com/chapter/10.1007/978-3-642-05072-5_13

  Nongenetic risk factors for DFSP remain unknown; there are also no details on genetic influences in terms of prevalence within families. […] New molecular research evidences frequent presentation of chromosomal translocations in DFSP tumor cells, finding a translocation between chromosomes 17 and 22 in over 90% of cases (17q22; 22q13). […] This translocation occurs mostly through fusion of collagen encoding gene (COL1A1) to cell-mediated growth factor platelet-derived growth factor beta (PDGF) encoding gene, frequently, though not always, forming a ring chromosome. […] The gene product of this fusion, a COL1A1-PDGF-Fusionsprotein, acts on a DFSP-cell binding site constitutively expressing PDGF-receptor as a continuous autocrine, developmental stimulus for the tumor cells. […] The acknowledgment of these solitary, autocrine stimulation pathways will allow for the development of a favorable, etiopathogenetically based, molecularly directed therapy for DFSP.

• #5 Dermatofibrosarcoma Protuberans: Update on the Diagnosis and Treatment

  https://www.mdpi.com/2077-0383/9/6/1752

  Cytogenetic and molecular studies have demonstrated that more than 90% of DFSPs are characterized by either supernumerary ring chromosomes derived from chromosomes 17 and 22 or chromosomal translocation t(17; 22) (q22; q13), resulting in the fusion of collagen type 1-alpha 1(COL1A1 at 17q22) and platelet-derived growth factor beta (PDGFB at 22q13) genes. […] The gene fusion places the PDGFB gene under the control of the COL1A1 promoter, leading to PDGFβ overexpression and dimerization, and subsequently resulting in continuous activation of the PDGF receptor β protein-tyrosine kinase. […] Interaction of PDGFβ and PDGF receptor β is involved in multiple signaling pathways including Ras mitogen-activated protein kinases (RAS-MARK) and phosphatidylinositol 3-kinase-akt-rapamycin (mTOR) (PI3K-AKT-mTOR).

• #6 A case report of abdominal metastatic dermatofibrosarcoma protuberans misdiagnosed as gastrointestinal stromal tumor | Diagnostic Pathology | Full Text

  https://diagnosticpathology.biomedcentral.com/articles/10.1186/s13000-023-01430-9

  Dermatofibrosarcoma protuberans (DFSP) is a low-grade malignant soft-tissue tumor that originates from the skin. It has a slow onset in the early stages, non-specific clinical symptoms, low specificity, and can easily be overlooked, missed, or misdiagnosed by clinicians and pathologists. […] The molecular pathogenesis of DFSP is relatively clear. Studies have shown that over 90% of cases are characterized by the characteristic t (17; 22) (q22; q13) chromosomal translocation and the formation of additional ring chromosomes r (17; 22) due to t (17; 22). Both mechanisms can form the COL1A1-PDGFB fusion gene. Under normal conditions, the PDGFB gene is suppressed, but the COL1A1 in the fusion gene can provide a promoter and signal peptide for PDGFB. The fusion protein produced by COL1A1-PDGFB is then processed into mature PDGFB, which interacts with the PDGFB receptor (platelet-derived growth factor receptor-, PDGFR-) on the surface of DFSP, leading to dysfunction of PDGF, activation of downstream signaling pathways RAS-MAPK and PI3K-AKT-mTOR, and ultimately promoting the proliferation of DFSP cells.

• #7 Dermatofibrosarcoma Protuberans | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/20385

  Ninety percent of patients with DFSP, including those who develop the fibrosarcomatous variant (DFSP-FS), have the t(17;22)(q22;q13) translocation. […] An alternative translocation involving the platelet-derived growth factor subunit B (PDGFB) gene on chromosome 22 may be present in patients without the t(17;22)(q22;q13) translocation. In certain instances, the progression from DFSP to DFSP-FS is associated with genomic gain affecting the PDGFB/COL1A1 fusion gene, although this occurrence is variable. […] The t(17;22)(q22;q13) translocation results in the formation of supernumerary ring chromosomes from chromosome 22 and contains low-level amplified sequences from 17q22-qter and 22q10-q13.1. […] The ring chromosomes and the translocated linear derivative of chromosome 22 harbor a fusion gene where PDGFB merges with the collagen type 1A1 (COL1A1) gene. The usually suppressed PDGFB now becomes activated by the COL1A1 promoter. This genetic rearrangement induces PDGFB upregulation, resulting in excessive platelet-derived growth factor (PDGF) production, continuous activation of the tyrosine kinase PDGFRB receptor, cellular proliferation, and tumor development.

• #8 Dermatofibrosarcoma Protuberans – SFA

  https://curesarcoma.org/sarcoma-subtypes/dermatofibrosarcoma-protuberans/

  DFSP is characterized by the presence of supernumerary ring chromosomes that contain the centromere of chromosome 22 and comprise interspersed sequences from chromosomes 17 and 22. […] Additional aberrations, such as trisomy 5 and trisomy 8, are also observed. […] Unbalanced t(17;22)(q21.3;q13.1) translocations are present in most children and rarely in adults. […] Most DFSP cells harbor not only a structural rearrangement but also a gain of 17q21.3-17qter and 22q10-q31 sequences. […] Both ring and der(22)t(17;22) chromosomes contain a chimeric gene fusing COL1A1 at 17q21.33 with PDGFB at 22q13.1. […] The breakpoint in COL1A1 is variable: the chimeric gene is composed of at least the first 6 exons up to exon 49 of COL1A1 and a consistent fragment retaining all but exon 1 of the PDGFB gene.

• #9

  https://www.omim.org/entry/607907

  A number sign (#) is used with this entry because dermatofibrosarcoma protuberans (DFSP) is caused in most cases by a specific fusion of the COL1A1 gene (120150) with the PDGFB gene (190040); see 190040.0002. […] Simon et al. (1997) characterized the breakpoints from translocations and rings in DFSP and its juvenile form, giant cell fibroblastoma, on the genomic and RNA levels. They found that these rearrangements fuse the PDGFB gene and the COL1A1 gene. Simon et al. (1997) commented that PDGFB has transforming activity and is a potent mitogen for a number of cell types, but its role in oncogenic processes was not fully understood. They noted that neither COL1A1 nor PDGFB had hitherto been implicated in tumor translocations. The gene fusions deleted exon 1 of PDGFB and released this growth factor from its normal regulation.

• #10 Orphanet: Dermatofibrosarcoma protuberans

  https://www.orpha.net/en/disease/detail/31112

  Dermatofibrosarcoma protuberans (DFSP) is a rare infiltrating soft tissue sarcoma, generally of low grade malignancy, arising from the dermis of the skin and characteristically associated with a specific chromosomal translocation t(17;22). […] DFSP is most likely fibroblastic in origin: over 90% of cases are associated with dysregulated platelet-derived growth factor (PDGF) production resulting from chromosomal translocation or a supernumerary ring chromosome derived from t(17;22). The translocation breakpoint most often involves the second exon of the PDGFB gene on chromosome 22 (22q13.1), with fusion to the collagen, type I, alpha 1 gene (COL1A1) on chromosome 17 (17q21.33). This chromosomal translocation results in the upregulation of the PDGFB gene in the form of a fused proto-oncogene COL1A1/PDGFB.

• #11 Dermatofibrosarcoma protuberans of the breast: A case report

  https://www.spandidos-publications.com/10.3892/ol.2017.6206

  Dermatofibrosarcoma protuberans (DFSP) is a rare malignant tumor of subcutaneous tissue characterized by slow infiltrative growth. […] Genetically, DFSP is characterized by a reciprocal translocation t(17;22)(q22;q13), or more often, as a supernumerary ring chromosome involving chromosomes 17 and 22. […] This translocation mechanism results in the transcriptional upregulation of the platelet derived growth factor subunit B (PDGFB) gene, in the form of a collagen type I 1 chain-PDGFB fusion oncogene. […] Genetically, DFSP is characterized by a reciprocal translocation t(17;22)(q22;q13), or more often, as a supernumerary ring chromosome involving chromosomes 17 and 22. […] The main consequence of the t(17;22)(q22;q13) translocation is the overproduction of PDGFB by tumor cells, which leads to a constitutive activation of the PDGFB receptor, which is a type III tyrosine kinase receptor.

• #12 Advances in molecular characterization and targeted therapy in dermatofibrosarcoma protuberans – PubMed

  https://pubmed.ncbi.nlm.nih.gov/21559214/

  The molecular pathogenesis of dermatofibrosarcoma protuberans (DFSP) involves distinctive rearrangement of chromosomes 17 and 22 leading to formation of the COL1A1-PDGFB fusion gene. […] The knowledge of molecular events underlying development of DFSP resulted in the implementation of targeted therapy with imatinib-a tyrosine kinase inhibitor (TKI), to the clinical practice. […] The striking efficacy of imatinib in advanced cases of DFSP has been demonstrated in a few clinical trials. […] Thus, imatinib is currently considered the gold standard in the treatment of inoperable and/or metastatic and/or recurrent cases of DFSP. […] Therapy with imatinib may potentially facilitate resection or decrease possible disfigurement related to radical surgical procedure. […] Following partial response on imatinib significant percentage of patients may be rendered free of the disease by surgery of the residual tumor.

• #13 Dermatofibrosarcoma Protuberans in Childhood | Actas Dermo-Sifiliográficas

  https://www.actasdermo.org/en-dermatofibrosarcoma-protuberans-in-childhood-articulo-S1578219012003046

  PDGFB is a growth factor that acts as a potent mitogen for connective tissue cells. The product of the COL1A1-PDGFB fusion gene induces tumor formation through increased expression of PDGFB in tumor cells, leading to autocrine or paracrine stimulation of the tumor, by activation of the PDGFB receptors. This molecular abnormality is essential for the development of DFSP.

• #13 Dermatofibrosarcoma Protuberans in Childhood | Actas Dermo-Sifiliográficas

  https://www.actasdermo.org/en-dermatofibrosarcoma-protuberans-in-childhood-articulo-S1578219012003046

  Dermatofibrosarcoma protuberans (DFSP) is a fibrohistiocytic tumor of intermediate malignancy that is very rare in childhood. Only 6% of these tumors present in children. Clinical diagnosis is very difficult in the early stages of disease, but to ensure appropriate treatment it is important to identify DFSP as early as possible and rule out benign conditions that are more common at this age. […] The histogenesis of DFSP is a subject of debate. DFSP is probably a slow-growing tumor originating in fibroblasts or histiocytes or arising from an undifferentiated mesenchymal cell with fibroblast, muscle-like, or neural-like characteristics. Trauma has been considered a possible etiologic factor given that 16.5% of a series of 115 patients reported prior injury in the region of the lesion. […] In most children, there are specific cytogenetic abnormalities in the tumor cells, and translocations in chromosomes 17 and 22 in particular. This topic will be dealt with in more detail later.

• #14

  https://drpress.org/ojs/index.php/HSET/article/view/13687

  Dermatofibrosarcoma protuberans (DFSP) is a kind of infrequent tumor of the soft tissues distinguished by its gradual proliferation and a preference for regional reoccurrence, despite its limited capacity for metastasis. At the molecular level, a significant majority of DFSP cases manifest the t (17;22) (q22; q13) chromosomal translocation, resulting in the fusion of the collagen type I alpha chain (COL1A1) gene and platelet-derived growth factor B chain (PDGFB) gene. This fusion results in PDGFB overexpression, consequently activating the PDGF Receptor-beta (PDGFR-). The activated PDGFR- serves as a central nexus for numerous intracellular signaling pathways, initiating cascades including Phosphatidylinositol 3-kinase (PI3K)/Akt, Mitogen-Activated Protein Kinase (MAPK)/extracellular signal-regulated kinase (ERK), and STATs pathways. These cascades collectively enhance DFSP cell growth, proliferation, and invasiveness. […] Mitogenic activity of dermatofibrosarcoma protuberans is mediated via an extracellular signal related kinase dependent pathway.

• #15 Dermatofibrosarcoma Protuberans: Update on the Diagnosis and Treatment

  https://www.mdpi.com/2077-0383/9/6/1752

  Correspondingly, increased expression of the phosphorylated Akt-mTOR pathway proteins including Akt, mTOR, 4EBP1, and S6RP and phosphor-PDGFRα/β have been demonstrated in about half of DFSP tissues by immunoperoxidase studies, suggesting that Akt-mTOR pathways are involved in the tumorigenesis of DFSP. […] Gene fusion transcript of COL1A1−PDGFB can be detected by either fluorescent in situ hybridization (FISH) or multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) in formalin fixed, paraffin embedded tissues. […] These are helpful for the diagnosis, differential diagnosis and guiding treatment of DFSP, especially when the tumor’s histomorphology is not typical or when the tyrosine kinase inhibitors are considered for treatment. […] The COL1A1-PDGFB fusion transcript cannot be detected in about 8% of DFSPs.

• #16 Dermatofibrosarcoma Protuberans – SFA

  https://curesarcoma.org/sarcoma-subtypes/dermatofibrosarcoma-protuberans/

  Fewer than 5% of typical DFSP cases are negative for the COL1A1-PDGFB fusion gene by routine molecular testing; alternative COL6A3-PDGFD and EMILIN2-PDGFD fusion genes have been identified, and in some cases, COL1A1-PDGFB rearrangement is cryptic. […] The COL1A1-PDGFB fusion gene encodes a fusion protein that is proteolytically processed to normal PDGFB ligand. […] Because tumor cells express the PDGFRB receptor on their cell surfaces, autocrine stimulation of neoplastic cells drives tumorigenesis. […] This molecular pathway provides a rationale for targeted therapy with tyrosine kinase inhibitors for unresectable DFSP or metastatic fibrosarcomatous DFSP. […] Alteration of the PDGFRB/AKT/mTOR pathway is seen in fibrosarcomatous DFSP.

• #17 Dermatofibrosarcoma protuberans, fibrosarcomatous – Wikipedia

  https://en.wikipedia.org/wiki/Dermatofibrosarcoma_protuberans,_fibrosarcomatous

  While the COL1A1-PDGFB fusion gene is present in 90% of DFSP-FS and DFSP cases, recent studies have also found the COL6A3-PDGFD and EMILIN2-PDGFD fusion genes in 2% of DFSP-FS or DFSP cases, the TNC-PDGFD fusion gene in one case of DFSP-FS, the COL1A2-PDGFB fusion gene in one case of DFSP, and the CSPG2-PTK2B fusion gene in one case of DFSP-FS. Further studies are needed to determine the latter five fusion genes’ prevalence in, and contribution to the development and/or progression of, DFSP and DFSP-FS.

• #18 Dermatofibrosarcoma Protuberans: Update on the Diagnosis and Treatment

  https://www.mdpi.com/2077-0383/9/6/1752

  Other reported genetic translocations in DFSP include COL1A2-PDGFB, COL6A3-PDGFD and elastin microfibril interface 2 (EMILIN2)-PDGFD. […] These data suggest that multiple factors including oncogenes, tumor suppressor genes and immunodeficiency are involved in the development of DFSP. Further investigation is required to understand the relationship of these risk factors to the development of DFSP.

• #19

  https://omim.org/entry/607907

  This suggested that not only fusion of the COL1A1 and PDGFB genes but also DNA chromosome number gains in the 17q and 22q regions is crucial in the pathogenesis of DFSP. […] Molecular investigations have shown that the breakpoint in PDGFB is remarkably constant, placing exon 2 under the control of the COL1A1 promoter. […] In approximately 8% of DFSP cases, the COL1A1/PDGFB fusion is not found, suggesting that genes other than COL1A1 or PDGFB may be involved in a subset of cases. PDGFB may act as a mitogen in DFSP cells by autocrine stimulation of the PDGF receptor (173410).

• #20 Dermatofibrosarcoma Protuberans: An Updated Review of the Literature

  https://www.mdpi.com/2072-6694/16/18/3124

  Importantly, the above microscopic picture differs in case of fibrosarcomatous transformation. […] This transformation, when presenting in more than 5% of the tumor’s volume, leads to a higher incidence of local relapse and distant metastasis. […] Systemic dissemination is strongly associated with previous tumor recurrence and fibrosarcomatous transformation within DFSP.

• #21

  https://journals.lww.com/jpat/fulltext/2024/28020/low_grade_dermatofibrosarcoma_protuberance___a.26.aspx

  Dermatofibrosarcoma protuberans (DFSP) is a soft tissue lesion originating from the dermal layer of the skin, comprising approximately 1.8% of all soft tissue sarcomas and 0.1% of all cancers. […] In about 5% to 20% of cases, DFSP have high-grade fibrosarcomatous (FS) components and this transformation is responsible for their high incidence of local relapse and distant metastases. […] Studies have implicated that in DFSP, there is chromosomal translocation, resulting in the fusion protein COL1A1-PDGFB, which promotes tumour growth through the overproduction of platelet-derived growth factor (PDGF). […] The neoplastic cells often infiltrate into subcutaneous adipose tissue in a honeycomb pattern which is also seen in our case. This poses a challenge to determine the true extent of the tumour tissue.

• #22 Dermatofibrosarcoma protuberans of the breast: A case study

  https://www.spandidos-publications.com/10.3892/mco.2021.2212

  Dermatofibrosarcoma protuberans (DFSP) is a superficial mesenchymal neoplasm that originates from the dermal fibroblasts and tends to be locally aggressive. […] The majority of DFSP presents as low-grade tumours, but in 5-10% of cases the tumour contains fibrosarcomatosous cells that upgrade the neoplasm in intermediate grade with a higher aggressivity. […] The etiology is not completely known. A history of previous trauma has been suggested as predisposing factor in approximately 10-20% of the cases. […] But, the vast majority of cases arise from the rearrangement of chromosomes 17 and 22, creating a supernumerary ring chromosome composed of hybrid material derived from t (17;22). […] This translocation leads to a continuous activation of platelet derived growth factor receptor -protein tyrosine kinase due to a fusion of PDGFB gene with collagen Type Ia1 gene (COL1A1).

• #23 Clinicopathological and molecular analysis of a dermatofibrosarcoma protuberans with fibrosarcomatous transformation in the breast | npj Precision Oncology

  https://www.nature.com/articles/s41698-025-00905-w

  A recent study using PDGFB RNA chromogenic in situ hybridization (CISH) demonstrated that fibrosarcomatous DFSP had stronger PDGFB expression than conventional DFSP, providing additional support that genomic gains encompassing this gene are correlated with fibrosarcomatous transformation. […] Some additional events identified in this tumor are also recurrent events in DFSP, including copy number gains and CRKL amplification. […] DFSP is characterized by CD34 positive staining and COL1A1::PDGFB fusion in over 90% of the cases. […] The Soft Tissue and Sarcoma Multidisciplinary Conference discussed the pathology and molecular alterations after the complete surgical resection of the lesion with negative margins.

• #24

  https://www.omim.org/entry/607907

  Kiuru-Kuhlefelt et al. (2001) suggested that cytogenetically, DFSP is often characterized by supernumerary ring chromosomes containing material from chromosomes 17 and 22. Kiuru-Kuhlefelt et al. (2001) used comparative genomic hybridization to analyze DNA copy number changes in 11 cases of typical DFSP and 10 cases of fibrosarcoma-DFSP. All cases in both groups exhibited a gain or high-level amplification on 17q and most also on 22q. This suggested that not only fusion of the COL1A1 and PDGFB genes but also DNA chromosome number gains in the 17q and 22q regions is crucial in the pathogenesis of DFSP. In the fibrosarcoma cases, the trend toward increase in number of DNA copy was not statistically significant. […] Sirvent et al. (2003) reviewed the cytogenetics of DFSP. DFSP cells are characterized at the cytogenetic level by either supernumerary ring chromosomes, which have been shown by FISH techniques to be derived from chromosome 22 and to contain low-level amplified sequences from 17q22-qter and 22q10-q13.1, or t(17;22), that are most often unbalanced. Both the rings and linear der(22) contain a specific fusion of the COL1A1 gene with the PDGFB gene. […] In approximately 8% of DFSP cases, the COL1A1/PDGFB fusion is not found, suggesting that genes other than COL1A1 or PDGFB may be involved in a subset of cases. PDGFB may act as a mitogen in DFSP cells by autocrine stimulation of the PDGF receptor (173410).

• #25 Dermatofibrosarcoma protuberans pathology

  https://dermnetnz.org/topics/dermatofibrosarcoma-protuberans-pathology

  Dermatofibrosarcoma protuberans (DFSP) is a locally aggressive tumour of fibroblastic origin. The initial lesion is a skin-coloured plaque which develops a red/brown colour and nodular surface. […] Dermatofibrosarcoma protuberans consists of a proliferation of spindle-shaped cells in the deep dermis with later lesions infiltrating the subcutaneous fat. Invasion of muscle may occur. There is often superficial sparing, however, the involvement of the epidermis and ulceration is sometimes seen. Spindled tumour cells are quite uniform in appearance with elongated nuclei and little or no pleomorphism and may be arranged in a storiform manner. […] Characteristic positivity for CD34. Negative CD31 and smooth muscle actin. […] Fibrosarcomatous dermatofibrosarcoma protuberans a variant of dermatofibrosarcoma protuberans representing tumour progression. A focal fascicular or 'herring-bone’ pattern is present. More cellular than usual dermatofibrosarcoma protuberans with increased nuclear pleomorphism and mitotic figure count. Staining for CD34 is reduced.

• #26 Dermatofibrosarcoma protuberans

  https://dermnetnz.org/topics/dermatofibrosarcoma-protuberans

  The cause of dermatofibrosarcoma protuberans is unknown, but an injury to the affected skin may be a predisposing factor. […] Recent advances show tumour cells carry abnormal chromosomes within the tumour cells (17;22)(q22;q13) resulting in the fusion gene COL1A1-PDGFB. This encodes a protein that causes a tumour to grow by autocrine overproduction of platelet-derived growth factor (PDGF). […] Dermatofibrosarcoma protuberans’s chromosomal abnormalities can be detected using reverse transcription-polymerase chain reaction (RT-PCR) or fluorescence in-situ hybridisation (FISH).

• #27 SciELO Brazil – Myoid differentiation in dermatofibrosarcoma protuberans and its fibrosarcomatous variant: 10 years’ experience in a tertiary hospital Myoid differentiation in dermatofibrosarcoma protuberans and its fibrosarcomatous variant: 10 years’ ex

  https://www.scielo.br/j/acrep/a/ZBNR64ZCTbMyBj6bD3y9ccD/

  Dermatofibrosarcoma protuberans (DFSP) is a relatively rare, locally aggressive, and dermal-based fibroblastic tumor. Myoid differentiation in DFSP is rare, and more often found in fibrosarcomatous DFSP. Myoid differentiation is defined as tumor cells with brightly eosinophilic cytoplasm, well-defined cytoplasmic margins, and vesicular nuclei. The myoid areas show positive staining, albeit patchy to focal, for smooth muscle markers, including smooth muscle actin, muscle-specific actin, caldesmon, and calponin. Staining for CD34, in those areas, is weak or negative. This may create diagnostic difficulty with smooth muscle tumors or myofibroblastic lesions, especially in a small biopsy sample. Myoid differentiation is uncommon in DFSP, and more often found in fibrosarcomatous DFSP. The nature of the myoid cells is uncertain. Some suggested that they are likely to be related to hyperplasia of myofibroblasts in stroma rather than myofibroblastic differentiation of tumor cells based on its association with blood vessels. While some suggested that this might represent fibroblastic/myofibroblastic line of differentiation of tumor cells. In our study, two out of ten cases show focal myoid differentiation, including the only case of fibrosarcomatous DFSP. In the case of fibrosarcomatous DFSP, the myoid areas form confluent nodules, and are in close proximity with vessels. While in the case of usual DFSP, the myoid areas are more diffuse and mingled with the surrounding areas with classic morphology. This indicates that myoid differentiation may show different architecture, and the appreciation of cells with brightly eosinophilic cytoplasm, well-defined cytoplasmic margins and vesicular nuclei is the key to the correct diagnosis. The myoid areas in DFSP can show positive staining (albeit patchy to focal) for smooth muscle markers, such as SMA, muscle-specific actin, caldesmon, and calponin. Staining for CD34 can be weak or even negative. These may create a diagnostic pitfall towards smooth muscle tumors or myofibroblastic lesions (e.g. leiomyoma, leiomyosarcoma, myofibroma), especially in small biopsy samples where areas of classic DFSP morphology may not be sampled. Although there is no specific immunostain to aid the diagnosis of DFSP, there is characteristic chromosomal translocation t(17;22)(q22;q13) in the large majority of DFSP. It is a fusion gene involving the collagen type 1 alpha 1 (COL1A1) gene on chromosome 17 and the platelet-derived growth factor (PDGFB) gene on chromosome 22. The detection of COL1A1-PDGFB fusion by fluorescence in situ hybridization can be used to confirm the diagnosis, especially in histologically challenging cases.

• #28

  https://journals.lww.com/ajsp/fulltext/2012/12000/primary_intrathoracic_dermatofibrosarcoma.19.aspx

  Dermatofibrosarcoma protuberans (DFSP) is defined as a low-grade sarcoma derived from an uncertain cell of origin in the reticular dermis. […] The diagnosis of FS-DFSP was confirmed molecularly by the demonstration of a COL1A1-PDGFB fusion by fluorescence in situ hybridization and reverse transcription-polymerase chain reaction analyses. […] The implication of this case on expanding the clinical spectrum of DFSP will have to be elucidated in future studies by applying molecular pathologic tools in deep-seated sarcomas in the proper morphologic context.

• #29

  https://www.orthobullets.com/pathology/8066/dermatofibrosarcoma-protuberans

  Nonoperative treatment includes imatinib, which inhibits PDGF-receptor tyrosine kinase, with a 65% response rate in adult patients with unresectable, recurrent, and/or metastatic DFSP. […] Operative treatment involves wide surgical resection with adjuvant radiation therapy, especially in patients with positive margins or in whom adequate wide excision alone may result in major cosmetic or functional deficits. […] Worse prognosis is seen with regional lymph node involvement, fibrosarcomatous progression DFSP variant, and histologic features such as high number of mitotic figures, increased cellularity, DNA aneuploidy, TP53 gene overexpression, and the presence of fibrosarcomatous changes.

• #30 Clinical Features, Pathological Findings and Treatment of Recurrent Dermatofibrosarcoma Protuberans

  https://www.jcancer.org/v08p1319.htm

  Dermatofibrosarcoma protuberans (DFSP) is a relatively rare and low-grade sarcoma of the skin and soft tissue. […] The pathogenesis of DESP is controversial and not completely understood. Molecular studies revealed that chromosomal translocation plays an important pathogenic role in this tumor. The chromosomal translocation is found in more than 90% of cases, and involves 17q22 and 22q13. […] The translocation fuses the genes COL1A1 with the platelet-derived growth factor beta (PDGF), usually with a ring chromosome formation. This gene codes for a fusion protein, which binds to the constitutively expressed PDGF receptor and acts as an autocrine factor to stimulate the growth of DFSP cells. […] Advances in the understanding of the molecular mechanisms of DFSP have applied in clinical practice via targeted therapy acting on PDGFR. The first effective systemic therapy in DFSP introduced into clinical practice was imatinib mesylate. […] Multiple studies have reported that FS-DFSP was more aggressive form of DFSP than O-DFSP. This difference may explain why FS-DFSP presented a shorter time to recurrence.

• #31 Dermatofibrosarcoma protuberans of the breast: A case study

  https://www.spandidos-publications.com/10.3892/mco.2021.2212

  Interestingly, this PDGFB continuous loop is thought to be the main reason for the sensitivity that this tumor has to imatinib, which is a tyrosine kinase inhibitor. […] There is increasing evidence that positive immunoreactivity with CD34 and D2-40 antibody might be the most accurate predictor for the latter. […] Moreover, increased age, high mitotic index and increased cellularity are predictors of poor clinical outcome. […] As far as treatment is concerned, surgical excision is the standard of care, since DFSPs are resistant to chemotherapy and radiotherapy. […] The exact margin of resection is still unknown, but due to histologically tumour-free margins varying significantly from clinically-free ones, an excision with no less than 2-3 cm with skin, subcutaneous tissue and fascia included is wide accepted.

• #32 Dermatofibrosarcoma Protuberans of the Vulva: A Report of 2 Cases of Unusual Localization

  https://www.jogcr.com/article_697282.html

  Dermatofibrosarcoma protuberans (DFSP) of the vulva is a rare, slow-growing, low-to-intermediate-grade malignant tumor of the dermis layer of the skin classified as a sarcoma that usually invades the subcutaneous tissue and muscles. […] Although the exact cause of the DFSP of the vulva is unknown, studies have implicated a chromosomal translocation. […] The DFSP is strongly stained for CD 34 and vimentin as seen on immunohistochemical studies in our cases. […] Translocation of chromosomes 17 and 22 (t(17:22)) is observed in over 90% of DFSPs. […] Currently, the exact cause of the development of vulvar DFSP is unclear, and no definitive risk factors have been reported. […] The suspicious factors contributing to DFSP entail the site of trauma, a region of extensive burns, surgical incision sites, vaccination sites (BCG vaccination), arsenic poisoning, and other risk factors. […] Age over 50 years appears to be a risk factor for local recurrence. […] Wide local excision surgery resection with a margin of 2-3 cm of normal tissue is recommended for both primary and recurrent DFSP.

• #33 Dermatofibrosarcoma Protuberans | Actas Dermo-Sifiliográficas

  https://www.actasdermo.org/en-dermatofibrosarcoma-protuberans-articulo-S1578219012002740

  Dermatofibrosarcoma protuberans (DFSP) is a cutaneous tumor representative of the advances in diagnosis and treatment in oncology gained through an understanding of molecular biology. Certain cases can be diagnosed through the presence of a specific translocation and there is a promising protein tyrosine kinase inhibitor that has opened up the possibility of treatment of advanced disease. […] The expression in DFSP of nestin, an intermediate filament expressed on neuroectodermal stem cells, suggests that DFSP originates from pluripotent neuromesenchymal stem cells. […] The essential characteristic of DFSP is the way it infiltrates the subcutaneous cell tissue. Infiltration usually occurs along the septa, and even along the lobes, to give a honeycomb appearance. […] Different studies suggest that the result of translocation with the COL1A1-PDGFB fusion gene in DFSP leads to a chimeric protein that is subsequently processed to give rise to mature and fully functional PDGFB. […] Therefore, t(17;22) in DFSP is associated with activation of the PDGFB receptor through autocrine and paracrine production of a functional ligand that translates into a chronic mitogenic signal, able to induce neoplastic transformation.

• #34 A Rare Orbital Pathology: A Large Orbital Dermatofibrosarcoma Protuberans – Turkish Journal of Ophthalmology

  https://oftalmoloji.org/articles/a-rare-orbital-pathology-a-large-orbital-dermatofibrosarcoma-protuberans/doi/tjo.galenos.2022.46383

  Dermatofibrosarcoma protuberans (DFSP) is a rare sarcoma of the dermis. It is a malignant, locally aggressive, and infiltrative tumor with frequent recurrence. […] DFSP is a primary, well-differentiated mesenchymal tumor of the dermis with an incidence of 0.8-5 per million. It constitutes 0.1% of malignancies in the head and neck region and 1% of soft tissue sarcomas. It is a locally aggressive tumor with a high rate of local recurrence and low metastasis rate. […] The tumorigenesis of DFSP involves the t(17;22)(q22:13) reciprocal translocation. The expression of CD34 and vimentin strongly supports the diagnosis of DFSP. […] The main principle in the treatment of DFSP is excision with a wide margin of safety. […] Local recurrence is around 20-50% and mostly occurs within three years.

• #35

  https://journals.lww.com/jpat/fulltext/2024/28020/low_grade_dermatofibrosarcoma_protuberance___a.26.aspx

  DFSPs have multiple histological variants including myxoid, pigmented, giant cell, giant cell fibroblastoma, granular cell, sclerotic and fibrosarcomatous components; these variants reflect the morphologic heterogeneity which is associated with the spindle cell differentiation during tumour development. […] Immunohistochemically, spindle cells typically show strong and diffuse cytoplasmic expression of CD34, but negative expression for other immunohistochemical stains, such as alpha-smooth muscle actin, factor XIIIa, S-100 and melan-A.

• #36 Dermatofibrosarcoma protuberans (DFSP) | Sarcoma UK

  https://sarcoma.org.uk/about-sarcoma/what-is-sarcoma/types-of-sarcoma/dermatofibrosarcoma-protuberans-dfsp/

  DFSP is thought to be caused when someone has extra chromosomes, or when someone has certain chromosomes that have been broken apart and put back together in the wrong way. […] Researchers are still trying to find out why these things happen and whether they cause DFSP. […] In DFSP, researchers have been learning more about treatment known as immunotherapy. […] Researchers have found that some targeted therapies and immunotherapies have worked well in clinical trials. But, more research and trials are needed before these treatments are approved.

• #37 Adjuvant radiotherapy for dermatofibrosarcoma protuberans: a case report – Hu – Therapeutic Radiology and Oncology

  https://tro.amegroups.org/article/view/5323/html

  Because DFSP is a rare tumor, there are no prospective randomized trials evaluating adjuvant RT in decreasing local recurrence. […] These findings suggest that adjuvant RT following surgery is considered as a treatment modality for DFSP. […] In summary, DFSP is a rare malignancy with a high recurrence rate, especially in patients with positive margin status. Adjuvant RT has the potential efficacy to reduce the local recurrence. Furthermore, for patients with large tumors, especially when wide excision with negative margins may cause undesired cosmetic or functional outcomes, postoperative RT is highly recommended.

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