RARE DISEASE
Dermatofibrosarcoma protuberans
Dermatofibrosarcoma protuberans
Dermatofibrosarcoma protuberans
Synonyms: DFSP
Synonyms: DFSP
Synonyms: DFSP
Drug discovery
2
drugs
With orphan designations
Overview
Dermatofibrosarcoma protuberans (DFSP) is a rare, slow-growing dermal sarcoma with infiltrative growth and low metastatic potential (<5%). It arises from fibroblastic cells, driven by COL1A1-PDGFB fusion in >90% of cases, causing dysregulated PDGFR signaling. Diagnosis involves biopsy (CD34+ staining) and imaging (MRI/CT) to assess depth. Local recurrence rates reach 10-20% with standard excision but drop to <5% with Mohs micrographic surgery (MMS). Metastasis correlates with fibrosarcomatous transformation, tumor size ≥3 cm, and head/neck/genital locations [1][4][11].
Categories: rare genetic diseases, rare neoplastic diseases, rare skin diseases
Research Papers
638 drug discovery papers about Dermatofibrosarcoma protuberans, with 2 first-in-class and 3 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
638 drug discovery papers about Dermatofibrosarcoma protuberans, with 2 first-in-class and 3 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
cell therapies
2026-03-23 | Forehead dermatofibrosarcoma protuberans treated exclusively with full-thickness skin grafting: a unique case report and review of the literature.
Dermatofibrosarcoma protuberans (DFSP) is a rare, locally aggressive cutaneous sarcoma. Forehead involvement is uncommon and poses significant reconstructive challenges due to complex aesthetic and functional demands. Most reported reconstructions utilize staged flaps or tissue expansion. To the best of our knowledge and based on a comprehensive literature review, there are no previous reports specifically documenting forehead DFSP reconstruction performed exclusively with full-thickness skin grafting (FTSG) following wide local excision.We report a case highlighting this technique's reconstructive and aesthetic advantages. A 50-year-old woman presented with a long-standing, enlarging paramedian forehead mass above the right eyebrow, measuring approximately 7.5 × 6.5 cm. A punch biopsy and imaging confirmed DFSP. Wide local excision with 3 cm margins was performed, resulting in a 10.5 × 9 cm defect. Reconstruction was achieved using a single-stage FTSG harvested from the suprapubic region, including a segment of hair-bearing skin aligned to restore the forehead hairline. At 10 month follow-up, the patient had full graft take, preserved frontalis function, and satisfying aesthetic outcome with no recurrence. Forehead DFSP reconstruction typically involves complex, multi-stage flap procedures that risk distortion of key facial landmarks and increased morbidity. Our case demonstrates that immediate full-thickness skin grafting offers a simpler, single-stage alternative preserving eyebrow position, facial symmetry, and function. Harvesting the graft from the suprapubic area, utilizing a prior cesarean scar, allowed restoration of the hairline with hair-bearing skin-an innovative aesthetic advantage not previously reported. This unique case demonstrates that FTSG can provide favorable aesthetic and functional outcomes in selected forehead DFSP cases, representing a valuable addition to reconstructive options.
2026-02-09 | Two-Day Mohs Excision of Large Scalp Dermatofibrosarcoma Protuberans Reconstructed With a Rotation Flap.
Dermatofibrosarcoma protuberans (DFSP) is a rare, slow-growing, locally aggressive, cutaneous sarcoma with a high recurrence risk. Mohs micrographic surgery (MMS) offers superior margin control but presents significant reconstructive challenges in large scalp lesions. We present a 36-year-old male with a large (10 x 10 cm) DFSP of the frontal scalp requiring staged two-day MMS for complete clearance. Despite an extensive defect down to the periosteum and partial calvarium exposure, closure was achieved with a large rotational advancement flap with a split-thickness skin graft. This case highlights that even exceptionally large scalp DFSP lesions can be successfully excised under local anesthesia with MMS.
2026-02-05 | Customized Non-invasive Brachytherapy With Tailored Surface Moulds: An Experience From a Tertiary Care Centre.
Surface mould brachytherapy (SMBT) is an effective non-invasive treatment option for patients with skin cancer and other superficial tumours. We describe the detailed technique of uniquely treated patients of various histology using customized tailor-made surface moulds and evaluated clinical outcomes, toxicity profile, and quality of life of patients treated with SMBT. In this retrospective study, we have evaluated nine patients treated with surface moulds using iridium-192-based high-dose-rate brachytherapy. The median age was 34 years. The histopathological diagnosis included squamous cell carcinoma (n=4), followed by giant cell tumour (n=2), and 1 each of angiosarcoma, dermatofibrosarcoma protuberans, and clear cell sarcoma. The most common radiotherapy dose schedule was 60-66 Gray at 2 Gray per fraction. After a median follow-up of 24 months, local control was 100%. At the end of five years, overall survival (OS) and disease-free survival (DFS) were 88.89%. The maximum acute skin and subcutaneous toxicity grade II was observed in 5 (55.6%) patients and grade III in 4 (44.4%) patients, maximum late toxicity was grade III in 3 (33.3%) patients. Poorer Dermatology Life Quality Index scores were statistically significantly associated with higher overdose index (>0) (P=.039), and V150% >40% (P=.039). SMBT is an effective modality to achieve excellent local control in patients of skin and superficial tumours. After five years, OS and DFS both were 88.89%. It was well tolerated with manageable grade II,III acute and late skin toxicities.
2026-01-27 | Frozen Section Mohs Micrographic Surgery for Dermatofibrosarcoma Protuberans-A Case Series of 38 Patients in NSW, Australia.
Dermatofibrosarcoma protuberans (DFSP) is a rare cutaneous tumour with a locally infiltrative growth pattern that has high rates of recurrence. Mohs micrographic surgery is recommended as the gold-standard treatment over wide local excision (WLE) due to tissue-sparing and reduced recurrence rates. No previous data on surgical outcomes following Mohs Micrographic Surgery (MMS) for DFSP have been reported in Australia to date. This study aims to review the outcomes of DFSP treated with frozen-section MMS across three centres in New South Wales (NSW), Australia, and compare these outcomes with those in the current literature. A retrospective review of patients who underwent MMS for DFSP between 2010 and 2023 was performed. Patient demographics, histological findings, surgical treatment and follow-up data were collected. Recurrence was assessed through electronic medical records, clinical assessments by a dermatologist or general practitioner, and patient self-report. In all, 38 cases of DFSP were included (27 female, 11 male; median age 39 years, range 16-64). The trunk was the most common site. Clinical margins and Mohs stages were recorded in 37 of 38 cases, with 73% of cases cleared with clinical margins of ≤ 20 mm. Clinical or self-reported follow-up was available for 28 of 38 patients (73.6%) over a mean of 51 months (range, 5-132 months). No local recurrences were identified during this period. This is the first Australian case series on MMS for DFSP. Our findings demonstrate no recurrences with follow-up and demonstrate that MMS may achieve clearance with smaller clinical margins than WLE. These results support international guidelines recommending MMS as the gold-standard treatment and highlight the need to improve access to MMS in Australia.
2026-01-22 | Vulvar dermatofibrosarcoma protuberans in a 55-year-old female: A case report, surgical reconstruction approach and literature review.
Dermatofibrosarcoma protuberans (DFSP) is a rare, locally aggressive soft tissue sarcoma characterized by a high risk of local recurrence. Vulvar involvement is exceedingly uncommon and often misdiagnosed as a bening lesion, resulting in delayed diagnosis. Complete surgical excision with negative margins is essential but can be challenging in anatomically sensitive areas as the vulva. A 55-year-old Puerto Rican woman presented with a slowly enlarging lesion of the left labia majora that was initially managed as a furuncle. Progressive growth and symptoms prompted biopsy, which confirmed DFSP. Staging imaging revealed no metastatic disease. The patient underwent a single-stage left radical hemivulvectomy with immedate reconstruction using a V-Y fasciocutaneous advancement flap. Histopathologic examination demonstrated classic DFSP with uniform spindle cellls in a storiform pattern, stong diffuse CD34 positivity, and negative surgical margins. Postoperative recovery was uncomplicated, with excellent wound healing and flap viability. This case emphasizes the importance of early biopsy of persistent vulvar lesions and highlights the role of multidiciplinary surgical planning. Single-stage radical excision with immediate reconstruction can achieve favorable oncologic and functional outcomes in vulvar DFSP. Long-term surveillance remains essential due to the potential for late local recurrence.
antibodies
2025-11-01 | 131 Evaluating the Diagnostic Utility of PRAME and CD34 Dual Staining in Fibrosarcomatous Dermatofibrosarcoma Protuberans
Abstract Introduction/Objective Preferentially expressed Antigen in Melanoma (PRAME) is a melanoma-associated antigen helpful in distinguishing melanoma from nevi but is also expressed in other malignancies. Fibrosarcomatous dermatofibrosarcoma protuberans (FS-DFSP), a high-grade DFSP variant which shows increased mitotic activity and higher metastatic risk. Diagnosing FS-DFSP can be challenging, especially when CD34 expression is reduced or absent. We report a case of FS-DFSP with CD34 loss and PRAME immune-reactivity. Methods/Case Report A 49-year-old African American male presented with a progressively enlarging mass on the anterior chest and neck over a 12-month period, arising at the site of an old scar from a previous motorcycle accident. Imaging revealed a 6.0 cm lobulated soft tissue mass in the anterior neck/upper thorax. Biopsy showed a monomorphic spindle cell tumor with storiform architecture. Initial immunohistochemistry confirmed conventional DFSP (CD34 positive and negative pancytokeratin, SOX10, Factor XIIIa, SMA, desmin, and ERG). Wide excision revealed areas with higher cellularity, herringbone architecture, nuclear atypia, and increased mitoses (32/10 HPF, Ki-67: 25–30%). CD34 was lost in these areas, which showed diffuse PRAME positivity. Results NA Conclusion PRAME may aid in distinguishing FS-DFSP from conventional DFSP. This dual-staining approach with CD34 can improve diagnostic precision and may offer future therapeutic potential through PRAME-targeted immunotherapy.
2025-04-15 | Clinicopathological and molecular analysis of a dermatofibrosarcoma protuberans with fibrosarcomatous transformation in the breast.
Dermatofibrosarcoma protuberans (DFSP) is a rare soft tissue sarcoma with low potential for metastases. To date, only a few cases of DFSP in the breast have been reported, and none have reported comprehensive genetic signatures. We report, for the first time, the largest DFSP in the breast with multidisciplinary tumor board discussion and comprehensive molecular analysis. This DFSP is 18.5 cm with fibrosarcomatous transformation, distinct gene rearrangement translocation t(17;22) (q22;q13), COL1A1::PDGFB fusion, and subsequent segmental amplification of chromosomes 17q and 22q. The high-level of amplifications of genomic regions containing the COL1A1 and PDGFB genes (6 copies) compared to the reported DFSP cases (2-3 copies) supports the gene dosage effect correlated with aggressive behavior and high-grade tumor histology. This case highlights the importance of precise genetic alteration in the clinicopathological and phenotypic expression of DFSP with fibrosarcomatous transformation, and it helps guide clinical management and informs the role of targeted therapy.
2024-07-31 | Cellular and molecular landscape of primary dermatofibrosarcoma protuberans: Insights from single-cell RNA sequencing analysis.
Dermatofibrosarcoma protuberans (DFSP) is a rare cutaneous sarcoma characterized by the COL1A1-PDGFB fusion gene. This study utilized single-cell RNA sequencing to dissect the cellular and molecular landscape of primary DFSP. Distinct DFSP cell clusters, exhibiting fibroblast-like traits, revealed variations in pathways associated with proliferation, inflammation and metabolism. Differential gene expression analysis during the differentiation from tumour stem cells to DFSP cells unveiled SMOC2, DCN and TGFBR3 as potential regulators of tumour invasion and immune infiltration through VEGF/TGF-β signalling modulation. Cellular communication analysis highlighted interactions within DFSP cell clusters and with endothelial cells, implicating molecules such as NAMPT, ANGPT2 and PTN in pathogenesis and treatment resistance. These findings offer insights into DFSP intratumour heterogeneity, elucidate molecular mechanisms underlying tumour behaviour, and suggest potential therapeutic targets.
2024-05-13 | Head-and-neck dermatofibrosarcoma protuberans: Survival analysis and Clinically relevant immunohistochemical indicators.
Head and neck dermatofibrosarcoma protuberans (HNDFSP) is extremely rare and not entirely understood. To investigate the clinicopathological features of HNDFSP and identify the expression of its clinically relevant indicators, with the expectation of improving the existing treatment strategies. A long-term follow-up of patients with HNDFSP who received treatment between 2000 and 2021 at Shanghai Ninth People's Hospital was conducted. The clinical, histological, and immunohistochemical data of the patients were retrieved and analyzed. The endpoint of the study was the incidence of significant disease-related clinical events (recurrences or metastasis). A total of 49 patients with HNDFSP were included in the study, with males (92.7%) predominating than females (7.3%). Eighteen patients developed recurrent disease (36.8%) after surgery, and the median time of recurrence was 48 months (interquartile, 20-74 months). Metastasis occurred in two cases (4.1%). Two patients died during follow-up, both with local recurrence, and one of them with intestinal metastasis. Post-operation radiotherapy was administered to eight patients (16.3%) and the effect in local control was remarkable. Age, tumor size, and negative margins with sufficient safety width were the main independent factors affecting the disease-free survival. Several potential targeted therapeutic indicators, including EZH2 (80.0%), EGFR (91.4%), PDGF (97.1%), PD-L1 (77.1%), and VEGF (77.1%), were positively expressed in most tumor samples. HNDFSP is rare, significantly challenging to control locally, and has a worse prognosis with current treatment strategies. Wide local excision and long-term follow-up are needed. Radiotherapy could improve the prognosis of patients with HNDFSP.
2023-10-01 | 60P Spindle cell sarcomas with tyrosine kinase rearrangement
A group of spindle cell tumors with characteristic morphologic features and recurrent gene rearrangements has recently been described. Genome-wide DNA methylation profiling has emerged as a powerful tool for both robust classification of known sarcoma entities and identification of novel and clinically relevant subclasses of soft tissue tumors with characteristic alterations. Anchored Multiplex polymerase chain reaction amplicons were sequenced on Illumina MiSeq and the data were analyzed using the Archer and Arriba software. Genome-wide DNA methylation profiling was performed using Infinium Methylation EPIC (EPIC) BeadChip (Illumina). We identified 6 spindle cell sarcoma cases with rearrangement/SNV in BRAF gene, 3 pediatric spindle cell sarcomas with NTRK1 fusion, 1 high-grade sarcoma with ALK fusion and 1 pediatric sarcoma with tyrosine-kinase duplication of EGFR gene. We show that CDKN2A deletion was the most prevalent DNA copy number aberration in spindle cell sarcomas for which this deletion is a typical change and connecting element across different subgroups of spindle cell sarcomas and this change was associated with poor clinical outcome. DNA methylation profiling demonstrated that 5 of our BRAF altered spindle cell sarcomas clustered within MPNST-like methylation class, but methylation analysis classified the next BRAF rearranged case (with CUX1::BRAF fusion) near to angiomatoid fibrous histiocytomas or inflammatory myofibroblastic tumors. Our patients with LMNA::NTRK1 fusion gene clustered within dermatofibrosarcoma protuberans methylation class. Methylation analysis of the sample with ALK fusion did not classify the sample in any of the defined class of methylation classifier. The current study demonstrates, that all detected rearrangements in our spindle cell cohort are potentially therapeutically targetable. We provide evidence for the pathobiological and epigenetical heterogeneity of spindle cell sarcomas generally, and also of spindle cell sarcomas that shows alteration of the tyrosin-kinase genes.
proteins
2025-09-04 | Digital Spatial Profiling Demonstrates Differences Between Fibrosarcomatous Transformation of Dermatofibrosarcoma Protuberans and Its Conventional Counterparts.
Dermatofibrosarcoma protuberans (DFSP) is a neoplasm of the dermis with a tendency for aggressive local growth and recurrence. A minority of DFSP cases may transform into higher-grade sarcoma (fibrosarcomatous transformation [FST]) (DFSP-FST), which is associated with more aggressive behavior and risk of metastasis. The histologic diagnosis of DFSP-FST may be challenging, particularly in small biopsies. Currently, there are no specific markers to reliably support the diagnosis of DFSP-FST. We identified 33 DFSP from 32 patients, including 9 patients with FST and 1 distant metastasis. Tissue microarrays (TMAs) were created using representative areas of all cases, including DFSP-FST, conventional regions from DFSP-FST, and pure conventional DFSP. Digital spatial profiling of the entire transcriptome was performed on the TMAs using the Nanostring GeoMx platform. Expression data were queried to identify differentially expressed genes specific to the regions of transformation in DFSP. Immunohistochemistry for PReferentially expressed Antigen in MElanoma (PRAME) was subsequently performed using a clinically validated protocol. Digital spatial profiling demonstrated significant gene expression differences between DFSP-FST and conventional DFSP. Genes that were overexpressed in DFSP-FST include PRAME, CTAG1B, and MMP11. Immunohistochemical analysis for PRAME showed positive expression in 7 of 10 DFSP-FST (70%) and 1 of 23 conventional DFSP (4%) (P < .0001). Gene expression profiling shows significant upregulation of PRAME and CTAG1B in DFSP-FST compared with conventional DFSP, a finding that was validated by immunohistochemistry for PRAME. Therefore, immunohistochemistry for PRAME may be useful to support the diagnosis of FST, especially in small biopsies. Increased expression of CTAG1B (NY-ESO-1) in DFSP-FST may also offer future therapeutic potential.
2022-11-11 | Dermatofibrosarcoma protuberans surgery: Experiences of four African surgical oncology units and literature review.
Dermatofibrosarcoma is a locally malignant tumor. This gives surgery a place of choice. The advent of imatinib has improved outcomes. Our aim is to describe the indications, techniques and results of surgery. A retrospective, multicenter, descriptive study conducted in four West African surgical oncology units. It covers dermatofibrosarcoma surgery performed between January 1, 1988 and December 31, 2020. We took into account the surgical procedure, the mode of skin coverage, adjuvant treatments and survival. Comparisons were possible using Student's t-test and Pearson's χ2 . We recorded 81 cases of dermatofibrosarcoma. Surgery was effective in 90.1% of cases. Wide resection was the principle with a mean resection margin of 3.8 ± 1.9 cm. healing by primary intention, flaps and healing by secondary intention were the methods of skin coverage in 30.1%, 24.7% and 41.1% respectively. The type of skin coverage was related to the topography and size of the tumor (p < 0.0001). The healing time is associated with the type of skin cover. The recurrence rate was not related to the type of skin coverage (p = 0.8). Wide and deep resection in the absence of Mohs micrographic surgery ensures healthy margins. Oncoplasty reduces the healing time without increasing the risk of recurrence.
2021-06-07 | Hyaluronidase in Dermatology: Uses Beyond Hyaluronic Acid Fillers.
Hyaluronidase is mostly widely recognized for its off-label use in correction of complications of hyaluronic acid fillers. However, its utility in other aspects of dermatology is less widely acknowledged. We describe the varied uses of hyaluronidase in dermatology and the underlying evidence base for its dermatological indications. This includes its uses in enhancing drug delivery (for local anesthesia, keloid and hypertrophic scars, and for Kaposi’s sarcoma), in the treatment of disorders associated with mucin deposition (myxedema, scleroderma, scleredema, and cutis verticis gyrata) and its potential uses in surgery (as a pre-operative adjuvant in dermatofibrosarcoma protuberans, for periorbital edema, and for hematomas). In select circumstances, hyaluronidase might be more efficacious than more established treatments with fewer adverse effects. We propose hyaluronidase as the latest addition to our global dermatological armamentarium and implore dermatologists to consider its use to enhance their practice. J Drugs Dermatol. 2020;19(10):993-998. doi:10.36849/JDD.2020.5416.
1999-03-01 | Adjuvant Therapy with Hyaluronidase Prior to Excision of Dermatofibrosarcoma Protuberans
Background. Dermatofibrosarcoma protuberans (DFSP) are uncommon, low grade cutaneous malignancies, which rarely metastasize. Although surgery is the main therapy for these tumors, they commonly recur in spite of wide excisions. Hyaluronidase (HD) has been used both intralesionally as well as intravenously as an adjuvant in therapy of both epithelial and mesenchymal malignancies to decrease local spread, to potentiate differentiation induced apoptosis, and to potentiate the tissue penetration of chemotherapeutic agents. In addition, there is a long history of intralesional HD use without significant complications. The biologic characteristics of DFSP including the observation that hyaluronic acid is commonly present and sometimes is increased in these tumors and the known effects of HD therapy in other malignancies suggested to us that HD pretreatment may be a helpful adjuvant in the surgical management of DFSPs. Following diagnostic biopsy of a recurrent DFSP, the patient was treated for 4 weeks with intralesional HD injections. Results. Based on margins necessary for complete excision from past studies, this patient had decreased margin width and thus had a postoperative wound size less than was expected. The patient has had no evidence of recurrence at 24 months follow-up.
1998-09-01 | Pretreatment with intralesional hyaluronidase prior to excision of dermatofibrosarcoma protuberans1The opinions or assertions herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army, the Department of the Navy, or the Department of Defense.1
Dermatofibrosarcoma protuberans (DFSPs) are an uncommon malignancy that commonly recur, but rarely metastasize. The origin of DFSPs is controversial; however, they stain with the progenitor marker CD34. DFSPs usually show increased stromal mucin, mainly hyaluronic acid (HA). HA increases cellular proliferation, delays differentiation and increases cellular motion. We evaluated the pretreatment of DFSPs with intralesional injections of hyaluronidase (HD) prior to the surgical excision. Five of nine cases of DFSPs were pretreated with HD. In HD-pretreated cases the margins for excision of the residual tumor were reduced. HD pretreatment also decreased CD34 staining and increased polarizable collagen in the residual tumor.
small molecules
2026-07-28 | Investigating the Spatial Immune Tumor Microenvironment of Dermatofibrosarcoma Protuberans 2266312
Abstract Introduction Dermatofibrosarcoma Protuberans (DFSP) is a rare, locally aggressive cutaneous sarcoma driven by the COL1A1-PDGFB fusion. While its molecular drivers are well-defined, the DFSP tumor immune microenvironment remains poorly characterized. Understanding immune-stromal interactions in DFSP may reveal opportunities to complement surgical resection with immunotherapy or targeted approaches. Methods We performed spatial transcriptomics on 16 DFSP patient samples using 10X Genomics Visium v2 (n = 12) and Visium HD (n = 4), integrated with single-cell RNA sequencing. Results Our analysis revealed distinct tumor, stromal, and immune populations with high PDGFB-high tumor cells spatially segregated from infiltrating immune compartments. We identified transcriptionally distinct cancer-associated fibroblast (CAF) subsets, including populations enriched for extracellular matrix remodeling and inflammatory signatures that may modulate local immunity. Immune profiling uncovered spatially heterogeneous T cell and macrophage infiltration, with distinct immune-rich and immune-desert zones across patients. Notably, we observed tertiary lymphoid structure (TLS) formation in multiple samples, characterized by elevated TLS signature scores and spatial co-localization of B and T cell markers. CXCL13 and CCL19 emerged as key chemokines defining TLS-associated immune-stromal communication networks. Using cyclic immunofluorescence, we validated the spatial organization of TLS-associated immune niches, confirming co-localization of CD3+ T cells, CD20+ B cells, and CD68+ macrophages within TLS-enriched regions at protein level. Conclusion This work provides the first spatial immune atlas of DFSP, revealing organized lymphoid structures and CAF-mediated immune regulation that could inform combination strategies targeting PDGFR signaling alongside immune checkpoint or stromal modulation. Funding Source n/a Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)
2026-06-26 | Proteomics-based approach reveals the involvement of spliceosomal components SF3B and SerpinB9 in dermatofibrosarcoma protuberans
Abstract Background Dermatofibrosarcoma protuberans (DFSP) is a rare cutaneous soft tissue sarcoma which is prone to high recurrence rate, and the fibrosarcomatous transformation of DFSP (FS-DFSP) is associated with a poorer prognosis and significant metastatic potential. Although the translocation of regions of chromosomes 17 and 22 that results in COL1A1-PDGFB fusion is generally acknowledged as a key genetic feature of DFSP, there is no established salvage treatment following resistance to imatinib, which targets the PDGFB pathway. In this study, we performed quantitative proteomics analyses of DFSP tumor tissues and paired adjacent normal skin, to uncover novel molecular mechanisms and potential therapeutic targets. Findings were validated using immunohistochemistry, Western Blot, Real-Time Quantitative PCR and cell viability assay. Results Pathway enrichment analysis including KEGG and GSEA revealed that spliceosome pathways and ECM-receptor interaction were associated with DFSP pathogenesis. The spliceosomal components SF3B, and SerpinB9, which is the endogenous inhibitor of granzyme B, were validated to be upregulated in tumor tissues. SerpinB9 was significantly overexpressed in the FS-DFSP subtype compared with the classic-type DFSP. Treatment with the SF3B1 inhibitor, Pladienolide-B, significantly reduced tumor cell viability. siRNA-mediated knockdown of SF3B1 and SF3B2, as well as Pladienolide-B treatment, inhibited SERPINB9 expression without affecting pre-SERPINB9 mRNA levels, suggesting splicing-dependent regulation. Additionally, quantitation of the tumor microenvironment cells using the MCP-counter algorithm indicated NK cells activation. The CD56 (NK cell surface marker), biomarkers of tumor-associated macrophage (TAM) such as CD14 and CD163, and transforming growth factor-β induced (TGFBI) which is associated with TAM infiltration stained positive in DFSP tumors. SERPINB9 mRNA expression showed a positive correlation with both NK cell abundance and FCGR3A (NK cell marker) mRNA level. Conclusions SerpinB9 overexpression is associated with fibrosarcomatous features in DFSP and may represent a candidate prognosis biomarker. The SF3B/SERPINB9 axis is a potential therapeutic vulnerability, particularly in FS-DFSP. NK cell- and macrophage-related signatures were evident in DFSP tumor microenvironment, warranting further functional studies.
2026-06-10 | Data Sheet 1_Integrating contrast-enhanced ultrasound to optimize margin delineation in Mohs micrographic surgery for primary dermatofibrosarcoma protuberans: a retrospective cohort study.pdf
Introduction Dermatofibrosarcoma protuberans (DFSP) is characterized by infiltrative “tentacle-like” extensions, making accurate preoperative margin delineation challenging. While high-frequency ultrasound (HFUS) visualizes subclinical spread, its ability to fully capture tumor extent remains limited. Contrast-enhanced ultrasound (CEUS), by depicting microvascular perfusion, may improve delineation, but its clinical impact on Mohs micrographic surgery (MMS) remains unclear. Methods This retrospective cohort study included 220 primary DFSP patients treated with MMS. Preoperative margin delineation utilized HFUS-only or HFUS+CEUS. The primary outcome was extra peripheral Mohs stages. Secondary outcomes included extra deep and total stages, margin positivity, and other surgical characteristics. Multivariable Poisson regression with LASSO-based variable selection was used, alongside cohort-restriction, covariate-specification, and propensity score–matched (PSM) analyses. Risk-stratified and subgroup analyses explored effect heterogeneity. Results HFUS+CEUS was associated with fewer extra peripheral Mohs stages than HFUS-only (adjusted incidence rate ratio [aIRR], 0.310; P = 0.049). Peripheral margin positivity was reduced from 17.4% to 5.1% (P = 0.020). These findings were consistent across sensitivity analyses and in the PSM cohort (aIRR, 0.309; P = 0.033). The relative effect was most pronounced in the high-risk stratum (IRR, 0.124; P = 0.041), although interaction testing was not statistically significant (P = 0.077). No significant differences were observed in deep or total stages, likely due to ultrasound depth limitations. Conclusions Integrating CEUS with HFUS enhances the precision of preoperative margin delineation for DFSP, reducing extra peripheral Mohs stages. This multimodal imaging strategy represents a valuable, tissue-sparing refinement to the preoperative workflow of MMS, particularly for patients with higher baseline risk.
2026-05-29 | Case Report of Giant Myxoid Fibrosarcomatous Dermatofibrosarcoma Protuberans Compressing the Right Jugular Vein: A Multidisciplinary Approach to Complex Surgical Management.
Dermatofibrosarcoma protuberans (DFSP) is a locally aggressive low-grade cutaneous neoplasm with high cure rates following complete surgical resection. However, 5-15% of classic DFSP cases undergo fibrosarcomatous transformation, resulting in fibrosarcomatous DFSP (FS-DFSP), a more aggressive variant with significantly higher rates of local recurrence, metastasis, and mortality. This case presents a rare myxoid variant of FS-DFSP with complex anatomical involvement requiring multidisciplinary management. A 56-year-old East Asian female presented with a giant recurrent chest mass measuring 15 × 12 × 6 cm, initially misdiagnosed as fibroma 19 years prior. Advanced imaging revealed an 8 × 13 × 12 cm poorly defined soft tissue mass involving the pectoralis major and extending to the sternocleidomastoid muscles, with compression of the proximal right jugular vein. Histopathological examination confirmed FS-DFSP with myxoid differentiation, characterized by diffuse spindle cell infiltration in a fascicular pattern. Immunohistochemistry revealed CD34+, EMA+, and actin+ staining with negative desmin, S100, and STAT-6. COL1A1-FISH analysis demonstrated COL1A1/PDGFB fusion in 8% of cells. Management included tumor vascular embolization, surgical resection with 3 cm margins, skin grafting, local flap repair, and adjuvant radiation therapy due to anatomical constraints and residual tumor involvement of the anterior sternum. Four-year follow-up shows no evidence of recurrence. This case highlights the myxoid variant of FS-DFSP, emphasizing the importance of comprehensive histopathological evaluation, multidisciplinary treatment planning, and long-term surveillance. The successful management with combined surgical and radiation therapy demonstrates the need for individualized treatment approaches in complex anatomical locations. Four-year remission demonstrated the efficacy of comprehensive multimodal therapy in preventing local recurrence in FS-DFSP.
2026-04-08 | Anesthetic and Analgesic Management of Pediatric Patients for Staged Repeat Same-Day Surgery.
Dermatofibrosarcoma protuberans (DFSP) is a rare dermatologic malignancy in children requiring a multidisciplinary approach for surgical excision and postoperative care. The modified "slow Mohs" repeat staged excision and the associated anesthetic technique are not well described in the pediatric literature. We describe three pediatric patients whose staged excision procedures were completed using general anesthesia plus systemic multimodal analgesia (all patients), including tunneled epidural catheters (two patients with truncal tumors) or a scheduled long-acting opioid (one patient with a forehead lesion). Complete dermatologic excision and excellent surgical analgesia were achieved in all patients. Specific interventions to verify epidural catheter position and allow potential prolonged catheter use were of particular utility in perioperative management. Children with DFSP present a unique challenge to provide optimal surgical and cosmetic results with serial staged Mohs excision while ensuring adequate ongoing analgesia. Close interdisciplinary communication and advance planning are essential. Multimodal analgesia, including tunneled epidural catheters if anatomically appropriate, or scheduled long-acting opioid, is a key component of successful management. Confirmation of epidural catheter position likely improves analgesic efficacy and reduces the need for catheter replacement. We suggest that the care of pediatric patients undergoing slow Mohs staged repeat excision is best undertaken in a tertiary care setting with adequate multidisciplinary subspecialist support.
other
2026-01-13 | Abstract A019: Investigating of the impact of COL1A1::PDGFB fusion in mouse Col1a2+ dermal embryonic fibroblasts as a potential cell of origin of dermatofibrosarcoma protuberans
Abstract Dermatofibrosarcoma protuberans (DFSP) is the most common cutaneous sarcoma and is characterized by chromosomal translocations, most frequently t(17;22) encoding the fusion protein COL1A1::PDGFB. This malignancy arises in the dermis of the skin and exhibits spindle cell morphology and deep invasion to the subcutis. DFSP is presumed to arise as a result of COL1A1::PDGFB fusion-driven uncontrolled PDGFB expression by the COL1A1 promoter, which is highly active in dermal fibroblasts. However, the cell of origin of DFSP remains unclear, as this tumor exhibits expression of neural markers and CD34 positivity, leading to longstanding speculation regarding a non-fibroblastic cell of origin. Interestingly, several pediatric cases of DFSP are noted at the time of birth, raising the possibility of an embryonic cell-of-origin in some patients. In addition, emerging evidence suggests that early stem cell populations can be reprogrammed by oncogenic fusion proteins and impact cellular phenotypes. We sought to test the hypothesis that embryonic dermal fibroblasts expressing a modified fusion protein could develop DFSP-like tumors in mouse skin. To test this, a 747 base pair fusion protein cDNA was designed to include the regions of the COL1A1::PDGFB conserved across human DFSP tumors, particularly the COL1A1 signal peptide and exons 2-7 of PDGFB in a DNA construct that contains fibroblast-specific promoter and enhancer elements of Col1a2. An internal ribosome entry site (IRES) followed by the mCherry red fluorescent protein (RFP) sequence allowed identification of transgene expression by RFP fluorescence. This construct was introduced into fertilized mouse oocytes via pronuclear injection and embryos were collected for analysis. Effective transgene expression was detected by RFP and genotypes were confirmed by PCR with transgene-specific primers. A total of 15 out of 99 (15.2%) of embryos harbored the transgene and revealed a spectrum of phenotypes. Strong transgene expression caused severe embryonic malformations, whereas weaker expression was associated with abnormal development of the dermis, epidermis, and hair follicles. No tumors or obvious proliferations were present in any embryos evaluated. Taken together, this work shows that fusion oncogene and/or high-level PDGFB signaling in developing dermal fibroblasts causes embryonic toxicity, whereas lower degrees of signaling demonstrate impaired development of normal cutaneous structures. Further studies to investigate other putative cells of origin, as well as strategies to mitigate embryonic toxicity (such as using an inducible system which allows for postnatal transgene expression) are warranted. These studies suggest a degree of oncogene toxicity due to COL1A1::PDGFB expression in some cells. Future studies to investigate how cells tolerate this oncogene may lead to new insights regarding the growth and survival of DFSP cells that could be exploited for therapy. Citation Format: Elisabeth A. Pedersen, Li-Jyun Syu, Andrzej A. Dlugosz, Monique E. Verhaegen. Investigating of the impact of COL1A1::PDGFB fusion in mouse Col1a2+ dermal embryonic fibroblasts as a potential cell of origin of dermatofibrosarcoma protuberans [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Fusion-Positive Cancer: From Discovery to Therapy; 2026 Jan 13-15; Philadelphia PA. Philadelphia (PA): AACR; Cancer Res 2026;86(1_Suppl):Abstract nr A019.
2024-02-26 | Novel role of fluorescent in situ hybridization technique (FISH) in recommended surgical margins of dermatofibrosarcoma protuberans: A preliminary study.
Dermatofibrosarcoma protuberans (DFSP) is a rare skin tumor. There is no standard recommendation for its surgical management. The currently used histological analysis are HES (hematoxylin eosin saffron) staining and immunohistochemistry for CD34 expression in particular cases. Fluorescent in situ hybridization (FISH) technique is only used to qualify the DFSP as translocated or non-translocated and is not used as a diagnostic method. The aim of our study was to determine by FISH (as a diagnostic method) whether cancerous cells that could not be identified through HES staining±immunohistochemistry were present at the two-centimeter margins that were found to be tumor-free. Samples from patients who underwent surgery between 2010 and 2018 were collected. Intralesional and peripheral (at 2cm margins) paraffin slides were included. An average of 7.4 slides per specimen was analyzed. Firstly, the preselected slides were reread by a senior pathologist to confirm the absence of microscopic findings of DFSP at 2cm margins. Secondly a FISH analysis was used as a quantitative diagnostic approach, in order to find the t(17;22) translocation. Among the seven specimens that included 2cm margins, two samples presented one or more translocations, which were not visible in standard morphology assessments at two centimeters tumor-free margins. FISH analysis can have a new role in defining tumor-free margins. This would reduce the incidence of disease recurrence after resection and improve the post-operative complementary care.
2022-06-08 | Genomic alterations of dermatofibrosarcoma protuberans revealed by whole-genome sequencing.
Dermatofibrosarcoma protuberans (DFSP) is a rare and marginal cutaneous sarcoma of intermediate-grade malignancy, for which the genomic landscape remains unclear. Understanding the landscape of DFSP will help to further classify the genomic pathway of malignant development in soft tissue. To identify the comprehensive molecular pathogenesis of DFSP. In this study, the comprehensive genomic features, with 53 tumour-normal pairs of DFSP, were revealed by whole-genome sequencing. The mutational signature 1 (C > T mutation at CpG dinucleotides) is featured in DFSP, resulting in higher mutations in DNA replication. Interestingly, the recurrence of DFSP is correlated with low tumour mutation burden. Novel mutation genes in DFSP were identified, including MUC4/6, KMT2C and BRCA1, and subsequently, three molecular subtypes of DFSP were classified on the basis of MUC4 and MUC6 mutations. Various structural aberrations including genomic rearrangements were identified in DSFPs, particularly in 17q and 22q, which cause oncogene amplification (AKT1, SPHK1, COL1A1, PDGFβ) or tumour suppressor deletion (CDKN2A/B). In addition to gene fusion of COL1A1-PDGFβ [t(17;22)], we identified gene fusion of SLC2A5-BTBD7 [t(1;14)] in DFSP through whole-genome sequencing, and verified it experimentally. Enrichment analysis of altered molecules revealed that DNA repair, cell cycle, phosphoinositide 3-kinase and Janus kinase pathways were primarily involved in DFSP. This is the first large-scale whole-genome sequencing for DFSP, and our findings describe the comprehensive genomic landscape, highlighting the molecular complexity and genomic aberrations of DFSP. Our findings also provide novel potential diagnostic and therapeutic targets for this disease. What is already known about this topic? Chromosomal translocation between chromosome 17 and chromosome 22 is the main feature in the pathogenesis of dermatofibrosarcoma protuberans (DFSP). What does this study add? We describe the comprehensive genomic landscape of DFSP, highlighting the molecular complexity and genomic aberrations. Our findings provide novel potential diagnostic and therapeutic targets for this disease. What is the translational message? Our study revealed novel molecular subtypes of DFSP based on genetic mutations, which benefits precision diagnosis. We also found oncogene amplification, including AKT1 and SPHK1, which provides novel potential target molecules for further DFSP treatment. In addition to gene fusion of COL1A1-PDGFβ, we identified a novel gene fusion of SLC2A5-BTBD7 in DFSP, which is a novel potential diagnostic and therapeutic target for this disease.
cell therapies
2026-03-23 | Forehead dermatofibrosarcoma protuberans treated exclusively with full-thickness skin grafting: a unique case report and review of the literature.
Dermatofibrosarcoma protuberans (DFSP) is a rare, locally aggressive cutaneous sarcoma. Forehead involvement is uncommon and poses significant reconstructive challenges due to complex aesthetic and functional demands. Most reported reconstructions utilize staged flaps or tissue expansion. To the best of our knowledge and based on a comprehensive literature review, there are no previous reports specifically documenting forehead DFSP reconstruction performed exclusively with full-thickness skin grafting (FTSG) following wide local excision.We report a case highlighting this technique's reconstructive and aesthetic advantages. A 50-year-old woman presented with a long-standing, enlarging paramedian forehead mass above the right eyebrow, measuring approximately 7.5 × 6.5 cm. A punch biopsy and imaging confirmed DFSP. Wide local excision with 3 cm margins was performed, resulting in a 10.5 × 9 cm defect. Reconstruction was achieved using a single-stage FTSG harvested from the suprapubic region, including a segment of hair-bearing skin aligned to restore the forehead hairline. At 10 month follow-up, the patient had full graft take, preserved frontalis function, and satisfying aesthetic outcome with no recurrence. Forehead DFSP reconstruction typically involves complex, multi-stage flap procedures that risk distortion of key facial landmarks and increased morbidity. Our case demonstrates that immediate full-thickness skin grafting offers a simpler, single-stage alternative preserving eyebrow position, facial symmetry, and function. Harvesting the graft from the suprapubic area, utilizing a prior cesarean scar, allowed restoration of the hairline with hair-bearing skin-an innovative aesthetic advantage not previously reported. This unique case demonstrates that FTSG can provide favorable aesthetic and functional outcomes in selected forehead DFSP cases, representing a valuable addition to reconstructive options.
2026-02-09 | Two-Day Mohs Excision of Large Scalp Dermatofibrosarcoma Protuberans Reconstructed With a Rotation Flap.
Dermatofibrosarcoma protuberans (DFSP) is a rare, slow-growing, locally aggressive, cutaneous sarcoma with a high recurrence risk. Mohs micrographic surgery (MMS) offers superior margin control but presents significant reconstructive challenges in large scalp lesions. We present a 36-year-old male with a large (10 x 10 cm) DFSP of the frontal scalp requiring staged two-day MMS for complete clearance. Despite an extensive defect down to the periosteum and partial calvarium exposure, closure was achieved with a large rotational advancement flap with a split-thickness skin graft. This case highlights that even exceptionally large scalp DFSP lesions can be successfully excised under local anesthesia with MMS.
2026-02-05 | Customized Non-invasive Brachytherapy With Tailored Surface Moulds: An Experience From a Tertiary Care Centre.
Surface mould brachytherapy (SMBT) is an effective non-invasive treatment option for patients with skin cancer and other superficial tumours. We describe the detailed technique of uniquely treated patients of various histology using customized tailor-made surface moulds and evaluated clinical outcomes, toxicity profile, and quality of life of patients treated with SMBT. In this retrospective study, we have evaluated nine patients treated with surface moulds using iridium-192-based high-dose-rate brachytherapy. The median age was 34 years. The histopathological diagnosis included squamous cell carcinoma (n=4), followed by giant cell tumour (n=2), and 1 each of angiosarcoma, dermatofibrosarcoma protuberans, and clear cell sarcoma. The most common radiotherapy dose schedule was 60-66 Gray at 2 Gray per fraction. After a median follow-up of 24 months, local control was 100%. At the end of five years, overall survival (OS) and disease-free survival (DFS) were 88.89%. The maximum acute skin and subcutaneous toxicity grade II was observed in 5 (55.6%) patients and grade III in 4 (44.4%) patients, maximum late toxicity was grade III in 3 (33.3%) patients. Poorer Dermatology Life Quality Index scores were statistically significantly associated with higher overdose index (>0) (P=.039), and V150% >40% (P=.039). SMBT is an effective modality to achieve excellent local control in patients of skin and superficial tumours. After five years, OS and DFS both were 88.89%. It was well tolerated with manageable grade II,III acute and late skin toxicities.
2026-01-27 | Frozen Section Mohs Micrographic Surgery for Dermatofibrosarcoma Protuberans-A Case Series of 38 Patients in NSW, Australia.
Dermatofibrosarcoma protuberans (DFSP) is a rare cutaneous tumour with a locally infiltrative growth pattern that has high rates of recurrence. Mohs micrographic surgery is recommended as the gold-standard treatment over wide local excision (WLE) due to tissue-sparing and reduced recurrence rates. No previous data on surgical outcomes following Mohs Micrographic Surgery (MMS) for DFSP have been reported in Australia to date. This study aims to review the outcomes of DFSP treated with frozen-section MMS across three centres in New South Wales (NSW), Australia, and compare these outcomes with those in the current literature. A retrospective review of patients who underwent MMS for DFSP between 2010 and 2023 was performed. Patient demographics, histological findings, surgical treatment and follow-up data were collected. Recurrence was assessed through electronic medical records, clinical assessments by a dermatologist or general practitioner, and patient self-report. In all, 38 cases of DFSP were included (27 female, 11 male; median age 39 years, range 16-64). The trunk was the most common site. Clinical margins and Mohs stages were recorded in 37 of 38 cases, with 73% of cases cleared with clinical margins of ≤ 20 mm. Clinical or self-reported follow-up was available for 28 of 38 patients (73.6%) over a mean of 51 months (range, 5-132 months). No local recurrences were identified during this period. This is the first Australian case series on MMS for DFSP. Our findings demonstrate no recurrences with follow-up and demonstrate that MMS may achieve clearance with smaller clinical margins than WLE. These results support international guidelines recommending MMS as the gold-standard treatment and highlight the need to improve access to MMS in Australia.
2026-01-22 | Vulvar dermatofibrosarcoma protuberans in a 55-year-old female: A case report, surgical reconstruction approach and literature review.
Dermatofibrosarcoma protuberans (DFSP) is a rare, locally aggressive soft tissue sarcoma characterized by a high risk of local recurrence. Vulvar involvement is exceedingly uncommon and often misdiagnosed as a bening lesion, resulting in delayed diagnosis. Complete surgical excision with negative margins is essential but can be challenging in anatomically sensitive areas as the vulva. A 55-year-old Puerto Rican woman presented with a slowly enlarging lesion of the left labia majora that was initially managed as a furuncle. Progressive growth and symptoms prompted biopsy, which confirmed DFSP. Staging imaging revealed no metastatic disease. The patient underwent a single-stage left radical hemivulvectomy with immedate reconstruction using a V-Y fasciocutaneous advancement flap. Histopathologic examination demonstrated classic DFSP with uniform spindle cellls in a storiform pattern, stong diffuse CD34 positivity, and negative surgical margins. Postoperative recovery was uncomplicated, with excellent wound healing and flap viability. This case emphasizes the importance of early biopsy of persistent vulvar lesions and highlights the role of multidiciplinary surgical planning. Single-stage radical excision with immediate reconstruction can achieve favorable oncologic and functional outcomes in vulvar DFSP. Long-term surveillance remains essential due to the potential for late local recurrence.
antibodies
2025-11-01 | 131 Evaluating the Diagnostic Utility of PRAME and CD34 Dual Staining in Fibrosarcomatous Dermatofibrosarcoma Protuberans
Abstract Introduction/Objective Preferentially expressed Antigen in Melanoma (PRAME) is a melanoma-associated antigen helpful in distinguishing melanoma from nevi but is also expressed in other malignancies. Fibrosarcomatous dermatofibrosarcoma protuberans (FS-DFSP), a high-grade DFSP variant which shows increased mitotic activity and higher metastatic risk. Diagnosing FS-DFSP can be challenging, especially when CD34 expression is reduced or absent. We report a case of FS-DFSP with CD34 loss and PRAME immune-reactivity. Methods/Case Report A 49-year-old African American male presented with a progressively enlarging mass on the anterior chest and neck over a 12-month period, arising at the site of an old scar from a previous motorcycle accident. Imaging revealed a 6.0 cm lobulated soft tissue mass in the anterior neck/upper thorax. Biopsy showed a monomorphic spindle cell tumor with storiform architecture. Initial immunohistochemistry confirmed conventional DFSP (CD34 positive and negative pancytokeratin, SOX10, Factor XIIIa, SMA, desmin, and ERG). Wide excision revealed areas with higher cellularity, herringbone architecture, nuclear atypia, and increased mitoses (32/10 HPF, Ki-67: 25–30%). CD34 was lost in these areas, which showed diffuse PRAME positivity. Results NA Conclusion PRAME may aid in distinguishing FS-DFSP from conventional DFSP. This dual-staining approach with CD34 can improve diagnostic precision and may offer future therapeutic potential through PRAME-targeted immunotherapy.
2025-04-15 | Clinicopathological and molecular analysis of a dermatofibrosarcoma protuberans with fibrosarcomatous transformation in the breast.
Dermatofibrosarcoma protuberans (DFSP) is a rare soft tissue sarcoma with low potential for metastases. To date, only a few cases of DFSP in the breast have been reported, and none have reported comprehensive genetic signatures. We report, for the first time, the largest DFSP in the breast with multidisciplinary tumor board discussion and comprehensive molecular analysis. This DFSP is 18.5 cm with fibrosarcomatous transformation, distinct gene rearrangement translocation t(17;22) (q22;q13), COL1A1::PDGFB fusion, and subsequent segmental amplification of chromosomes 17q and 22q. The high-level of amplifications of genomic regions containing the COL1A1 and PDGFB genes (6 copies) compared to the reported DFSP cases (2-3 copies) supports the gene dosage effect correlated with aggressive behavior and high-grade tumor histology. This case highlights the importance of precise genetic alteration in the clinicopathological and phenotypic expression of DFSP with fibrosarcomatous transformation, and it helps guide clinical management and informs the role of targeted therapy.
2024-07-31 | Cellular and molecular landscape of primary dermatofibrosarcoma protuberans: Insights from single-cell RNA sequencing analysis.
Dermatofibrosarcoma protuberans (DFSP) is a rare cutaneous sarcoma characterized by the COL1A1-PDGFB fusion gene. This study utilized single-cell RNA sequencing to dissect the cellular and molecular landscape of primary DFSP. Distinct DFSP cell clusters, exhibiting fibroblast-like traits, revealed variations in pathways associated with proliferation, inflammation and metabolism. Differential gene expression analysis during the differentiation from tumour stem cells to DFSP cells unveiled SMOC2, DCN and TGFBR3 as potential regulators of tumour invasion and immune infiltration through VEGF/TGF-β signalling modulation. Cellular communication analysis highlighted interactions within DFSP cell clusters and with endothelial cells, implicating molecules such as NAMPT, ANGPT2 and PTN in pathogenesis and treatment resistance. These findings offer insights into DFSP intratumour heterogeneity, elucidate molecular mechanisms underlying tumour behaviour, and suggest potential therapeutic targets.
2024-05-13 | Head-and-neck dermatofibrosarcoma protuberans: Survival analysis and Clinically relevant immunohistochemical indicators.
Head and neck dermatofibrosarcoma protuberans (HNDFSP) is extremely rare and not entirely understood. To investigate the clinicopathological features of HNDFSP and identify the expression of its clinically relevant indicators, with the expectation of improving the existing treatment strategies. A long-term follow-up of patients with HNDFSP who received treatment between 2000 and 2021 at Shanghai Ninth People's Hospital was conducted. The clinical, histological, and immunohistochemical data of the patients were retrieved and analyzed. The endpoint of the study was the incidence of significant disease-related clinical events (recurrences or metastasis). A total of 49 patients with HNDFSP were included in the study, with males (92.7%) predominating than females (7.3%). Eighteen patients developed recurrent disease (36.8%) after surgery, and the median time of recurrence was 48 months (interquartile, 20-74 months). Metastasis occurred in two cases (4.1%). Two patients died during follow-up, both with local recurrence, and one of them with intestinal metastasis. Post-operation radiotherapy was administered to eight patients (16.3%) and the effect in local control was remarkable. Age, tumor size, and negative margins with sufficient safety width were the main independent factors affecting the disease-free survival. Several potential targeted therapeutic indicators, including EZH2 (80.0%), EGFR (91.4%), PDGF (97.1%), PD-L1 (77.1%), and VEGF (77.1%), were positively expressed in most tumor samples. HNDFSP is rare, significantly challenging to control locally, and has a worse prognosis with current treatment strategies. Wide local excision and long-term follow-up are needed. Radiotherapy could improve the prognosis of patients with HNDFSP.
2023-10-01 | 60P Spindle cell sarcomas with tyrosine kinase rearrangement
A group of spindle cell tumors with characteristic morphologic features and recurrent gene rearrangements has recently been described. Genome-wide DNA methylation profiling has emerged as a powerful tool for both robust classification of known sarcoma entities and identification of novel and clinically relevant subclasses of soft tissue tumors with characteristic alterations. Anchored Multiplex polymerase chain reaction amplicons were sequenced on Illumina MiSeq and the data were analyzed using the Archer and Arriba software. Genome-wide DNA methylation profiling was performed using Infinium Methylation EPIC (EPIC) BeadChip (Illumina). We identified 6 spindle cell sarcoma cases with rearrangement/SNV in BRAF gene, 3 pediatric spindle cell sarcomas with NTRK1 fusion, 1 high-grade sarcoma with ALK fusion and 1 pediatric sarcoma with tyrosine-kinase duplication of EGFR gene. We show that CDKN2A deletion was the most prevalent DNA copy number aberration in spindle cell sarcomas for which this deletion is a typical change and connecting element across different subgroups of spindle cell sarcomas and this change was associated with poor clinical outcome. DNA methylation profiling demonstrated that 5 of our BRAF altered spindle cell sarcomas clustered within MPNST-like methylation class, but methylation analysis classified the next BRAF rearranged case (with CUX1::BRAF fusion) near to angiomatoid fibrous histiocytomas or inflammatory myofibroblastic tumors. Our patients with LMNA::NTRK1 fusion gene clustered within dermatofibrosarcoma protuberans methylation class. Methylation analysis of the sample with ALK fusion did not classify the sample in any of the defined class of methylation classifier. The current study demonstrates, that all detected rearrangements in our spindle cell cohort are potentially therapeutically targetable. We provide evidence for the pathobiological and epigenetical heterogeneity of spindle cell sarcomas generally, and also of spindle cell sarcomas that shows alteration of the tyrosin-kinase genes.
proteins
2025-09-04 | Digital Spatial Profiling Demonstrates Differences Between Fibrosarcomatous Transformation of Dermatofibrosarcoma Protuberans and Its Conventional Counterparts.
Dermatofibrosarcoma protuberans (DFSP) is a neoplasm of the dermis with a tendency for aggressive local growth and recurrence. A minority of DFSP cases may transform into higher-grade sarcoma (fibrosarcomatous transformation [FST]) (DFSP-FST), which is associated with more aggressive behavior and risk of metastasis. The histologic diagnosis of DFSP-FST may be challenging, particularly in small biopsies. Currently, there are no specific markers to reliably support the diagnosis of DFSP-FST. We identified 33 DFSP from 32 patients, including 9 patients with FST and 1 distant metastasis. Tissue microarrays (TMAs) were created using representative areas of all cases, including DFSP-FST, conventional regions from DFSP-FST, and pure conventional DFSP. Digital spatial profiling of the entire transcriptome was performed on the TMAs using the Nanostring GeoMx platform. Expression data were queried to identify differentially expressed genes specific to the regions of transformation in DFSP. Immunohistochemistry for PReferentially expressed Antigen in MElanoma (PRAME) was subsequently performed using a clinically validated protocol. Digital spatial profiling demonstrated significant gene expression differences between DFSP-FST and conventional DFSP. Genes that were overexpressed in DFSP-FST include PRAME, CTAG1B, and MMP11. Immunohistochemical analysis for PRAME showed positive expression in 7 of 10 DFSP-FST (70%) and 1 of 23 conventional DFSP (4%) (P < .0001). Gene expression profiling shows significant upregulation of PRAME and CTAG1B in DFSP-FST compared with conventional DFSP, a finding that was validated by immunohistochemistry for PRAME. Therefore, immunohistochemistry for PRAME may be useful to support the diagnosis of FST, especially in small biopsies. Increased expression of CTAG1B (NY-ESO-1) in DFSP-FST may also offer future therapeutic potential.
2022-11-11 | Dermatofibrosarcoma protuberans surgery: Experiences of four African surgical oncology units and literature review.
Dermatofibrosarcoma is a locally malignant tumor. This gives surgery a place of choice. The advent of imatinib has improved outcomes. Our aim is to describe the indications, techniques and results of surgery. A retrospective, multicenter, descriptive study conducted in four West African surgical oncology units. It covers dermatofibrosarcoma surgery performed between January 1, 1988 and December 31, 2020. We took into account the surgical procedure, the mode of skin coverage, adjuvant treatments and survival. Comparisons were possible using Student's t-test and Pearson's χ2 . We recorded 81 cases of dermatofibrosarcoma. Surgery was effective in 90.1% of cases. Wide resection was the principle with a mean resection margin of 3.8 ± 1.9 cm. healing by primary intention, flaps and healing by secondary intention were the methods of skin coverage in 30.1%, 24.7% and 41.1% respectively. The type of skin coverage was related to the topography and size of the tumor (p < 0.0001). The healing time is associated with the type of skin cover. The recurrence rate was not related to the type of skin coverage (p = 0.8). Wide and deep resection in the absence of Mohs micrographic surgery ensures healthy margins. Oncoplasty reduces the healing time without increasing the risk of recurrence.
2021-06-07 | Hyaluronidase in Dermatology: Uses Beyond Hyaluronic Acid Fillers.
Hyaluronidase is mostly widely recognized for its off-label use in correction of complications of hyaluronic acid fillers. However, its utility in other aspects of dermatology is less widely acknowledged. We describe the varied uses of hyaluronidase in dermatology and the underlying evidence base for its dermatological indications. This includes its uses in enhancing drug delivery (for local anesthesia, keloid and hypertrophic scars, and for Kaposi’s sarcoma), in the treatment of disorders associated with mucin deposition (myxedema, scleroderma, scleredema, and cutis verticis gyrata) and its potential uses in surgery (as a pre-operative adjuvant in dermatofibrosarcoma protuberans, for periorbital edema, and for hematomas). In select circumstances, hyaluronidase might be more efficacious than more established treatments with fewer adverse effects. We propose hyaluronidase as the latest addition to our global dermatological armamentarium and implore dermatologists to consider its use to enhance their practice. J Drugs Dermatol. 2020;19(10):993-998. doi:10.36849/JDD.2020.5416.
1999-03-01 | Adjuvant Therapy with Hyaluronidase Prior to Excision of Dermatofibrosarcoma Protuberans
Background. Dermatofibrosarcoma protuberans (DFSP) are uncommon, low grade cutaneous malignancies, which rarely metastasize. Although surgery is the main therapy for these tumors, they commonly recur in spite of wide excisions. Hyaluronidase (HD) has been used both intralesionally as well as intravenously as an adjuvant in therapy of both epithelial and mesenchymal malignancies to decrease local spread, to potentiate differentiation induced apoptosis, and to potentiate the tissue penetration of chemotherapeutic agents. In addition, there is a long history of intralesional HD use without significant complications. The biologic characteristics of DFSP including the observation that hyaluronic acid is commonly present and sometimes is increased in these tumors and the known effects of HD therapy in other malignancies suggested to us that HD pretreatment may be a helpful adjuvant in the surgical management of DFSPs. Following diagnostic biopsy of a recurrent DFSP, the patient was treated for 4 weeks with intralesional HD injections. Results. Based on margins necessary for complete excision from past studies, this patient had decreased margin width and thus had a postoperative wound size less than was expected. The patient has had no evidence of recurrence at 24 months follow-up.
1998-09-01 | Pretreatment with intralesional hyaluronidase prior to excision of dermatofibrosarcoma protuberans1The opinions or assertions herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army, the Department of the Navy, or the Department of Defense.1
Dermatofibrosarcoma protuberans (DFSPs) are an uncommon malignancy that commonly recur, but rarely metastasize. The origin of DFSPs is controversial; however, they stain with the progenitor marker CD34. DFSPs usually show increased stromal mucin, mainly hyaluronic acid (HA). HA increases cellular proliferation, delays differentiation and increases cellular motion. We evaluated the pretreatment of DFSPs with intralesional injections of hyaluronidase (HD) prior to the surgical excision. Five of nine cases of DFSPs were pretreated with HD. In HD-pretreated cases the margins for excision of the residual tumor were reduced. HD pretreatment also decreased CD34 staining and increased polarizable collagen in the residual tumor.
small molecules
2026-07-28 | Investigating the Spatial Immune Tumor Microenvironment of Dermatofibrosarcoma Protuberans 2266312
Abstract Introduction Dermatofibrosarcoma Protuberans (DFSP) is a rare, locally aggressive cutaneous sarcoma driven by the COL1A1-PDGFB fusion. While its molecular drivers are well-defined, the DFSP tumor immune microenvironment remains poorly characterized. Understanding immune-stromal interactions in DFSP may reveal opportunities to complement surgical resection with immunotherapy or targeted approaches. Methods We performed spatial transcriptomics on 16 DFSP patient samples using 10X Genomics Visium v2 (n = 12) and Visium HD (n = 4), integrated with single-cell RNA sequencing. Results Our analysis revealed distinct tumor, stromal, and immune populations with high PDGFB-high tumor cells spatially segregated from infiltrating immune compartments. We identified transcriptionally distinct cancer-associated fibroblast (CAF) subsets, including populations enriched for extracellular matrix remodeling and inflammatory signatures that may modulate local immunity. Immune profiling uncovered spatially heterogeneous T cell and macrophage infiltration, with distinct immune-rich and immune-desert zones across patients. Notably, we observed tertiary lymphoid structure (TLS) formation in multiple samples, characterized by elevated TLS signature scores and spatial co-localization of B and T cell markers. CXCL13 and CCL19 emerged as key chemokines defining TLS-associated immune-stromal communication networks. Using cyclic immunofluorescence, we validated the spatial organization of TLS-associated immune niches, confirming co-localization of CD3+ T cells, CD20+ B cells, and CD68+ macrophages within TLS-enriched regions at protein level. Conclusion This work provides the first spatial immune atlas of DFSP, revealing organized lymphoid structures and CAF-mediated immune regulation that could inform combination strategies targeting PDGFR signaling alongside immune checkpoint or stromal modulation. Funding Source n/a Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)
2026-06-26 | Proteomics-based approach reveals the involvement of spliceosomal components SF3B and SerpinB9 in dermatofibrosarcoma protuberans
Abstract Background Dermatofibrosarcoma protuberans (DFSP) is a rare cutaneous soft tissue sarcoma which is prone to high recurrence rate, and the fibrosarcomatous transformation of DFSP (FS-DFSP) is associated with a poorer prognosis and significant metastatic potential. Although the translocation of regions of chromosomes 17 and 22 that results in COL1A1-PDGFB fusion is generally acknowledged as a key genetic feature of DFSP, there is no established salvage treatment following resistance to imatinib, which targets the PDGFB pathway. In this study, we performed quantitative proteomics analyses of DFSP tumor tissues and paired adjacent normal skin, to uncover novel molecular mechanisms and potential therapeutic targets. Findings were validated using immunohistochemistry, Western Blot, Real-Time Quantitative PCR and cell viability assay. Results Pathway enrichment analysis including KEGG and GSEA revealed that spliceosome pathways and ECM-receptor interaction were associated with DFSP pathogenesis. The spliceosomal components SF3B, and SerpinB9, which is the endogenous inhibitor of granzyme B, were validated to be upregulated in tumor tissues. SerpinB9 was significantly overexpressed in the FS-DFSP subtype compared with the classic-type DFSP. Treatment with the SF3B1 inhibitor, Pladienolide-B, significantly reduced tumor cell viability. siRNA-mediated knockdown of SF3B1 and SF3B2, as well as Pladienolide-B treatment, inhibited SERPINB9 expression without affecting pre-SERPINB9 mRNA levels, suggesting splicing-dependent regulation. Additionally, quantitation of the tumor microenvironment cells using the MCP-counter algorithm indicated NK cells activation. The CD56 (NK cell surface marker), biomarkers of tumor-associated macrophage (TAM) such as CD14 and CD163, and transforming growth factor-β induced (TGFBI) which is associated with TAM infiltration stained positive in DFSP tumors. SERPINB9 mRNA expression showed a positive correlation with both NK cell abundance and FCGR3A (NK cell marker) mRNA level. Conclusions SerpinB9 overexpression is associated with fibrosarcomatous features in DFSP and may represent a candidate prognosis biomarker. The SF3B/SERPINB9 axis is a potential therapeutic vulnerability, particularly in FS-DFSP. NK cell- and macrophage-related signatures were evident in DFSP tumor microenvironment, warranting further functional studies.
2026-06-10 | Data Sheet 1_Integrating contrast-enhanced ultrasound to optimize margin delineation in Mohs micrographic surgery for primary dermatofibrosarcoma protuberans: a retrospective cohort study.pdf
Introduction Dermatofibrosarcoma protuberans (DFSP) is characterized by infiltrative “tentacle-like” extensions, making accurate preoperative margin delineation challenging. While high-frequency ultrasound (HFUS) visualizes subclinical spread, its ability to fully capture tumor extent remains limited. Contrast-enhanced ultrasound (CEUS), by depicting microvascular perfusion, may improve delineation, but its clinical impact on Mohs micrographic surgery (MMS) remains unclear. Methods This retrospective cohort study included 220 primary DFSP patients treated with MMS. Preoperative margin delineation utilized HFUS-only or HFUS+CEUS. The primary outcome was extra peripheral Mohs stages. Secondary outcomes included extra deep and total stages, margin positivity, and other surgical characteristics. Multivariable Poisson regression with LASSO-based variable selection was used, alongside cohort-restriction, covariate-specification, and propensity score–matched (PSM) analyses. Risk-stratified and subgroup analyses explored effect heterogeneity. Results HFUS+CEUS was associated with fewer extra peripheral Mohs stages than HFUS-only (adjusted incidence rate ratio [aIRR], 0.310; P = 0.049). Peripheral margin positivity was reduced from 17.4% to 5.1% (P = 0.020). These findings were consistent across sensitivity analyses and in the PSM cohort (aIRR, 0.309; P = 0.033). The relative effect was most pronounced in the high-risk stratum (IRR, 0.124; P = 0.041), although interaction testing was not statistically significant (P = 0.077). No significant differences were observed in deep or total stages, likely due to ultrasound depth limitations. Conclusions Integrating CEUS with HFUS enhances the precision of preoperative margin delineation for DFSP, reducing extra peripheral Mohs stages. This multimodal imaging strategy represents a valuable, tissue-sparing refinement to the preoperative workflow of MMS, particularly for patients with higher baseline risk.
2026-05-29 | Case Report of Giant Myxoid Fibrosarcomatous Dermatofibrosarcoma Protuberans Compressing the Right Jugular Vein: A Multidisciplinary Approach to Complex Surgical Management.
Dermatofibrosarcoma protuberans (DFSP) is a locally aggressive low-grade cutaneous neoplasm with high cure rates following complete surgical resection. However, 5-15% of classic DFSP cases undergo fibrosarcomatous transformation, resulting in fibrosarcomatous DFSP (FS-DFSP), a more aggressive variant with significantly higher rates of local recurrence, metastasis, and mortality. This case presents a rare myxoid variant of FS-DFSP with complex anatomical involvement requiring multidisciplinary management. A 56-year-old East Asian female presented with a giant recurrent chest mass measuring 15 × 12 × 6 cm, initially misdiagnosed as fibroma 19 years prior. Advanced imaging revealed an 8 × 13 × 12 cm poorly defined soft tissue mass involving the pectoralis major and extending to the sternocleidomastoid muscles, with compression of the proximal right jugular vein. Histopathological examination confirmed FS-DFSP with myxoid differentiation, characterized by diffuse spindle cell infiltration in a fascicular pattern. Immunohistochemistry revealed CD34+, EMA+, and actin+ staining with negative desmin, S100, and STAT-6. COL1A1-FISH analysis demonstrated COL1A1/PDGFB fusion in 8% of cells. Management included tumor vascular embolization, surgical resection with 3 cm margins, skin grafting, local flap repair, and adjuvant radiation therapy due to anatomical constraints and residual tumor involvement of the anterior sternum. Four-year follow-up shows no evidence of recurrence. This case highlights the myxoid variant of FS-DFSP, emphasizing the importance of comprehensive histopathological evaluation, multidisciplinary treatment planning, and long-term surveillance. The successful management with combined surgical and radiation therapy demonstrates the need for individualized treatment approaches in complex anatomical locations. Four-year remission demonstrated the efficacy of comprehensive multimodal therapy in preventing local recurrence in FS-DFSP.
2026-04-08 | Anesthetic and Analgesic Management of Pediatric Patients for Staged Repeat Same-Day Surgery.
Dermatofibrosarcoma protuberans (DFSP) is a rare dermatologic malignancy in children requiring a multidisciplinary approach for surgical excision and postoperative care. The modified "slow Mohs" repeat staged excision and the associated anesthetic technique are not well described in the pediatric literature. We describe three pediatric patients whose staged excision procedures were completed using general anesthesia plus systemic multimodal analgesia (all patients), including tunneled epidural catheters (two patients with truncal tumors) or a scheduled long-acting opioid (one patient with a forehead lesion). Complete dermatologic excision and excellent surgical analgesia were achieved in all patients. Specific interventions to verify epidural catheter position and allow potential prolonged catheter use were of particular utility in perioperative management. Children with DFSP present a unique challenge to provide optimal surgical and cosmetic results with serial staged Mohs excision while ensuring adequate ongoing analgesia. Close interdisciplinary communication and advance planning are essential. Multimodal analgesia, including tunneled epidural catheters if anatomically appropriate, or scheduled long-acting opioid, is a key component of successful management. Confirmation of epidural catheter position likely improves analgesic efficacy and reduces the need for catheter replacement. We suggest that the care of pediatric patients undergoing slow Mohs staged repeat excision is best undertaken in a tertiary care setting with adequate multidisciplinary subspecialist support.
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2026-01-13 | Abstract A019: Investigating of the impact of COL1A1::PDGFB fusion in mouse Col1a2+ dermal embryonic fibroblasts as a potential cell of origin of dermatofibrosarcoma protuberans
Abstract Dermatofibrosarcoma protuberans (DFSP) is the most common cutaneous sarcoma and is characterized by chromosomal translocations, most frequently t(17;22) encoding the fusion protein COL1A1::PDGFB. This malignancy arises in the dermis of the skin and exhibits spindle cell morphology and deep invasion to the subcutis. DFSP is presumed to arise as a result of COL1A1::PDGFB fusion-driven uncontrolled PDGFB expression by the COL1A1 promoter, which is highly active in dermal fibroblasts. However, the cell of origin of DFSP remains unclear, as this tumor exhibits expression of neural markers and CD34 positivity, leading to longstanding speculation regarding a non-fibroblastic cell of origin. Interestingly, several pediatric cases of DFSP are noted at the time of birth, raising the possibility of an embryonic cell-of-origin in some patients. In addition, emerging evidence suggests that early stem cell populations can be reprogrammed by oncogenic fusion proteins and impact cellular phenotypes. We sought to test the hypothesis that embryonic dermal fibroblasts expressing a modified fusion protein could develop DFSP-like tumors in mouse skin. To test this, a 747 base pair fusion protein cDNA was designed to include the regions of the COL1A1::PDGFB conserved across human DFSP tumors, particularly the COL1A1 signal peptide and exons 2-7 of PDGFB in a DNA construct that contains fibroblast-specific promoter and enhancer elements of Col1a2. An internal ribosome entry site (IRES) followed by the mCherry red fluorescent protein (RFP) sequence allowed identification of transgene expression by RFP fluorescence. This construct was introduced into fertilized mouse oocytes via pronuclear injection and embryos were collected for analysis. Effective transgene expression was detected by RFP and genotypes were confirmed by PCR with transgene-specific primers. A total of 15 out of 99 (15.2%) of embryos harbored the transgene and revealed a spectrum of phenotypes. Strong transgene expression caused severe embryonic malformations, whereas weaker expression was associated with abnormal development of the dermis, epidermis, and hair follicles. No tumors or obvious proliferations were present in any embryos evaluated. Taken together, this work shows that fusion oncogene and/or high-level PDGFB signaling in developing dermal fibroblasts causes embryonic toxicity, whereas lower degrees of signaling demonstrate impaired development of normal cutaneous structures. Further studies to investigate other putative cells of origin, as well as strategies to mitigate embryonic toxicity (such as using an inducible system which allows for postnatal transgene expression) are warranted. These studies suggest a degree of oncogene toxicity due to COL1A1::PDGFB expression in some cells. Future studies to investigate how cells tolerate this oncogene may lead to new insights regarding the growth and survival of DFSP cells that could be exploited for therapy. Citation Format: Elisabeth A. Pedersen, Li-Jyun Syu, Andrzej A. Dlugosz, Monique E. Verhaegen. Investigating of the impact of COL1A1::PDGFB fusion in mouse Col1a2+ dermal embryonic fibroblasts as a potential cell of origin of dermatofibrosarcoma protuberans [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Fusion-Positive Cancer: From Discovery to Therapy; 2026 Jan 13-15; Philadelphia PA. Philadelphia (PA): AACR; Cancer Res 2026;86(1_Suppl):Abstract nr A019.
2024-02-26 | Novel role of fluorescent in situ hybridization technique (FISH) in recommended surgical margins of dermatofibrosarcoma protuberans: A preliminary study.
Dermatofibrosarcoma protuberans (DFSP) is a rare skin tumor. There is no standard recommendation for its surgical management. The currently used histological analysis are HES (hematoxylin eosin saffron) staining and immunohistochemistry for CD34 expression in particular cases. Fluorescent in situ hybridization (FISH) technique is only used to qualify the DFSP as translocated or non-translocated and is not used as a diagnostic method. The aim of our study was to determine by FISH (as a diagnostic method) whether cancerous cells that could not be identified through HES staining±immunohistochemistry were present at the two-centimeter margins that were found to be tumor-free. Samples from patients who underwent surgery between 2010 and 2018 were collected. Intralesional and peripheral (at 2cm margins) paraffin slides were included. An average of 7.4 slides per specimen was analyzed. Firstly, the preselected slides were reread by a senior pathologist to confirm the absence of microscopic findings of DFSP at 2cm margins. Secondly a FISH analysis was used as a quantitative diagnostic approach, in order to find the t(17;22) translocation. Among the seven specimens that included 2cm margins, two samples presented one or more translocations, which were not visible in standard morphology assessments at two centimeters tumor-free margins. FISH analysis can have a new role in defining tumor-free margins. This would reduce the incidence of disease recurrence after resection and improve the post-operative complementary care.
2022-06-08 | Genomic alterations of dermatofibrosarcoma protuberans revealed by whole-genome sequencing.
Dermatofibrosarcoma protuberans (DFSP) is a rare and marginal cutaneous sarcoma of intermediate-grade malignancy, for which the genomic landscape remains unclear. Understanding the landscape of DFSP will help to further classify the genomic pathway of malignant development in soft tissue. To identify the comprehensive molecular pathogenesis of DFSP. In this study, the comprehensive genomic features, with 53 tumour-normal pairs of DFSP, were revealed by whole-genome sequencing. The mutational signature 1 (C > T mutation at CpG dinucleotides) is featured in DFSP, resulting in higher mutations in DNA replication. Interestingly, the recurrence of DFSP is correlated with low tumour mutation burden. Novel mutation genes in DFSP were identified, including MUC4/6, KMT2C and BRCA1, and subsequently, three molecular subtypes of DFSP were classified on the basis of MUC4 and MUC6 mutations. Various structural aberrations including genomic rearrangements were identified in DSFPs, particularly in 17q and 22q, which cause oncogene amplification (AKT1, SPHK1, COL1A1, PDGFβ) or tumour suppressor deletion (CDKN2A/B). In addition to gene fusion of COL1A1-PDGFβ [t(17;22)], we identified gene fusion of SLC2A5-BTBD7 [t(1;14)] in DFSP through whole-genome sequencing, and verified it experimentally. Enrichment analysis of altered molecules revealed that DNA repair, cell cycle, phosphoinositide 3-kinase and Janus kinase pathways were primarily involved in DFSP. This is the first large-scale whole-genome sequencing for DFSP, and our findings describe the comprehensive genomic landscape, highlighting the molecular complexity and genomic aberrations of DFSP. Our findings also provide novel potential diagnostic and therapeutic targets for this disease. What is already known about this topic? Chromosomal translocation between chromosome 17 and chromosome 22 is the main feature in the pathogenesis of dermatofibrosarcoma protuberans (DFSP). What does this study add? We describe the comprehensive genomic landscape of DFSP, highlighting the molecular complexity and genomic aberrations. Our findings provide novel potential diagnostic and therapeutic targets for this disease. What is the translational message? Our study revealed novel molecular subtypes of DFSP based on genetic mutations, which benefits precision diagnosis. We also found oncogene amplification, including AKT1 and SPHK1, which provides novel potential target molecules for further DFSP treatment. In addition to gene fusion of COL1A1-PDGFβ, we identified a novel gene fusion of SLC2A5-BTBD7 in DFSP, which is a novel potential diagnostic and therapeutic target for this disease.
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Drug Discovery Landscape
2 orphan drug designations for Dermatofibrosarcoma protuberans, including 1 approved therapy.
2 orphan drug designations for Dermatofibrosarcoma protuberans, including 1 approved therapy.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
imatinib mesylate [Gleevec] | small molecules | FDA | 2005-12-19 | 2006-10-19 | Novartis Pharmaceuticals Corporation |
Imatinib mesilate [Glivec] | small molecules | EMA | 2005-08-26 | — | Novartis Europharm Limited |
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