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:
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.
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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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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