Review of dermatofibrosarcoma protuberans.

The clinical features, histological subtypes and management of dermatofibrosarcoma protuberans (DFSP) are reviewed in this article. DFSP is an uncommon cutaneous sarcoma first described in 1890. It has a high local recurrence rate, low metastatic rate and low mortality. The crude incidence rate in England in 2019 was reported as 3.0 per million person-years. A fusion of platelet-derived growth factor subunit B (PDGFB) and COL1A1, t(17;22)(q22;q13), has been found in over 90% of people with DFSP. This fusion is thought to upregulate PDGFB expression, stimulating cell growth by activation of Ras mitogen-activated protein kinases and PI3K-AKT-mTOR, potentiating oncogenesis. DFSP usually presents as an asymptomatic flesh-coloured, thickened, rubbery plaque or nodule with an uneven surface. The most common sites are the trunk followed by lower limbs, head and neck and upper limbs. Larger tumours can infiltrate underlying local structures and around 1% metastasize. Key histological features in DFSP are spindle cells arranged in a storiform pattern with intense CD34 staining. Histological subtypes include classical DFSP, Bednar, myxoid, giant cell fibroblastoma, atrophic and DFSP-fibrosarcomatous. The gold standard management for localized tumours is surgical: current recommendations favour Mohs micrographic surgery over wide local excision. Adjuvant radiotherapy may be offered after surgery. Imatinib can be used as neoadjuvant therapy and in patients with inoperable or metastatic tumours. Further research should be conducted to better understand pathogenesis of DFSP, identify associated risk factors and standardize management.

Dermatofibrosarcoma Protuberans: What Is This?

Dermatofibrosarcoma protuberans (DFSP) is a rare, locally aggressive dermal-based sarcoma. Metastatic potential is extremely low, primarily in the setting of fibrosarcomatous transformation. DFSP is characterized by a t(17;22) (q22;q13) translocation that results in active PDGFB signaling. Surgical resection with negative margins (typically including the underlying fascia) is the potentially curative treatment. Delayed wound closure should be considered for cases requiring extensive resection or tissue rearrangement. Tyrosine kinase inhibitors, such as imatinib, have shown response rates of 50% to 60% in patients with locally advanced or metastatic disease. Radiation can be useful for residual or recurrent diseases.

Dermatofibrosarcoma Protuberans Of Trunk In A Male Patient.

Dermatofibrosarcoma protuberans is a rare cutaneous malignancy. Usual sites of origin are trunk and extremities. Aetiology of the condition is not well understood but a genetic basis is explained as a reciprocal translocation t (17l;22) (q22; q13). Distant metastasis is quite rare as it is mostly a locally advancing tumour. Histopathology is the most accurate investigation to make a diagnosis. Imaging is still required to rule out distant metastasis. Surgical excision is the treatment option for stage I tumours. Imatinib, a tyrosine kinase inhibitor, has shown promising results in management of locally advanced and metastatic disease.

Rare Cutaneous Malignancies in Skin of Color.

BACKGROUND: There is a scarcity of information regarding the clinical characteristics of rare cutaneous malignancies in skin of color that has yet to be comprehensively explored. OBJECTIVE: To review and compile the racial differences in epidemiology, clinical presentation, histology, treatments, and outcomes of 3 rare skin cancers: dermatofibrosarcoma protuberans (DFSP), Merkel cell carcinoma (MCC), and sebaceous carcinoma (SC). METHODS: Several searches with keywords denoting specific skin cancer type and race were conducted on PubMed to complete this narrative review. RESULTS: We analyzed 50 sources that were relevant to the initial objective. CONCLUSION: The literature demonstrates that there are nuances in DFSP, MCC, and SC unique to African Americans, Asians/Pacific Islanders, and Hispanics that may differ significantly from Caucasian counterparts. African Americans consistently suffer from the worst clinical outcomes in all 3 rare cutaneous malignancies reviewed. Greater physician awareness and knowledge of the discussed racial differences is the preliminary step to address these disparities.

Impact of human adipose tissue-derived stem cells on dermatofibrosarcoma protuberans cells in an indirect co-culture: an in vitro study.

BACKGROUND: Autologous adipose tissue transfer may be performed for aesthetic needs following the resection of dermatofibrosarcoma protuberans (DFSP), the most common cutaneous soft tissue sarcoma, excluding Kaposi sarcoma. The regenerative effectiveness of cell-assisted lipotransfer is dependent on the presence of adipose tissue-derived stem cells (ADSCs). This is the first study to evaluate the potential oncological risks as ADSCs could unintentionally be sited within the proximity of the tumor microenvironment of DFSP cells. METHODS: Primary DFSP cells were indirectly co-cultured with ADSCs in a conditioned medium or in a Transwell system. The impact was analyzed by assessing proliferation, migration, invasion, angiogenesis, and tumor-associated genes and proteins. Results of these assays were compared between co-culture and mono-culture conditions. RESULTS: Our experimental results showed that ADSCs were able to promote proliferation, migration, invasion, and angiogenesis of DFSP cells; this was accompanied by a significant increase in the expression levels of beta-type platelet-derived growth factor receptor, collagen type I alpha 1 chain, vascular endothelial growth factor, hepatocyte growth factor, and basic fibroblast growth factor. CONCLUSIONS: The current report clearly demonstrates that ADSCs can enhance different malignant properties of DFSP cells in vitro, which should not be neglected when considering the clinical use of human ADSCs and its related derivatives in skin regenerative therapies.

Management of dermatofibrosarcoma protuberans.

PURPOSE OF REVIEW: Provide an up to date review of the diagnosis, workup and treatment of dermatofibrosarcoma protuberans (DFSP). DFSP can be a challenging disease to manage and adequate understanding of the most up to date literature can help provide comprehensive treatment strategies. RECENT FINDINGS: DFSP is an infiltrative cutaneous sarcoma. It tends to have deep local invasion with a high risk of local recurrence, but a low risk of distant metastasis. It presents typically as a slow growing, asymptomatic skin lesion. It presents rarely in the head and neck, only 15% of the time. Recent data has discussed the role of wide local excision (WLE) vs. Mohs surgery. In addition, for unresectable disease the role of systemic therapy and immunomodulatory agents such as Imatinib has shown success. SUMMARY: Typically, surgical management is the first line for DFSP, however the risk for local recurrence still remains high with negative margins. Due to this risk, lifelong surveillance is required after initial diagnosis and management. Similar to other head and neck tumors, most recurrences happen within the first 3 years after treatment. DFSP can be treated with WLE or Mohs. For aggressive disease that is considered unresectable systemic therapy does exist, including molecular targeted therapies.

SEOM Clinical Guideline of management of soft-tissue sarcoma (2020).

Soft-tissue sarcomas constitute an uncommon and heterogeneous group of tumors of mesenchymal origin. Diagnosis, treatment, and management should be performed by an expert multidisciplinary team. MRI/CT of the primary tumor and biopsy is mandatory before any treatment. Wide surgical resection with tumor-free tissue margin is the mainstay for localized disease. Radiotherapy is indicated in large, deep, high-grade tumors, or after marginal resection not suitable for re-excision. Perioperative chemotherapy should be discussed for high-risk sarcomas of the extremities and trunk-wall. In the case of oligometastatic disease, patients should be considered for local therapies. First-line treatment with anthracyclines (or in combination with ifosfamide) is the treatment of choice. Other drugs have shown activity in second-line therapy and in specific histological subtypes but options are limited and thus, a clinical trial should always be discussed.

Dermatofibrosarcoma Protuberans: A Clinicopathologic and Therapeutic Analysis of 254 Cases at a Single Institution.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a rare low-grade tumor that typically does not metastasize but often recurs. Fibrosarcomatous DFSP (FS-DFSP) is associated with a substantially higher rate of metastasis and a poorer prognosis. OBJECTIVE: This study sought to investigate the epidemiological, histopathological, and clinical characteristics of DFSP, especially with a particular focus on FS-DFSP. MATERIALS AND METHODS: Clinical data from 254 patients treated between January 1999 and July 2018 were retrospectively reviewed. Endpoints of the study were the incidence of significant disease-related clinical events. RESULTS: Follow-up data from 211 patients were available for analysis, with a median follow-up time of 38 months (range: 1-196 months). The 5-year recurrence-free survival rate of patients underwent wide-local excision (WLE) was 97.1%. Patients underwent WLE exhibited a significantly decreased recurrence rate relative to patients treated through local excision (2.9% vs 37.7%; p < .001). Fibrosarcomatous DFSP had significantly higher rates of distant metastasis (66.7% [n = 4] vs 2.0% [n = 4]; p < .001) and long-term mortality (50.0% [n = 3] vs 1.5% [n = 3]; p < .001), compared with classical DFSP (C-DFSP). CONCLUSION: Wide-local excision is an effective means of reducing DFSP recurrence. Rates of metastasis are higher for FS-DFSP than for C-DFSP, with the former having significantly poorer outcomes.

Dermatofibrosarcoma Protuberans: The Current State of Multidisciplinary Management.

Dermatofibrosarcoma protuberans (DFSP) is a rare, infiltrative, soft tissue tumor. It has a propensity for deep invasion but a low risk for distant metastasis. The classic presentation is a slowly progressive, painless, and erythematous to purpuric patch on the trunk or arms. A deep, subcutaneous punch biopsy or incisional biopsy should be performed for diagnosis in all suspected cases; wide undermining of the skin is to be avoided for minimizing the risk of tumor seeding and for retaining the feasibility of histopathologic examination of re-excisions. Histopathologic distinction of DFSP from dermatofibroma requires immunohistochemical assessment for CD34, factor XIIIa, nestin, apolipoprotein D, and cathepsin K. Management of this cutaneous sarcoma involves a multidisciplinary oncologic approach. Surgical excision is usually the first step in management. DFSP has a high propensity for local recurrence, even when surgical margins are negative; therefore, radiation therapy or rarely systemic therapy is recommended, especially for locally advanced or metastatic cases. The indolent nature of DFSP requires lifelong surveillance for recurrence; however, most recurrences occur within 3 years of the primary excision. The median time for the development of a local recurrence is estimated to be 32 months. An emerging theragnostic transmembrane receptor target, folate hydrolase-1 (FOLH1; prostate-specific membrane antigen), has been expressed in benign dermatofibromas and in high-grade sarcomatous phenotypes. These findings suggest that DFSP may also express FOLH1, which could allow for surveillance with FOLH1 PET/CT and antibody-mediated brachytherapy.

[Dermatofibrosarcoma protuberans†: clinico-pathological aspects and management]. / Dermatofibrosarcoma protuberans†: aspects clinico-pathologiques et prise en charge.

The dermatofibrosarcoma protuberans (DFSP) is the most common form of low-grade cutaneous sarcoma; its infiltrating growth occurs by fingerlike projections, which explain the high rate of recurrence in case of inappropriate surgical procedure. Based on an extensive review of the existing literature, we propose here to discuss the actual criteria for early recognition, diagnosis and optimal take of care of DFSP.

Le dermatofibrosarcoma protuberans (DFSP) est la forme la plus fréquente de sarcome cutané. Son caractère infiltrant du fait de projections tumorales digitiformes caractéristiques expose à un taux de récidive locale très élevé en cas de prise en charge chirurgicale inappropriée. Sur la base d'une revue extensive de la littérature existante, nous proposons ici de revoir les critères diagnostiques du DFSP ainsi que la prise en charge recommandée.

Dermatofibrosarcoma protuberans: lo diagnosticamos en la edad pediátrica / Dermatofibrosarcoma protuberans: we diagnose it in the pediatric age

El dermatofibrosarcoma protuberans (DFSP) es un tumor cutáneo, de baja frecuencia, fibrohistiocítico, infiltrante, de lento crecimiento, de agresividad local, de malignidad intermedia; con escasas probabilidades de metástasis pero con alto índice de recurrencia local. El diagnóstico debe sospecharse y confirmarse con histología e inmunohistoquímica. El tratamiento de elección es con cirugía convencional y/o cirugía micrográfica de Mohs, con márgenes de 2-4 cm. Se considera que la prevalencia del DFSP en la edad pediátrica es baja, debido al escaso índice de sospecha. En el presente trabajo compartimos cinco casos de DFSP en la edad pediátrica, estudiados en el Hospital General de Niños Pedro de Elizalde. (AU)

Dermatofibrosarcoma protuberans (DFSP) is a cutaneous, low frequency, fibrohistiocytic, infiltrating, slow growing, local aggressiveness, intermediate malignancy tumor; with little chance of metastasis but with a high rate of local recurrence. The diagnosis should be suspected and confirmed with histology and immunohistochemistry. The treatment of choice is with conventional surgery and / or Mohs micrographic surgery, with margins of 2-4 cm. The prevalence of DFSP in pediatric age is considered to be low, due to the low index of suspicion. In this paper we share five cases of DFSP in the pediatric age, studied at the Pedro de Elizalde Children's General Hospital. (AU)

Dermatofibrosarcoma Protuberans.

Dermatofibrosarcoma protuberans (DFSP) is an uncommon dermal neoplasm that exhibits a high rate of local recurrence and infiltrative behavior, but has a low risk of metastasis. It arises as a slowly progressive, painless pink or violet plaque. Histologically, DFSP is characterized by a monomorphous spindle cell proliferation in a storiform pattern. The gold standard of treatment is surgical resection with negative margins. In cases where obtaining clear margins is not possible, radiation and systemic therapy with tyrosine kinase inhibitors, such as imatinib mesylate, has been shown to be effective.

Perspectives of Patients With Dermatofibrosarcoma Protuberans on Diagnostic Delays, Surgical Outcomes, and Nonprotuberance.

Importance: Dermatofibrosarcoma protuberans (DFSP) may have a deceptively benign clinical appearance, including a nonprotuberant presentation. Patients with DFSP often perceive misdiagnoses and delays in receiving a diagnosis. Use of existing, patient-designed Facebook patient support groups (FBSGs) to recruit large numbers of patients with rare diseases may be an effective novel research method. Objectives: To collaborate with patients with rare disease through social media and answer questions important to both patients and the medical field, including sources of diagnostic delay, risk of recurrence, and flat presentation of DFSP. Design, Setting, and Participants: A multiple-choice survey created by a team of medical practitioners and patients with DFSP was administered to 214 patients with DFSP or family members from international DFSP FBSGs and a nonprofit foundation patient database via Lime Survey from October 30 to November 20, 2015. The survey asked questions designed to determine risk of recurrence and metastasis, surgical outcomes, sources of diagnostic delay, symptoms of recurrence, number of recurrences, scar size, and number of clinicians seen before biopsy. Statistical analysis was performed from January 1, 2016, to April 1, 2019. Main Outcomes and Measures: The study goal was to collect at least 200 survey responses. Results: Of 214 survey respondents (169 females and 45 males; mean [SD] age, 40.7 [12.1] years; range, <1 to 72 years), 199 were patients with DFSP and 15 were family members. Delays occurred between the patient noticing the DFSP lesion and receiving a diagnosis of DFSP (median, 4 years; range, <1 to 42 years). Most patients (112 [52.3%]) believed that they received a misdiagnosis at some point: by dermatologists (35 of 107 [32.7%]), primary care clinicians (80 of 107 [74.8%]), or another type of physician (27 of 107 [25.2%]). The most frequent prebiopsy clinical suspicion included cyst (101 [47.2%]), lipoma (30 [14.0%]), and scar (17 [7.9%]). Many patients first noticed their DFSP as a flat plaque (87 of 194 [44.8%]). Of these lesions, 73.6% (64 of 87) became protuberant eventually. Surgical treatments included Mohs micrographic surgery (56 of 194 [28.9%]), wide local excision (122 of 194 [62.9%]), and conservative excision (16 of 194 [8.2%]). The reported rate of recurrence was 5.4% (3 of 56) for Mohs micrographic surgery, 7.4% (9 of 122) for wide local excision, and 37.5% (6 of 16) for conservative excision. The higher rate of recurrence for conservative excision was significant (P = .001); there was no significant difference in the rate of recurrence between Mohs micrographic surgery and wide local excision (P = .76). Conclusions and Relevance: This study reports what appears to be disease-relevant statistics from the largest survey of patients with DFSP to date. Because of the dissonance between the name of the neoplasm and its clinical presentation, the alternative term dermatofibrosarcoma, often protuberant is proposed. This study suggests that FBSGs are useful tools in medical research, providing rapid access to large numbers of patients with rare diseases and enabling synergistic collaborations between patients and medical researchers.

[Outcome of locally advanced Darier and Ferrand dermatofibrosarcoma: about a case and literature review]. / Une réponse complète d'un dermatofibrosarcome de Darrier et Ferrand localement avancé: à propos d'un cas et revue de la littérature.

Darier and Ferrand dermatofibrosarcoma (DFS) is a rare skin tumor characterized by its local aggressiveness and a high risk of recurrences. Prognosis depends essentially on the quality of treatment. Complete response in Darier and Ferrand dermatofibrosarcoma with healthy margins, initially judged inoperable after 1 year of neoadjuvant imatinib-based treatment, has been rarely described in literature. We here report the case of a young female patient treated in the Department of Medical Oncology in FES for locally advanced DFS with complete response, in order to assess the role of imatinib and of targeted therapies in the treatment of DFS.

S1 guidelines for dermatofibrosarcoma protuberans (DFSP) - update 2018.

While dermatofibrosarcoma protuberans (DFSP) is a rare cancer entity overall, it is nevertheless the most common type of cutaneous sarcoma. The tumor is of fibroblastic origin and characterized by slow, undermining and locally destructive growth. Metastatic spread is very rare. Given its nonspecific clinical appearance, diagnosis is frequently delayed. Biopsy and subsequent histopathology are key diagnostic tools. Standard treatment for primary tumors consists of complete excision with surgical margins of 1 to 2 cm. Smaller margins are associated with high local recurrence rates. Inoperable and metastatic DFSP may be treated with radiation therapy. Approximately 80-90 % of DFSP lesions harbor a fusion gene that results in continuous activation of the PDGF-ß signaling pathway. Consequently, molecular targeted therapy inhibiting PDGF-ß is an effective option for advanced (inoperable) and metastatic DFSP. The first agent to be approved for systemic treatment of DFSP is the multikinase inhibitor imatinib, showing objective response rates of about 50 % in clinical trials.

Dermatofibrosarcoma protuberans with fibrosarcomatous transformation: our experience, molecular evaluation of selected cases, and short literature review.

Dermatofibrosarcoma protuberans with fibrosarcomatous transformation (DFSP-FS) is a higher grade tumor arising from dermatofibrosarcoma protuberans (DFSP). Recent literature highlights its impact on recurrence rates, metastatic rates, and survival. In this article, we aim to describe our experience with 13 cases of DFSP-FS in terms of pathologic findings, molecular alterations, clinical outcomes, management, and also perform a short recent literature review.

Current Update on the Molecular Biology of Cutaneous Sarcoma: Dermatofibrosarcoma Protuberans.

OPINION STATEMENT: Cutaneous sarcoma is a group of malignant mesenchymal tumors primarily involving the dermis, and it is characterized by extreme clinicopathological heterogeneity. Although its occurrence rate is rare, dermatofibrosarcoma protuberans (DFSP) is one of the most common types of dermal sarcoma. DFSP grows slowly and tends to relapse locally after inadequate resection. There are various histological variants of DFSP tumors and it often mimics benign lesions such as dermatofibroma and scar, which make accurate diagnosis difficult and delayed, and some cases progress to the stage where the tumor is unresectable. Recent advancements in cancer genetics and molecular biology methods have elucidated the COL1A1-PDGFB fusion gene, some novel fusion gene variants and pathways related to DFSP pathogenesis that have resulted in the evolution of cutaneous sarcoma diagnosis and treatment. For example, some clinical studies have confirmed the efficacy of imatinib methylate, an αPDGFR-targeted therapy for unresectable or metastatic DFSP. The present review summarizes recent updates in DFSP research, diagnostics, and treatment.

Giant Dermatofibrosarcoma Protuberans With Bilateral Orbital Involvement.

Dermatofibroma sarcoma protuberans (DFSP) is a rare, locally aggressive soft tissue sarcoma with a tendency for recurrence after excision. Although reports of unilateral orbital and bilateral eyelid disease exist, there have been no prior reports of DFSP with bilateral orbital involvement and no previously described cases of DFSP associated with transient optic neuropathy. The authors present a case report of a 34-year-old woman with a giant scalp DFSP involving the bilateral orbits. Despite radical resection with 5 cm margins where possible, multiple positive margins remained including deep positive margins at the bilateral superomedial retroseptal soft tissue. The patient completed adjuvant radiation for surgically unresectable disease. This case highlights the challenge of achieving local control given the disease extent and infiltration of the bilateral eyelids and orbits. This is the first reported case of DFSP with bilateral orbital involvement and associated transient optic neuropathy.

[Perianal dermatofibrosarcoma protuberans: a case report, review and update]. / Dermatofibrosarcoma protuberans en región perianal: estudio de un caso, revisión y actualización.

Dermatofibrosarcoma protuberans is a low-grade sarcoma typically originating in the dermis but with local invasion of subcutaneous cell and muscle tissue. We report a case of perianal dermatofibrosarcoma protuberans in a 41-year-old male complaining of anal pain and constipation. To date, only two cases of perianal dermatofibrosarcoma protuberans have been reported. The unusual location hinders surgical treatment. The characteristic translocation t(17;22)(q22;q13) leading to the formation of COL1A1/PDGFß fusion transcripts is not only of diagnostic value but also enables an alternative imatinib-based therapy in inoperable or metastatic cases. The pertinent literature is reviewed.