Cutaneous Sarcoma Research Articles (Page 1)

Clinicopathologic features and treatment outcomes of dermatofibrosarcoma protuberans: a 25-year retrospective study.

Bednar’s tumor is a rare pigmented variant of dermatofibrosarcoma protuberans (DFSP)—a cutaneous sarcoma of low to intermediate malignancy, characterized by a tendency for local recurrence. Histologically, it is defined by the presence of spindle-shaped cells arranged in a storiform pattern and melanin-containing dendritic cells. Clinically, the lesions often resemble melanoma or other pigmented dermal tumors. We present the case of a 66-year-old male with a long-standing, asymptomatic pigmented lesion in the right subclavicular region. Histopathological examination confirmed the diagnosis of Bednar’s tumor based on its characteristic morphology and immunohistochemical profile: diffuse CD34 expression in spindle cells and S-100 positivity in melanin-laden components. Radical surgical excision with a 2 cm margin was performed. Follow-up over a two-year period revealed no evidence of recurrence or metastasis, as confirmed by PET/CT. This case highlights the importance of early diagnosis, immunohistochemical distinction from melanoma, and the need for a multidisciplinary approach in managing rare cutaneous sarcomas with atypical presentation.

Cutaneous leiomyosarcoma is a rare, malignant tumor that arises from smooth muscle cells, accounting for less than 3% of all cutaneous sarcomas. Our case report details a 63-year-old male patient who presented with a rapidly growing, painful nodule in the popliteal region. The patient underwent initial surgical excision in September 2021, followed by three subsequent resections until March 2022 due to local recurrence. Histopathological analysis of all specimens revealed a dermal neoplasm composed of spindle cells arranged in intersecting fascicles with storiform patterns. The immunohistochemistry profile showed strong positivity for the markers SMA and desmin, confirming the diagnosis. Despite early interventions, the deep surgical margins were positive, and further surgeries were required until tumor-free margins were achieved. This case emphasizes the morphological characteristics, clinical behavior, and therapeutic challenges in managing cutaneous leiomyosarcoma. A favorable prognosis is achieved with long-term follow-up and a multidisciplinary approach.

Dermatofibrosarcoma protuberans is the most common type of cutaneous sarcoma in children. We performed a single-center retrospective chart review describing the clinical characteristics and treatment outcomes of patients < 18 years old with a histologically confirmed diagnosis of DFSP. Fifteen patients were included; 60% (n = 9) were treated with Mohs micrographic surgery, 40% (n = 6) with wide local excision, and the average wound size was 60.8 cm2 (SD 47.5) and 77.4 cm2 (SD 64.9), respectively, with no recurrence or metastases noted in either group. Our study suggests that both types of surgery may have comparable results when their indications are performed after a multidisciplinary evaluation.

Dermato fibrosarcoma protuberans presents challenges in diagnosis and treatment, especially in children. Awareness of its aggressive local recurrence and its potential for multifocal presentation is crucial. Wide surgical resection with adequate margins remains the basis of management, in association with regular follow-up of affected patients. Dermatofibrosarcoma protuberans (DFSP) is a rare, locally aggressive cutaneous sarcoma, particularly uncommon in children. We report the case of a 13-year-old boy who initially presented with a firm mass on the left foot, later diagnosed as DFSP following histological and immunohistochemical analysis. The tumor was surgically excised with a wide margin, and a skin graft was used for coverage. Despite an initial favorable outcome, a new DFSP lesion developed at the proximal left thigh 1 year later, requiring further wide surgical excision and coverage with a tensor fascia lata flap. Both sites remained free of recurrence at one-year follow-up. This case underscores the importance of long-term vigilance in managing DFSP due to the potential risk of recurrence and multifocal involvement.

Dermatofibrosarcoma protuberans (DFSP) is a rare, locally invasive cutaneous sarcoma with a high propensity for recurrence, even following complete surgical excision. DFSP exhibits a low metastatic potential and is characterized by a distinctive honeycomb-like architecture composed of uniformly arranged spindle cells that frequently show CD34 immunostaining. Common surgical approaches include wide local excision (WLE), Mohs micrographic surgery (MMS), and, in severe cases, amputation.This literature review explores the impact of the surgical incision site on DFSP recurrence, placing particular emphasis on anatomically challenging regions, such as the head and neck, where achieving tumor-free margins is often difficult due to complex structures and limited tissue for resection. Our primary hypothesis is that DFSP cases arising in these intricate anatomical areas exhibit a higher recurrence risk compared to those on the trunk or extremities, where broader margins are more feasible. To investigate this hypothesis, data from a range of peer-reviewed studies and case reports were analyzed, including diverse patient populations from international sources, institutional case series, and large-scale database analyses, such as the Surveillance, Epidemiology, and End Results (SEER) Program. We evaluated recurrence rates, the adequacy of surgical margins, and anatomical influences across these studies while also focusing on histopathological findings like the presence of fibrosarcomatous (FS) variants, which are known to correlate with aggressive behavior and recurrence. We also reviewed emerging targeted therapies, particularly imatinib, as promising options for managing cases of unresectable or recurrent DFSP, thereby expanding therapeutic choices for clinicians when surgery alone proves inadequate.Our findings suggest a marked increase in recurrence risk for DFSP cases located in the head and neck region, attributed to limitations in achieving wide excision margins in these areas. This review underscores the importance of detailed preoperative planning, precise excision strategies, and individualized approaches based on tumor location to enhance surgical outcomes. Long-term surveillance remains crucial in DFSP management, particularly in high-risk locations, and continued research into targeted therapies offers hope for reducing recurrence rates and improving the quality of life for affected patients.

Kaposi's sarcoma is an angioproliferative disease of endothelial origin associated with human herpes virus-8 (HHV-8), or Kaposi's sarcoma herpesvirus. The disease was first described in 1872 by Moritz Kaposi as a pigmented cutaneous sarcoma localized on the lower extremities. The disease is considered quite rare, but at present there is an increase in the incidence worldwide, due to which there is a growing interest in this problem. Today, it remains the leading skin pathology among HIV-positive patients, occurring in 20%. However, the assessment of the pathological process can be difficult, and the diagnosis may not be made at all, due to atypical clinical manifestations (especially in HIV-negative patients), so the problem of Kaposi's sarcoma diagnostics remains relevant for doctors of any specialty, especially dermatovenerologists and oncologists. Kaposi's sarcoma can affect almost any organ, including the skin. The most common localization is on the skin of the extremities and face. Clinical manifestations are rashes in the form of spots, nodules, plaques, nodes. Kaposi's sarcoma is classified according to clinical and epidemiological forms: classical, endemic, epidemic and iatrogenic. Recently, a fifth form has been described, called non-epidemic Kaposi's sarcoma, which is observed in HIV-negative men who have sex with other men. The persistence of HHV-8 alone in the human body is not sufficient for Kaposi's sarcoma to occur, as the development of the disease is dependent on immunosuppressive conditions such as HIV infection, cytostatic drugs, and chronic systemic inflammatory diseases (e.g., rheumatoid arthritis). The interaction between human immune dysfunction and the local inflammatory response to herpesvirus creates a favourable environment for the onset and progression of the disease. These clinical cases demonstrate an atypical clinical course of Kaposi's sarcoma of the skin with the absence of HIV-1, HIV-2 and HHV-8 in the blood of the presented patients.

Background: Dermatofibrosarcoma protuberans (DFSP) is a rare cutaneous sarcoma with a propensity for local recurrence but a low risk of distant metastasis. Fibrosarcomatous transformation (FS-DFSP) is a rare but aggressive variant associated with increased metastatic potential. Case presentation: We present the case of a 39-year-old male with recurrent DFSP involving the scalp, mandible, and humerus, complicated by fibrosarcomatous transformation and distant metastases to the lungs and bones. The patient underwent multiple excisions, radiation therapy, and systemic treatments including chemotherapy and imatinib, but ultimately experienced disease progression. Conclusion: This case highlights the challenges in managing recurrent DFSP with fibrosarcomatous transformation. The rarity of this entity necessitates a high index of suspicion for early diagnosis and aggressive multidisciplinary management to improve patient outcomes. Further research is needed to identify effective treatment strategies for this aggressive variant of DFSP.

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.

(1) Background: Rare skin cancers include epithelial, neuroendocrine, and hematopoietic neoplasias as well as cutaneous sarcomas. Ultraviolet (UV) radiation and sunburns are important drivers for the incidence of certain cutaneous sarcomas; however, the pathogenetic role of UV light is less clear in rare skin cancers compared to keratinocyte cancer and melanoma. In this study, we compared the degree of actinic elastosis (AE) as a surrogate for lifetime UV exposure among selected rare skin cancers (atypical fibroxanthoma [AFX], pleomorphic dermal sarcoma [PDS], dermatofibrosarcoma protuberans [DFSP], Kaposi sarcoma [KS], Merkel cell carcinoma [MCC], and leiomyosarcoma [LMS]) while taking into account relevant clinical variables (age, sex, and body site). (2) Methods: We newly established a semi-quantitative score for the degree of AE ranging from 0 = none to 3 = total loss of elastic fibers (basophilic degeneration) and multiplied it by the perilesional vertical extent (depth), measured histometrically (tumor-associated elastosis grade (TEG)). We matched the TEG of n = 210 rare skin cancers from 210 patients with their clinical variables. (3) Results: TEG values were correlated with age and whether tumors arose on UV-exposed body sites. TEG values were significantly higher in AFX and PDS cases compared to all other analyzed rare skin cancer types. As expected, TEG values were low in DFSP and KS, while MCC cases exhibited intermediate TEG values. (4) Conclusions: High cumulative UV exposure is more strongly associated with AFX/PDS and MCC than with other rare skin cancers. These important results expand the available data associated with rare skin cancers while also offering insight into the value of differentiating among these tumor types based on their relationship with sun exposure, potentially informing preventative, diagnostic and/or therapeutic approaches.

Dermatofibrosarcoma protuberans (DFSP) is a cutaneous sarcoma with an infiltrative growth pattern that makes it challenging to clear margins. High quality data regarding DFSP natural history, management, and outcomes are limited. Data were retrospectively collected for adult DFSP patients who underwent resection at 10 institutions in eight countries. Demographics, tumor characteristics, treatment strategies, and outcomes were analyzed. Analysis included 347 patients consisting of young (median, 42 years), White (76.2%), males (54.2%) with truncal lesions (57.3%). The majority (76.8%) were symptomatic at presentation. Preoperative imaging was used in 55.9% of cases. Diagnosis was established with excisional biopsy in 50.9% versus incisional biopsy in 25.0% of cases. Despite planned margins of >1.0 cm in 67.4% of cases, only 69.0% of patients achieved R0 resection. Twenty-two percent of patients underwent at least one re-excision. R0 resection was achieved at a second procedure in 80.2% and a third procedure in 86.2%. Ultimately, R0 resection was feasible in 89.5% of all patients. Fibrosarcomatous transformation (FST) was observed in 12.6%. In total, 6.6% (N=23) recurred (17 local, six distant). Of the six distant recurrences, 50.0% had FST. With a median follow-up of 47.0 months, disease-specific survival rate was 98.8%. In multivariable analysis, R0 margins at index resection were associated with wider circumferential margins and non-FST histology. In this international, multicenter collaborative, DFSP practice patterns were heterogeneous but achieved favorable recurrence rates and survival. Multiple excisions to clear margins remain commonplace and can inform future efforts to optimize margin selection.

Darier Ferrand's dermato fibrosarcoma protruding is the most common tumor of cutaneous sarcomas, recognized by its high potential for aggressiveness and local recurrences after surgery of up to 40%. The location of the DFS on the breast has been described as extremely rare. Histologically consisting of bundles of spindle cells arranged in a storiform pattern, but due to the immunoreactivity of CD34 in DFSP, its presentation can be confused with other malignancies or even benign lesions. The objective of this observation is to describe the anamnestic, clinical, histological, therapeutic and evolutionary aspects of a DFS located on the infero-outer quadrant of the left breast in a 38-year-old patient compared to the data in the literature. Our patient had consulted for a skin mass located on the infero-external quadrant of the left breast, with irregular surface, with multiple protruding and exophytic nodular lesions evolving for several years, without ulcerations, pain and no axillary lymphadenopathy. We find in his history a notion of chest trauma. Wide and deep surgical excision with a margin of 5cm in healthy skin was done and histopathological examination of the operative specimen confirmed the diagnosis of DFS. Adjuvant radiotherapy 60Gray at a rate of 2Gray per fraction 5 days per week was administered. This reputedly rare location overlaps in several aspects (anamnestic, clinical, epidemiological, evolutionary and therapeutic) with data from the literature. Keywords: Dermatofibrosrcoma, Darier and Ferrand, Cutaneous sarcomas, Recurrence.

Abstract Cutaneous sarcomas comprise 5% of skin cancers yet carry great morbidity and mortality. They include atypical fibroxanthoma (AFX), pleomorphic dermal sarcoma (PDS), leiomyosarcoma (LMS), dermatofibrosarcoma protuberans (DFSP) and angiosarcoma (AS) (Stoneham S, Hunter A, Raahimi M et al. Cutaneous sarcoma: a review and practical approach to management. Clin Exp Dermatol 2023; 48: 866–72). Standardized agreed national guidelines for the management of these rare tumours are lacking, and we rely on guidance from sarcoma specialists (Dangoor A, Seddon B, Gerrand C et al. UK guidelines for the management of soft tissue sarcomas. Clin Sarcoma Res 2016; 6: 20). However, these tumours are lower grade, and do not carry the same local and metastatic recurrence risk as noncutaneous sarcomas. The aim of this study at a tertiary UK centre was to review the treatment and follow-up outcomes of patients with sarcoma managed locally. All patients with biopsy-proven cutaneous sarcomas discussed at our skin cancer multidisciplinary team (MDT) from March 2020 to January 2024 were retrospectively reviewed. Patient demographics, and histology were gathered along with the treatments offered, recurrence and follow-up outcome. All patients were restaged using the American Joint Committee on Cancer soft tissue sarcoma criteria. In total 40 patients met the criteria; their mean age at diagnosis was 70 years (range 24–91) and 25% were immunosuppressed. The cohort was followed up for an average of 11.3 weeks (range 1–36). The diagnoses included PDS (35%), AFX (20%), LMS (20%), DFSP (15%) and AS (5%); all but one had T1 or T2 disease. Overall, 97% of patients received surgery first line, with a clearance rate of 85% (29 of 34). Two patients had recurrence: one with PDS, requiring further surgery, and one with AS, who was managed at a sarcoma unit. There were no metastases reported or deaths due to disease. Most patients (80%) remain in clinical remission. Appropriate imaging and follow-up recommendations were made in most cases, according to their diagnosis. In summary, many of the patients with cutaneous sarcoma in the study had superficial disease. Despite our conservative surgical margins offered and a short duration of follow-up, we observed a 5% recurrence rate with no metastases. This study highlights the importance of an MDT approach to cutaneous sarcomas, which helps draw expertise from different specialties. Our lower recurrence rate and metastases compared with literature suggests that patients with cutaneous sarcoma could be safely managed in local skin cancer MDTs. We propose national guidance to help similar skin cancer MDTs and clinicians to standardize and reduce variation in care, as well as to provide an evidence base on which to recommend monitoring of this rare group of tumours.

2506 Background: The benefit of immune checkpoint inhibition is limited to 20-40% of patients. Moreover, acquired resistance often arises. Also, certain tumor types like breast are more CI-refractory. Therefore, the focus is on new combination strategies to increase clinical benefit. This multicenter phase 2 trial evaluated AdAPT-001, an oncolytic adenovirus armed with a “TGF-β trap” that neutralizes the immunosuppressive cytokine, TGF-β, +/- a checkpoint inhibitor (CI) in resistant patients some of whom previously failed a CI. Methods: Eligible patients with refractory tumors, many of them sarcomas, received 1 or more intratumoral injections of AdAPT-001 at dose level 1 x 1012 viral particles every 2 weeks +/- a CI at Investigator discretion. The CI was administered every 2nd-3rd week. Adverse events were recorded and managed. The primary endpoints of this combination therapy were objective response rate (ORR) and progression free survival (PFS). Results: 36 patients (22 males and 14 females) enrolled with a median age of 60.8 years (range 23-86) from Feb 2023-Dec 2023. 24/36 enrolled patients received AdAPT-001 with a CI and 12 patients received AdAPT-001 single agent. The most common treatment related adverse events (TRAE) were transient flu-like symptoms (fever, chills, vomiting, fatigue) 10/36 (27.7%), and injection related events 10/36 (27.7%). Notably, only 1 patient, 1/24 (4.0%), developed an immune-related AE, hypophysitis. All other related AEs were Grade 1/2. 33/36 patients were evaluable for response analysis; monotherapy produced 2/9 (22.2%) favorable responses (complete response (CR): eccrine carcinoma; confirmed partial response (cPR): acral melanoma); and produced a 4/9 (44.4%) clinical benefit rate defined as CR/PR/SD greater than 12 weeks. The combination of AdAPT-001 plus a CI produced 7/24 (29.1%) favorable responses (1 clinical CR: angiosarcoma; 6 cPRs: 3 sarcoma, 1 triple negative breast cancer, 1 head and neck cancer, 1 squamous cell carcinoma; and a 15/24 (62.5%) clinical benefit rate defined as CR/PR/SD greater than 12 weeks. 21/33 failed a CI before enrollment (16/24 before AdAPT-001 + CI). The PFS was 3.5 months (95% CI: 1.8-NA months). Conclusions: Combination therapy of AdAPT-001 with a CI is well tolerated and demonstrates a high ORR including 1 patient with a CR per RECIST 1.1, 1 patient with a clinical CR and 6 PRs. In several cutaneous sarcomas treated with AdAPT-001 plus a CI, radiologic SD belied how much better they looked visually--not only smaller, but less irregular and more circumscribed. Clinical trial information: NCT04673942 . [Table: see text]

Sarcomas are rare malignant neoplasms originating from mesenchymal layer, which comprises of less than 1% of adult malignancies. Among all the sarcomas, cutaneous sarcomas are found rarely. Surgery remains the main stay of treatment for majority of sarcomas. Awareness about such clinical entity and feasibility of diagnostic accurate histological type is important for managing these patients in a better way. Long term follow-up of patient is required to detect early recurrence. Here, we report a case of spindle cell sarcoma developed as a groin swelling in a 40-year-old male patient at rural tertiary care center in North Gujarat.

Dermatofibrosarcoma protuberans (DFSP) stands as the most prevalent cutaneous sarcoma, marked by slow growth and a protuberant papulonodular appearance. Although rare, its impact is significant, necessitating a comprehensive understanding of its characteristics and optimal management. DFSP typically affects adults, though age variability exists, presenting diagnostic challenges. Histological evaluation, often utilizing CD34 immunohistochemical staining, is crucial for accurate diagnosis. The primary treatment modality remains complete surgical excision, emphasizing the importance of generous margins. Imatinib emerges as a valuable therapeutic option for unresectable or metastatic cases. Complementary approaches such as adjuvant radiation therapy and Mohs surgery enhance the treatment armamentarium, allowing for a tailored, multidisciplinary strategy. Regular follow-up is essential for monitoring and addressing potential complications. While local recurrence is a concern, DFSP generally carries a favorable prognosis, especially with early detection and appropriate intervention. Ongoing research continues to refine treatment paradigms, promising improved outcomes for individuals affected by this distinctive cutaneous sarcoma.

Melanoma, the most common cutaneous sarcoma, poses a significant health threat due to its metastatic potential. This review explores the causes, risk factors, and associations of melanoma, emphasizing its diverse presentations and diagnostic considerations. UV light exposure, genetic predisposition, and somatic mutations contribute to melanoma development. The disease affects individuals of all races, with varied clinical manifestations. Prevention strategies involve sun protection behaviors, and early detection through surveillance is crucial for optimal outcomes. Treatment modalities, including surgical excision and adjuvant therapies, are contingent on disease stage. Ongoing monitoring and counseling play key roles in comprehensive care. This review aims to enhance understanding of melanoma, guiding efforts toward prevention, early detection, and effective management.

Dermatofibrosarcoma Protuberans (DFSP) is a rare cutaneous sarcoma with an overall incidence of 4.1 cases per million/year according to the largest population-based study of DFSP. This cutaneous sarcoma has an overall ten-year survival of 99.1% [1].

Dermatofibrosarcoma protuberans (DFSP) is a rare and indolent cutaneous sarcoma, with the risk of aggressive fibro-sarcomatous transformation. Limited effective options are available for un-resectable or metastatic DFSP beyond targeting the oncogenic PDGF pathway with imatinib therapy. We established a patient-derived xenograft (PDX) and cell line model (designated MDFSP-S1) of imatinib-resistant DFSP with fibro-sarcomatous transformation. Whole genome sequencing identified high-level amplification at chromosomes 17 and 22, whilst homozygous deep deletion was demonstrated at chromosome 9 (CDKN2A, CDKN2B, MTAP). RNA sequencing followed by Sanger sequencing confirmed the pathognomonic COL1A1-PDGFB t (17;22) rearrangement in the original tumour, PDX and cell line model. Immunohistochemistry profiles of the PDX model were consistent with the patient's tumour sample (CD34 + /MIB1 + /SOX10- ). Gene set enrichment analysis highlighted top-scoring Hallmark gene sets in several oncogenic signalling pathways, including potentially targetable MTORC1 signalling and angiogenesis pathways. Antiangiogenic agents (sunitinib, regorafenib, pazopanib, axitinib) and the third-generation irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor osimertinib exhibited modest anti-proliferative activity in the cell line, with IC50 values between 1 and 10µM at 72h. No significant activity was observed with imatinib, palbociclib, everolimus, olaparib, gefitinib and erlotinib (IC50 all > 10µM). In conclusion, we established MDFSP-S1, a new PDX and cell line model of imatinib-resistant DFSP with fibro-sarcomatous transformation.

Dermatofibrosarcoma protuberans (DFSP) is a rare cutaneous sarcoma. Limited population-based epidemiological studies on DFSP have been conducted. We aimed to estimate the incidence and disease burden of DFSP in China. We conducted a cross-sectional study using data from the national databases of the Urban Basic Medical Insurance scheme. Cases were identified by ICD code and Chinese language diagnostic terms. National incidence from 2014 to 2016 was estimated by gender and age, and associated medical costs were calculated. A total of 175 patients were confirmed with DFSP from 2014 to 2016. Crude incidence varied from 0.353 per 100,000 (95%CI: 0.203-0.503) in 2014 to 0.367 per 100,000 (95%CI: 0.279-0.455) in 2016. Incidence was higher in males than in females. The first incidence peak was observed between the ages of 20 and 39 years and the highest incidence rates were in those aged over 60 years. Average medical costs of DFSP were higher than the per capita disposable income of residents. Incidence of DFSP in mainland urban China is lower than in most developed countries and has remained relatively stable from 2014 to 2016. Further research is expected to clarify the potential pathophysiological mechanisms of DFSP.