Dermatofibrosarcoma Research Articles

Dermatofibrosarcoma Protuberans With Sarcomatous Transformation Treated With Mohs Surgery Leads to Limb-Sparing Durable Remission.

Dermatofibrosarcoma Protuberans With Sarcomatous Transformation Treated With Mohs Surgery Leads to Limb-Sparing Durable Remission.

Achieving Adherence With NCCN Guidelines for Nonmelanoma Skin Cancer Regarding Peripheral and Deep En Face Margin Assessment (PDEMA)

Peripheral and deep en face margin assessment (PDEMA), formerly termed by NCCN as complete circumferential peripheral and deep margin assessment (CCPDMA), has the advantages of histologic visualization of the entire marginal surface, highly accurate resection of involved tissue, and sparing of uninvolved tissue. Owing to its highest reported cure rates, PDEMA is the NCCN-preferred treatment for dermatofibrosarcoma protuberans, high-risk basal cell carcinoma, and very-high-risk cutaneous squamous cell carcinoma. In the United States, Mohs micrographic surgery (Mohs) is the most common method of PDEMA. In Germany and some other countries, non-Mohs methods of PDEMA referred to as the Tubingen torte and muffin techniques are more widely used. The Tubingen methods of PDEMA require close communication between surgeon and pathologist. This article describes the background of both Mohs and Tubingen PDEMA, reviews what constitutes PDEMA, and provides a protocol for Tubingen PDEMA detailing critical components in a stepwise fashion using illustrative photos and diagrams. We hope to broaden understanding of the NCCN Guidelines and their rationale, align practice, and optimize patient outcomes.

Congenital Dermatofibrosarcoma Presenting as an Atrophic Plaque

Dermatofibrosarcoma protuberans (DFSP) is a rare sarcoma that most commonly occurs on the trunk of adult patients. However, DFSP can present congenitally, and this rarity may lead to misdiagnosis or late diagnosis. The authors present a case of a congenital DFSP that was not diagnosed until the patient was 17 years old. Her tumour was successfully treated with Mohs micrographic surgery. It is important to have DFSP on the differential for atrophic plaques or violaceous to red-brown nodules, even at a young age.

Case of recurrent Dermatofibrosarcoma Protuberans- factors and pitfalls

Case of recurrent Dermatofibrosarcoma Protuberans- factors and pitfalls

Sarcomas of the Head and Neck Region

Introduction: Sarcomas are relatively rare malignant tumors of mesenchymal origin, representing only about 1% of tumors in the head and neck region. Materials and Methods: A retrospective study involved patients with sarcomas of the head and neck region who were diagnosed and treated over a 5-year period. Results: Nine patients were included, 4 men and 5 women. The mean age of the patients was 51 years. Eight patients had soft tissue sarcomas, and 1 patient had osteosarcoma. The most common histologic types were dermatofibrosarcoma protuberans and angiosarcoma. Tumors presented predominantly with local symptomatology. All patients were treated only by surgical excision. No distant or regional metastases were found in any patient. Complete surgical excision was achieved in all cases, except in patients with chondrosarcoma of the nose and sinuses, who died due to local progression in the second year of follow-up. Other patients were disease-free during the observed period; a patient with osteosarcoma died in the fourth year of follow-up without recurrence of the malignant disease. Conclusion: Large prospective and multicenter studies are necessary to provide relevant data on the distribution of different types of sarcoma in the head and neck region, their clinical behavior and response to therapeutic modalities, as well as on recurrence, presence of metastases, and survival.

PRAME expression in fibrosarcomatous dermatofibrosarcoma protuberans

PRAME (PReferentially expressed Antigen in MElanoma) was first identified as a malignant melanoma-specific antigen. Recently, a few cases of fibrosarcomatous dermatofibrosarcoma protuberans (FS-DFSP) were shown to have positivity for PRAME, while conventional dermatofibrosarcoma protuberans (C-DFSP) was negative. Because PRAME may be of diagnostic utility in FS-DFSP and is raising expectations as a new immunotherapy target, we examined the positivity of PRAME in FS-DFSP. Twenty-one cases of FS-DFSP and age/sex/location-matched cases of C-DFSP as a control group were examined by immunohistochemistry for CD34 and PRAME. The results were then evaluated by H-score, which was objectively and semi-quantitatively calculated using the open-source bioimaging analysis software QuPath. The results revealed that the PRAME H-score in FS-DFSP was significantly higher than that in C-DFSP (p = 0.0137). As for CD34, the H-score in FS-DFSP was significantly lower than that in C-DFSP (p < 0.001). Using these two immunohistochemical analyses in combination, the sensitivity and specificity for the diagnosis of FS-DFSP were 86% and 90%, respectively. Double staining of CD34 and PRAME revealed that PRAME-positive and CD34-positive areas did not overlap. This is the largest study to examine PRAME expression in FS-DFSP, and it confirmed the usefulness of PRAME in diagnosing this condition.

ALK-rearranged, CD34-positive spindle cell neoplasms resembling dermatofibrosarcoma protuberans: a study of seven cases.

The majority of dermatofibrosarcoma protuberans (DFSP) harbour PDGFB or PDGFD rearrangements. We encountered ALK expression/rearrangement in a PDGFB/D-negative CD34-positive spindle cell neoplasm with features similar to DFSP, prompting evaluation of ALK-rearrangements in DFSP and plaque-like CD34-positive dermal fibroma (P-LDF). We searched the archives of academic institutions for cases previously coded as DFSP and P-LDF. NGS-naïve or PDGFB-negative DFSP were screened for ALK (clone D5F3) expression by immunohistochemistry. NGS or ALK FISH was performed on ALK-positive cases. Methylome profiling studies were performed and compared with conventional DFSP. One case of "DFSP" and two "P-LDF" with ALK expression were identified from the archives, while four cases were detected prospectively. These seven cases (6F:1M; 8 months to 76 years) arose in the dermis of the arm (two), scalp, eyelid, thigh, abdomen, and shoulder and ranged from 0.4 to 4.2 cm. Tumours were composed of spindled cells and displayed a storiform growth pattern. Cytologic atypia was absent, and mitotic figures were scarce (0-2/10 HPFs, high power fields). The lesional cells were diffusely positive for CD34 and ALK and negative for S100 protein. By NGS (n = 5), ALK fusion partners included DCTN1 (2), PLEKHH2, and CLIP2 in DFSP-like cases and FLNA in P-LDF-like lesions. ALK FISH was positive in one (of two) cases previously labelled P-LDF. Methylome profiling of two (of three) ALK-rearranged DFSP-like tumours showed clustering with conventional DFSP in the UMAP dimension reduction plot. To date, no tumour has recurred (n = 2; 26, 27 months). We describe a cohort of novel ALK-rearranged tumours with morphologic features similar to DFSP.

Racial and Ethnic Differences in Patient Presentation and Treatments in Head and Neck Dermatofibrosarcoma Protuberans

AbstractHead and neck dermatofibrosarcoma protuberans (HNDFSP) is a rare neoplasm with a high rate of local infiltration and local recurrence but a low rate of distant metastasis. Given the limited literature on HNDFSP and existing studies pointing to possible racial and ethnic differences, further research is needed to understand important clinical correlates that may impact treatment and prognosis. The National Cancer Database (NCDB) was queried for all cases of HNDFSP diagnosed from 2004 to 2016. Demographic characteristics of the included patients were compared using chi-squared and t-tests. Kaplan-Meier and Cox multivariable regression analyses were performed to assess survival differences. Of the 778 included patients, 526 (67.6%) patients were white, 113 (14.5%) were black, 33 (4.2%) were Asian, 87 (11.2%) were Hispanic, and 19 (2.4%) were classified as Other. White patients presented at a significantly older age (43.8 years) than did black (38.9 years) and Hispanic patients (37.9 years) (p = 0.02). White patients with HNDFSP had significantly higher income status (p = 0.0001), were more likely to be insured (p = 0.0001), and were more likely to have a high school diploma (p = 0.0001). There were no significant racial differences in 5-year (96.1%) or 10-year (92.0%) overall survival. None of the variables yielded a statistically significant value in Cox analysis. Differences exist in HNDFSP presentation between racial groups. Specifically, differences in income, insurance status, education level, and age of presentation exist between these groups. Future studies focused on morbidity are needed to better understand the consequences of these difference on HNDFSP patients.

Dermatofibrosarcoma Protuberans MRI: A Preliminary Comparison of Different Sequences

The purpose of this study was to compare the image quality of different MRI sequences regarding the presentation of Dermatofibrosarcoma Protuberans (DFSP). We retrospectively collected MRI images of 40 patients who had been pathologically diagnosed with DFSP, including 21 primary tumors and 19 recurrent tumors. The image quality of different MRI sequences was assessed subjectively by two radiologists, taking into account the display of the lesions, artifacts, and distortions, as well as the overall impact of the image quality. Among the 40 cases, 22 cases involved the trunk, 14 cases involved the shoulders and limbs, 2 cases involved the head and neck, 1 case involved the breast, and 1 case involved the groin. In terms of image quality, fat suppression T2-weighted images were superior to T1-weighted images and T2-weighted images (P<0.05). The difference between fat suppression T2-weighted images and contrast-enhanced images was not significant (P>0.05). As far as lesion contrast is concerned, diffusion-weighted images, fat suppression T2-weighted images, and contrast-enhanced images did not differ significantly (P>0.05). On the DWI images, there were severe magnetic artifacts and deformations. Fat suppression T2-weighted images and enhanced sequences produce the highest quality images, while diffusion-weighted images provide the best lesion contrast.

Exploring the Uncommon: A Series on Dermatofibrosarcoma Protuberans with Rare Locations, Unusual Sites of Metastasis, and Their Close Mimics

Abstract Dermatofibrosarcoma protuberans (DFSP) is an uncommon, slowly growing soft-tissue tumor that involves the dermis, subcutaneous fat and very rarely involves, muscle and deep fascia. It is locally aggressive and an intermediate-grade fibroblastic neoplasm that rarely metastasizes. It is important to know about this entity as it is locally aggressive and has a higher rate of transformation into fibrosarcoma which has an aggressive growth pattern and frequently metastasizes. Apart from this, there are diagnostic challenges, especially in small biopsies, where they resemble other spindle cell neoplasms. This article reviews the clinical and histological features of DFSP as well as possible pitfalls in their diagnosis and how to resolve them. Diagnosed cases of DFSP were retrieved from pathology archives. Their locations and histopathological features along with Immunohistochemistry (IHC) features were reviewed. Our study identified 26 cases of DFSP for 5 years from January 2019 to January 2024 in a tertiary care hospital. The age of study subjects was in the range of 11–70 years. Male:female ratio was 1.30:1. The most common site was shoulder (n = 5). Immunohistochemistry (HC) was performed in cases with diagnostic dilemmas and cases of high-grade transformation. The aim of this study was to perform a retrospective analysis of histopathological features of DFSP to distinguish it from other mimics and emphasize its local aggressiveness, reoccurrence, and rare site of metastasis, especially in cases with fibrosarcomatous transformation. The careful histomorphological examination particularly in smaller biopsies can be challenging, especially in peripheral laboratories and in resource-limited settings.

Non-protuberant Lesions and Diagnostic Delays in Dermatofibrosarcoma Protuberans: A Single Institutional Retrospective Analysis.

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Accuracy of Preoperative Imaging in Assessing the Positivity of the Deep Periosteal Margin in Dermatofibrosarcoma Protuberans of the Scalp.

The locally aggressive nature and high recurrence rate of dermatofibrosarcoma protuberans (DFSP) make it challenging to manage, especially when present on the scalp, owing to its ability to invade the underlying periosteum, bone, dura, or brain. Preoperative imaging is used to plan resection, but the true correlation between periosteal or osseous changes on imaging and the presence of tumor within the periosteum is unclear. We present our institutional experience of managing DFSP of the scalp with emphasis on the imaging used. A retrospective review of 33 patients with DFSP of the scalp treated at a tertiary center was conducted. Data on demographics, tumor characteristics, preoperative imaging (magnetic resonance imaging or computed tomography), and surgical outcomes were analyzed. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of each imaging modality were calculated. Patients underwent surgical resection at a mean age of 37.11 years and had a median follow-up of 28.34 months. Preoperative imaging was available for 26 patients (CT only: 5, MRI only: 12, CT and MRI: 9). Calvarial abnormalities were seen in 3 patients. Treatment included Mohs surgery (66.7%) and wide local excision (33.3%). In 10 patients with positive periosteal margins, bone involvement was managed by burring (7) or craniectomy (3). The sensitivity and PPV of CT for periosteal margin positivity were 25% and 100%, and for MRI were 33% and 100%, respectively. The specificity and NPV were 100% and 50% for CT, and 100% and 66% for MRI. Preoperative CT and MRI have low sensitivity and NPV but high specificity and PPV in determining depth of involvement and are essential to guiding reconstruction in DFSP of the scalp.

Abstract B138: The association of neighborhood-level socioeconomic status and treatment outcomes in dermatofibrosarcoma protuberans: A United States cohort analysis

Abstract Dermatofibrosarcoma protuberans (DFSP) is a rare, locally aggressive soft tissue sarcoma predominantly affecting the dermis and subcutaneous fat. There has been a lack of research on the intersection of socioeconomic status (SES) and DFSP. Therefore, this study aims to investigate the impact of SES on DFSP outcomes, specifically with differing treatments, an area previously underexplored due to the disease’s rarity. Cases of malignant DFSP from 2006-2018 in the Surveillance, Epidemiology, and End Results Census Tract-level SES and Rurality Database were identified to conduct a retrospective cohort analysis. SES was categorized into 5 groups using the Yost Index, a composite census-tract level measure of SES which incorporates factors like household income, educational level, and home value. Multivariable Cox-proportional hazards regression was conducted to assess relationships of reported characteristics with overall survival. Multivariable logistic regression was used to assess for independent predictors of receipt of Mohs surgery. The associations were also stratified by race/ethnicity. Among the 4995 DFSP cases identified, patients were mostly female (53%), white (52%), and of highest SES (Yost Index Group 5, 29%). Most patients received surgical excision, including Mohs surgery, (93%; Mohs: 9.1%). Higher SES was associated with better overall survival compared to lower SES patients (highest vs lowest SES: hazard ratio [HR], 0.39; 95% confidence interval [CI], 0.26-0.58). Mohs surgery was also the only surgical intervention associated with better survival, compared to no surgery (HR, 0.40; 95% CI, 0.16-0.95). When stratified by race/ethnicity, the association of higher SES with better survival was present in both white (highest vs lowest SES: HR, 0.47; 95% CI, 0.24-0.90) and non-white patients (highest vs lowest SES: HR, 0.34; 95% CI, 0.20-0.58). Higher SES was associated with an increased likelihood of receiving Mohs (highest vs lowest SES: odds ratio [OR], 2.77; 95% CI, 1.80-4.25), and Black patients (23%) were less likely than white patients to receive Mohs (OR, 0.49; 95% CI, 0.33-0.72). When stratified by race/ethnicity, the association of higher SES with receipt of Mohs was present in white patients (highest vs lowest SES: OR, 5.44; 95% CI, 2.88-10.3), though it was not significant in non-white patients. This study demonstrates that higher SES and Mohs were associated with better overall survival for patients with DFSP. Higher SES also increased the likelihood of receiving Mohs, an optimal DFSP treatment. Our study emphasizes that patients with lower SES may have reduced access to more effective treatments like Mohs for DFSP, which may lead to poorer survival. This indicates a need for healthcare policies that address these disparities to improve treatment for patients of all socioeconomic statuses, including racial/ethnic minorities. *Both authors contributed equally Citation Format: Fatima N. Mirza, Megan Hoang, Hayley S Goldbach, Oliver J. Wisco, Tiffany J. Libby, Martin A. Weinstock, Abrar A. Qureshi, Eunyoung Cho. The association of neighborhood-level socioeconomic status and treatment outcomes in dermatofibrosarcoma protuberans: A United States cohort analysis [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B138.

Recurrent Dermatofibrosarcoma Protuberans with Fibrosarcomatous Transformation: A Case Report

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: An Updated Review of the Literature.

Dermatofibrosarcoma protuberans (DFSP) is a rare proliferative condition representing skin sarcomas which is known to locally recur yet very rarely metastasizes. Its genetic background is a reciprocal translocation t(17;22)(q22;q13) that produces COL1A1-PDGFB gene fusion. Complete resection is the primary treatment. The aim of this review is to outline the pathogenesis, diagnosis, and management of DFSP. A clear-cut distinction between low-to-moderate-grade DFSP with excellent prognosis and high-grade fibrosarcomatous DFSP with a much worse prognosis is underlined. Malignant transformation within DFSP (or high histologic grade), older age, being female, large primary tumor size (≥10 cm), narrow surgical margins of excision (<3 cm), surgical margin positivity for tumor cells, short time to recurrence, numerous recurrences, tumor that was recently rapidly enlarging, and presence of pain in the tumor have all been proposed as clinicopathological risk factors for recurrence and metastasis. A tendency for local growth and local relapses of well- and moderately differentiated DFSPs is an argument for their surgical excision, possibly combined with reconstructive surgery, even in patients of advanced age. Another main point of this review is that cases of DFSP with fibrosarcomatous transformation are a challenge and require careful medical attention. Both anatomopathological evaluation of the presence of lymphovascular space invasion and sentinel lymph node biopsy at DFSP surgery merit further study.

EP264 - Dermatofibrosarcoma protuberance of the perianal region

Abstract Introduction Dermatofibrosarcoma protuberans (DFSP) is a rare low-grade sarcoma affecting dermis and subcutaneous fat. Typically presents as slow-growing lump on the trunk, extremities or head and neck.(1) It can be locally aggressive with a high recurrence rate.(2) Only 6 reported cases of DFSP in peri-anal region. Case Description A 26-year-old male presented with slow-growing peri-anal lump for over a year with intermittent localised pain and episodes of bleeding. No other symptoms or trauma to peri-anal area noted. No relevant medical or surgical history. Examination revealed an irreducible two-by-five by one-centimetre semi-pedunculated perianal lump extending from the seven o’clock to eleven o’clock position. It was firm and tethered to the skin. Case Description Flexible sigmoidoscopy was normal. Excision biopsy histology reported diffuse infiltration of spindle cells with storiform pattern of growth without clear margins. Immunohistochemistry analysis expressed CD34 with minimal focal expression of SMA and variable Ki-67 proliferation indexed up to 15-20% in most active areas. SOX10, S100, desmin, factor XIIIA, MNF116 and CD31 were negative. Diagnosis was DFSP. Local lower gastrointestinal multi-disciplinary arranged urgent imaging and referral to tertiary centre. Magnetic resonance imaging of the pelvis identified no definite underlying localised restricted diffusion or solid enhancing nodule. Wide local excision at tertiary centre with histopathology confirmed clear margins. Conclusion Patient is under follow-up locally and at the tertiary. Urgency and a singular episode of stool incontinence was reported at two-weeks follow-up which subsequently normalised. He is currently under 3-6 monthly reviews with repeat MRI prior to next appointment. Patient has returned to normal activities.

SP9.10 - The Sarcoma Hub and Spoke Diagnostic Service Can be Safely and Effectively Rolled-Out and Continued

Abstract Aims To understand the safety and effectiveness of the newly established Sarcoma Hub and Spoke Service (SHSS) in detecting malignancies through assessment of the performance of one Spoke Service in triaging lesions of concern. Methods Patients referred to our Diagnostic Service on the 2 week-wait pathway (2WW) and have had their lesion(s) of interest removed between an 18-month period were identified from our Hospital Information System. Data was collected for post-op histology, suspicion of diagnosis in the pre-op MDT, compatibility between the two, and whether patient was cleared from suspicion of malignancy before removal of the lesion. Results 119 patients meeting the criteria were identified. 90 had been cleared of suspicion for malignancy prior to surgery. 83/90 of these had samples sent for histology, yielding 82 benign and 1 malignant (dermatofibrosarcoma protruberans) results. Of the 29 patients who had excision biopsy on the 2WW, 5/29 returned histology for risk of (e.g. possible sarcoma or atypical lipoma) or confirmed malignancies. 46/119 cases were discussed at our SHSS MDT and have both pre-op MDT diagnosis records and histology results; 37/46 of these were compatible – all correctly predicted benign pathologies. Where pre-op MDT diagnosis and histology were incompatible, 1/9 predicted benign diagnosis but returned malignant histology. Conclusion Our SHSS Diagnostic Service’s process of triaging lesions concerning for sarcoma, including our MDT and surgical excision biopsies, is accurate. Preliminary data shows that the Sarcoma Hub and Spoke Service is a safe way to aid in diagnosing or ruling out soft tissue sarcoma.

Growth Rate and Outcomes in Locally Recurrent Extremity and Truncal Soft Tissue Sarcoma.

Improved prognostic tools are needed for patients with locally recurrent extremity or truncal soft tissue sarcoma (STS). To examine the association between average local recurrence (LR) growth rate and outcomes following resection of locally recurrent extremity or truncal STS. This retrospective cohort study used a prospectively maintained database from a single high-volume tertiary sarcoma referral center in the US to identify patients 16 years of age or older who underwent repeat resection of a locally recurrent extremity or truncal STS between July 1, 1982, and December 31, 2021. Patients with atypical lipomatous tumors, desmoid tumors, dermatofibrosarcoma protuberans, angiosarcomas, and prior or synchronous distant recurrence were excluded. Data were analyzed from November 1, 2022, to June 17, 2024. Average LR growth rate, defined as the sum of recurrent tumor maximal diameters divided by the disease-free interval after index operation. The primary outcomes were cumulative incidences of disease-specific death (DSD), with death from other causes as a competing risk, and second LR, with death from any cause as a competing risk. The study cohort included 253 patients (median [IQR] age, 64 [51-73] years; 140 [55.3%] male). The 5-year cumulative incidence of DSD after repeat resection was 29%. Multivariable analysis indicated that LR growth rate (hazard ratio [HR], 1.12 [95% CI, 1.08-1.18]; P < .001), younger age (HR, 0.98 [95% CI, 0.97-0.99]; P = .002), R1 or R2 margins (HR, 1.71 [95% CI, 1.03-2.84]; P = .04), high LR grade (HR, 2.90 [95% CI, 1.17-7.20]; P = .02), and multifocality (HR, 2.92 [95% CI, 1.70-5.00]; P < .001) were independently associated with higher incidence of DSD. Using the minimum P value method, the optimal cutoff for growth rate was found to be 0.68 cm/mo. Patients with values above this cutoff had higher 5-year incidences of DSD following repeat resection (63% vs 19%; permutation test P < .001) and higher amputation rates (19% vs 7%; P = .008). Only R1 margins were independently associated with higher incidence of second LR (HR, 1.81 [95% CI, 1.19-2.78]; P = .006). In this cohort study of patients undergoing resection of a locally recurrent extremity or truncal STS, LR growth rate was independently associated with DSD. These findings suggest that patients with growth rates higher than 0.68 cm/mo who undergo LR resection may have high disease-specific mortality and amputation rates and should be considered for perioperative systemic therapy.

Increased frequency of CHEK2 germline pathogenic variants among individuals with dermatofibrosarcoma protuberans

PurposeTo identify candidate susceptibility genes for dermatofibrosarcoma protuberans (DFSP). MethodsAll individuals with DFSP from the International Sarcoma Kindred Study (n = 3767 individuals with sarcoma diagnoses from Australia, Europe, New Zealand, and United States) and cohorts that were not ascertained based on sarcoma status or other phenotypes (Geisinger MyCode, n = 170,503 individuals, United States; UK Biobank, n = 469,789 individuals, United Kingdom) were evaluated for germline pathogenic or likely pathogenic (P/LP) variants in 156 cancer genes. ResultsThere were 92 unrelated individuals with DFSP across the 3 cohorts. The mean age at diagnosis (standard deviation) in International Sarcoma Kindred Study, Geisinger, and UK Biobank was 40.8 (14.5), 50.3 (9.4), and 49.4 (13.2) years, respectively. Germline P/LP variants were most common in the CHEK2 gene (4/92 [4.3%]). CHEK2-related cases were often associated with early onset disease (age at diagnosis: 30-39 years) and were observed in all 3 cohorts. Among 640,292 individuals in Geisinger and UK Biobank who were not ascertained based on phenotype, there was a significantly increased frequency of CHEK2 P/LP variants among individuals with DFSP (n = 3/65 [4.6%]) od with those without (n = 6388/640,227 [1.0%]) (Fisher exact, P = .03). Additional genes with P/LP variation (1 case for each gene) included ACD, ERCC5, ERCC1, DOCK8, GBA1, ATM, MUTYH, TP53, RECQL4, and COL7A1. ConclusionThis study of multiple cohorts identifies CHEK2 as a candidate susceptibility gene for DFSP. Additional epidemiologic and functional studies are needed to further characterize this potential gene-tumor relationship.

53313 Factors associated with time to surgical treatment for dermatofibrosarcoma protuberans

53313 Factors associated with time to surgical treatment for dermatofibrosarcoma protuberans