An unusual presentation of dermatofibrosarcoma protuberans: A case of fibrosarcomatous dermatofibrosarcoma protuberans with pleomorphic angiectatic tumor-like changes.

Dermatofibrosarcoma protuberans (DFSP) is a locally aggressive superficial mesenchymal neoplasm characterized by monomorphic spindle-cell proliferation with a storiform pattern. It can demonstrate pigmentation, myxoid changes, myoid differentiation, plaque-like growth, and fibrosarcomatous features; its varied presentation often complicates diagnosis. We report an extremely rare case of fibrosarcomatous DFSP with features reminiscent of a pleomorphic hyalinizing angiectatic tumor (PHAT) in a 73-year-old male. The diagnosis was confirmed using a reverse transcription polymerase chain reaction. To the best of our knowledge, PHAT-like changes in DFPS have not been described so far. Therefore, this report provides a novel variant of DFSP and expands the differential diagnosis of DFSP and PHAT.

Review on the Role of Paraffin-embedded Margin-controlled Mohs Micrographic Surgery to Treat Skin Tumors. / [Artículo traducido] Revisión del rol de la cirugía micrográfica con cortes en parafina en el tratamiento de tumores cutáneos.

Paraffin-embedded margin-controlled Mohs micrographic surgery (PMMS) includes various procedures such as slow Mohs or deferred Mohs technique, the Muffin and Tübingen techniques, and staged margin excision, or the spaghetti technique. PMMS is a variation of conventional Mohs micrographic surgery (MMS) that allows histopathological examination with delayed margin control. PMMS requires minimum training and may be adopted by any hospital. The setback is that PMMS can require procedures across multiple days. PMMS lowers the rate of recurrence of basal cell carcinoma vs wide local excision in high-risk basal cell carcinoma, and improves the rates of recurrence and survival in lentigo maligna. PMMS can be very useful in high-risk squamous cell carcinoma treatment. Finally, it is a promising technique to treat infrequent skin neoplasms, such as dermatofibrosarcoma protuberans, or extramammary Paget's disease, among others. In this article, we present a literature narrative review on PMMS, describing techniques and indications, and highlighting long-term outcomes.

Dermatofibrosarcoma protuberans of the breast.

Dermatofibrosarcoma protuberans (DFSP) of the breast is an infrequent soft tissue sarcoma that usually affects young to middle-aged women. Our case report describes a unique occurrence of DFSP of the breast in an adolescent girl, which was initially being managed as a keloid for 2 years under dermatology despite being refractory to treatment. Once the diagnosis of DFSP was confirmed through punch biopsy, our patient underwent surgical excision of the lesion under general anaesthesia. Our patient was at an increased risk of damage to the ductal system due to proximity of the lesion to the nipple-areolar complex, warranting the need for early recognition and treatment. As demonstrated by our case, DFSP of the breast can be difficult to diagnose since it resembles a range of benign and malignant pathologies of the breast.

Multiple primary dermatofibrosarcoma protuberans tumors in a single patient with chromosomal microarray analysis: A case report and review.

Dermatofibrosarcoma protuberans (DFSP) is a cutaneous sarcoma with a high propensity for local invasion and recurrence. Although it is a rare event, the occurrence of multiple tumors in a single patient raises a diagnostic dilemma, as metastatic disease should be differentiated from multiple primary malignant events. In more than 90% of DFSP, a pathogenic t(17;22) translocation leads to the expression of COL1A1::PDGFB fusion transcripts. Karyotype analysis, fluorescence in situ hybridization, and RT-PCR can be useful ancillary studies in detecting this characteristic rearrangement, and sequencing of the fusion transcript can be used to support a clonal origin in metastatic and multifocal disease. However, previous reports have demonstrated variable sensitivity of these assays, in part due to the high sequence variability of the COL1A1::PDGFB fusion. Here, we report a patient who developed two distinct DFSP tumors over the course of 7 years. Chromosomal microarray analysis identified distinctive genomic alterations in the two tumors, supporting the occurrence of multiple primary malignant events.

A case report of abdominal metastatic dermatofibrosarcoma protuberans misdiagnosed as gastrointestinal stromal tumor.

Dermatofibrosarcoma protuberans (DFSP) is a low-grade malignant soft-tissue tumor that originates from the skin. It has a slow onset in the early stages, non-specific clinical symptoms, low specificity, and can easily be overlooked, missed, or misdiagnosed by clinicians and pathologists. In addition, DFSP is prone to recurrence after local surgical treatment; however, distant metastasis, especially abdominal metastasis, is rare, which is also a challenge for the accurate diagnosis of DFSP when it progresses distantly. Now a case of abdominal metastasis of DFSP is reported. The patient has been treated with imatinib for ten years, and the lesion has shrunk, but because the patient has been receiving imatinib treatment, his abdominal lesion was once misdiagnosed as gastrointestinal stromal tumor. Therefore, we report on this case to enhance the understanding of the diagnosis and treatment of DFSP, and to provide reference for the pathological diagnosis and precise treatment of such patients.

Disease-Specific Mortality of Dermatofibrosarcoma Protuberans After Mohs Surgery Versus Wide Local Excision: A Systematic Review and Meta-Analysis.

BACKGROUND: Although advances have been made in the understanding of recurrence patterns in dermatofibrosarcoma protuberans, the current understanding of disease-specific mortality after surgical management is limited. OBJECTIVE: To understand disease-specific mortality rates associated with dermatofibrosarcoma protuberans treated with wide local excision (WLE) versus Mohs micrographic surgery (MMS). MATERIALS AND METHODS: A systematic literature search was conducted on March 6, 2023, to identify patients treated with MMS or WLE for dermatofibrosarcoma protuberans. RESULTS: A total of 136 studies met inclusion criteria. Overall, the disease-specific mortality rate was not significantly different after treatment with MMS (0.7%, confidence interval [CI] 0.1-1.2, p : 0.016) versus WLE (0.9%, CI 0.6-1.2, p < .001). For recurrent tumors, the MMS treatment group had a statistically significantly lower disease-specific mortality rate (1.0%, CI 0.0-2.0, p 0.046) compared with the WLE treatment group (3.5%, CI 2.0-5.1, p < .001). The mean follow-up for all studies was 57.6 months. CONCLUSION AND RELEVANCE: The authors' meta-analysis suggests there is no substantial difference in disease-specific mortality between MMS and WLE in patients with dermatofibrosarcoma protuberans, except in the case of recurrent tumors, where MMS seems to confer a survival advantage.

Establishment and characterization of NCC-DFSP5-C1: a novel patient-derived dermatofibrosarcoma protuberans cell line.

Dermatofibrosarcoma protuberans (DFSP) is the most prevalent dermal sarcoma, characterized by the presence of the fusion of the collagen type I alpha 1 (COL1A1) gene with the platelet-derived growth factor beta chain (PDGFB) gene. Although PDGF receptor inhibitor imatinib mesylate was approved for the treating patients with unresectable or metastatic DFSP, disease progression was shown in 9.2% of the patients. Therefore, developing novel therapeutic strategies is crucial for improving the prognosis of DFSP. Patient-derived cell lines play a vital role in preclinical studies; however, only a limited number of DFSP cell lines are currently available in public cell banks. Here, we successfully established a novel DFSP cell line (NCC-DFSP5-C1) using surgically resected tumor tissue from a patient with DFSP. NCC-DFSP5-C1 cells were confirmed to carry the COL1A1-PDGFB translocation and maintain the same mutation as the original tumor tissue. They exhibited consistent growth, formed spheroids, and were invasive. By screening a drug library using NCC-DFSP5-C1 and four previously established DFSP cell lines, we identified anti-cancer drugs that inhibit DFSP cell proliferation. Our observations suggest that the NCC-DFSP5-C1 cell line holds promise as a valuable tool for conducting fundamental and preclinical studies for DFSP.

Review on the Role of Paraffin-embedded Margin-controlled Mohs Micrographic Surgery to Treat Skin Tumors.

Paraffin-embedded margin-controlled Mohs micrographic surgery (PMMS) includes various procedures such as slow Mohs or deferred Mohs technique, the Muffin and Tübingen techniques, and staged margin excision, or the spaghetti technique. PMMS is a variation of conventional Mohs micrographic surgery (MMS) that allows histopathological examination with delayed margin control. PMMS requires minimum training and may be adopted by any hospital. The setback is that PMMS can require procedures across multiple days. PMMS lowers the rate of recurrence of basal cell carcinoma vs wide local excision in high-risk basal cell carcinoma, and improves the rates of recurrence and survival in lentigo maligna. PMMS can be very useful in high-risk squamous cell carcinoma treatment. Finally, it is a promising technique to treat infrequent skin neoplasms, such as dermatofibrosarcoma protuberans, or extramammary Paget's disease, among others. In this article, we present a literature narrative review on PMMS, describing techniques and indications, and highlighting long-term outcomes.

COL1A1::PDGFB fusion-associated uterine fibrosarcoma: A case report and review of the literature.

BACKGROUND: Mesenchymal neoplasms of the uterus encompass a diverse group of tumors, with varying characteristics and origins, collectively accounting for 8% of uterine malignancies. The most common variants include uterine leiomyosarcoma, low-grade and high-grade endometrial stromal sarcoma, adenosarcoma, and undifferentiated sarcoma. Clinical presentation is often nonspecific and can lead to delayed diagnosis. Uterine sarcomas are generally aggressive, resulting in poorer prognosis compared to carcinomas. Recent advances in molecular techniques, such as next-generation sequencing (NGS), have led to the identification of new subtypes of uterine sarcomas, including COL1A1::PDGFB fusion-associated fibrosarcoma, which has a specific chromosomal translocation t(17;22)(q22;q13). Imatinib, a tyrosine kinase inhibitor (TKI), is an effective treatment for dermatofibrosarcoma protuberans (DFSP), marked by this translocation. CASE: We present the case of a 42-year-old woman diagnosed with COL1A1::PDGFB fusion-associated uterine fibrosarcoma. The patient underwent total hysterectomy and excision of the tumor, initially misdiagnosed as a low-grade leiomyosarcoma. Subsequent histological examination, immunohistochemistry, and fluorescence in situ hybridization (FISH) confirmed the diagnosis. After 10 months, disease recurrence was detected, and Imatinib therapy was initiated at a dose of 400 mg daily. An allergic reaction led to a temporary discontinuation, but upon resumption with appropriate medication, a positive radiological response was observed. The patient achieved a complete remission after 2 years and is still on Imatinib treatment. CONCLUSIONS: COL1A1::PDGFB fusion-associated uterine fibrosarcoma is an extremely rare mesenchymal neoplasm. In a case we present herein, we treated a patient with imatinib as first-line medical therapy. The patient is currently in complete remission after 37 months from treatment start. To the best of our knowledge, this represents a unique observation. We also provide a detailed literature review of the published cases so far. Prospective case series are needed to further understand the natural history of these tumors and optimize treatment strategies.

Dermatofibrosarcoma Protuberans: A Study of 148 Patients.

INTRODUCTION: Dermatofibrosarcoma protuberans (DFSP) is the most common sarcoma of the skin. Although distant metastases are infrequent, DFSP is highly aggressive locally with frequent local recurrences. It has been reported that the presence within the tumour of areas histopathologically mimicking fibrosarcoma may increase the risk of recurrence. OBJECTIVE: The objective of this study was to review the clinical features of our patients with DFSP and the factors associated with recurrence of the tumour, focussing on the presence of fibrosarcomatous areas. METHODS: Retrospective study of patients with DFSP diagnosed in 1990-2021 in a tertiary university hospital. The medical records were reviewed to obtain the following data: age, sex, tumour location, diameter, evolution time, presence of fibrosarcomatous areas, development of recurrence, and follow-up. Factors possibly associated with disease-free survival were analysed with Kaplan-Meier method and multivariate Cox regression. RESULTS: 148 patients (74 women/74 men, mean age 46.28 years, SD 14.431) were included in the study. Tumours involved the head and neck in 15 cases, thorax in 31, abdomen in 16, upper back in 43, lower back in 10, upper extremities in 10, and lower extremities in 23. Fibrosarcoma-like areas were observed in 16 tumours (10.81%). In 17 patients (11.49%), recurrences were observed (13 local recurrences, 3 lung metastasis, and 1 local recurrence with lung metastasis). Fibrosarcomatous DFSP recurred more frequently than classic DFSP (50% vs. 6.82%, respectively), and its disease-free survival was significantly lower (p < 0.001). In multivariate Cox regression, the presence of fibrosarcomatous areas was the only factor influencing disease-free survival. CONCLUSIONS: It is important to identify the fibrosarcomatous variant since it recurs more frequently and has lower recurrence-free survival. Distant metastases, mainly in the lung, are also more frequent in fibrosarcomatous DFSP.

Survival outcomes of rare cutaneous malignancies within an insured cohort of patients, 1988-2018.

BACKGROUND: There are limited survival data on cutaneous angiosarcoma (CAS), dermatofibrosarcoma protuberans (DFSP), Merkel cell carcinoma (MCC), and sebaceous carcinoma (SC). OBJECTIVE: To analyze survival trends in CAS, DFSP, MCC, and SC among a racially diverse, insured cohort of patients. METHODS: Using data from the Kaiser Permanente Southern California Cancer Registry, we identified adults diagnosed with CAS, DFSP, MCC, or SC between January 1, 1988 and December 31 2018, followed through December 31, 2021. RESULTS: Our cohort consisted of 83 diagnoses of CAS, 490 diagnoses of DFSP, 411 diagnoses of MCC, and 249 diagnoses of SC. Our analysis revealed no significant differences in overall or disease-specific 1000 person-years mortality rates among our populations of non-Hispanic Whites, Hispanics, African American/Blacks, and Asian American/Pacific Islanders diagnosed with CAS, DFSP, MCC, or SC. On multivariate analysis, controlling for patient and tumor characteristics, there was similarly no increased risk of overall mortality for minorities diagnosed with CAS, DFSP, MCC, or SC. LIMITATIONS: Retrospective nature of the analysis and small sample size. CONCLUSION: Contrary to existing literature, our results show a notable lack of racially driven survival disparities among insured individuals with CAS, DFSP, MCC, and SC, emphasizing the importance of health care coverage.

[Fascio-cutaneous exeresis of a dermatofibrosarcoma of Darier-Ferrand of the right flank]. / Exérèse fascio-cutanée d'un dermatofibrosarcome de Darier-Ferrand du flanc droit.

INTRODUCTION: Darrier-Ferrand dermatofibrosarcoma (DFSC) is the most common cutaneous sarcoma. It generally affects subjects with an average age of 40 years, without gender or race predominance. It is a tumour characterised by a slow evolution and local aggressiveness. The reasons for consultation are pain, pruritus or rapidly progressive evolution. There are no specific imaging studies for this tumour. The diagnosis of certainty is based on immunohistochemistry with positive CD34 labelling. Treatment is surgical based on wide excision. MATERIAL AND METHODS: This is an observation of a patient operated in our department for the initial diagnosis of cutaneous leiomyosarcoma of the right flank that rapidly increased in volume to 10cm in six months. A large fasciocutaneous excision was performed. The postoperative course was simple. DISCUSSION: In our patient, this lesion occurred on an old burn scar. This notion of skin trauma preceding the appearance of DFSC is reported in 10 to 20% of cases. The rapid increase in volume was the reason for consultation. The diagnosis of DFSC could only be made on definitive analysis of the surgical specimen, which showed positive immunostaining for CD34. The occurrence of metastases, although rare, confers a survival of no more than two years. The prognostic factors depend on the quality of the surgical excision, the presence of metastases and certain locations (head, neck), which make the surgery particularly mutilating. Only long-term monitoring attests to definitive cure, given the frequency of recurrence. CONCLUSION: DFSC is a rare and slowly evolving tumour. Wide surgical excision should be attempted in most cases. In inoperable cases, the use of targeted therapies (IMATINIB) has led to complete cures in some cases.

A study of collagen refractility in dermatofibroma and dermatofibrosarcoma protuberans using diffractive microscopy.

BACKGROUND: Diffractive microscopy creates contrast within samples that are otherwise uniform under bright light. This technique can highlight subtle differences in refractive indices within birefringent samples containing varying amounts of mature collagen. Dermatofibroma (DF) and dermatofibrosarcoma protuberans (DFSP) possess differences in their mature collagen content and, therefore, may be distinguishable using diffractive microscopy. METHODS: Two hundred forty-two DF and 85 DFSP hematoxylin-eosin (H&E)-stained specimens were analyzed using diffractive microscopy. Data regarding the distribution pattern and strength of refractility was recorded. RESULTS: DFSP was more frequently found to be focally, weakly, or non-refractile (82.9%; n = 68) under diffractive microscopy, while DF more often showed diffusely bright refractility (52.9%; n = 128). DFSP samples with diffuse refractility in portions of the lesion (17.1%; n = 14) also exhibited a unique checkerboard pattern distinct from that which was seen in DF samples. CONCLUSIONS: The absence of diffuse refractility was more closely associated with DFSP, as was the presence of a unique checkerboard diffraction pattern. Despite high sensitivity (Sn = 82.9%), absent refractility was not a specific test (Sp = 52.9%), with 47.1% (n = 114) of DF samples sharing this feature. The distinction between DF and DFSP is often diagnosed using H&E alone. In difficult cases, examination of collagen under diffractive microscopy may be useful in distinguishing DFSP from DF and provide an alternative cost-effective tool to immunohistochemical staining.

Unraveling intratumoral complexity in metastatic dermatofibrosarcoma protuberans through single-cell RNA sequencing analysis.

Dermatofibrosarcoma protuberans (DFSP) stands as a rare and locally aggressive soft tissue tumor, characterized by intricated molecular alterations. The imperative to unravel the complexities of intratumor heterogeneity underscores effective clinical management. Herein, we harnessed single-cell RNA sequencing (scRNA-seq) to conduct a comprehensive analysis encompassing samples from primary sites, satellite foci, and lymph node metastases. Rigorous preprocessing of raw scRNA-seq data ensued, and employing t-distributed stochastic neighbor embedding (tSNE) analysis, we unveiled seven major cell populations and fifteen distinct subpopulations. Malignant cell subpopulations were delineated using infercnv for copy number variation calculations. Functional and metabolic variations of diverse malignant cell populations across samples were deciphered utilizing GSVA and the scMetabolism R packages. Additionally, the exploration of differentiation trajectories within diverse fibroblast subpopulations was orchestrated through pseudotime trajectory analyses employing CytoTRACE and Monocle2, and further bolstered by GO analyses to elucidate the functional disparities across distinct differentiation states. In parallel, we segmented the cellular components of the immune microenvironment and verified the presence of SPP1+ macrophage, which constituted the major constituent in lymph node metastases. Remarkably, the CellChat facilitated a comprehensive intercellular communication analysis. This study culminates in an all-encompassing single-cell transcriptome atlas, propounding novel insights into the multifaceted nature of intratumor heterogeneity and fundamental molecular mechanisms propelling metastatic DFSP.

Connexin 43 in Dermatofibroma and Dermatofibrosarcoma Protuberans: Diagnostic, Pathogenic, and Therapeutic Implications.

ABSTRACT: Connexins play a crucial role in the formation of gap junctions that connect cells to each other, as well as cells to the surrounding environment. In recent years, connexin 43 has been extensively studied in various human tumors. In this study, we conducted an immunohistochemical analysis to evaluate the expression of connexin in 16 dermatofibromas (DFs) and 13 dermatofibrosarcoma protuberans (DFSP). Connexin was diffusely expressed in the cytoplasm of all DFs with moderate or strong intensity, whereas all DFSPs showed negative staining. In addition to its diagnostic implications, the loss of Cx43 may elucidate the invasive capacity of DFSP and offer a potential avenue for future therapeutic interventions.

Dermatofibrosarcoma protuberans: A rare presentation in the scalp. Case report.

BACKGROUND: Dermatofibrosarcoma protuberans of the scalp (DFSP) is a rare soft tissue neoplasm originating from the dermal layer of the skin, usually affecting the adults. CASE REPORT: The current case report presents a 48-year old male with a huge lump on the right side of parietal region. A wide local excision of the tumor was performed and the excised specimen was sent for histopathological examination. Histopathology and Immunohistochemistry was suggestive of DFSP. CONCLUSION: Dermatofibrosarcoma protuberans is a rare neoplasm affecting the head and neck region. This unusual entity is more likely to recur when a small margin of surgical excision is performed. Wide local excision is the gold standard treatment and radiotherapy is preferred in recurrent diseases.