Sclerosing Dermatofibrosarcoma Protuberans: A Possible Diagnosis When a Small Biopsy Shows Sclerotic Fibroma-Like Features.

ABSTRACT: Dermatofibrosarcoma protuberans (DFSP) is a neoplasm of intermediate malignancy with high local recurrence rates. The sclerosing variant is characterized by the presence of sclerotic areas in more than 50% of tumors and is rarely reported. In this report, we describe a case of sclerosing DFSP with areas histopathologically resembling sclerotic fibroma, where the initial biopsy tissue presented a diagnostic challenge. A 77-year-old man presented with a 2-cm firm, erythematous nodule on the chest. A punch biopsy revealed plywood-like sclerosis and spindle cells with a vaguely storiform pattern. The tumor cells were positive for CD34. Sclerotic fibroma and DFSP were considered differential diagnoses. Subsequent excisional biopsy revealed that the tumor comprised 3 different histopathological areas: classic DFSP, sclerotic fibroma-like, and giant cell fibroblastoma-like. This report highlights the importance of reevaluating the clinical context and excision for further characterization.

Metastatic presentation of dermatofibrosarcoma protuberans as massive lower gastrointestinal bleed.

Dermatofibrosarcoma protuberans (DFSP) is an aggressive tumour with multiple local recurrences and rare metastatic potential. Fibrosarcomatous transformation occurs in a few cases of DFSP which makes them more aggressive in terms of recurrence and metastasis. Here we report the case of a woman in her late 30s who presented with massive lower gastrointestinal (GI) bleeding with a history of multiple surgeries for DFSP on her anterior abdominal wall. The bleeding source was identified to be a mass lesion in the jejunum, which was excised. The patient recovered well and the histopathology revealed fibrosarcoma of the jejunum. Follow-up investigations showed multiple lung nodules, ascites and abdominal lymph nodes suggesting progressive disease. She is currently receiving chemotherapy and progressing well 3 months postoperatively. Patients with fibrosarcomatous changes within DFSP must be followed up closely as it is associated with increased metastatic potential.

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

AIMS: 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). METHODS AND RESULTS: 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). CONCLUSION: We describe a cohort of novel ALK-rearranged tumours with morphologic features similar to DFSP.

Analysis of surgical margins and prognostic factors in dermatofibrosarcoma protuberans after wide local excision: A multicenter study of 116 Japanese patients.

Cutaneous dermatofibrosarcoma protuberans (DFSP) is a fibrohistiocytic tumor characterized by a high risk of local recurrence but a low risk of metastasis. Wide local excision (WLE) has been an important treatment option, but its clinical outcomes and safety have not been thoroughly evaluated in previous reports. The aim of this study was to determine appropriate surgical margins (deep and lateral) and prognostic factors associated with recurrence-free survival (RFS) of DFSP. A database collected by two dermatology departments in Japan was retrospectively reviewed to identify 116 patients with DFSP who underwent complete resection with WLE between 1994 and 2021. Sixty-one men (53%) and 55 women (47%) were included in our cohort. The primary sites of DFSP were as follows: 11 head and neck (9%); seven face (7%); 12 upper extremities (10%); 20 lower extremities (17%); and 66 trunk (57%). There were 103 cases (89%) of primary DFSP and 13 cases (11%) of recurrent DFSP. Total 10-year RFS was 96.6%. There were significant differences in RFS by tumor size (median size: 3 cm), disease status (primary versus recurrent DFSP), and fibrosarcomatous change (positive versus negative) (all p < 0.05). Two patients (1.7%) with buccal or head lesions had positive deep margins. In all cases, the lateral margin was negative at the postoperative evaluation. Tumor size, disease status, and fibrosarcomatous change are important risk factors for recurrence. Both face and head-neck lesions were more likely to have positive deep margins than other anatomic areas in DFSP. Although this study was limited by its retrospective design, a narrow 2-cm lateral margin is especially considered for low-risk patients.

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.

A cutaneous spindle cell neoplasm characterized by a COL3A1::PDGFRA fusion.

Cutaneous spindle cell neoplasms can be challenging to diagnose using routine histopathological techniques alone, and the growing repertoire of molecular studies can assist in diagnosis. We describe a cutaneous spindle cell neoplasm characterized by a COL3A1::PDGFRA rearrangement predicted to lead to constitutive activation of the PDGFRA kinase domain. The lesion shows some similarities to dermatofibrosarcoma protuberans and also benign and epithelioid fibrous histiocytomas but is distinct from these entities histopathologically and molecularly. This tumor is considered to represent an entity in the spectrum of PDGFR-driven cutaneous mesenchymal neoplasms.

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.

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.

[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.

Dermatofibrosarcoma Protuberans Occurring in an Adult Presenting with Chronic Lymphedema: A Case Study and Literature Review.

BACKGROUND Dermatofibrosarcoma protuberans (DFSP) is a rare soft-tissue tumor typically located in the trunk. We report a unique case of DFSP in the right inguinal region of an adult presenting with chronic lymphedema. Only 1 case of DFSP and chronic lymphedema association has been previously reported in the literature. Since we could not provide adjuvant radiotherapy (RT), we conducted an extensive review of its application in similar cases, exploring various surgical treatments. CASE REPORT A 42-year-old Cameroonian man with unexplained chronic lymphedema presented with a tumor in the inguinal region of the affected limb. The patient underwent wide local excision (WLE) of the mass, including regional lymph node dissection. Pathological exam confirmed DFSP with a fibrosarcomatous component. Adjuvant RT was considered but not pursued due to the patient;s non-compliance. CONCLUSIONS This DFSP is reported for its rarity of site and the unique co-occurrence with chronic lymphedema. Considering both conditions are uncommon and the rarity of site of the DFSP, we assume that in this patient, chronic lymphedema was a contributing factor of occurrence of the DFSP. Remarkably, no prior reports have detailed an association between chronic lymphedema and DFSP onset. For that reason, we want to point out the value of better follow-up of chronic lymphedema and better knowledge of DFSP treatment options to improve patient healthcare and limit DFSP recurrence. In addition, we found adjuvant RT is an interesting treatment option that might be considered in all patients undergoing surgical excision, even in cases where negative surgical margins were achieved.

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.

Pigmented dermatofibrosarcoma (Bednar tumour) of scalp.

Pigmented dermatofibrosarcoma protuberans (DFSP) also known as Bednar tumour is a very rare variant of DFSP which is considered to be of intermediate grade along with the presence of melanin-containing dendritic cells. Only a handful of cases have been described in the literature so far. It is centred around the dermis or subcutis and can pose a diagnostic challenge by being confused with other pigmented lesions of the skin. We hereby report one such unusual case of a man in his late 20s presenting with swelling over the forehead for the past 7 years. Hence a diagnosis of pigmented DFSP should always be considered while reporting pigmented subcutaneous lesions with spindle cell morphology.