Dermatofibrosarcoma Protuberans Arising From a Keloid-like Benign Sclerotic Plaque

Dermatofibrosarcoma protuberans (DFSP) is a rare cutaneous and subcutaneous mesenchymal malignant tumor characterized by high rates of local recurrence and low risk of metastasis. Histopathological and immumohistochemical study can be used to diagnose DFSP. Recent studies have shown that cell genetics and molecular biology, imagiology, dermatoscopy and cutaneous computed tomography (reflectance confocal microscopy) can also play an important auxiliary role in the diagnosis, treatment and evaluation of DFSP. At present, the surgical treatment of DFSP mainly includes wide local excision (WLE) and Mohs micrographic surgery (MMS) . Each of the two approaches has its advantages and disadvantages. After surgery, radiation therapy and comprehensive immunological treatment can serve as adjuvant treatment. Cryotherapy is effective in patients with recurrent DFSP, and the targeted agent imatinib can be combined for inoperable patients or patients with positive surgical margins. In addition, antiestrogenic drugs (such as tamoxifen) or the new targeted agent heparanase inhibitor roneparstat (SST0001) may have some therapeutic effects. Key words: Dermatofibrosarcoma; Pathology, clinical; Diagnosis; Mohs surgery; Therapeutic Uses

Dermatofibrosarcoma protuberans (DFSP) is an uncommon low-grade malignant soft tissue sarcoma, representing less than 0.1% of all malignant neoplasms and 1% of soft tissue sarcomas. It generally manifests in the third and fourth decades of life, with a greater prevalence in males. DFSP originates from dermal fibroblasts and is distinguished by gradual, infiltrative proliferation, local recurrence, and a minimal propensity for metastasis. This case report describes a 17-year-old female with a two-year history of a rapidly growing nodular mass on the anterior chest wall. Diagnostic assessments, comprising MRI, FNAC, and histology, validated the diagnosis. The patient had a broad local excision with negative margins, and immunohistochemistry indicated CD34 positivity. The postoperative follow-up indicated no recurrence. Timely identification, interdisciplinary care, and prolonged surveillance are crucial to enhance outcomes and reduce recurrence risk in DFSP cases.

Dermatofibrosarcoma protuberans (DFSP) is an intermediate malignancy of the skin. Although COL1A1/PDGFB fusion gene was identified in the tumor cells recently, not all of the cases were positive for the fusion gene, and further researches are still needed to clarify the pathogenesis of DFSP. In this study, we investigated the role of microRNAs in the tumor. microRNA PCR array showed several microRNAs increased or decreased in DFSP in vivo compared with dermatofibroma (DF) and normal skin. Among them, the expression of miR-205 was down-regulated in DFSP compared with DF and normal skin. In situ hybridization showed that miR-205 expression was evident in dermal fibroblasts of normal skin although hardly detected in tumor cells of DF or DFSP. miR-205 inhibitor increased cell proliferation and the luciferase activity of 3'UTR of low-density lipoprotein receptor-related protein-1 (LRP-1) in cultured normal dermal fibroblasts. Immunohistochemistry showed the expression of LRP-1 was increased in DFSP tissue. Knockdown of LRP-1 suppressed cell growth and down-regulated extracellular signal-regulated kinase (ERK) phosphorylation without affecting MEK phosphorylation in cultured DFSP cells. Taken together, LRP-1 overexpression caused by the miR-205 down-regulation may play a role in the abnormal proliferation of DFSP cells via directly regulating ERK phosphorylation.

Dermatofibrosarcoma protuberans (DFSP) is a fibrohistiocytic tumor of intermediate malignancy. It is characterized by a locally aggressive growth and a high rate of local recurrence. Metastases are very rare and the most common sites of metastasis are the lungs and lymph nodes. We report a 53-year-old female patient with a DFSP on the scalp. She developed local recurrence of DFSP 4 years after simple excision and right frontal lobe metastasis in the sixth year. The pathological examinations revealed dedifferentiation from low-grade DFSP to higher grade fibrosarcomatous features in the recurrent and metastatic lesions. Immunohistochemical studies showed diffuse CD34 expression in recurrent tumor and focal loss of CD34 expression associated with fibrosarcomatous change in the brain metastatic tumor. DFSP is not only locally invasive but also has a definite metastatic potential. The importance of complete local excision with close surveillance, especially for the patients with poor prognostic factors, should be emphasized.

The clinicopathologic relevance of various gene rearrangements underlying dermatofibrosarcoma protuberans (DFSP) remains insufficiently characterized. In 188 DFSPs, we determined PDGFB, COL1A1, PDGFD, COL6A3, and EMILIN2 rearrangements by fluorescence in situ hybridization (FISH). The clinicopathologic significance of rearrangement types and factors related to recurrence and metastasis were statistically analyzed. In all, classic PDGFB rearrangement, cryptic COL1A1-PDGFB fusion, and PDGFD rearrangement were identified in 172 (91.4%), 8 (4.3%), and 8 (4.3%: 4 COL6A3-PDFGD, 4 EMILIN2-PDGFD) cases, respectively. In an index DFSP harboring the cryptic fusion, the COL1A1-PDGFB transcript was confirmed by both RNA sequencing and reverse transcription-polymerase chain reaction. In comparison with cases harboring classic PDGFB rearrangement, cryptic PDGFB-rearranged DFSPs usually exhibited higher 5'-COL1A1 copy numbers. In a combined reappraisal of published and current cases, COL6A3-PDGFD-positive DFSPs (n=16) predominated in females (n=14, 88%) and torso (n=14, 88%), especially the breast (n=7, 44%); EMILIN2-PDGFD-positive DFSPs (n=6) preferentially demonstrated near exclusively subcutaneous growth (n=5, 83%) and fibrosarcomatous transformation (n=5, 83%). In our cohort, local recurrence was related to fibrosarcomatous variant (P=0.029, odds ratio=3.478) and head and neck location (P=0.046, odds ratio=3.508). Distant metastasis only occurred in the fibrosarcomatous variant (9/73, 12.3%) but not in other cases. In conclusion, 8.6% of DFSPs are negative for PDGFB break-apart FISH, which, especially those with challenging subcutaneous and circumscribed manifestation, require complementary diagnosis by FISH assays targeting COL1A1 and PDGFD. The types of fusion gene rearrangements, head and neck location, and fibrosarcomatous transformation may account for clinicopathologic and prognostic variations in DFSPs and warrant future independent validation.

Giant cell fibroblastoma mimicking a soft fibroma arising within a dermatofibrosarcoma protuberans

Dermatofibrosarcoma protuberans (DFSP) is uncommon but represents one of the most common dermal sarcomas, which is said to be a locally aggressive, low grade, and relatively uncommon cutaneous tumour, which has a high propensity for local relapse with low metastatic potential. Over 90% DFSPs are genetically characterized by chromosomal rearrangements (translocation t (17;22) (q22; q13), resulting in the collagen type-1 alpha 1 (COL1A1)-platelet-derived growth factor â (PDGFB) fusion gene with well-known risk factors for developing DFSP, some cases develop at the site of previous trauma and reports have included a burn scar and the site of vaccination. The mainstay mode of treatment of DFSPs is wide local excision with traditionally 3-cm gross margins excision surgery. Mohs Micrographic Surgery (MMS) is highly recommended surgery for DFSP and is very useful treatment choice for recurrent DFSP. This case report discusses two patients with confirmed DFSP and have received adequate therapy. It also reviews salient features of evaluation and prompt management of DFSP and much emphasis on long-term follow-up of patients. Key Messages : Early diagnosis of pediatric DFSP is critical to minimize surgical disfiguration. We emphasize early evaluation of any suspicious skin lesion should not be ignored and should be excised and sent for histopathology. Undertreating a DFSP is even more problematic, as the tumour is locally destructive, can metastasize, and can prove fatal without treatment. A full metastatic workup should be done and patient should be regularly followed up, if it turns out to be malignant.

Dermatofibrosarcoma protuberans (DFSP) is a mesenchymal neoplasm that is usually located in the dermis or subcutis and is locally aggressive. Rarely, these lesions may undergo fibrosarcomatous transformation, which is thought to increase their metastatic potential. DFSP is classically associated with a 17;22 translocation (or ring chromosome thereof) resulting in fusion of the COL1A1 and PDGFB genes. However, variant fusions involving PDGFD have been recently reported. Herein, we present two morphologically diverse cases of DFSP with PDGFD rearrangement. Case 1 is a 68-year-old female with a left dorsal foot lesion. Morphologically, the lesion is unusual as it is a well-circumscribed, hypercellular, subcutaneous nodule with uniform CD34-positive spindle cells arranged in a herringbone pattern without storiform arrangement or "honeycombing" fat entrapment. It was diagnosed as pure fibrosarcomatous DFSP. Case 2 is a 37-year-old male with a right supra-auricular lesion. Morphologically, the lesion displays classic DFSP features including bland CD34-positive spindle cells with storiform growth, fat entrapment, and infiltrative borders. Both lesions were negative for COL1A1-PDGFB fusion but positive for PDGFD rearrangement by fluorescence in situ hybridization (FISH) analysis. FISH testing for PDGFD rearrangement should be performed in cases where there is a high suspicion for DFSP but initial studies for COL1A1-PDGFB are negative.

<div>Abstract<p><b>Purpose:</b> Dermatofibrosarcoma protuberans (DFSP) is a rare cutaneous tumor. <i>COL1A1–PDGFB</i> gene fusion is frequent in DFSP, rendering tumor cell proliferation and survival dependent on PDGFRβ (platelet-derived growth factor receptor β) signaling. This trial investigated imatinib as neoadjuvant treatment of DFSP, including long-term follow-up.</p><p><b>Experimental Design:</b> The primary endpoint of this multicenter phase II trial was response; secondary endpoints were safety, tumor relapse, and response biomarkers. Patients with advanced primary or locally recurrent DFSP and measurable disease by RECIST (response evaluation criteria in solid tumors) were eligible and received imatinib 600 mg/d until definitive surgery with histopathologic proof of tumor-free margins.</p><p><b>Results:</b> Sixteen patients received imatinib, and 14 patients were evaluable for all endpoints. Median treatment duration was 3.1 months; median tumor shrinkage was 31.5%. Best overall response was 7.1% complete response (CR), 50.0% partial response (PR), 35.7% stable disease, and 7.1% progressive disease (PD). Toxicity was moderate with 25.0% grade 3 and 4 events. During a median follow-up of 6.4 years, one patient developed secondary resistance to imatinib but responded to second-line sunitinib. This patient also presented local recurrence, distant metastasis, and death from DFSP. Exploratory analysis showed that response to imatinib was associated with decreased tumor cellularity and formation of strong hyalinic fibrosis. Weak PDGFRB phosphorylation and pigmented-type DFSP were associated with nonresponse. Additional to PDGFRB, the kinases EGFR and insulin receptor were found activated in a high percentage of DFSPs.</p><p><b>Conclusion:</b> The neoadjuvant use of imatinib 600 mg/d in DFSP is efficacious and well tolerated. Long-term follow-up results do not definitely support smaller surgical margins after successful imatinib pretreatment, and presume that secondary resistance to imatinib might promote accelerated disease progression. <i>Clin Cancer Res; 20(2); 499–510. ©2013 AACR</i>.</p></div>

Dermatofibrosarcoma protuberans (DFSP) is uncommon but represents one of the most common dermal sarcomas, which is said to be a locally aggressive, low grade, and relatively uncommon cutaneous tumour, which has a high propensity for local relapse with low metastatic potential. Over 90% DFSPs are genetically characterized by chromosomal rearrangements (translocation t (17;22) (q22; q13), resulting in the collagen type-1 alpha 1 (COL1A1)-platelet-derived growth factor â (PDGFB) fusion gene with well-known risk factors for developing DFSP, some cases develop at the site of previous trauma and reports have included a burn scar and the site of vaccination.The mainstay mode of treatment of DFSPs is wide local excision with traditionally 3-cm gross margins excision surgery. Mohs Micrographic Surgery (MMS) is highly recommended surgery for DFSP and is very useful treatment choice for recurrent DFSP.This case report discusses two patients with confirmed DFSP and have received adequate therapy. It also reviews salient features of evaluation and prompt management of DFSP and much emphasis on long-term follow-up of patients.Key Messages:Early diagnosis of pediatric DFSP is critical to minimize surgical disfiguration. We emphasize early evaluation of any suspicious skin lesion should not be ignored and should be excised and sent for histopathology. Undertreating a DFSP is even more problematic, as the tumour is locally destructive, can metastasize, and can prove fatal without treatment. A full metastatic workup should be done and patient should be regularly followed up, if it turns out to be malignant.

Dermatofibrosarcoma protuberans (DFSP) is a rare soft tissue sarcoma with aggressive local behavior but with a low metastatic potential. Although slow growing and indolent, they rarely reach huge sizes. Very uncommonly, these locally invasive tumors undergo fibrosarcomatous transformation with a more aggressive clinical course, with higher rate of recurrence risk and distant metastases. A 32-years-old lady, presented with a gradually progressive lump in the upper central back for the past 6 years, with rapid progression in size during the last 6 months. On examination, she had a single lump of size 18×18 cm in the midline of the upper back, with prominent veins over its surface. Magnetic resonance imaging (MRI) showed no connection with the spinal canal and appeared flush with the paraspinal muscles. Core needle biopsy showed DFSP. The patient underwent a wide local excision with split skin grafting. The histopathology now showed a fibrosarcomatous transformation of DFSP. The patient again underwent a wide re-excision with a 3 cm margin. Histology reported no evidence of tumor cells in the specimen. The patient’s postoperative period was uneventful and she was referred for adjuvant radiotherapy. DFSP is a rare, slow-growing malignant fibroblastic mesenchymal skin tumor with low metastatic potential. However, in any patient with long standing DFSP with a recent increase in size, this fibrosarcomatous transformation must be kept in mind as it represents an uncommon form of DFSP that tends to follow a more aggressive clinical course, with higher rate of recurrence risk and distant metastases.

Dermatofibrosarcoma protuberans (DFSP) is an uncommon, slow growing, sarcoma of dermal and subcutaneous tissue with an infiltrative growth pattern. Although DFSP has a high rate of local recurrence, it rarely metastasizes. DFSP is characterized by a chromosomal translocation involving the collagen type I a 1 (COL1A1) gene on chromosome 17 and the platelet-derived growth factor B-chain (PDGFB) gene on chromosome 22. Various exons of the COL1A1 gene have been reported to be involved in the fusion with exon 2 of the PDGFB gene. In this study, we examined the COL1A1-PDGFB fusion transcripts using frozen specimens from three patients with DFSP. The molecular biology study with reverse transcriptase polymerase chain reaction (RT- PCR) and sequencing showed that the ends of exons 25, 31, and 45 in the COL1A1 gene were fused with PDGFB. The exon 2 of the PDGFB gene fused with exon 31 of the COL1A1 gene was a novel fusion gene.

Appearance of recurrent dermatofibrosarcoma protuberans in postoperative MRI follow-up

Background:Dermatofibrosarcoma protuberans (DFSP) is a low-to-intermediate grade sarcoma of dermal origin [1-3] that rarely presents in the vulva [1,2]. It typically presents on the trunk of young to middle-aged adults[4]. Even though it has a low potential for distant metastases, it often recurs locally [5]. Histopathologically, DFSP typically consists of spindle cells in a “storiform” pattern and stain positive for CD34, which can aid in establishing a diagnosis [1,6-8]. The traditional treatment of choice has been wide surgical excision, but multiple resections are often required for clearance of the lesion [9]. Mohs micrographic surgery (MMS) has recently been described as an alternative treatment option to help decrease the rate of recurrence. Objective: To present a case of dermatofibrosarcoma protuberans of vulva in a young patient treated with excisional surgery with a systematic review of the condition. Case:This patient is a 35-year-old female, G0P0, from The Republic of the Congo (Central Africa), who presented with an eight-year history of a “large left keloid of the mons pubis”. The patient stated the mass was non-tender and the size of a ping-pong ball that changed in size. The patient underwent surgical excision of the “large left keloid of mons pubis”. The specimen consisted of a 6 x 3 x 3 cm elevated portion of smooth tan skin with subcutaneous tissue. It was determined that the specimen was composed of extensive, ill-defined, firm, smooth, homogeneous tan tissue and was sent to pathology for further evaluation. The pathological specimen findings were “Dermatofibrosarcoma protuberans with positive margin”. A second surgery was performed to excise the positive margins of DFSP that remained. Review of an intraoperative frozen specimen found no tumor in the tissue margins. The patient had an uneventful postoperative course and was discharged two days after the surgery was performed. Conclusion:Dermatofibrosarcoma protuberans (DFSP) infrequently involves the vulva and should be considered in the differential diagnosis of other spindle cell lesions presenting in this unusual site [10,11]. The role of immunohistochemical staining with CD34 is imperative in establishing the diagnosis. The rate of local recurrence is high, but it rarely shows metastasis [12]. Surgical excision is the treatment of choice and close follow-up to detect recurrence is imperative [1].

Dermatofibrosarcoma protuberans is a rare soft tissue sarcoma of low to intermediate malignant potential. Incidence is estimated to be 0.8 to 4.5 cases per million persons per year. The tumor is highly aggressive locally and is known to recur. Punch biopsy or excisional biopsy (in case of small tumors) are diagnostic. Computer tomography (CT) and magnetic resonance imaging (MRI) are useful in determining the size and extent of the tumor’s treatment is primarily surgical, with a wide local excision with at 2 cm margin. However, local recurrence after apparently adequate surgical excision is common. Mohs micrographic surgery has been recommended as it enables maximum preservation of tissue. When surgery is insufficient, imatinib mesylate is shown as a safe and effective treatment in dermatofibrosarcoma protuberans (DFSP), especially in cases of locally advanced or metastatic disease. Here, we report a case of a giant fibrosarcoma on the anterior abdominal wall, measuring 27×18×9 cm, which occurred in a recurrent dermatofibrosarcoma protuberans. Diagnosis was done by histopathological examination (HPE) of the previously excised tumor and CT was done. The tumor was excised with a 3 cm margin and extensive reconstruction of the anterior abdominal wall defect was done using synthetic mesh, myocutaneous flaps and split skin grafting. Keeping in view the recurrent nature of our case, large tumor size, DFSP-fibrosarcomatous (FS) transformation and close negative margins in the HPE of the postoperative specimen, the patient was planned for adjuvant radiotherapy.