Dermatofibrosarcoma protuberans with platelet-derived growth factor-D rearrangement; two cases with morphologically distinct presentations.

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.

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.

Dermatofibrosarcoma protuberans (DFSP) is a rare, plaque-like tumor of the cutaneous tissue occurring more on the trunk than the extremities and neck. More than 95% of DFSP present anomalies on the 17q22 and 22q13 chromosomal regions leading to the fusion of COL1A1 and PDGFB genes. Surgery is the optimal treatment for DFSP, but less effective in locally advanced or metastatic patients, as is the case with chemotherapy and radiotherapy. The aim of this study was to assess retrospectively the therapeutic activity and safety of imatinib on 22 Chinese patients with locally inoperative or metastatic DFSP at a single institution.In the collected data of 367 Chinese patients with DFSP, we analyzed retrospectively 22 patients with locally advanced or metastatic DFSP, all of whom received imatinib therapy at 1 center from January 2009 to October 2014. Patients were administered with imatinib at an initial dose of 400 mg and escalated to 800 mg daily after they developed imatinib resistance. The median follow-up time was 36 months, and the median treatment time was 15 months.The results showed that 10 locally advanced DFSP patients and 12 metastatic DFSP patients received imatinib therapy. Apart from 1 patient who developed primary imatinib resistance, 15 patients achieved partial remission (PR), and 6 patients achieved stable disease (SD). Both fibrosarcomatous DFSP and classic DFSP patients demonstrated similar response to imatinib. Median PFS was estimated to be 19 months. Median overall survival (OS) has not been reached, and estimated 1- and 3-year OS rates were 95.5% (21/22) and 77.3% (17/22), respectively. Four out of 10 patients with primarily unresectable DFSP received complete surgical resection after neoadjuvant treatment of imatinib.Imatinib therapy is well tolerated with a safety profile and is the therapy of choice in locally inoperative or metastatic DFSP. Neoadjuvant treatment of locally advanced or metastatic DFSP with imatinib improves surgical outcomes and may facilitate resection of difficult tumors.

Enhancing techniques to evaluate tumor margins

Análisis del gen de fusión COL1A1-PDGFB en un caso de dermatofibrosarcoma protuberans con componente de fibrosarcoma

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

COL1A1-PDGFB fusion in a pediatric Bednar tumor with 2 copies of a der(22)t(17;22)

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 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.

Platelet-derived growth factor (PDGF) is known to stimulate the proliferation of fibroblasts, although the role of PDGF and its receptors in the development of fibrohistiocytic tumors has not been clarified. In this study, we investigated this role by immunohistochemically staining PDGF and PDGF beta-receptors in paraffin-embedded dermatofibroma (DF), dermatofibrosarcoma protuberans (DFSP) and malignant fibrous histiocytoma (MFH) tissue. We also immunohistochemically investigated the relationship between PDGF beta-receptors and CD34, which is a known immunohistochemical marker for DFSP. Immunohistochemical studies using anti-PDGF-AA or BB antibodies showed that PDGF-AA and BB was found in 20 to 40% of the tumor cells in DF, DFSP, and MFH. No definite relationship for each tumor type was found. The expression of PDGF beta-receptors in DFSP and that of MFH tissue was significantly greater in comparison to DF and scar tissue. The expression of CD34 and PDGF beta-receptors in DFSP was observed in identical areas. These findings suggest that autocrine or paracrine growth stimulation, through PDGF beta-receptors, is related to the tumorous proliferation of fibrohistiocytic tumors, and the expression of PDGF beta-receptors might play a role in the proliferation of CD34 positive tumor cells.

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.

Pediatric Dermatofibrosarcoma Protuberans: Multi-Institutional Outcomes

Dermatofibrosarcoma protuberans (DFSP) is an intermediate-grade tumor originating from the dermal fibroblasts. It's a locally invasive tumor with a potential of distant site metastasis. It usually forms after a long plaque which can be in an atrophic or a kleoid-like sclerotic character. The lesion very rarely settles in the breast. Here we report a 52 year-old Caucasian woman with a dermatofibrosarcoma protuberans in her right breast. Patient's lesion arose from a long time keloid-like scleroatrophic looking plaque. Histopathologic examination did not reveal any malignant cells in the sclerotic plaque where the nodule arose from. Cells from nodular part of the lesion were CD34 positive immunohistohemically but there was no positive staining in the sclerotic plaque. The lesion was excised together with the pectoralis fascia. For reconstruction, an elliptically shaped latissimus dorsi musculocutaneous flap was designed. There were no recurrences in the postoperative 2nd year follow-up. To our knowledge this is the first reported case of dermatofibrosarcoma protuberans of a breast arising from a benign keloidlike sclerotic plaque.

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 (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...