Analysis of the COL1A1-PDGFB fusion gene in a case of dermatofibrosarcoma protuberans with a fibrosarcoma component

Dermatofibrosarcoma protuberans (DFSP) is an infrequent tumor of intermediate malignancy, with little tendency to develop metastases but with a high rate of local recurrence. Cytogenetically, DFSP is characterized by a reciprocal translocation, t(17;22)(q22;q13), which is a conditioning factor in the fusion of the collagen type I alpha I gene (COL1A1) in chromosome 17q with the platelet-derived growth factor beta chain gene (PDGFB) in chromosome 22q. The fusion of these genes is variable, involving one of the 51 exons of the COL1A1 gene and exon 2 of the PDGFB gene. We present the case of a 37-year-old woman with a tumor on the arm whose histology showed a neoplastic infiltration of the subcutaneous cellular tissue made up of fusiform cells with an elongated nucleus in a storiform pattern and other more pleomorphic cells in a herringbone pattern, compatible with DFSP with a fibrosarcoma component. The molecular biology study with RT-PCR analysis of paraffin-embedded material and later sequencing showed a new fusion of exon 19 of the COL1A1 gene and exon 2 of PDGFB, supporting a diagnosis of DFSP. A study of the COL1A1-PDGFB fusion products is useful in cases where histology and immunohistochemistry are insufficient for the differential diagnosis of DFSP versus other sarcomas. It also justifies the use of new avenues of treatment with tyrosine kinase inhibitors.     

Pseudocystic dermatofibrosarcoma protuberans: report of two cases and demonstration of COL1A1-PDGFB rearrangement

We report two unique cases of dermatofibrosarcoma protuberans (DFSP) that included a pseudocystic component. Molecular analysis of one of the cases showed a characteristic COL1A1-PDGFB rearrangement in both the main tumor and also in the cells lining the pseudocystic portion of the tumor, confirming the diagnosis and indicating that the lining represented a component of the proliferation. It is important to raise awareness of this rare variant within the varied spectrum of DFSP. Shvartsbeyn M, Lazar AJF, Lopez-Terrada D, Meehan SA. Pseudocystic dermatofibrosarcoma protuberans: report of two cases and demonstration of COL1A1-PDGFB rearrangement.     

Detection of COL1A1-PDGFB fusion transcripts and platelet-derived growth factor alpha and beta receptors in giant cell fibroblastoma of the postsacrococcygeal region

We describe a 2-year-old girl with recurrent giant cell fibroblastoma (GCF) of the postsacrococcygeal region. Both the initial and recurrent tumours contained solid and angiectoid areas. The former was composed of loosely arranged wavy spindle cells and giant cells with a well-vascularized myxoid to collagenous stroma. The angiectoid spaces were often lined by multinucleated giant cells. Immunohistochemically, the tumour cells and small vessels in the tumour tissue were positive for platelet-derived growth factor (PDGF) alpha and beta receptors. Molecular analysis revealed fusion of collagen type Ialpha1 exon 26 with PDGF-B chain exon 2 that induced unscheduled production of PDGF-BB. These findings suggest that PDGF and its receptors significantly contribute to the development of GCF in both an autocrine and a paracrine manner.     

Application of COL1A1–PDGFB fusion gene detection by fluorescence in situ hybridization in biopsy tissue of dermatofibrosarcoma protuberans

Several uncommon variants of dermatofibrosarcoma protuberans (DFSP) and the limitations of small biopsies render pathological diagnosis difficult. The aim of this study was to analyze the utility of fluorescence in situ hybridization (FISH) in the detection of the collagen type I‐α1/platelet derived growth factor‐β (COL1A1–PDGFB) fusion gene in biopsies of DFSP. Twenty‐three consecutive biopsy specimens of DFSP were reviewed for clinicopathological features and examined with the COL1A1–PDGFB fusion probe and PDGFB break‐apart probe using FISH analysis. The 23 tumor samples consisted of 11 males and 12 females (mean age at diagnosis, 37 years; range, 14–75 years). Eighteen conventional DFSP, one Bednar tumor, two myxoid DFSP and two fibrosarcomatous DFSP samples were included in the group. Strong and extensive CD34 expression was observed in 19 of 23 cases (83%). Twenty‐one cases (91%) were positive for both the COL1A1–PDGFB fusion signal and the PDGFB break‐apart signal. This is one of the few studies to demonstrate the value of FISH analysis of the COL1A1–PDGFB gene, which could validate complicated and suspected diagnoses in the routine biopsy of DFSP.     

额部隆突性皮肤纤维肉瘤一例

患者男,56岁,因左前额部肿块1年余入院.患者20年前左前额部因黄豆大小肿块,曾行切除术.1年前肿块复发并增大,无明显自觉症状来我院就诊.皮肤科检查:左前额部见3 cm×2 cm×1 cm大小的肿块,呈淡红色半球形隆起于皮面,表面皮肤光滑,紧张,质地较硬,与皮肤粘连,但与深筋膜无明显粘连,无触压痛.肿块周围可见明显凹陷区.皮损组织病理:真皮中下层及脂肪内可见大量梭形细胞增生,细胞轻度异形,呈编织状排列.免疫组化染色:CD34(+),波形蛋白(+),CK(-),S-100(-),上皮膜抗原(-).诊断为隆突性皮肤纤维肉瘤.切除肿瘤并行游离全厚皮片移植,术后皮片生长良好,效果满意.     

额部隆突性皮肤纤维肉瘤一例

A 56-year-old male was admitted to the hospital for a mass on the left forehead for more than one year. Twenty years prior to the presentation, the patient developed a broad bean-sized nodule on the left forehead, thereafter, an in situ resection was performed. One year prior to the presentation, the lesion recurred and gradually enlarged with no evident symptom. Physical examination showed a pink, painless and indurated mass measuring 3 cm × 2 cm × 1 cm on the left forehead. The lesion appeared as a hemispheroid-shaped elevation, had a smooth and tense surface, and was adherent to skin but not to deep fascia. There was an obvious depression around the mass. Histopathological examination revealed an evident proliferation of spindle cells with a braid-like distribution in the mid- and lower dermis. Mild atypia was observed in these cells.Immunohistochemistry revealed that the tumor cells were positive for CD34 and vimentin, but negative for CK, S-100 and epithelial membrane antigen. A diagnosis of dermatofibrosarcoma protuberans was made. The lesion was resected followed by a free full thickness skin graft. After operation, the flap survived well, and a satisfactory outcome was achieved.     

Dermatofibrosarcoma protuberans: an early non-protuberant phase of the tumour

A 40-year-old female patient presented with a flat scar like plaque on the upper chest. The patient's perception of subtle change in the lesion was of paramount importance in the decision to biopsy this lesion of innocuous clinical appearance. Histopathological findings were those of dermatofibrosarcoma protuberans. This case illustrates the early clinical features of the tumour and a recommendation for taking a biopsy of any scar-like plaque where there is no clear history of preceding trauma.     

Dermatofibrosarcoma protuberans in childhood and adolescence: report of eight patients

Abstract:  We reviewed all occurrences of dermatofibrosarcoma protuberans in children under 17 years of age who were evaluated at Sainte-Justine Hospital, a tertiary-care pediatric center, between 1980 and 2002. The medical records and histologic features of all were reviewed. Eight patients were identified, three boys and five girls. The interval between apparent onset and diagnosis ranged from 3 months to 14 years. All lesions except one were removed by surgical excision with a margin of 1.5 to 3 cm including underlying fascia or by Mohs technique. Follow-up ranged from 2 to 15 years with median of 5 years. To date all the patients are alive and none has had a recurrence.     

Dermatofibrosarcoma protuberans: report of a case with a variant ring chromosome and metastases following pregnancy

Background: The most frequent molecular abnormality observed in dermatofibrosarcoma protuberans (DFSP) is the formation of a supernumerary ring chromosome or translocation resulting in fusion of the gene encoding the α‐chain of type 1 collagen, COL1A1 from 17q22, to the platelet‐derived growth factor β‐chain, PDGFB gene from 22q13. Rare cases documenting variant ring or marker chromosomes involving regions other than 17q22 and 22q13 have been reported. Further analysis in three of these cases demonstrated the presence of the COL1A1 and PDGFB genes. Methods: We report a further case of DFSP with a rare variant ring chromosome. The tumor appeared to undergo accelerated growth during pregnancy, then metastasized following pregnancy. We describe the clinical, histological, immunohistochemical, and cytogenetic features. Results: The metastatic tumor showed a variant r(17;?) chromosome. A locus‐specific probe was required to demonstrate presence of the PDGFB gene within the ring, indicating cryptic molecular rearrangement between chromosomes 17 and 22, and recombination with an unknown chromosome. Conclusions: Cryptic rearrangement of chromosomes 17 and 22 should be suspected in variant ring chromosomes and translocations. Pregnancy may contribute to accelerated growth of DFSP, and delay in surgical resection should be avoided.     

RNAi-mediated inhibition of COL1A1 and COL3A1 in human skin fibroblasts

Types I and III collagens are the major collagens comprising skin connective tissue. Defects in these collagens lead to diseases of dermal connective tissue and fibre hyperplasia. RNA interference (RNAi) provides a powerful tool to inhibit specific gene expression. In this study, we generated small interfering RNAs (siRNA) expression cassettes (SECs) by polymerase chain reaction (PCR) as a method to quickly screen the efficacy of siRNAs. We then cloned the most efficient SECs into vectors, using a rapid and novel method intrinsic to the design of the SEC, and transfected human skin fibroblasts (HSF) to generate stable lines. We show that the transfection of SECs into HSFs resulted in specific and effective repression of COL1A1 and COL3A1 expression (5.00% and 6.48% of control levels) provided a rapid method for testing candidate siRNA sequences. We report the use of vector-based RNAi to establish stable HSF cell lines with persistent knockdown over at least 30 days (25.21% and 22.12% of control levels). These stably modified HSF cell lines may be used for the study of other types of collagen or proteins of the extracellular matrix (ECM).     

Dermatofibrosarcoma protuberans: a population-based cancer registry descriptive study of 66 consecutive cases diagnosed between 1982 and 2002

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a rare malignant tumour of the skin, with an estimated incidence of 0.8 to five cases per 1 million people per year. OBJECTIVE: To study epidemiological, immunohistochemical and clinical features, delay in diagnosis, type of treatment and outcome of DFSP from 1982 to 2002. METHODS: Using data from the population-based cancer registry, 66 patients with pathologically proved DFSP were included (fibrosarcomatous DFSP were excluded). Each patient lived in one of the four departments of Franche-Comté (overall population of 1 million people) at the time of diagnosis. The main data sources came from public and private pathology laboratories and medical records. The rules of the International Agency for Research on Cancer were applied. RESULTS: The estimated incidence of DFSP in Franche-Comté was about three new cases per 1 million people per year. Male patients were affected 1.2 times as often as female patients were. The trunk (45%) followed by the proximal extremities (38%) were the most frequent locations. DFSP occurred mainly in young adults between 20 and 39 years of age. Mean age at diagnosis was 43 years, and the mean delay in diagnosis was 10.08 years. Our 66 patients initially underwent a radical local excision. Among them, 27% experienced one or more local recurrences during 9.6 years of follow-up. There was one regional lymph node recurrence without visceral metastases. These recurrences were significantly related to the initial peripheral resection margins. We observed a local recurrence rate of 47% for margins less than 3 cm, vs. only 7% for margins ranging from 3 to 5 cm [P=0.004; OR=0.229 (95%, CI=0.103-0.510)]. The mean time to a first local recurrence was 2.65 years. Nevertheless, there was no death due to the DFSP course at the end of the follow-up, and the final outcome was favourable. CONCLUSION: Our study emphasizes the importance of wide local excision with margins of at least 3 cm in order to prevent local recurrence. However, the recent development of inhibitors of signal transduction by the PDGFB pathway should soon modify the surgical strategy, which is often too mutilating.     

Dermatofibrosarcoma protuberans with lymph node involvement. A case report of simultaneous occurrence with an atypical fibroxanthoma of the skin

A 40-year-old man had dermatofibrosarcoma protuberans of the neck with rapid local recurrence, satellite nodules, and a cervical lymph node metastasis, occurring simultaneously with an atypical fibroxanthoma of the scrotum. These two tumors, with distinct clinical and pathologic features, are classified as histogenetically related lesions within the spectrum of the fibrous histiocytomas. The place for the dermatofibrosarcoma protuberans at the malignant end of this spectrum is clinically and ultrastructurally documented further in our patient.     

Dermatofibrosarcoma protuberans with fibrosarcomatous transformation: our experience,molecular evaluation of selected cases,and short literature review

Dermatofibrosarcoma protuberans with fibrosarcomatous transformation (DFSP-FS) is a higher grade tumor arising from dermatofibrosarcoma protuberans (DFSP). Recent literature highlights its impact on recurrence rates, metastatic rates, and survival. In this article, we aim to describe our experience with 13 cases of DFSP-FS in terms of pathologic findings, molecular alterations, clinical outcomes, management, and also perform a short recent literature review.