Expression of embryonic stem cell markers SOX2 and nestin in dermatofibrosarcoma protuberans and dermatofibroma

Background: Dermatofibrosarcoma protuberans (DFSP) was recently proposed to originate from a nestin‐positive stem cell. In postnatal skin, nestin and another embryonic stem cell marker, SOX2, display a similar expression pattern with immunoreactivity in the hair follicle papilla and scattered cells of the perifollicular connective tissue sheath. The distribution pattern differs only in early embryogenesis, when nestin but not SOX2 is also expressed throughout the entire interfollicular dermis. We speculated that DFSP would not only be nestin‐positive but also SOX2‐positive. Methods: With appropriately reacting external and internal controls, we examined 24 examples of DFSP for SOX2 and nestin. For comparison, we included 10 dermatofibromas (DFs). Results: All 24 cases of DFSP were immunoreactive for nestin but negative for SOX2. The DFs were both nestin‐negative and SOX2‐negative. Conclusions: The observed staining pattern may indicate that DFSP derives from a subtype of nestin‐immunoreactive mesenchymal stem cell that is different from the nestin‐ and SOX2‐positive cell population of the perifollicular mesenchyme. Alternatively, nestin expression in DFSP may represent a recapitulation of the staining pattern in early embryogenesis without necessarily indicating that the nestin‐positive cells represent stem cells. Also, DFSP may derive from hair follicle‐associated mesenchymal stem cells that have lost their SOX2 expression. Sellheyer K, Nelson P, Patel RM. Expression of embryonic stem cell markers SOX2 and nestin in dermatofibrosarcoma protuberans and dermatofibroma.     

Stromelysin-3 expression in the differential diagnosis of dermatofibroma and dermatofibrosarcoma protuberans: comparison with factor XIIIa and CD34

BACKGROUND: The distinction between dermatofibroma (DF) and dermatofibrosarcoma protuberans (DFSP) is a well-known challenge for dermatopathologists. Immunohistochemical stains have been used to augment routine histological examination to aid in differentiating DF from DFSP. Stromelysin-3 (ST3) is a member of the matrix metalloproteinase (MMP) family, MMP-11, which is expressed in the skin during wound healing and in the stroma of basal cell carcinoma. Recent studies demonstrated that DFs expressed ST3, whereas DFSPs were only rarely ST3 positive. OBJECTIVES: To assess the expression of ST3 in DF and DFSP and to ascertain whether ST3 is superior to factor XIIIa or CD34 in differentiating DF from DFSP, by comparison with factor XIIIa and CD34 expression. METHODS: Immunohistochemical staining was performed on 23 cases of DF and 17 cases of DFSP, using antibodies to ST3, factor XIIIa and CD34. RESULTS: ST3 was expressed in all cases of DF (23 of 23) but only one case showed weakly positive staining in DFSP (one of 17). The mean +/- SD ST3 immunohistochemistry (IHC) score in DF was 4.52 +/- 0.67. The sensitivity of ST3 was 100% and the specificity was 94%. Factor XIIIa was expressed in all cases of DF (23 of 23) and in five of the 17 DFSPs. The mean +/- SD factor XIIIa IHC score in the DFs was 4.43 +/- 0.73. The sensitivity of factor XIIIa was 100% and the specificity was 71%. CD34 was expressed in four of the 23 DFs and 16 of the 17 DFSPs. The mean +/- SD CD34 IHC score in the DFSPs was 4.41 +/- 1.37. The sensitivity of CD34 was 94% and the specificity was 83%. CONCLUSIONS: Immunohistochemical staining with a commercial anti-ST3 antibody can be successfully carried out in routine dermatopathology. We confirmed that ST3 is a positive marker for DF and that ST3 staining might be more reliable than factor XIIIa staining in differential diagnosis of DF and DFSP. As the present study showed that ST3 was not absolutely negative in all cases of DFSP, the combination with CD34 immunostaining could make the distinction more reliable.     

The expression levels and the differential expression of transforming growth factor-beta receptors in dermatofibroma and dermatofibrosarcoma protuberans

BACKGROUND: Dermatofibroma (DF) and dermatofibrosarcoma protuberans (DFSP) are benign and intermediate malignant fibrotic dermal tumours, respectively. The contribution of transforming growth factor (TGF)-beta has been implicated in the progression of sclerosis in fibrotic diseases. OBJECTIVES: To investigate the expression of TGF-beta receptors in these fibrotic tumours. METHODS: We examined the expression levels of TGF-beta type I and type II receptors (TGFbeta-RI and TGFbeta-RII) in DF and DFSP using in situ hybridization and immunohistochemical analysis. We also examined the expression of TGF-beta1 and collagen type I using immunohistochemical analysis. RESULTS: We detected strong expression of TGFbeta-RI and TGFbeta-RII on epidermis and epidermal appendages, moderate expression in vascular endothelial cells, smooth muscle cells and neural tissues, and weak expression in fibroblasts in normal skin sections. The expression levels of TGFbeta-RI and TGFbeta-RII were elevated in the tissue sections of DF in comparison with normal dermal sections using in situ hybridization and immunohistochemical staining. Furthermore, the expression of TGFbeta-RI and TGFbeta-RII was strong in spindle-shaped cells around DF. The expression of TGFbeta-RI and TGFbeta-RII was decreased in DFSP in comparison with DF, and their expression was found to be homogeneous in each DFSP tumour cell. The staining for TGF-beta1 was found prominently on matrix and spindle-shaped tumour cells of DF, and peripheral regions of DFSP. Weak expression of TGF-beta1 was found on normal skin or tumour cells in the central part of DFSP. Type I collagen expression was found on spindle-shaped tumour cells in DF, but not in tumour cells of DFSP. CONCLUSIONS: These results suggest the possibility that TGF-beta signalling may contribute to the fibrosis around DF, and that TGF-beta receptors may play important roles in TGF-beta signalling. The expression patterns of TGFbeta-RI and TGFbeta-RII may be helpful in distinguishing these diseases.     

Dermatofibrosarcoma protuberans: a tumour of nestin‐positive cutaneous mesenchymal stem cells?

Background There is an increasing body of evidence suggesting that malignancies arise from mutated stem cells, which has led to the formulation of the cancer stem cell hypothesis. It has also been suggested that cutaneous malignancies originate from a mutated stem cell. To date, mesenchymal tumours of the skin have not been the focus of the cancer stem cell hypothesis. A population of mesenchymal stem cells has recently been identified in the dermal compartment of the skin. These proposed stem cells are positive for the neuroepithelial stem cell marker nestin. Objectives  To describe the expression pattern of nestin, a neuroepithelial stem cell protein, in dermatofibrosarcoma protuberans (DFSP). Methods Immunohistochemical evaluation of DFSP with a monoclonal antibody against nestin was performed using standard techniques. For comparison we also analysed dermatofibromas (DF). In addition, we used antibodies against CD34 and Factor XIIIa; the proliferation marker Ki67 was also used. Results Strong immunoreactivity for nestin was found in DFSP whereas all DF cases were nestin‐negative. Conclusions We propose that DFSP may represent a clonal expansion of a nestin‐positive mesenchymal stem cell which would put this tumour in line with other neoplasms for which the cancer stem cell hypothesis was formulated. We suggest the use of nestin as an additional marker for DFSP, especially in cases of negative immunoreactivity for CD34. Nestin may also be employed for margin evaluation of DFSP in micrographic (Mohs) surgery.     

幼年隆突性皮肤纤维肉瘤

报告1例幼年隆突性皮肤纤维肉瘤。患儿男,8岁。左侧腹股沟皮肤红色结节5个月。皮肤科检查：左侧腹股沟皮肤见一花生米大的半球形粉红色结节,表面光滑,境界清楚,结节质中等,与皮肤粘连,浸润感明显。皮损组织病理检查：表皮基本正常,真皮有增生的梭形细胞组成的细胞团块,部分梭形细胞呈特征性席纹状排列,未见明显细胞异形及核分裂象。免疫组化：增殖核抗原（Ki-67）(5%+),CD34(+),S-100蛋白（-）。分子生物学检测：COL1A1-PDGFB融合基因比例70%。诊断：隆突性皮肤纤维肉瘤。治疗上予扩大切除术辅以术后放疗,随访无复发。     

Clinical variants of the preprotuberant stage of dermatofibrosarcoma protuberans

BACKGROUND: Some cases of dermatofibrosarcoma protuberans (DFSP) do not protrude above the skin. OBJECTIVES: To assess the prevalence of these DFSPs and further to describe their presentation and course. METHODS: One hundred and forty-three patients were retrospectively collected. They were asked to complete a standardized questionnaire indicating the history and appearance of the DFSP from the first skin changes identified to the time of diagnosis. RESULTS: Eighty-one DFSPs were described as protuberant ab initio, and 62 as initially nonprotuberant (npDFSP). The latter remained at this stage for a mean period of 7.6 years. Twenty-nine per cent of npDFSPs were 'morphoea-like', 19% were 'atrophoderma-like' and 42% were 'angioma-like'. Age at diagnosis was similar for both initial presentations. npDFSPs were most often misdiagnosed by physicians. CONCLUSIONS: Nearly half the patients first identified their early DFSP-related skin changes as patches. Both this frequency and the long duration at this preprotuberant stage should prompt dermatologists to consider the diagnosis of DFSP earlier, in order to make surgical treatment easier.     

先天性黏液型隆突性皮肤纤维肉瘤一例并文献复习

先天性DFSP临床罕见,其临床表现可类似血管性病变。黏液型先天性隆突性皮肤纤维肉瘤(congenital dermatofibrosarcoma protuberans,DFSP)是DFSP独特而罕见的亚型,具有其特征性病理组织学改变,生物学行为属交界恶性/潜在低度恶性。先天性黏液型DFSP更为罕见,国外仅有2例散发病例报道。本文报道一例并回顾相关文献。患儿,女,1岁9个月。出生后即有背部肿物,曾于外院误诊为血管瘤,予盐酸噻吗诺尔眼药水外敷治疗1年余,效果不佳。肿物不断增大,就诊我科后,予手术切除肿物并行病理组织学及免疫组织化学检查,诊断为先天性黏液型隆突性皮肤纤维肉瘤。考虑病理回报底切缘最近距离仅0.25 mm,根据指南行肿瘤边缘1 cm扩大切除治疗,随访2年未发现复发及转移。     

Atrophic dermatofibrosarcoma protuberans: an uncommon and misleading variant

A 23-year-old man presented with an atrophic lesion on his left anterior shoulder that had been present for at least 10 years. A previous biopsy had suggested a fibrohistiocytic origin; however, clinically it resembled morphoea or atrophoderma, and the lesion was observed. Fifteen months later, the lesion was noted to have grown slightly. A repeat biopsy showed dermatofibrosarcoma protuberans, with a storiform spindle cell proliferation with positive CD34 staining. The lesion was excised with a 3-cm margin. Awareness of this rare presentation may assist in earlier diagnosis.     

Congenital dermatofibrosarcoma protuberans: 30 years of follow‐up

Dermatofibrosarcoma protuberans (DFSP) is a rare fibrohistiocytic tumor that commonly appears in adult patients. Few cases of DFSP in childhood have been reported. We describe a case of congenital DFSP that had been incompletely excised in childhood, and again at 28 years of age. The 33‐year‐old woman presented with a recurrence. When comparing the histologic features of the previous specimens excised in 1970 and 30 years later, the similar typical storiform pattern of fibromatous cells was found. The small number of proliferation‐marker‐positive cells was not altered over the course of 30 years. In line with a few additional reports, we suggest that congenital dermatofibrosarcoma protuberans is a tumor with a low malignant potential.     

Atrophic dermatofibrosarcoma protuberans with diffuse eosinophilic infiltrate

Atrophic dermatofibrosarcoma protuberans (atrophic DFSP) is a variant of dermatofibrosarcoma protuberans (DFSP), and is clinically characterized by depressed lesions. We report a patient with a typical atrophic DFSP lesion with marked eosinophilic infiltration. The patient was a 55-year-old woman with a dark-red, depressed lesion in the epigastric region. Histopathological examination of the lesion showed proliferation of fibroblast-like cells in a storiform pattern in the dermis and subcutaneous tissue. Immunohistochemical staining of tumor cells was positive for CD34. The lesion was histopathologically typical of DFSP, but no elevated lesion was clinically observed. Thus, a diagnosis of atrophic DFSP was made. Moreover, this tumor tissue exhibited marked eosinophilic infiltration. To our knowledge, they are no reports of eosinophilic infiltration in DFSP tissue. Therefore, this seems to be an extremely rare case of DFSP.     

A case of childhood dermatofibrosarcoma protuberans without detected cytogenetic abnormality

Dermatofibrosarcoma protuberans (DFSP) is a rare, infiltrative skin tumour of intermediate malignancy, with a limited potential for metastasis but a high rate of recurrence; specific cytogenetic abnormalities are now known. Childhood DFSP has been considered a rarity in the past, but it is now recognized that many cases of childhood DFSP are diagnosed only in adulthood. Despite advances in the understanding of its pathogenesis as well as the development of valuable immunohistochemical and cytogenetic diagnostic techniques, there often remains a significant delay between the initial presentation and diagnosis of DFSP. We report a case of childhood DFSP in which the diagnosis was reached only after a nodular lesion developed in a plaque that was initially present. Causes for delay between initial presentation and diagnosis in childhood DFSP are discussed. Histology and immunostaining in our patient showed the typical features of DFSP, but the G-banded cytogenetic analysis of short-term tissue culture was negative. However, this technique offers only a detection rate between 50% and 80%. Clinicians should be aware of the limitations of newer diagnostic techniques. Increasing recognition amongst paediatricians and paediatric dermatologists that childhood DFSP is not as rare as once believed will probably lead to the use of newer diagnostic methods at an earlier stage, and so reduce the delay between the onset of symptoms and diagnosis.     

Tissue culture study of dermatofibrosarcoma protuberans

We cultured non-epithelial cells derived from dermatofibrosarcoma protuberans (DFSP). The cells proliferated well, to the same degree as fibroblasts. DFSP cells, however, differed from fibroblasts in several aspects: 1) DFSP cells were bigger than fibroblasts, and grew in various directions, 2) acid phosphatase, and non-specific esterase stained abundantly demonstrated in DFSP cells, 3) DFSP cells showed immunophagocytosis of Candida albicans and Staphylococcus aureus, and 4) DFSP cells had Fc and C3 receptors. DFSP cells are, therefore, considered to originate from histiocytes.     

纤维肉瘤型隆突性皮肤纤维肉瘤一例

摘要] 报告1例纤维肉瘤型隆突性皮肤纤维肉瘤(DFSP-FS)。患者女,36岁。背部反复丘疹、结节12年。曾经2次手术切除。组织病理检查示瘤细胞排列呈涡纹状,形态较一致,呈梭形,部分区域内瘤细胞排列成鱼骨状,异型性及分裂相均较前者为高。免疫组化检查示涡纹状结构区域内瘤细胞CD34弥漫强阳性,鱼骨状区域仅个别细胞CD34表达阳性。诊断：纤维肉瘤型隆突性皮肤纤维肉瘤。行广泛切除术,术后9个月,未见复发。     

伴有隆突性皮肤纤维肉瘤的副肿瘤性天疱疮1例报告

目的：报告1例伴有隆突性皮肤纤维肉瘤的副肿瘤性天疱疮。方法：对副肿瘤性天疱疮并隆突性皮肤纤维肉瘤病例的临床表现进行表述，并检查了组织病理和免疫病理。结果：经临床和实验室检查证实，为副肿瘤性天疱疮伴发隆突性皮肤纤维肉瘤。结论：副肿瘤性天疱疮不但与内脏肿瘤有关，也可伴发皮肤肿瘤。     

Nodular sclerotic change in dermatofibrosarcoma protuberans: a potential diagnostic problem

Nodular sclerotic change in dermatofibrosarcoma protuberans (DFSP) is not a well-recognized event. Sclerotic change is reported in three patients with DFSP: a 33-year-old woman with a left subclavian mass, a 29-year-old woman with a mass on the left crus and a 31-year-old man with a mass on the left cheek. Histologically, lesions consisted of two types of feature, one type being typical of DFSP and the other being rich in collagen. In the first patient, each type formed a distinct compartment, each of which contained scattered cells containing melanin pigment. In the second patient, foci with typical DFSP histology were distributed within the collagen-rich area and also formed a substantial compartment in the periphery of the lesion, with pigmented cells being distributed mainly in and around the cellular area. In the third patient, the collagenous area occupied about half of the lesion. There was no pigmentation. In all three cases the collagen-rich area contained sparsely distributed fibroblast-like cells that stained positive with CD34. Sclerotic change in DFSP could cause substantial difficulty in diagnosis if the biopsy material were partial and small. The clinical history and knowledge about the existence of this kind of histological variation in DFSP are important.     

色素性隆突性皮肤纤维肉瘤一例

患者,女,40岁.背部肿物6年余.组织病理示:真皮及皮下组织巨大肿物,其内大量梭形细胞呈席纹状排列,其间见轻微核异型,并可见大量黑素细胞及黑素颗粒.诊断:色素性隆突性皮肤纤维肉瘤.治疗:手术沿肿物扩大2 cm切除,随访3个月无复发.     

Establishment of a human dermatofibrosarcoma protuberans cell line: cytological characteristics

We established a dermatofibrosarcoma protuberans (DFSP) cell line derived from a DFSP tumor from a 69-year-old female. The population doubling time of the cells was about 45 hours. The cells were mostly round, although a few triangular or spindle-shaped cells were also found. They could not be transplanted into nude mice. These cells had some histiocyte characteristics which are not observed in fibroblasts: 1) Electron microscopically, there were more lysosomes and phagolysosomes than in fibroblasts. Dense bodies and myelin figures derived from lysosomes were also observed. 2) Staining with acid phosphatase (ACPase), esterase, and alpha-1-antitrypsin was positive. 3) The cells had C3 receptors but no Fc receptors. However, there were two differences between DFSP cells in the established line and those in the early stages: in the former, the capacity for immunophagocytosis (Fc receptors and phagocytosis of Candida albicans) and collagen synthesis were almost entirely absent.