Acral dermatofibrosarcoma protuberans with myoid differentiation: A report of 2 cases

Dermatofibrosarcoma protuberans (DFSP) is a low‐grade mesenchymal neoplasm with a tendency for local recurrence; it is rarely metastatic. Dermatofibrosarcoma protuberans typically arises in the trunk and proximal extremities. However, it can arise in unusual sites such as the hands and feet. Several variants have been described, including DFSP with myoid differentiation, which is very uncommon. This variant tends to be observed more with the fibrosarcomatous variant, and it can be either in the form of myoid bundles and nodules with no vascular relationship or represent hyperplastic blood vessels within the tumor. Here, we report 2 cases of DFSP with myoid differentiation (ordinary and fibrosarcomatous) on the foot. To the best of our knowledge, these cases represent the first 2 cases of acral DFSP with myoid differentiation.     

Leiomyomatous nodules and bundles of vascular origin in the fibrosarcomatous variant of dermatofibrosarcoma protuberans

We report 5 cases of the fibrosarcomatous variant of dermatofibrosarcoma protuberans, 4 of which presented a morphologic change of intraneoplastic blood vessels not previously recognized. This change consisted of focal proliferation of smooth muscle cells, resulting in hypertrophy, generally eccentric, of vascular walls with reduction and collapsing of vascular lumina. In 3 cases the proliferation was so intense it formed leiomyomatous nodules and bundles. This proliferation may originate in the smooth muscle cells of the vessel walls either by means of a hyper-plastic mechanism or in the pericytes via a line of differentiation leading to mature smooth muscle cells. In either case, we believe that it concerns a reactive process of the vessel walls very probably induced by adjacent neoplastic cells. The cases recently reported by Calonje and Fletcher as "myoid differentiation" of neoplastic cells in dermatofibrosarcoma protuberans (DFSP) may well be an expression of the same phenomenon, and therefore the presence of leiomyomatous areas in this tumor should not be used to support the theory of a fibroblastic/myofibroblastic line of differentiation for DFSP.     

Intravascular myopericytoma

BACKGROUND: Myopericytoma is a benign tumor composed of cells that show apparent differentiation towards putative perivascular myoid cells called myopericytes. It arises most commonly in the dermis or subcutaneous tissue of the extremities in adults. METHODS: We describe a myopericytoma that was unusual in its intravascular location. RESULTS: A 54-year-old man presented with a 10-year history of a painful slowly growing 1.5-cm nodule in the subcutaneous tissue of the thigh. Histologic examination of the excised lesion showed that is was entirely contained within the lumen of a vein. It was composed of a proliferation of myoid-appearing spindle cells, which were arranged in a striking concentric pattern around numerous blood vessels, in a manner that accentuated the vessel walls. This pattern is characteristic of myopericytoma. In some areas, fascicles of spindle cells, embedded in a myxoid stroma, bulged into the lumina of lesional vessels, reminiscent of myofibroma/myofibromatosis. Lesional spindle cells were diffusely positive for smooth muscle actin, focally positive for CD34 and were negative for desmin, cytokeratin, S100 protein, HMB-45 and CD31. CONCLUSION: This case illustrates that myopericytoma can be entirely intravascular in its location.     

Pigmented dermatofibrosarcoma protuberans with prominent meningothelial-like whorls

Dermatofibrosarcoma protuberans (DFSP) is a locally aggressive skin tumor. In addition to the conventional type, several morphologic variants have been described. Recognition of these uncommon variants will facilitate the diagnosis. We report herein a peculiar case of pigmented DFSP (Bednar tumor) with prominent meningothelial-like whorls, a distinctive pattern that has not been described previously in DFSP. The tumor occurred in a 40-year-old man who presented with a slowly growing mass on his left shoulder. The overall histological features were consistent with Bednar tumor. However, unexpected numerous meningothelial-like whorls were found in some areas of the tumor. Like the tumor cells in typical areas of Bednar tumor these meningothelial-like whorls were also positive for CD34 but negative for epithelial membrane antigen and S100 protein. The meningothelial-like whorls in Bednar tumor represent an eccentric arrangement of the tumor cells. We propose the term 'pigmented DFSP with prominent meningothelial-like whorls' to highlight the distinctive pattern of this novel DFSP variant.     

Vascular congenital dermatofibrosarcoma protuberans: a new histological variant of dermatofibrosarcoma protuberans

We describe a case of congenital dermatofibrosarcoma protuberans (DFSP) that masqueraded as a vascular tumor both clinically and histologically. Based on the infiltrative growth pattern, presence of capillary-sized vessels, and spindle cell areas with slit-like vascular spaces and numerous thin-walled vessels at the periphery of the tumor, a kaposiform hemangioendothelioma was initially diagnosed. Strong diffuse CD34 positivity and the extension into the subcutaneous fat with a sieve-like effect prompted the fluorescence in situ hybridization analysis, which demonstrated a reciprocal t(17;22) translocation. According to our knowledge, this is the first report of a vascular histological variant of DFSP. This unique variant represents a potential pitfall for dermatopathologists and underlines the importance of cytogenetic diagnostics in unusual cases of DFSP.     

皮肤纤维瘤与隆突性皮肤纤维肉瘤的临床病理比较

对皮肤纤维瘤（DF）与隆突性皮肤纤维肉瘤（DFSP）在临床、组织形态及免疫组化等方面进行了比较。DF20例,平均年龄37.75岁,好发于四肢,平均直径0.8cm。瘤细胞呈束状或旋涡状排列,局部可见车辐结构。平均每50个高倍视野核分裂为0.75个。常伴组织细胞和炎细胞浸润、胶原增生、表皮增生及黑色素增多,CD34（－）。瘤细胞密度与胶原增生及炎细胞浸润呈负相关,提示DF可能为反应性病变。DFSP10例,平均年龄49.1岁,好发于躯干,平均年龄49.1岁,好发于躯干,平均直径3.23cm。瘤细胞呈典型的车辐状排列,平均每50个高倍视野核分裂为5.5个。肿瘤背景清晰,少数可见炎细胞浸润及表皮增生,无胶原增生及黑色素增多,CD34（＋）。这些临床及病理特征有助于两者的鉴别诊断。     

A Case of Myxoid Dermatofibrosarcoma Protuberans

Dermatofibrosarcoma protuberans (DFSP) is a slowly growing dermal spindle cell tumor and its myxoid variant, a rare type of DFSP, is characterized by extensive myxoid degeneration. We present the case of a 69-year-old woman with a multinodular reddish plaque on her trunk. Histopathologically, the tumor was located in the dermis and consisted of uniform spindle-shaped cells, showing strongly positive reaction for CD34, and negative for both S-100 and desmin. In addition to the typical storiform pattern, prominent myxoid stromal changes were demonstrated. Herein, we report an interesting case of myxoid DFSP, rarely reported in the dermatology literature.     

Congenital Myxoid and Pigmented Dermatofibrosarcoma Protuberans: A Case Report

Dermatofibrosarcoma protuberans (DFSP) is a low‐grade, mesenchymal, spindle cell tumor. In addition to the classical form characterized by a storiform pattern of tumor cells, pigmented (Bednar's tumor) and myxoid variants can be observed. Classical DFSP and Bednar's tumor are easily diagnosed. The myxoid variant represents a diagnostic challenge. Pigmented and myxoid variants are rare and thus far have never been reported in association in congenital DFSP. We came across a unique DFSP that was, at the same time, congenital, pigmented, and myxoid. The tumor was surgically excised with broad free margins and no recurrence. The differential diagnosis with other entities such as giant cell fibroblastoma, CD34‐positive plaque‐like dermal fibroma, superficial plaque‐like CD34 DFSP, and neurocristic hamartoma is discussed. The recognition of this hybrid variant of congenital DFSP is important to avoid under‐ or overtreatment.     

CD34-positive eruptive fibromas

The list of entities comprising a proliferation of CD34 (+) spindle cells continues to grow. Described, herein, is a patient who had an indolent eruption of scattered papules composed of CD34 (+) spindle cells, beginning in adolescence.
An 18-year-old female patient presented with asymptomatic, tan/brown papules over the neck, chest, and proximal extremities. They appeared 6 years previously and had slowly increased in number. Biopsy from the neck showed a proliferation of plump spindle cells, associated with delicate collagen, in the upper reticular dermis. No atypia nor mitotic figures were present. The spindle cells were negative for S-100, muscle actins, and Factor XIIIa, but stained intensely with CD34. This unusual mesenchymal proliferation of CD34 (+) apparent dermal dendrocytes did not have the storiform pattern, short fascicles, nor mitotic figures of DFSP. The completely negative muscle markers helped to exclude dermatomyofibroma, and no morphological evidence of vasoformative differentiation was seen. The clinical picture militated against solitary fibrous tumor. These eruptive tumors are benign and thought to represent a distinctive fibroma produced by proliferated CD34 (+) stromal cells.     

CD34 immunoreactivity distinguishes between scar tissue and residual tumor in re-excisional specimens of dermatofibrosarcoma protuberans

Dermatofibrosarcoma protuberans (DFSP) is a locally aggressive tumor that often recurs after simple excision, and therefore usually requires wide surgical re-excision. It is sometimes difficult to distinguish histologically between residual tumor and scar tissue formed in response to the original biopsy. In an effort to solve this diagnostic problem, we have examined CD34 immunoreactivity in 10 primary biopsies of DFSP, 12 scars, and 7 re-excisional DFSP specimens containing residual tumor adjacent to scar tissue. In all 10 primary biopsies of DFSP, the tumor cells strongly and uniformly expressed CD34. In the 12 scars, only periaclnexal cells, enclothclial cells, and rare, scattered dendritic cells in the clermis were immunolabeled for CD34. In the 7 re-excisions of DFSP, the foci of residual DFSP were strongly immunolabeled, while the surrounding scar tissue was not. The pattern of CD34 immunoreactivity distinguishes DFSP from scar tissue, and thereby may permit more accurate assessment of surgical margins in re-excisional specimens of DFSP.     

Myxoid dermatofibrosarcoma protuberans: clinicopathologic, immunohistochemical, and molecular analysis of eight cases

Dermatofibrosarcoma protuberans (DFSP) represents a locally aggressive mesenchymal neoplasm of skin and subcutis with characteristic clinicopathologic, immunohistochemical, and molecular findings. In addition to typical cases, morphologic variants such as pigmented, fibrosarcomatous, myofibroblastic, and granular cell DFSP have been described. Purely or predominantly myxoid DFSP is extremely rare, and may cause considerable diagnostic problems. Eight cases of predominantly myxoid DFSP were studied. Paraffin-embedded blocks and slides were retrieved from the files of the authors. Clinical data were obtained from the referring pathologists and dermatologists. Immunohistochemistry was performed using the ABC method, and three cases were studied by polymerase chain reaction technique. There were six male and two female patients (age range: 29 to 74 years). Locations included the inguinal area (three cases), thigh, upper arm, shoulder, abdominal wall, and back (one each). The patients were treated by wide excision as well as reexcision. Tumor size ranged from 1.5 to 12 cm. Histologically, a nodular growth with peripheral diffuse infiltration, as well as a diffusely infiltrating growth of relatively uniform spindled and stellated tumor cells containing slightly enlarged nuclei, was noted. Three cases were entirely myxoid, and in five cases more than 80% of the tumor area showed myxoid stromal changes. In two cases each, focal fibrosarcomatous and focal giant cell fibroblastoma-like changes were present. At least focally, hypocellular areas were evident in one case. Scattered enlarged tumor cells were seen in two cases. The mitotic rate ranged from 1 to 10 mitoses in 10 high-power fields. Numerous blood vessels with slightly fibrosed vessel walls were seen in seven cases. Immunohistochemically, tumor cells in all cases stained positively for CD34, and in one case each a focal expression of alpha-smooth muscle actin and epithelial membrane antigen (EMA) was noted. The remaining antibodies (CD99, CD31, S-100, Factor XIIIa) were all negative. Polymerase chain reaction technique showed in one case the characteristic COL1A1-PDGFB fusion gene. Follow-up information in seven cases (range: 2 months to 10 years; mean: 62 months; median: 48 months) revealed a local recurrence at 5 years. In conclusion, myxoid DFSP represents a very rare morphologic variant with characteristic changes that has to be distinguished from benign and malignant myxoid mesenchymal neoplasms as superficial angiomyxoma, superficial acral fibromyxoma, myxoid solitary fibrous tumor, myxoid perineurioma, low-grade myxofibrosarcoma, low-grade fibromyxoid sarcoma, myxoid liposarcoma, and myxoid synovial sarcoma.     

CD34 expression in desmoplastic melanoma

BACKGROUND: Primary and metastatic malignant melanoma can simulate various soft tissue tumors, including dermatofibrosarcoma protuberans (DFSP). Expression of CD34, a marker characteristic of DFSP, as well as other spindle cell tumors, has not been previously documented in malignant melanoma. METHODS: We present here an unusual case of metastatic malignant melanoma with a strong histologic resemblance to DFSP and also CD34 expression. RESULTS: The patient, a 72-year-old man with a history of an invasive malignant melanoma of the skin of the right lower abdomen, presented with a right axillary mass. Histologic sections revealed intersecting fascicles of spindle cells with nuclear pleomorphism and numerous mitotic figures, diffusely infiltrating the adipose tissue in a pattern closely simulating that seen in DFSP. In other foci, epithelioid neoplastic cells with abundant cytoplasm, prominent nucleoli, nuclear pseudoinclusions, and focal cytoplasmic melanin pigment were seen. The neoplastic spindle cells were strongly labeled by two anti-CD34 monoclonal antibodies. Some of the spindle cells and the majority of the epithelioid neoplastic cells expressed S-100 protein and focally tyrosinase. The tumor cells were negative for HMB-45 and MART-1. Melanosomes were not identified by electron microscopy. CONCLUSION: This case demonstrates the potential of melanoma to simulate DFSP closely, on both morphologic and immunohistochemical grounds, and confirms the utility of employing a broad panel of immunohistochemical reagents in problematic cases.     

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.     

CD34‐positive infantile myofibromatosis: Case report and review of hemangiopericytoma‐like pattern tumors

We describe a case of CD34‐positive infantile myofibromatosis with hemangiopericytoma‐like pattern. A 2‐day‐old Japanese boy presented with multiple hemispherical nodules on the extremities and back. There was a biphasic histological growth in the dermis, accompanied by a hemangiopericytoma‐like pattern with antler‐like branching vessels. Tumor cells were oval to spindle‐shaped myoid cells with bland appearance. Immunohistochemically, vimentin, calponin and CD34 were positive, while α‐smooth muscle actin, h‐caldesmon, HHF35 and desmin were negative. Although CD34 was positive, the present case could be diagnosed as infantile myofibromatosis. Myopericytoma, myofibroma/myofibromatosis, glomus tumor, glomangiopericytoma and angioleiomyoma share a continuous spectrum of benign hemangiopericytoma‐like pattern tumors. Myofibroma/myofibromatosis is nearly included in myopericytoma among pericytic (perivascular) tumors, and could be positive for CD34. Several immunohistochemical panels of smooth muscle markers are needed for the diagnosis of pericytic (perivascular) tumors.     

Myoid differentiation in dermatofibrosarcoma protuberans and its fibrosarcomatous variant: clinicopathologic analysis of 5 cases

We report a series of five cases of dermatofibrosarcoma protuberans, four of which were fibrosarcomatous and all of which showed histologic and immunohistochemical evidence of focal myoid/myofibroblastic differentiation (accounting for up to 5% of each tumor). These lesions were identified amongst 208 cases of dermatofibrosarcoma protuberans including 24 examples of the fibrosarcomatous variant. Three of the five patients were male and two were females; all were adults (37–72 years). One case arose on the scalp and two cases each on the abdominal wall and upper trunk. All tumors were less than 5cm in diameter and preoperative duration ranged from 2 months to 10 years. In three cases with follow-up there was no recurrence. Histologically, all tumors were typical fibrosarcomatous or ordinary dermatofibrosarcoma protuberans but for the presence of scattered to confluent nodules and bundles of eosinophilic spindle cells associated with well-defined cytoplasmic margins and vesicular nuclei associated with focal stromal hyalinization. While the typical dermatofibrosarcoma protuberans areas were CD34 positive, the myoid areas were negative for this antibody and positive for smooth muscle actin and pan-muscle actin. All tumors were desmin negative. Recognition of myofibroblastic differentiation in fibrosarcomatous dermatofibrosarcoma protuberans is important not only because it gives support to the theory of a fibroblastic/myofibroblastic line of differentiation for this type of tumor, but also because it might be a source of confusion with other myofibroblastic lesions (e.g. myofibromatosis, adult myofibroma), especially when small biopsies are evaluated.     

Immunohistochemical analysis of platelet-derived growth factor and its receptors in fibrohistiocytic tumors

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 β-receptors in paraffin-embedded dermatofibroma (DF), dermatofibrosarcoma protuberans (DFSP) and malignant fibrous histiocytoma (MFH) tissue. We also immunohistochemically investigated the relationship between PDGF β-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 β-receptors in DFSP and that of MFH tissue was significantly greater in comparison to DF and scar tissue. The expression of CD34 and PDGF β-receptors in DFSP was observed in identical areas. These findings suggest that autocrine or paracrine growth stimulation, through PDGF β-receptors, is related to the tumorous proliferation of fibrohistiocytic tumors, and the expression of PDGF β-receptors might play a role in the proliferation of CD34 positive tumor cells.     

Atypical Response of Xeroderma Pigmentosum to 5‐Fluorouracil: A Histopathological Image Analysis Study Reveals New Insight into Etiopathogenesis

The histological distinction between dermatofibroma (DF) and dermatofibrosarcoma protuberans (DFSP) may be difficult. CD34 and Factor XIIIa have been used to differentiate DF from DFSP, but there is a lack of specificity. CD44 is a membrane glycoprotein which has multiple isoforms generated by alternative splicing of variant exons. CD44 is the principal cell surface receptor for hyaluronate (HA). In this study we explored the expression of standard CD44 (CD44s) and its isoforms (CD44v3, CD44v4, CD44v5, CD44v6, CD44v7, CD44v7v8, and CD44v10), and HA in DF and DFSP. Immunohistochemistry was performed on the biopsy specimens of 15 cases of DF and 4 cases of DFSP, using antibodies for the CD44s and its isoforms, and hyaluronate binding protein (HABP). Tumor cells displayed a strong CD44s immunoreactivity in all cases of DF whereas a faint HA positivity was observed in the tumor stroma. DF cells were negative for CD44v3, CD44v4, CD44v6, CD44v7 and CD44v7v8 but they showed a strong reactivity for CD44v5 and CD44v10. CD44s expression was significantly reduced or absent in all DFSP lesions and the tumor stroma displayed a strong staining for HA. Our results indicate that CD44 and HA can be used as additional diagnostic markers to distinguish DF from DFSP.     

A study of CD117 expression in dermatofibrosarcoma protuberans and cellular dermatofibroma

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a relatively uncommon spindle cell tumor of the skin. It is locally aggressive and can be a therapeutic challenge. There are case reports of partial response of DFSP to the tyrosine kinase inhibitor STI571 (Imatinib), despite the reported negativity of the tumor cells for CD117. At least one publication reported focal CD117 positivity of DFSP cells, and we would like to clarify the issue. Cellular dermatofibroma (CDF) can mimic DFSP, but typical cases are easily differentiated from DFSP by their staining pattern for CD34 and factor 13a. We also report our experience with CD117 staining of typical CDFs. METHODS: Thirty-seven cases of clear-cut DFSP and 13 cases of clear-cut CDF were retrieved from the archives of Sunnybrook Health Sciences Center between 2000 and 2005. RESULTS: All DFSPs were CD34 (+), factor 13a (-) and CD117 (-). All CDFs were factor 13a (+), CD34 (-) and CD117 (-). CONCLUSIONS: Our study on a relatively large number of cases confirms the negativity of DFSP and CDF for CD117. Therefore, if adjuvant therapy is attempted with drugs such as STI571 (Imatinib), the eligibility of patients should not be based on immunohistochemical assessment of CD117 expression.