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Distant metastasis of dermatofibrosarcoma protuberans of the scalp--case report.

A 49-year-old man presented with a rare dermatofibrosarcoma protuberans (DFSP) of the scalp associated with local recurrence and distant metastasis to the lung and abdomen. An elastic-hard small mass on the right occipital scalp was initially treated by simple resection in another clinic. Ten years later, recurrent tumor was associated with infiltration to the calvarium, and resection was performed again also in another clinic. Approximately 1.5 years later, the patient was transferred to our clinic because of recurrence with intracranial involvement. Repeated relapses and metastasis to the lung were recognized despite surgery, chemotherapy, and local radiation. Eventually, the patient died of distant metastasis to the abdomen 17 years after the initial diagnosis. Scalp DFSP is very uncommon but is an aggressive scalp tumor, so initial wide local resection and local radiation therapy after surgery are important to prevent local recurrence and distant metastasis.

Abdominal Neoplasms↗

Immunohistochemical expression of matrix metalloproteinases 1, 2, 9, and 14 in dermatofibrosarcoma protuberans and common fibrous histiocytoma (dermatofibroma).

CONTEXT: Common fibrous histiocytoma (cFH) or dermatofibroma and dermatofibrosarcoma protuberans (DFSP) are 2 spindle cell mesenchymal tumors that are distinguished in part by their microscopic growth patterns and clinically by the greater propensity for DFSP to recur. Matrix metalloproteinases (MMPs) potentially play a role in modulating the growth patterns of cFH and DFSP by remodeling the extracellular matrix. OBJECTIVE: To evaluate the immunohistochemical (IHC) expression of MMP-1, MMP-2, MMP-9, and MMP-14 in DFSP and cFH, because (1) MMP-1, MMP-2, MMP-9, and MMP-14 are synthesized by dermal fibroblasts, the major constituent of DFSP and cFH; and (2) platelet-derived growth factor B, which is overexpressed in most examples of DFSP because of t(17;22), activates ets-1, a transcription factor that regulates molecules associated with tumor invasion and metastasis, including MMP-1, MMP-3, and MMP-9. DESIGN: Immunohistochemical studies were performed on archived, formalin-fixed, paraffin-embedded tissue of DFSP (n = 48) and cFH (n = 47).Results.-Significant IHC expression (>10% of tumor cells) in cFH included MMP-14 (27 [59%] of 46 tumors positive), MMP-2 (21 [47%] of 45 tumors positive), MMP-9 (9 [20%] of 45 tumors positive), and MMP-1 (6 [13%] of 46 tumors positive). No DFSPs showed significant IHC expression of any of the MMPs evaluated. However, anti- MMP-2 highlighted a rich microvascular element within deep tumor tissue present in 81% of DFSPs with a prominent subcutaneous component. CONCLUSION: Our IHC results indicate that MMP-1 and MMP-9 are not up-regulated in DFSP. Convincing expression of MMP-14 in cFH suggests that this MMP may affect the growth pattern of the lesion, perhaps by activating MMP-2 expression in tumor cells. In DFSP, MMP-2 may play a role in tumor angiogenesis.

Dermatofibrosarcoma↗

The atrophic variant of dermatofibrosarcoma protuberans in childhood: a report of six cases.

Dermatofibrosarcoma protuberans (DFSP) is typically diagnosed during early adult life at a tumoral stage. It occurs only rarely in children. We report six childhood cases of DFSP which presented initially with the misleading clinical appearance of atrophic plaques, and we review over 140 cases of DFSP in childhood. As compared with adult forms, DFSP in children does not show distinctive features except for a tendency for acral localization. The diagnosis is difficult because of the slow course of the lesions, which present initially as apparently benign atrophic morphoeaor keloid-like plaques. We believe that DFSP in childhood is probably under-estimated, as a significant proportion of patients diagnosed as young adults had an onset several years earlier. Better knowledge of the initial appearance is important for making an early diagnosis and for an easier surgical treatment.

Adolescent↗

Acral dermatofibrosarcoma protuberans with metastases.

Dermatofibrosarcoma protuberans (DFSP) is an uncommon cutaneous tumor that occurs rarely on the extremities. This tumor has a particular propensity for local recurrence following seemingly adequate excision. Metastases are rare, and usually follow repeated local recurrences. On rare occasions, fibrosarcomatous change may arise in a DFSP, and appears to affect adversely the prognosis. The adequacy of the initial resection is the most important prognostic factor; however, suggested margins vary between 1.5 and 5 cm. The ideal margin of resection on the foot is unknown. We report a patient with recurrent, acral DFSP with fibrosarcomatous change and pulmonary parenchymal metastases in a 48-year-old black male.

Dermatofibrosarcoma↗

Dermatofibrosarcoma protuberans harboring t(9;22)(q32;q12.2).

More than 20 cases of dermatofibrosarcoma protuberans (DFSP) exhibiting chromosomal abnormalities have been reported. Approximately three fourths of these tumors have harbored supernumerary ring chromosomes, which have been suggested to be specific for this tumor. However, a small number of DFSPs with translocations such as t(2;17), t(X;7), and t(17;22) have recently been reported. We report a DFSP arising in a 23-year-old woman which unexpectedly exhibited the balanced translocation, t(9;22)(q32;q12.2) as the only anomaly with G-band technique. Dual-color fluorescence in situ hybridization (FISH) confirmed these cytogenetic findings. Similar to that previously reported for DFSPs with translocations, the present tumor also lacked ring chromosomes.

Adult↗

The dermatofibrosarcoma protuberans-associated collagen type Ialpha1/platelet-derived growth factor (PDGF) B-chain fusion gene generates a transforming protein that is processed to functional PDGF-BB.

Dermatofibrosarcoma protuberans (DFSP) displays chromosomal rearrangements involving chromosome 17 and 22, which fuse the collagen type Ialpha1 (COLIA1) gene to the platelet-derived growth factor (PDGF) B-chain (PDGFB) gene. To characterize the functional and structural properties of the COLIA1/PDGFB fusion protein, we generated a stable NIH3T3 cell line that contained a tumor-derived chimeric gene resulting from a COIA1 intron 7-PDGFB intron 1 fusion. Expression of the fusion protein led to morphological transformation and increased growth rate of these cells. The PDGF receptor kinase inhibitor CGP57148B reversed the transformed phenotype and reduced the growth rate of COLIA1/PDGFB-expressing cells but had no effects on control cells. The presence of dimeric COLIA1/PDGFB precursors was demonstrated through PDGFB immunoprecipitations of metabolically labeled cells and also by PDGFB immunoprecipitations followed by immunoblotting with COLIA1 antibodies. Pulse-chase studies demonstrated that the COLIA1/PDGFB precursor was processed to an end product that was indistinguishable from wild-type PDGF-BB. Finally, COLIA1/PDGFB-expressing cells generated tumors after s.c. injection into nude mice, and tumor growth was reduced by treatment with CGP57148B. We conclude that the COLIA1/PDGFB fusion associated with DFSP contributes to tumor development through ectopic production of PDGF-BB and the formation of an autocrine loop. Our findings, thus, suggest that PDGF receptors could be a target for pharmacological treatment of DFSP and giant cell fibroblastoma, e.g., through the use of PDGF receptor kinase inhibitors such as CGP57148B.

3T3 Cells↗

Dermatofibrosarcoma protuberans of the vulva: clinicopathologic and immunohistochemical analysis of four cases, one with fibrosarcomatous change, and review of the literature.

Only 18 cases of dermatofibrosarcoma protuberans (DFSP) of the vulva have been reported. This article describes the clinicopathologic and immunohistochemical findings of four additional vulvar DFSPs. The median patient age was 54 years (range, 36 to 69 years) and the most common clinical presentation was a slowly growing vulvar mass. The tumors occurred in the left paraclitoral area (1 case), right labium majus (1 case), left labium majus (1 case), and mons pubis (1 case). The tumor size, known in three cases, ranged from 1.2 to 5.0 cm in greatest dimension. Microscopically, the tumors were composed of bland spindle cells with oval or wavy nuclei arranged in a cartwheel pattern; in one case, fibrosarcomatous areas were apparent. CD34 immunostaining was positive in the three cases in which it was performed; positive staining was also seen in the area of fibrosarcoma. Estrogen and progesterone receptor immunostains were negative in three cases. Of the three patients who underwent surgery, one had tumor recurrences every 2 to 4 years for 18 to 20 years but has remained free of tumor in the 7 years since the last excision, one was free of tumor for 12 years before dying of an unrelated cause, and the other has been free of disease for 6 months. The fourth patient refused treatment and has persistent disease in the vulva. This study shows that the behavior of DFSP in the vulva is similar to its behavior in its more common locations.

Adult↗

Dermatofibrosarcoma protuberans: A clinicopathologic analysis of patients treated and followed at a single institution.

BACKGROUND: Despite optimal surgical therapy for patients with dermatofibrosarcoma protuberans (DFSP), some patients still continue to develop local recurrence. The authors' objective was to identify and analyze clinicopathologic factors for disease free survival in a large group of patients who were followed prospectively at a single institution. METHODS: Prospectively collected data and pathology slides were available for review from 159 patients with primary or recurrent DFSP who underwent treatment between July 1950 and July 1998. The study group was comprised of patients with either the "classic" form of DFSP or the fibrosarcomatous "high grade" variant of DFSP (FS-DFSP). Patient, tumor, pathologic, and treatment factors were analyzed using the log rank test for univariate influence and Cox regression analysis for multivariate influence. Local recurrence free survival was determined by the Kaplan-Meier actuarial method. RESULTS: Of the 159 patients who comprised the current study group, 134 (84%) had the classic form of DFSP. The FS-DFSP variant was found in the remaining 25 patients (16%). The overall 5-year local recurrence free survival rate was 75%, with a median follow-up of 4. 75 years. The 5-year recurrence free survival rate for each group was 81% and 28%, respectively. On univariate analysis, age > 50 years, very close (< 1 mm) to positive microscopic margins, FS-DFSP variant, high mitotic rate, and increased cellularity were unfavorable prognostic factors. Multivariate analysis determined very close (< 1 mm) to positive microscopic margins and FS-DFSP variant to be independent adverse prognostic factors. For the 34 patients who developed a recurrence after surgical resection (21%), the median time to local recurrence was 32 months. Of the patients in this group, two died from metastatic disease. CONCLUSIONS: The prognosis after surgical resection with negative and sometimes positive microscopic margins for patients with DFSP is very good. However, increased age, high mitotic index, and increased cellularity are predictors of poor clinical outcome. The FS-DFSP variant represents a much more aggressive tumor with metastatic potential. Patients who are treated with curative intent for FS-DFSP should undergo aggressive attempts at complete surgical resection. Patients with recurrent classic DFSP without evidence of adverse prognostic features may benefit from conservative management, especially in the setting of potentially unresectable disease.

Adolescent↗

Dermatofibrosarcoma protuberans of the jejunum.

We report a 55-year-old man with recurrent bleeding from the small intestine. Preoperative investigations suggested it to be a small intestine tumor. The resected specimen was diagnosed at histology as dermatofibrosarcoma protuberans of the small bowel.

Biopsy, Needle↗

Dermatofibrosarcoma protuberans of scalp : a case report.

A case of dermatofibrosarcoma protuberans of scalp involving the underlying bone, operated after recurrence by taking safety margin of 3 cm and skin deficit covered by transposition flap, is being reported. Modality of treatment has been discussed.

Dermatofibrosarcoma↗

[Fibrosarcomatous variant of dermatofibrosarcoma protuberans: clinicopathologic analysis of 4 cases].

We present a series of 4 cases of fibrosarcomatous dermatofibrosarcoma protuberans. This variant, which is composed of areas of typical DFSP associated with more cellular, fascicular foci, reminiscent of fibrosarcoma, should be recognised because of its more aggressive behavior, with a significant metastatic potential (15%). Our series illustrates the clinical, morphological, immunohistochemical and cytogenetic features of this uncommon tumor, with emphasis on differential diagnosis.

Adult↗

Growth inhibition of dermatofibrosarcoma protuberans tumors by the platelet-derived growth factor receptor antagonist STI571 through induction of apoptosis.

Dermatofibrosarcoma protuberans (DFSP) and giant cell fibroblastoma (GCF) are recurrent, infiltrative skin tumors that presently are treated with surgery. DFSP and GCF tumors are genetically characterized by chromosomal rearrangements fusing the collagen type Ialpha1 (COLIA1) gene to the platelet-derived growth factor B-chain (PDGFB) gene. It has been shown that the resulting COL1A1/PDGF-B fusion protein is processed to mature PDGF-BB. Autocrine PDGF receptor stimulation has therefore been predicted to contribute to DFSP and GCF tumor development and growth. Here we demonstrate presence of activated PDGF receptors in primary cultures derived from six different DFSP and GCF tumors. Three of the primary cultures were further characterized; their in vitro growth displayed an increased sensitivity to treatment with the PDGF receptor tyrosine kinase inhibitor STI571, as compared with normal fibroblasts. Transplantable tumors, displaying a DFSP-like histology, were established from one of the DFSP primary cultures. Treatment of tumor-bearing severe combined immunodeficient mice with STI571 reduced tumor growth. The growth-inhibitory effects in vitro and in vivo occurred predominantly through induction of tumor cell apoptosis. Our study demonstrates growth-inhibitory effects of PDGF receptor antagonists on human DFSP- and GCF-derived tumor cells and demonstrates that autocrine PDGF receptor stimulation provides antiapoptotic signals contributing to the growth of these cells. These findings suggest targeting of PDGF receptors as a novel treatment strategy for DFSP and GCF.

Adult↗

[Myoid/myofibroblastic differentiation in dermatofibrosarcoma protuberans: a clinicopathologic study of six cases].

OBJECTIVE: The nature of myoid/myofibroblastic differentiation in dermatofibrosarcoma protuberans (DFSP) and its clinical and pathological significance were studied. METHODS: 124 DFSPs were reviewed by light microscopy. 6 cases with areas of myoid/myofibroblastic differentiation were assayed with immunohistochemical technique and electron microscopy was applied in two cases. RESULTS: Myoid/myofibroblastic differentiation occurred most commonly in fibrosarcomatous DFSP (FS-DFSP). It was recognized histologically as peripherally distributed or randomly scattered small eosinophilic nodules or short bundles, which were composed of bland spindle cells, closely resembling smooth muscle cells or myofibroblasts. Immunohistochemically, cells in myoid/myofibroblastic areas showed positive staining for alpha-SMA, MSA and vimentin, but negative for desmin and CD34. Electron microscopic study displayed the presence of microfilament bundles, focal dense bodies and micropinocytic vesicles, consistent with those of myofibroblasts. CONCLUSION: Myoid/myofibroblastic areas in DFSP possibly represents the hyperplasia of stromal myofibroblasts, rather than true myofibroblastic differentiation of the neoplastic cells.

Actins↗

Dermatofibrosarcoma protuberans with lung metastasis in a patient with progressive systemic sclerosis.

A female patient with progressive systemic sclerosis and pulmonary fibrosis had a dermatofibrosarcoma protuberans on the right thigh. After resection of the tumor, new lesions occurred in the scar, and wide excision was repeated. Two years later, a lung metastasis was discovered, and segmental resection was done. After 1 year of follow-up, no local recurrences or metastases were found.

Dermatofibrosarcoma↗

Giant cell fibroblastoma: a report of three cases with histologic and immunohistochemical evidence of a relationship to dermatofibrosarcoma protuberans.

PROBLEM CONSIDERED: Giant cell fibroblastoma (GCF) is a rare mesenchymal neoplasm, which is classified as a fibrohistiocytic tumor of intermediate malignancy owing to its propensity for local recurrence, although metastasis has not been documented. Prior reports have linked GCF to dermatofibrosarcoma protuberans (DFSP), given overlapping clinical and histologic features. METHODS: This report documents three additional cases of GCF that further support the contention that this lesion is histogenetically related to DFSP. RESULTS: All three lesions occurred on the trunk of patients whose ages were 4, 28, and 38 years. One case that histologically resembled a GCF on initial excision recurred with areas of both GCF and DFSP. A second recurrence was composed entirely of DFSP. Another case contained areas of both GCF and DFSP, as well as a focus that was felt to be undergoing fibrosarcomatous change. The third case consisted entirely of GCF. Immunohistochemically, all three lesions showed intense immunoreactivity for CD34 in the GCF component. CD34 also strongly marked the cells in those cases with a DFSP component. CONCLUSIONS: Although GCF may not represent the "juvenile form" of DFSP, as previously suggested, the evidence strongly supports a histogenetic relationship between these two lesions, even though the cell of origin remains obscure.

Adult↗

EMA+ cells in dermatofibrosarcoma protuberans. A study of 11 tumors suggesting perineurial cell differentiation.

Expression of epithelial membrane antigen (EMA) was found in 11 of 57 (19%) cases of dermatofibrosarcoma protuberans (DFSP). These tumors with EMA+ cells showed the following histological features: classical storiform pattern in all 11 cases, myxoid areas in three cases, Bednar tumor pattern in one case, and fibrosarcoma-like areas in one case. The EMA+ cells had a tendency to occur in moderately cellular and collagen-rich areas with parallel cell arrangement (4 cases) and in perivascular areas (3 cases). In such parts, a nuclear palisading and a wavy appearance of the nuclei were seen focally. One tumor contained perineurioma-like areas with whorled cell arrangement and EMA+ cells. The EMA+ cells were also found in ordinary storiform areas (6 cases), but here they were isolated and scarce. In two cases, the EMA+ cells were juxtaneural; therefore their origin from a sheath of preexisting nerves can not be excluded. Expression of EMA may reflect true perineurial cell differentiation in DFSP, as suggested previously in several ultrastructural and cytogenetic studies. The knowledge of occasional EMA positivity in DFSP is needed for a differential diagnosis between DFSP and other EMA+ soft tissue lesions.

Adolescent↗