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Background

Dermatofibrosarcoma protuberans or DFSP is a sarcoma of low malignant potential. Its importance lies in its locally aggressive behavior which may necessitate a wide surgical excision with repeated local recurrences.

OUTLINE

Disease Associations  
Pathogenesis  
Laboratory/Radiologic/Other Diagnostic Testing  
Gross Appearance and Clinical Variants  
Histopathological Features and Variants  
Special Stains/
Immunohistochemistry/
Electron Microscopy
 
Differential Diagnosis  
Prognosis  
Treatment  
Commonly Used Terms  
Internet Links  

DISEASE ASSOCIATIONS CHARACTERIZATION
GIANT CELL FIBROBLASTOMA Cases have preceeded or followed this tumor or have shown histologic transition
LIPOMA  


Multiple spindle cell lipomas and dermatofibrosarcoma protuberans within a single patient: Evidence for a common neoplastic process of interstitial dendritic cells?

Harvell JD.

Department of Pathology, Stanford University Medical Center.

J Am Acad Dermatol 2003 Jan;48(1):82-5 Abstract quote

This case report describes a 48-year-old man with multiple spindle cell lipomas of the neck and a dermatofibrosarcoma protuberans (DFSP) with fibrosarcomatous transformation of the chest. The presence of familial and nonfamilial multiple spindle cell lipomas within a single patient is a rare event, with only two reports in the current literature.

This case represents the first report of multiple spindle cell lipomas occurring in association with a DFSP. It is of particular interest in that both spindle cell lipoma and DFSP represent, at least in part, neoplastic proliferations of CD34(+) spindled cells. The exact nature and differentiation of these spindled cells remains controversial, but prior studies have suggested that they could represent neoplastic interstitial dendritic cells.

The association of DFSP and spindle cell lipoma within this single patient suggests that these two tumors (and their histologic variants) may well be linked, conceptually, as neoplastic proliferations of CD34(+) interstitial dendritic cells.

NUCHAL TYPE FIBROMA  

Dermatofibrosarcoma protuberans association with nuchal-type fibroma.

Hafeez Diwan A, Horenstein MG.

Department of Pathology, University of Texas - M. D. Anderson Cancer Center, Houston, TX, and Department of Pathology, University of South Alabama, Mobile, AL, USA.

J Cutan Pathol. 2004 Jan;31(1):62-6 Abstract quote.  


BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a hypercellular, storiform, CD34-positive low-grade sarcoma with honeycomb entrapment of fat, which typically involves the trunk and extremities. Nuchal-type fibroma (NTF ) is a paucicellular, CD34-positive fibrous tumor with fat entrapment, which may occur in both nuchal and extranuchal locations and in association with Gardner syndrome.

METHODS: We report the association of DFSP with NTF in a 43-year-old male with no personal or family history of Gardner syndrome.

RESULTS: The patient had a past history of a DFSP removed from his back, which recurred 2 years later and was re-excised. Additionally, the patient had a typical NTF, in the posterior neck, removed at the same time. Histopathologic examination of the recurrent back lesion demonstrated a composite lesion with typical appearances of DFSP, centrally, blending into an NTF-like appearance, peripherally. Both components expressed CD34 and CD99, and lacked elastin. A review of the microscopic slides of the patient's previously excised DFSP revealed an identical lesion with surrounding NTF-like areas.

CONCLUSION: While an association between NTF and fibromatosis has recently been reported, this is to our knowledge the first report of an association between NTF and DFSP. The morphologic findings suggest that there may be a continuum between these two CD34-positive lesions that have a tendency to infiltrate adipose tissue and recur.

 

PATHOGENESIS CHARACTERIZATION
COL1A1-PDGFB GENE FUSION  
Dermatofibrosarcoma protuberans COL1A1-PDGFB fusion is identified in virtually all dermatofibrosarcoma protuberans cases when investigated by newly developed multiplex reverse transcription polymerase chain reaction and fluorescence in situ hybridization assays.

Department of Pathology at Texas Children's Hospital and Baylor College of Medicine, Houston, TX 77030, USA.

Hum Pathol. 2008 Feb;39(2):184-93. Abstract quote

Dermatofibrosarcoma protuberans (DFSP) is a cutaneous, locally aggressive spindle cell tumor of intermediate malignancy. Tumor cells are reactive for CD34 and characterized by a t(17;22) translocation or a supernumerary ring chromosome that results in the fusion of exon 2 of PDGFB to various exons of the COL1A1 gene.

We developed a multiplex reverse transcription polymerase chain reaction (RT-PCR) assay to detect fusion transcripts for all possible COL1A1 breakpoints. Twenty-seven formalin-fixed, paraffin-embedded DFSP cases were analyzed using 18 COL1A1 forward primers and 1 exon 2 PDGFB reverse primer. Sequence analysis was performed to definitively characterize breakpoints. Results were correlated with histology, immunohistochemistry, PDGFB break-apart fluorescence in situ hybridization analysis, and cytogenetics when available. Fusion transcripts were detected by RT-PCR in all but one DFSP case. Sequencing revealed a PDGFB exon 2 breakpoint in all cases. COL1A1 breakpoints were in exons 7 (1 patient), 10 (1), 29 (2), 40 (1), 46 (3), and 49 (2), and intronic between exons 13:14 (1), 26:27 (2), 30:31 (1) 33:34 (1), 43:44 (7), 45:46 (1), and 46:47 (1).

Three novel COL1A1 breakpoints were identified, intronic between exons 13:14 (1), 30:31 (1) and in exon 49 (2). There was no correlation found between breakpoints and age, sex, or histologic variants. Using this sensitive multiplex RT-PCR assay in combination with fluorescence in situ hybridization, we found COL1A1-PDGFB rearrangements appear more prevalent in DFSP than previously reported. Its detection may be particularly helpful in the differential diagnosis of atypical, fibrosarcomatous, and metastatic DFSP.
Gains of COL1A1-PDGFB genomic copies occur in fibrosarcomatous transformation of dermatofibrosarcoma protuberans.

1Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.

 

Mod Pathol. 2006 Nov;19(11):1512-8. Epub 2006 Sep 15. Abstract quote

Dermatofibrosarcoma protuberans is a superficial low-grade sarcoma that rarely evolves into a high-grade fibrosarcoma. Dermatofibrosarcoma protuberans is genetically characterized by the unbalanced chromosomal t(17;22)(q21;q13), usually in the form of a supernumerary ring chromosome. The product of this chromosomal translocation is the chimeric gene COL1A1-PDGFB (collagen type I alpha I-platelet-derived growth factor beta), which is amplified at low levels in the ring chromosome.

The aims of this study were to evaluate (1) whether genomic gains of this fusion gene occur during the clonal evolution of dermatofibrosarcoma protuberans into fibrosarcomatous dermatofibrosarcoma protuberans and (2) whether there is a difference between the number of genomic copies of COL1A1-PDGFB between classic dermatofibrosarcoma protuberans and dermatofibrosarcoma protuberans areas associated with fibrosarcomatous dermatofibrosarcoma protuberans. Eleven cases of fibrosarcomatous dermatofibrosarcoma protuberans with both dermatofibrosarcoma protuberans and fibrosarcomatous areas and 10 cases of classic dermatofibrosarcoma protuberans were studied. Genomic copies of COL1A1-PDGFB were evaluated by fluorescence in situ hybridization using a custom designed probe for the PDGFB locus on 4 mum thick paraffin-embedded tissue sections. Genomic gains of the COL1A1-PDGFB gene were observed in six (of 10) fibrosarcomatous dermatofibrosarcoma protuberans in the fibrosarcomatous areas when compared to the dermatofibrosarcoma protuberans areas of the same tumor (2-7 gene copies (median PDGFB copy gain, 2.8) versus 1-3 gene copies (median PDGFB copy gain, 1.7), respectively, P=0.004). Four fibrosarcomatous dermatofibrosarcoma protuberans did not show genomic gains of COL1A1-PDGFB fusion gene between the two areas. Essentially no difference in the copy number of COL1A1-PDGFB fusion gene was observed between dermatofibrosarcoma protuberans areas of classic dermatofibrosarcoma protuberans and dermatofibrosarcoma protuberans areas of fibrosarcomatous dermatofibrosarcoma protuberans (median PDGFB copy gain of 1.8 versus 1.7, respectively, P=0.36). Genomic gains of COL1A1-PDGFB fusion gene is possibly an oncogenic mechanism that is identified in the clonal evolution of a subset of dermatofibrosarcoma protuberans that evolves into fibrosarcomatous dermatofibrosarcoma protuberans.

Since this finding was not observed in all cases of fibrosarcomatous dermatofibrosarcoma protuberans, other oncogenic mechanisms may be operating in this form of tumor progression. Copy number of COL1A1-PDGFB fusion gene in the classic dermatofibrosarcoma protuberans areas does not seem to be a major predisposing mechanism for fibrosarcomatous transformation.

COL1A1-PDGFB Gene Fusion Demonstrates a Common Histogenetic Origin for Dermatofibrosarcoma Protuberans and Its Granular Cell Variant.

Maire G, Pedeutour F, Coindre JM.

UF Recherche clinique 0952 and Laboratoire de Cytogenetique (G.M., F.P.), CHU de Nice, Universite de Nice-Sophia Antipolis, and Laboratoire d'Anatomie Pathologique (J.-M.C.), Universite de Bordeaux II and Institut Bergonie, Bordeaux, France.

Am J Surg Pathol 2002 Jul;26(7):932-7 Abstract quote

Granular cell variant of dermatofibrosarcoma protuberans is very rare with only one report of two cases.

We report a new case in which we demonstrated the presence of the dermatofibrosarcoma protuberans-specific COL1A1-PDGFB fusion from paraffin-embedded tissue. This case analysis demonstrated the utility of molecular genetics as a powerful tool for the diagnosis of atypical forms of dermatofibrosarcoma protuberans.

OVERLAP WITH GIANT CELL FIBROBLASTOMA  


Dermatofibrosarcoma protuberans, giant cell fibroblastoma, and hybrid lesions in children: clinicopathologic comparative analysis of 28 cases with molecular data: a study from the French Federation of cancer centers sarcoma group.

Terrier-Lacombe MJ, Guillou L, Maire G, Terrier P, Vince DR, De Saint Aubain Somerhausen N, Collin F, Pedeutour F, Coindre JM.

Am J Surg Pathol 2003 Jan;27(1):27-39 Abstract quote

The clinicopathologic and immunohistochemical features of 28 dermatofibrosarcoma protuberans (DFSP), giant cell fibroblastomas (GCFs), and hybrid lesions occurring in children are presented, including molecular data for seven of them.

There were 19 pure adult-type DFSP (9 male and 10 female patients aged between a few days [neonate] and 13 years, median 7 years), 5 pure GCF (all males aged from 2 to 8 years, median 4 years), and 4 hybrid tumors (all males aged from 1 to 4 years, median 2.5 years). Tumor locations in pure adult-type DFSP included the trunk (6) and lower (11) and upper (2) limbs. Pure GCFs were observed on the trunk (4) and knee (1), and hybrid lesions on the trunk (2) and lower (1) and upper (1) extremities. Tumor size (n = 20) ranged from 0.6 to 5 cm (median 2 cm).

Histologically, pure DFSP presented as monotonous and infiltrative, low-grade, dermal/hypodermal storiform spindle cell proliferations, sparing adnexal structures. GCF showed a dense fibrous to myxoid matrix containing slender wavy spindle cells and multinucleated giant stromal cells often lining angiectoid spaces. Hybrid lesions showed varying combinations of DFSP and GCF areas. Mitotic activity ranged from 1 to 3 mitoses per 10 high power fields. All tumors were diffusely positive for vimentin and CD34 but negative for smooth muscle actin, desmin, epithelial membrane antigen, and cytokeratins; one pure adult-type DFSP was also S-100 protein positive; <1% of nuclei were Ki67 (Mib-1) positive.

One karyotyped adult-type DFSP showed an unbalanced t(17;22) (q22;q13) translocation. Multiplex RT-PCR analysis and sequencing of PCR products in seven cases showed gene fusion transcripts in two pure DFSP, two pure GCFs, and one hybrid lesion. Results were uncertain in one pure GCF; one adult-type DFSP was negative. Treatment procedures were known for 27 patients, consisting of 16 wide excisions and 11 marginal excisions.

Follow-up information on 15 widely excised tumors (median 24 months; range 5-144 months) showed no recurrence. Five of six marginally excised lesions with available follow up recurred 2 months to 6 years (median 2 years) after initial surgery; all but one were cured by wide reexcision. None of the tumors metastasized.

In conclusion, this study emphasizes 1) the occurrence of adult-type DFSP in children, 2) the close relationship between DFSP and GCF clinically, histologically, and molecularly, 3) the excellent prognostic of these lesions if widely excised, and 4) the diagnostic usefulness of RT-PCR analyses in detecting the gene fusion transcripts resulting from the t(17;22) (q22;q13) in paraffin-embedded tissues.

p53  

Microsatellite instability and p53 mutation associated with tumor progression in dermatofibrosarcoma protuberans.

Takahira T, Oda Y, Tamiya S, Yamamoto H, Kawaguchi K, Kobayashi C, Oda S, Iwamoto Y, Tsuneyoshi M.

Department of Anatomic Pathology, Graduate School of Medicine, Kyushu University, Fukuoka, Japan.
Hum Pathol. 2004 Feb;35(2):240-5 Abstract quote.


Dermatofibrosarcoma protuberans (DFSP) is a dermal and subcutaneous tumor categorized as a tumor of intermediate malignancy, and its progression in some cases to fibrosarcoma is well known. However, molecular analysis of tumor progression has been limited. The present study investigated microsatellite instability (MSI) of 7 microsatellite markers through high-resolution microsatellite analysis in addition to a mutational analysis of the p53 gene in 44 tumors in 36 patients.

The patients were divided into 2 groups: 9 patients with a fibrosarcomatous component in the primary or recurrent/metastasized tumor, designated as the DFSP+FS group, and the remaining 27 patients, designated as the DFSP group. Cases in which the percentage of markers with an additional peak among the markers successfully analyzed was more than 30% was considered MSI high (MSI-H); cases in which microsatellites were stable at all of the successfully examined markers were considered microsatellite stable (MSS); and the remaining cases were considered MSI low (MSI-L). MSI-H cases were observed more frequently in the DFSP+FS group (4 of 9 cases) than in the DFSP group (1 of 27 cases) (P = 0.028, Fischer's exact test). The MSI status of recurrent or metastatic tumors in both the DFSP+FS and the DFSP groups was the same as that in the corresponding primary neoplasms.

Furthermore, there was no difference in MSI status between an ordinary DFSP area and a fibrosarcomatous area in 7 tumors that exhibited both areas. p53 mutational analysis revealed 10 point mutations, composed of 4 missense mutations and 6 silent mutations, in 6 of 36 cases (16.7%). A missense mutation was more frequently observed in the DFSP+FS group (3 of 4) than in the DFSP group (1 of 4). Among 3 cases of a missense mutation in the DFSP+FS group, 2 had a mutation only in a fibrosarcomatous area and 1 had a mutation only in a metastatic tumor progressing to fibrosarcoma.

These results suggest that MSI and p53 mutations are involved in tumor progression of DFSP to fibrosarcoma as early and late events, respectively.
RING CHROMOSOME  
Dermatofibrosarcoma protuberans: report of a case with a variant ring chromosome and metastases following pregnancy.

Bigby SM, Oei P, Lambie NK, Symmans PJ.

Department of Histopathology, Diagnostic-Medlab, Auckland, New Zealand.

J Cutan Pathol. 2006 May;33(5):383-8. Abstract quote  

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 alpha-chain of type 1 collagen, COL1A1 from 17q22, to the platelet-derived growth factor beta-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.

 

CLINICAL VARIANTS CHARACTERIZATION
CONGENITAL  


Congenital dermatofibrosarcoma protuberans: variability in presentation.

Weinstein JM, Drolet BA, Esterly NB, Rogers M, Bauer BS, Wagner AM, Mancini AJ.

Division of Dermatology #107, Children's Memorial Hospital, 2300 Children's Plaza, Chicago, IL 60614.

Arch Dermatol 2003 Feb;139(2):207-11 Abstract quote

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is an uncommon low-grade fibrohistiocytic tumor that usually occurs on the trunk or proximal extremities and typically appears during the second to fifth decade of life. It most commonly begins as a red-blue plaque that grows slowly and ultimately becomes nodular. The tumor is associated with a high recurrence rate but low metastatic potential. It rarely presents in childhood and is even more rarely present at birth. The clinical diagnosis of DFSP in infancy or childhood may be difficult because, in its early stages, the tumor often resembles a vascular birthmark.

OBSERVATIONS: We studied 6 patients with congenital DFSP who were initially thought to have other diagnoses, highlighting the potential clinical variability in presentation. Half of the cases in this series occurred in areas of the body outside of the typically reported distribution pattern of acquired DFSP and in locations that, therefore, may not arouse suspicion of congenital DFSP.

CONCLUSIONS: Given the aggressive local potential and high recurrence rate of DFSP, early diagnosis is preferable to facilitate appropriate excision. We recommend that any infant or child presenting with a cutaneous plaque or nodule, even congenital, that does not have characteristic or diagnostic clinical features undergo tissue biopsy for histologic evaluation.

VULVA  


Dermatofibrosarcoma protuberans of the vulva and groin: detection of COL1A1-PDGFB fusion transcripts by RT-PCR.

Gokden N, Dehner LP, Zhu X, Pfeifer JD.

Lauren V. Ackerman Laboratory of Surgical Pathology, Barnes-Jewish Hospital, Washington University Medical Center, St Louis, MO,USA.

 

J Cutan Pathol 2003 Mar;30(3):190-5 Abstract quote

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is an uncommon infiltrative tumor of the dermis with characteristic cytogenetic features, specifically the translocation t(17;22)(q22;q13) which often manifests as a supernumerary ring chromosome r(17;22). The translocation results in the fusion of two genes, collagen type I alpha 1(COL1A1) and platelet-derived growth factor B-chain (PDGFB). The trunk and extremities are the anatomic sites of predilection for DFSP, whereas the vulva and groin are quite uncommon sites of involvement.

METHODS: This investigation evaluated seven DFSPs (four vulvar and three groin) for the presence of COL1A1-PDGFB fusion transcripts by reverse transcriptase-polymerase chain reaction (RT-PCR), using archival formalin-fixed, paraffin-embedded tissue.

RESULTS: Six of seven cases (three vulvar, three groin) contained a COL1A1-PDGFB fusion transcript. Sequence analysis of the PCR products revealed that the break-point of the COL1A1 gene was located after exon 40 in two patients, after exon 42 in one patient, after exon 44 in one patient, and after exon 47 in two patients; the break-point in the PDGFB gene was before exon 2 in all cases. No fusion transcript could be amplified in one case.

CONCLUSIONS: As in DFSP at other sites, COL1A1- PDGFB chimeric fusion transcripts are present in vulvar and groin DFSP. The transcripts can be detected in formalin-fixed, paraffin-embedded tumor tissues, and have the same general pattern of exon boundaries as in DFSP at other sites.

 

HISTOLOGICAL TYPES CHARACTERIZATION
GENERAL  

A morphologic study of dermatofibrosarcoma protuberans: expansion of a histologic profile.

Sigel JE, Bergfeld WF, Goldblum JR.

Department of Anatomic Pathology, The Cleveland Clinic Foundation, Ohio, USA.

J Cutan Pathol 2000 Apr;27(4):159-63 Abstract quote

Dermatofibrosarcoma protuberans (DFSP) is a fibrohistiocytic tumor of intermediate malignancy characterized by a distinctive storiform growth pattern and frequent local recurrences.

In this study, we retrospectively reviewed 48 cases of DFSP diagnosed at the Cleveland Clinic Foundation between 1970 and 1999 to determine the prevalence of morphologic variations including the presence of giant cell fibroblastoma (GCF)-like areas, multinucleated giant cells, hypercellular zones and fibrosarcomatous change.

RESULTS: The cohort consisted of 42 patients (20 males, 22 females) with a median age at diagnosis of 40 years (range: 10-73 years). Forty-one primary tumors and seven recurrences were evaluated from these 42 patients. Tumor sites included the trunk (22 cases), head and neck (8 cases), upper extremities (7 cases) and lower extremities (6 cases). GCF-like areas were identified in seven (14.6%), multinucleated giant cells in ten (20.8%), hypercellular zones in 12 (25%) and fibrosarcomatous change in six (12.5%) cases, respectively. Combinations included giant cells and GCF-like areas (two cases), giant cells and hypercellular zone (two cases), and GCF-like areas and hypercellular zones (one case).

Our findings suggest that DFSP has a wider range of morphologic features, including GCF-like areas, multinucleated giant cells, hypercellular zones and fibrosarcomatous change, than has been previously recognized in the literature.

VARIANTS  
ATROPHIC  


Atrophic dermatofibrosarcoma protuberans: a case report and review of the literature.

Fujimoto M, Kikuchi K, Okochi H, Furue M.

Department of Dermatology, Tokyo University Branch Hospital, Japan.

Dermatology 1998;196(4):422-4 Abstract quote

Dermatofibrosarcoma protuberans is not a difficult tumor to recognize because of its characteristic clinical appearance, although some unusual variants have been reported.

We describe the atrophic variant of dermatofibrosarcoma protuberans in a 21-year-old female. The lesion was a smooth-surfaced, oval depression on the left subclavicular area, with a violaceous plaque at the center. The suspected clinical diagnosis did not include fibrous tumors, although histological examination showed the typical picture of dermatofibrosarcoma protuberans. Positive CD34 staining was also helpful in the diagnosis.

We review 14 cases of the atrophic variant of dermatofibrosarcoma protuberans in the literature. Dermatologists should be aware of this uncommon but characteristic appearance of atrophic dermatofibrosarcoma protuberans.

BEDNAR TUMOR Melanin positive spindle cells scattered throughout the tumor


Bednar tumor associated with dermal melanocytosis: melanocytic colonization or neuroectodermal multidirectional differentiation?

Goncharuk V, Mulvaney M, Carlson JA.

Divisions of Dermatology and Dermatopathology, Albany Medical College, Albany, NY, Corporate Plaza, Albany, NY, USA.

 

J Cutan Pathol 2003 Feb;30(2):147-51 Abstract quote

BACKGROUND: Neuroectodermal differentiation or melanocytic colonization are the opposing theories of histogenesis for the Bednar tumor or pigmented dermatofibrosarcoma protuberans (DFSP).

OBSERVATION: A 31-year-old African-American woman presented with a 2-cm blue-black shoulder nodule of 1-year duration. Punch biopsy revealed a CD34+, Factor XIIIa-DFSP, harboring numerous, pigmented spindle S100+, Mart-1+ and HMB-45+ cells. Subsequent wide excision demonstrated pigmented dendritic and spindled cells widely scattered throughout the dermis of the 3-cm excisional margins and punch biopsy specimens of normal skin from both shoulders. This latter process was interpreted as dermal melanocytosis (nevus of Ito). The dermal pigmented spindle cells were Mart-1+ and CD34-, and were associated with non-pigmented CD34+, cytologically banal spindle cells, which were more numerous in the excisional margins than the contralateral shoulder.

CONCLUSION: Reported herein is a singular case of Bednar tumor associated with dermal melanocytosis. Although the coexistence of these processes implicates colonization of the DFSP by constituent dermal melanocytes, the mixed immunophenotype (CD34+ or Mart-1+ cells) of dispersed dermal spindle cells hints at the possibility of a common cell of origin: the putative neuromesenchymal cell. In effect, the Bednar tumor could represent one part of a spectrum of neural crest-derived dermal tumors that includes dermal melanocytosis, cellular blue nevus and conventional DFSP.

FIBROSARCOMATOUS TRANSFORMATION Am J Dermatopathol 1997;19:562-567
Fibrosarcomatous DFSP with giant rosettes

Am J Dermatopathol 2001;23:41-45

Tumor contained areas of low grade fibrosarcoma with giant rosettes, resembling cases of hyalinizing spindle cell tumor with giant rosettes (HSCTGR)

Both had CD34 positive areas suggesting a link between the two tumors

MFH AREAS Hum Pathol 1988;19:368-370
MYXOFIBROSARCOMA J Cutan Pathol 1998;25:445-449
MYOID DIFFERENTIATION J Cutan Pathol 1996;23:30-36
MYXOID Am J Surg Pathol 1983;7:445-450
Myxoid Dermatofibrosarcoma Protuberans: A Rare Variant Analyzed in a Series of 23 Cases.

Department of Pathology, Brigham and Womenʼs Hospital, and Harvard Medical School, Boston, MA.

 

Am J Surg Pathol. 2007 Sep;31(9):1371-1377 Abstract quote

The myxoid variant of dermatofibrosarcoma protuberans (DFSPs) is uncommon. It often presents a diagnostic challenge and is important to recognize to prevent both undertreatment and overtreatment.

To better characterize this unusual variant of DFSP, 23 myxoid DFSPs (DFSP with greater than 50% myxoid stroma) were retrieved from the authors' consult files. 13 patients were male and 10 were female (median age 40 years; range 9 months to 72 years of age). Tumor size ranged from 1.5 to 11 cm (median 2.8 cm).

The most frequent sites were the extremities (9) and head and neck (7), followed by the trunk (4) and anogenital region (3). Grossly, the tumors were white/tan/gray to yellow, firm to gelatinous soft tissue masses.

Histologically, tumor stroma ranged from 50 to 100% myxoid (median 80%). The majority of cases displayed an infiltrative sheet-like proliferation of bland spindle cells with palely eosinophilic cytoplasm and stellate nuclei without pleomorphism. The stroma was myxoid with prominent thin-walled vessels. All cases displayed honeycomb infiltration of fat and 16 cases showed cellular areas of more typical DFSP. Four tumors contained pigmented dendritic cells (Bednar variant), 1 showed areas of giant cell fibroblastoma and 1 showed progression to fibrosarcomatous DFSP. Mitoses ranged from 0 to 5 per 10 high power fields. 95% of cases (21 out of 22) were positive for CD34 and all cases were negative for S100 and muscle markers. Clinical follow-up in 8 cases, ranging from 3-21 years, (median follow-up 6 years), revealed local recurrence in 2 cases and no evidence of metastasis. All patients were free of disease following wide excision or excision followed by radiotherapy.

In summary, these low-grade lesions are clinically similar to typical DFSP, but their unusual morphology is easily confused with a variety of other tumor types.
NEUROFIBROMATOUS CHANGE  
Neurofibromatous changes in dermatofibrosarcoma protuberans: a potential pitfall in the diagnosis of a serious cutaneous soft tissue neoplasm.

Kovarik CL, Hsu MY, Cockerell CJ.

University of Texas, Southwestern Medical School, Dermatology, Dallas, TX, USA.
J Cutan Pathol. 2004 Aug;31(7):492-6. Abstract quote  

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a low-grade malignant neoplasm that has the potential for aggressive local growth and destruction if not treated appropriately. Although the storiform arrangement of spindle cells in DFSP is relatively characteristic, histologic patterns simulating other benign as well as malignant neoplasms such as dermatofibroma, neurofibroma, malignant fibrous histiocytoma, and atypical fibroxanthoma have been described.

METHODS: We collected and analyzed six cases of probable DFSP in which a specific diagnosis could not be rendered due to the predominant neurofibromatous changes in the histologic sections. In an attempt to reach a definitive diagnosis, the clinical history and physical characteristics of the lesions were taken into account, and all cases were further evaluated using immunostaining for CD34 and S-100 protein.

RESULTS: The average age of the patient was 56 years (range 21-80), and the male to female ratio was 1 : 1. The location of lesions included the scalp, neck, back, and abdomen. All cases displayed two distinct histological patterns: (i) a proliferation of spindle cells with wavy nuclei in a loose mucinous stroma suggesting neural differentiation and (ii) a proliferation of spindle cells which interweaved and filled the reticular dermis extending into the subcutis. The wide variety of clinical impressions and descriptions indicated that the diagnoses were not always straightforward, and clinical information did not always assist in the clinicopathologic correlation. All lesions stained positively for CD34; however, three of six cases also stained positively for S-100. The three cases which were CD34 positive and S-100 negative were likely DFSP, and this was the final diagnosis given. The three cases that were CD34 and S-100 positive did not allow for a straightforward diagnosis.

CONCLUSIONS: DFSP may demonstrate areas with features more characteristic of a benign neural lesion, such as a neurofibroma, which can lead to underdiagnosis and subsequent failure to treat. Clinicians and pathologists should recognize this potential diagnostic pitfall and understand that equivocal clinical information, combined with non-specific immunohistochemical staining patterns, can further complicate the dilemma. In these situations, where DFSP is the likely diagnosis but definitive evidence cannot be obtained, full excision of the lesion should be recommended to avoid mistreatment of a potentially malignant lesion.

 

SPECIAL STAINS/
IMMUNOPEROXIDASE
CHARACTERIZATION
APO D  
Apo D in Soft Tissue Tumors: A Novel Marker for Dermatofibrosarcoma Protuberans.

West RB, Harvell J, Linn SC, Lui CL, Prapong W, Hernandez-Boussard T, Montgomery K, Nielsen TO, Rubin BP, Patel R, Goldblum JR, Brown PO, Van De Rijn M.

Departments of *Pathology and paragraph signBiochemistry and Howard Hughes Medical Institute, Stanford University Medical Center, Stanford, CA; daggerDepartment of Pathology and Genetic Pathology Evaluation Centre, Vancouver General Hospital, Vancouver, British Columbia, Canada; double daggerDepartment of Anatomical Pathology, University of Washington Medical Center, Seattle, WA; and section signDepartment of Anatomic Pathology, Cleveland Clinic Foundation, Cleveland, OH.

Am J Surg Pathol. 2004 Aug;28(8):1063-1069. Abstract quote  

Using gene microarray expression profiling, we previously found that apolipoprotein D (Apo D) was highly expressed in dermatofibrosarcoma protuberans (DFSP).

In this study, we confirm that Apo D is highly and relatively specifically expressed in DFSP using immunohistochemistry. A tissue microarray containing 421 soft tissue tumors was constructed and stained with antibodies against Apo D and CD34. Cytoplasmic immunostaining for Apo D was found in 9 of 10 typical DFSPs. In addition, 3 of 3 Bednar tumors and 2 of 3 giant cell fibroblastomas stained in conventional sections. In contrast, Apo D was immunoreactive in only a very small subset of a diverse collection of other soft tissue tumors, including Malignant Fibrous Histiocytoma (MFH), glomus tumor, neurofibroma, and malignant peripheral nerve sheath tumors. Immunostains for Apo D were negative in conventional sections of 16 fibrous histiocytomas, and an additional 12 variants of fibrous histiocytoma. Digital images of all immunohistochemical and hematoxylin and eosin tissue microarray stains are available at the accompanying website (http://microarray-pubs.stanford.edu/tma_portal/apod/).

We conclude that Apo D is strongly expressed in DFSPs and neural lesions and may be useful in differentiating DFSP from fibrous histiocytoma.
CD34

Br J Dermatol 1992;127:79-84
Am J Dermatopathol 1997;19:562-567

Positive

If a tumor undergoes sarcomatous transformation, the sarcomatous area is also positive

CD44  


CD44 and hyaluronate in the differential diagnosis of dermatofibroma and dermatofibrosarcoma protuberans.

Calikoglu E, Augsburger E, Chavaz P, Saurat JH, Kaya G.

Department of Dermatology, Fatih University Medical School, Ankara, Turkey, and Department of Dermatology, DHURDV, University Hospital of Geneva, Geneva, Switzerland.

J Cutan Pathol 2003 Mar;30(3):185-9 Abstract quote

The histological distinction between dermatofibroma (DF) and dermatofibrosarcoma protuberans (DFSP) may be extremely difficult. CD34 and Factor XIIIa have been used to differentiate DF from DFSP. However, there is an overlap and relative lack of specificity of their expressions. CD44 is a widely distributed integral membrane glycoprotein, which is expressed as a multitude of isoforms generated by alternative splicing of at least 10 different variant exons and post-translational modifications. CD44 is currently thought to be the principal cell surface receptor for hyaluronate (HA), the major component of the extracellular matrix.

In this study we aimed to assess the expression of standard CD44 (CD44s) and its isoforms (CD44v3, CD44v4, CD44v5, CD44v6, CD44v7, CD44v7v8, and CD44v10), and HA in DF and DFSP. Immunohistochemical staining was performed on the biopsy specimens of 15 cases of DF and four cases of DFSP, using antibodies that recognize the CD44s, different CD44 isoforms and the 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. The DF cells were negative for CD44v3, CD44v4, CD44v6, CD44v7 and CD44v7v8 but showed a strong reactivity for CD44v5 and CD44v10.

In contrast, CD44s' expression was significantly reduced or absent in all DFSP lesions and the tumor stroma displayed strong staining for HA. Our results indicate that CD44 and HA can be used as additional diagnostic markers to distinguish DF from DFSP.

CD117  
A study of CD117 expression in dermatofibrosarcoma protuberans and cellular dermatofibroma.

Department of Pathology, Sunnybrook Health Sciences Center, University of Toronto, Toronto, Ontario, Canada.

 

J Cutan Pathol. 2007 Nov;34(11):857-60. Abstract quote

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.
CD163  
Expression of CD163 in dermatofibroma, cellular fibrous histiocytoma, and dermatofibrosarcoma protuberans: comparison with CD68, CD34, and Factor XIIIa.

Sachdev R, Sundram U.

Department of Pathology, Stanford University Medical Center, Stanford, CA, USA.

J Cutan Pathol. 2006 May;33(5):353-60. Abstract quote  

Background: Distinction between cellular fibrous histiocytomas (FHs) with a deep component and dermatofibrosarcoma protuberans (DFSPs) can pose diagnostic problems. While CD68, CD34, and Factor XIIIa are helpful in distinguishing between these entities, none are diagnostically absolute. Recent work with CD163, a hemoglobin scavenger receptor, has demonstrated that this marker has high specificity for monocytes, macrophages, and histiocytes. Our goal is to evaluate the utility of CD163 in the diagnosis of dermatofibromas (DFs), cellular FHs, and DFSPs.

Methods: Sixty cases including 19 DFs, 23 cellular FHs with a deep component, and 18 DFSPs were tested with antibodies against CD163, CD68, CD34, and Factor XIIIa. Results: CD163 was expressed in 17/19 (89%) DFs, 23/23 (100%) cellular FHs, and 3/18 (17%) DFSPs. CD68 was positive in 8/19 (42%) DFs, 19/23 (83%) cellular FHs, and 1/16 (6%) DFSPs. CD34 was expressed in 1/19 (5%) DFs, 5/23 (22%) cellular FHs, and 100% of DFSPs. Factor XIIIa labeled 4/19 (21%) DFs, 11/23 (48%) cellular FHs, and 0/17 cases of DFSPs.

Conclusions: CD163 expression is helpful in distinguishing between cellular FHs and DFSPs and will be useful in a panel of antibodies when these entities are in the differential diagnosis.
CYCLOOXYGENASE-2  
Cyclooxygenase-2 expression in dermatofibroma and dermatofibrosarcoma protuberans.

Department of Plastic and Reconstructive Surgery, Rabin Medical Center, Beilinson Campus, Petah Tiqwa, Israel.

 

J Cutan Pathol. 2008 Jun;35(6):532-5. Abstract quote

BACKGROUND: Dermatofibroma (DF) and dermatofibrosarcoma protuberans (DFSP) occasionally resemble each other histologically but differ in histogenesis and biological behavior. This study sought to determine if these lesions can be differentiated by the quantity or quality of expression of cyclooxygenase-2 (COX-2), an enzyme associated with both reactive and neoplastic processes.

PATIENTS AND METHODS: Formalin-fixed and paraffin-embedded samples from 20 DFs and 20 DFSPs were stained immunohistochemically with antibodies directed against COX-2. Staining was evaluated semiquantitatively for percentage and intensity using a three-tiered system. DFs were graded and analyzed by cellularity. Findings within the tumors were compared with fibrocyte staining in adjacent tissue. The results were analyzed.

RESULTS: Nineteen DFs (95%) and 15 DFSPs (75%) were immunopositive for COX-2; this difference was not statistically significant. Highly cellular DFs showed more widespread (p = 0.0039; r = 0.614) and more intense (p = 0.0586; r = 0.429) staining than less cellular DFs and more prominent staining in adjacent fibroblasts (p = 0.044; r = 0.608).

CONCLUSIONS: COX-2 immunostaining does not distinguish DFs from DFSPs. However, the enzyme is expressed more widely and more intensely in more cellular, possibly younger, DFs. The prominent expression of COX-2 in DFSP may have clinical implications for treatment with COX-2 inhibitors in tumors that are not amenable to surgery.
FACTOR XIIIa Rare positive cells but the majority of the spindle cells are negative
HMGA1 AND HMGA2  
Differential expression of HMGA1 and HMGA2 in dermatofibroma and dermatofibrosarcoma protuberans: potential diagnostic applications, and comparison with histologic findings, CD34, and factor XIIIa immunoreactivity.

Li N, McNiff J, Hui P, Manfioletti G, Tallini G.

Department of Pathology, Yale University School of Medicine, New Haven, CT 06504-8900, USA.
Am J Dermatopathol. 2004 Aug;26(4):267-72. Abstract quote  

The histologic distinction of dermatofibrosarcoma protuberans (DFSP) and dermatofibroma (DF) may be difficult, especially in the case of DF extending into the subcutaneous fat (deep DF). CD34 and Factor XIIIa staining is commonly used in separating DF from DFSP, but is not always helpful. HMGA1 and HMGA2 genes, members of the high mobility group protein family genes, encode proteins that act as architectural transcription factors and are frequently dysregulated in a variety of benign or locally aggressive mesenchymal tumors.

In this study, we evaluated the immunoreactivity of HMGA1 and HMGA2 in a series of DF and DFSP to determine the possible utility for these markers in the differential diagnosis of these two entities. Immunohistochemical stains were performed on paraffin-embedded tissues from 22 cases of DF, including 14 cases of deep DF and 14 cases of DFSP, using antibodies against HMGA1 and HMGA2. CD34 and Factor XIIIa immunoreactivity was also evaluated in these lesions and compared with the results of HMGA immunostaining. Immunopositivity for both HMGA1 and HMGA2 was seen in 21of 22 (96%) DFs, but in only 3 (21%) and 1 (7%) of 14 DFSPs, respectively.

While 100% of DFSP stained for CD34, 36% of DF also labeled for CD34. The immunoreactivity of HMGA1 and HMGA2 in DF was generally strong and diffuse, in contrast to weak and focal staining seen in DFSP. The proportion of cases with positive immunoreactivity for both markers was significantly higher in DF and in deep DF than in DFSP (P < 0.001).

We conclude that HMGA1 and HMGA2 expression can be used to distinguish DF from DFSP with a degree of accuracy that is fully equivalent to that of Factor XIIIa and CD34.
LOW AFFINITY NERVE GROWTH FACTOR (p75)  

Low-affinity nerve growth factor receptor (p75) in dermatofibrosarcoma protuberans and other nonneural tumors: A study of 1,150 tumors and fetal and adult normal tissues

Julie C. Fanburg-Smith, MD
Markku Miettinen, MD

Hum Pathol 32:976-983 Abstract quote

Low-affinity nerve growth factor receptor (p75) is a member of the tumor necrosis factor receptor family. It may modulate the binding of nerve growth factor (NGF) to the functional high-affinity receptor tyrosine kinase (trk) A. NGF is thought to be responsible for growth, apoptosis, and function of the nervous system.

The presence of this receptor (p75) was determined in a large group of neural and nonneural tumors and fetal and adult tissues. One thousand one hundred fifty tumors were analyzed with monoclonal antibody for p75, along with selected normal fetal and adult tissues. Immunoreactivity for p75 was present in adult pericytes, perivascular fibroblasts, basal cells of several types of epithelia, perineurial cells, and dendritic reticulum cells. Additionally, a wide zone of subepithelial mesenchyme and skeletal muscle were positive in the first-trimester fetus, but were diminished or negative in the adult.

Consistently positive nonneural mesenchymal tumors included dermatofibrosarcoma protuberans (DFSP), embryonal and alveolar rhabdomyosarcoma, synovial sarcoma, and spindle cell hemangio(endotheli)oma. Schwann cell tumors, ganglioneuroma, granular cell tumor, and malignant peripheral nerve sheath tumor (MPNST) were also p75 positive. Mesenchymal nonneural tumors that were variably positive (32% to 69%) for p75 included fibrosarcoma variants, solitary fibrous tumor, hemangiopericytoma, spindle cell lipoma, Ewing's sarcoma, mesenchymal chondrosarcoma, and malignant melanoma. Nervous system tumors such as paragangliomas, neuroblastoma, meningioma, and perineurioma and nonneural mesenchymal tumors, including extraskeletal osteosarcoma, benign fibrous histiocytomas, fibromas, alveolar soft part sarcoma, epithelioid sarcoma, smooth muscle and gastrointestinal stromal tumors, and angiosarcomas, were almost always negative for p75. Epithelial tumors that were consistently positive included mixed tumor and adenoid cystic carcinoma, whereas mesothelioma, adenocarcinomas, and most squamous cell carcinomas were negative. p75 is not a specific marker for nerve sheath tumors. It is present in a variety of other mesenchymal tumors including synovial sarcoma and in CD34-positive tumors such as DFSP, spindle cell lipoma, and hemangiopericytoma.

The presence of p75 in nonneural tumors such as DFSP and rhabdomyosarcoma mimic its presence in early fetal mesenchyme and skeletal muscle, suggesting oncofetal expression in these tumors. p75 may be useful to distinguish DFSP from benign fibrous histiocytoma.

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

Weinrach DM, Wang KL, Wiley EL, Laskin WB.

Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, Ill, USA.
Arch Pathol Lab Med. 2004 Oct;128(10):1136-41. Abstract quote  

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.
STROMELYSIN 3  
Stromelysin 3 expression: A useful marker for the differential diagnosis dermatofibroma versus dermatofibrosarcoma protuberans

Bernard Cribier, MD, PhD
Gérald Noacco, MD
Bernard Peltre
Edouard Grosshans, MD

Strasbourg, France





J Am Acad Dermatol 2002;46:408-13 Abstract quote

Background: Stromelysin 3 (ST3) is a member of the metalloproteinase family, which is expressed in tissue remodeling processes such as scarring, embryogenesis, or tumoral invasion. Although the prognosis of breast cancers and extracutaneous squamous cell carcinomas is correlated with the level of expression of ST3, this staining has not yet found a routine application in dermatopathology.

Objective: Our purpose was to study by immunohistochemistry the expression of ST3 in dermatofibromas and dermatofibrosarcoma protuberans (DFP).

Methods: We selected 40 cases of dermatofibromas, 40 histologically typical DFPs, and 10 giant dermatofibromas. Immunohistochemistry was carried out by means of the LSAB method, with monoclonal anti-ST3 antibody (provided by MC Rio, IGBMC Strasbourg). A semiquantitative scale (0-3) was used to evaluate the level of ST3 expression.

Results: Positively stained cells were observed in all cases of dermatofibromas (100%), including the 10 giant cases, but never in DFP (0%). The staining was intense (class 2 or 3) in 39 of the 50 dermatofibromas. The CD34 staining used as a control proved to be less efficient; 6 DFP were CD34 negative, whereas some of the dermatofibromas showed a marginal CD34 positivity.

Conclusion: Our results are consistent with those obtained by in situ hybridization in previous studies of smaller series of fibrous tumors. The study of ST3 expression in fibrous tumors of the skin shows that this immunostaining could be a useful tool in the purpose of differentiating DFP from giant or invasive dermatofibromas. Although ST3 is a “negative” marker for DFP and therefore does not demonstrate the margins of the neoplasm, it is more reliable than CD34 staining in differentiating this tumor from a dermatofibroma.

 

DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES
DERMATOFIBROMA CD34 negative

Indeterminate Fibrohistiocytic Lesions of the Skin Is There a Spectrum Between Dermatofibroma and Dermatofibrosarcoma Protuberans?

Marcelo G. Horenstein, M.D.; Victor G. Prieto, M.D., Ph.D.; J. Dean Nuckols, M.D., Ph.D.; James L. Burchette, MT(ASCP), QIHC; Christopher R. Shea, M.D.

From the Departments of Pathology (M.G.H., V.G.P., J.D.N., J.L.B., C.R.S.) and Medicine (Dermatology; V.G.P., C.R.S.), Duke University Medical Center, Durham, North Carolina; and the Department of Pathology (M.G.H.), University of South Alabama Medical Center, Mobile, Alabama

Am J Surg Pathol 2000;24:996-1003 Abstract quote

Routine histology and immunohistochemistry can usually distinguish dermatofibroma (DF) and dermatofibrosarcoma protuberans (DFSP). DF generally expresses factor XIIIa whereas DFSP generally expresses CD34.

The authors report 10 cutaneous fibrohistiocytic lesions combining clinical, histologic, and immunohistochemical features of both DF and DFSP. The lesions had an average size of 1.2 cm (range, 0.42.7 cm), and occurred on the trunk (n = 6), extremities (n = 3), and face (n = 1) of four men and six women (average age, 30.6 yrs; age range, 1550 yrs). Eight lesions exhibited acanthosis and densely cellular fascicles with focal storiform areas. All had keloidal collagen, infiltrated the subcutis in a honeycomb pattern, and had low mitotic counts (0 to 4 mitoses per square millimeter). All were diffusely immunoreactive for factor XIIIa (30%60% of the neoplastic cells) as well as CD34 (20%70%).

This series raises the possibility of a biologic spectrum between DF and DFSP; however, double-immunolabeling studies showed no notable coexpression of factor XIIIa and CD34 by individual cells, suggesting coexistence of two different cellular populations. After an average follow up of 22.3 months (range, 1046 mos) in six cases, a single recurrence was documented. The ambiguous histologic features and the potential for local recurrence suggest that performing a complete excision may be prudent in these diagnostically indeterminate lesions.

DIGITAL FIBROMAS  
Cellular digital fibromas: distinctive CD34-positive lesions that may mimic dermatofibrosarcoma protuberans.

McNiff JM, Subtil A, Cowper SE, Lazova R, Glusac EJ.

Departments of Dermatology and Pathology, Yale University School of Medicine, New Haven, CT, USA.

J Cutan Pathol. 2005 Jul;32(6):413-8. Abstract quote  

Background: Digital fibromas are common benign acral tumors typically reported as angiofibromas (AFs) or acquired digital fibrokeratomas (ADFs). Cellular variants are not well recognized.

Methods: We collected 14 acral fibrocytic lesions showing a spindle cell morphology from our files, and evaluated CD34, Factor XIIIa, epithelial membrane antigen (EMA), and S100 protein staining of these lesions. We compared the histologic and immunohistochemical features of these cellular fibromas with five digital AFs, five ADFs, and five digital dermatofibromas.
 
 
Results: The 14 cellular digital fibromas showed intersecting fascicles of thin delicate bland spindle cells in the superficial reticular dermis with a fibrotic-to-slight myxoid stroma. The spindle cells in all cases stained strongly for CD34, and only scattered stromal cells stained for Factor XIIIa. Five tested cases were negative for EMA and S100 protein. The digital AFs, fibrokeratomas, and dermatofibromas stained predominately for Factor XIIIa, with no or minimal staining for CD34.
 
 

Conclusions: These findings suggest that a subset of digital fibromas is characterized by a dense cellular proliferation of CD34-positive spindle cells. Awareness of this variant of digital fibroma and its staining pattern is critical in preventing misdiagnosis as dermatofibrosarcoma protuberans, particularly in superficial biopsies.

 

PROGNOSIS AND TREATMENT CHARACTERIZATION
PROGNOSTIC FACTORS

 

SARCOMATOUS TRANSFORMATION

Cancer 1989;64:721-729
Am J Surg Pathol 1992;16:921-925

Rare cases may undergo sarcomatous transformation with areas of fibrosarcoma or malignant fibrous histiocytoma

In these patients, local recurrence rates ranged from 42-58% and metastases ranged from 13.7-33%

The prognostic significance of fibrosarcomatous transformation in dermatofibrosarcoma protuberans.

Abbott JJ, Oliveira AM, Nascimento AG.

Division of Anatomic Pathology, Mayo Clinic, Rochester, MN.

Am J Surg Pathol. 2006 Apr;30(4):436-43. Abstract quote  

Dermatofibrosarcoma protuberans (DFSP) is a superficial tumor characterized by high rates of local recurrence and a small risk of metastasis. Fibrosarcomatous (FS) areas rarely arise in DFSP, and considerable controversy exists as to whether these tumors have a higher risk of metastasis than the typical DFSP.

The aim of this study was to reappraise the prognostic significance of FS changes in DFSP by analyzing 41 patients from the consultation files of our institution. The study included 23 females and 18 males, with a median age of 48 years (range, 16-100 years). Eighteen lesions were located on the trunk, 16 on the extremities, and 7 on the head/neck region. All tumors were treated with local excision, and the surgical margins were considered positive for tumor in 22 of 39 cases (56%). Fibrosarcomas arose de novo in 38 cases and as a recurrence in 3 cases. All tumors involved the dermis and subcutis, and the FS component comprised 5% to 95% of the tumor area (median, 60%). Mitotic rates of the FS component (median, 20 mitoses/10 high-power fields [HPFs]; range, 5-48/10 HPFs) were considerably higher than those of the neighboring DFSP component (0-2 mitoses/10 HPFs).

Immunohistochemical analyses showed that CD34 expression was stronger and more extensive in the DFSP component (97% positive; median intensity, 3+) than in the FS component (81% positive; median intensity, 2+). The MIB-1 labeling index was higher in the FS areas (median, 20%; range, 5%-45%) than in the DFSP areas (<3%). Expression of p53 was present in 92% of the FS areas and in only 3% of adjacent DFSP areas. Follow-up data revealed that 8 patients had local recurrences, 4 patients (10%) had metastases, and 2 patients died of disease. None of the variables evaluated, including margin status, FS proportion, and mitotic count, correlated with disease progression.

We demonstrate that FS change in DFSP is a form of tumor progression that carries an increased risk of metastasis over classic DFSP and is associated with gains of p53 mutations and increased proliferative activity.

Sarcomas Arising in Dermatofibrosarcoma Protuberans A Reappraisal of Biologic Behavior in Eighteen Cases Treated by Wide Local Excision With Extended Clinical Follow Up

John R. Goldblum, M.D.; John D. Reith, M.D.; Sharon W. Weiss, M.D.

From the Departments of Anatomic Pathology of the Cleveland Clinic Foundation, Cleveland, Ohio, U.S.A. (J.R.G.); University of Florida, Gainesville, Florida

Am J Surg Pathol 2000;24:1125-1130 Abstract quote

There is a prevailing view that sarcomas arising in dermatofibrosarcoma protuberans (DFSP) have a higher risk of metastasis than ordinary DFSP, but these data are based on cases with variable and often suboptimal treatment. There has not been a large study of sarcomas arising in DFSP in which all cases were treated by wide local excision, thereby arguably altering outcome.

Clinicopathologic features of 18 cases of sarcomas arising in DFSP treated by wide local excision and having follow up of at least 5 years were analyzed.

An estimate of the proportion of sarcoma and DFSP was made. The number of mitotic figures and degree of CD34 immunoreactivity were assessed in each case. The cohort included 13 females and 5 males (age, 2387 yrs; median, 47 yrs). The tumors involved the trunk (7), scalp (4), extremities (4), and inguinal region (3), and ranged from 1.5 to 7 cm (median, 4 cm). Sarcoma occurred de novo in 15 cases and in a recurrence in three. Sarcomas resembled fibrosarcoma (17) or malignant fibrous histiocytoma (1) and occupied between 20% and 80% of the tumor (median, 60%). Mitotic activity ranged from 2 to 16 per 10 high-power field (HPF; median 7 per 10 HPF) in the sarcomatous component and 0 to 3 per 10 HPF (median, 1 per 10 HPF) in the DFSP component. All tumors expressed CD34 in the DFSP component but only nine (50%) in the sarcomatous component. All patients were treated by wide local excision with negative margins; three additionally received radiation. Four patients (22%) developed recurrences, but none developed metastasis during the follow-up period of 62 months to 17 years (median, 81.5 mos).

In contrast to earlier studies, we demonstrate that patients with sarcomas arising in DFSP do not have an increased risk of distant metastasis within a 5-year follow-up period, provided they are treated by wide local excision with negative margins. This probably reflects the fact that wide local excision results in eradication of local tumor, thereby eliminating the source for subsequent dissemination. However, we cannot completely exclude the possibility that tumors in which clear margins are achieved represent a less aggressive subset, as has been suggested for high-grade extremity sarcomas.

Previous studies showing increased metastasis for sarcomas arising in DFSP should be re-evaluated to determine if, with treatment stratification, metastatic rate varies.

Recurrence Rate After wide local excision, recurrence in 18%
Metastasis May occur with progressive tumors undergoing sarcomatous transformation
TREATMENT Wide local excision, usually 2-3 cm beyond the tumor

Macpherson and Pincus. Clinical Diagnosis and Management by Laboratory Methods. Twentyfirst Edition. WB Saunders. 2006.
Rosai J. Ackerman's Surgical Pathology. Ninth Edition. Mosby 2004.
Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
Robbins Pathologic Basis of Disease. Seventh Edition. WB Saunders 2005.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 6th Edition. McGraw-Hill. 2003.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fifth Edition. Mosby Elesevier 2008


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