Giant Cell Fibroblastoma (GCF, Juvenile Dermatofibrosarcoma Protuberans)
Are You Confident of the Diagnosis?
What you should be alert for in the history
The clinical history for giant cell fibroblastoma (GCF) includes a slow-growing painless mass that is usually on the trunk or thigh, but has been described in a variety of anatomic locations.
Characteristic findings on physical examination
On physical exam, a nontender dermal or subcutaneous mass fixed to overlying skin is found.
Expected results of diagnostic studies
On histopathologic examination, GCF is an infiltrative, relatively hypocellular mass with ill-defined borders, composed of uniform, bland wavy spindled cells in parallel fascicles, with associated wiry collagen bundles and a hyalinized to myxoid stroma. There are also a variable number of pleomorphic hyperchromatic spindle cells and multinucleated tumor cells.
Sinusoidal or “angiectoid” spaces are characteristic, and are often lined by the giant multinucleated cells, but not endothelium. There is a “honeycomb” pattern of fat infiltration. GCF spares adnexal structures and rarely invades superficial muscle. The tumor is positive for CD34. Cytogenetic and molecular studies show t(17;22)(q22;q13) with a COL1A1-PDGFB fusion gene.
The main differential diagnosis is dermatofibrosarcoma protuberans (DFSP). DFSP and GCF are considered to be related or within the same tumor spectrum, and hybrid lesions occur. GCF can recur as DFSP, and vice versa.
DFSP occurs in adults and is hypercellular, with a “cartwheel” or storiform arrangement of tumor cells and no multinucleated cells. DFSP has the same translocation and fusion gene, often with ring chromosome r(17;22), which is not present in GCF.
Other entities in the differential include neurofibroma (S100 protein positive), vascular tumor (endothelial cells present, CD31 positive, lacks the GCF translocation), and sarcoma (clinical history, careful histopathologic evaluation, and molecular studies should distinguish from GCF).
Who is at Risk for Developing this Disease?
Most cases occur in first decade of life. Reported ages range from 6 months to 62 years. Males are affected more frequently. There are rare reports of occurence at site of trauma.
What is the Cause of the Disease?
The etiology of GCF is unknown. It may occur at the site of trauma.
GCF is thought to be a fibrohistiocytic neoplasm with benign behavior. The t(17;22)(q22;q13) results in the fusion gene COL1A1-PDGFB, which causes upregulation of a fusion protein. A PDGF-BB homodimer ultimately results, activating the tyrosine kinase receptor PDGFBR, stimulating cell proliferation.
Systemic Implications and Complications
There are negligible systemic implications or complications. GCF locally recurs after incomplete excision; recurrence as DFSP has been reported. No GCF metastases have been reported.
Surgical excision is the standard treatment, with wide local excision with up to 3cm margins. Some advocate:
2-3cm margins for patients older than 5 years of age
1cm margins for patients younger than 5 years of age
Mohs micrographic surgery has been described for GCF.
Imatinib mesylate could be considered in large (surgically difficult), locally advanced, or recurrent cases (as in DFSP), and this is under investigation.
Reported pediatric doses (for DFSP): 400-520mg/m2/day
Reported adult doses (for DFSP): 400mg/day to 400mg twice a day
Optimal Therapeutic Approach for this Disease
Complete excision with up to 3cm margins is standard and curative. Although GCF behaves in a benign fashion, a limited excision with positive margins has up to an 80% recurrence rate.
Mohs micrographic surgery has been reported to be successful (similar to DFSP), but there is a paucity of information specific to GCF in the literature.
Wide local excision with negative margins is curative. Patients with positive margins should have re-excision or be closely followed for local recurrence. Remember, this tumor can recur as DFSP.
Unusual Clinical Scenarios to Consider in Patient Management
This tumor, although most frequently seen in children, can occur in adults and should not be misdiagnosed as a sarcoma, which has therapeutic and prognostic significance.
What is the Evidence?
Barr, RJ, Young, EM, Liao, SY. "Giant cell fibroblastoma: an immunohistochemical study". J Cutan Pathol. vol. 13. 1986. pp. 301-7.(Early article describing features consistent with fibrohistiocytic origin)
Cook,, JL. "Giant cell fibroblastoma: a variant of dermatofibrosarcoma protuberans treated with Mohs’ micrographic surgery". Dermatol Surg. vol. 25. 1999. pp. 509-12.(Report of a case of GCF successfully treated with Mohs micrographic surgery)
Jha, P, Moosavi, C, Fanburg-Smith, JC. "Giant cell fibroblastoma: an update and addition of 86 new cases from the Armed Forces Institute of Pathology, in honor of Dr. Franz Enzinger". Ann Diag Pathol. vol. 11. 2007. pp. 81-8.(An excellent review of clinical and pathologic features of GCF from the institution that first described the entity)
Najarian, DJ, Morrison, C, Sait, SN, Meguerditchian, AN, Kane, J, Cheney, R. "Recurrent giant cell fibroblastoma treated wtih Mohs micrographic surgery". Dermatol Surg. vol. 36. 2010. pp. 417-21.(Report of a recurrent GCF with focal DFSP successfully treated with Mohs micrographic surgery)
Price, VE, Fletcher, JA, Zielenska, M, Cole, W, Viero, S, Manson, DE. "Imatinib mesylate: an attractive alternative in young children with large, surgically challenging dermatofibrosarcoma protuberans". Pediatr Blood Cancer. vol. 44. 2005. pp. 511-5.(First report of DFSP response to imatinib in a child [18-month-old girl with a large DFSP])
Rutkowski, P, Van Glabbeke, M, Rankin, CJ, Ruka, W, Rubin, BP, Debiec-Rychter, M. "Imatinib mesylate in advanced dermatofibrosarcoma protuberans: pooled analysis of two phase II clinical trials". J Clin Oncol. vol. 28. 2010. pp. 1772-9.(Results from two prematurely closed clinical trials with a reported almost 50% response rate)
Sandberg, AA, Bridge, JA. "Updates on the cytogenetics and molecular genetics of bone and soft tissue tumors: dermatofibrosarcoma protuberans and giant cell fibroblastoma". Cancer Genet Cytogenet. vol. 140. 2003. pp. 1-12.(A excellent comprehensive review of cytogenetics and molecular events in both DFSP and GCF)
Shmooker, BM, Enzinger, FM, Weiss, SW. "Giant cell fibroblastoma: a juvenile form of dermatofibrosarcoma protuberans". Cancer. vol. 64. 1989. pp. 2154-61.(Clinicopathologic features of twenty-eight cases of GCF, reported by the authors who originally described the entity)
Terrier-Lacombe, M, Guillou, L, Maire, G, Terrier, P, Vince, DR, de Saint Aubain Somerhausen, N. "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". Am J Surg Pathol. vol. 27. 2003. pp. 27-39.(A comprehensive comparison of the three lesions)
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