Using Imatinib as Neoadjuvant Therapy in Dermatofibrosarcoma Protuberans: Potential Pluses and Minuses

Abstract

Dermatofibrosarcoma protuberans (DFSP) is an uncommon, low grade soft-tissue malignancy associated with a high risk for local recurrence and widespread subclinical extension. Imatinib, a selective tyrosine kinase inhibitor, has been a beneficial adjuvant therapy in patients with unresectable, recurrent, or metastatic DFSP. Because of its characteristic infiltrative growth, effective surgical excision of DFSP may be limited by the risk for disfigurement or functional impairment. In recent cases, neoadjuvant imatinib mesylate therapy has been shown to reduce preoperative tumor size and lessen surgical morbidity associated with the removal of residual DFSP. Use of neoadjuvant imatinib before surgery, however, requires appropriate patient selection and careful weighing of the potential risks and benefits of this treatment.

Dermatofibrosarcoma protuberans – the use of neoadjuvant imatinib for treatment of an uncommon breast malignancy: a case report

“…DFSP of the breast is rare, and consequently can create a diagnostic challenge [3]. DFSP has a low rate of metastatic spread, however, its local growth can be destructive and disfiguring if left untreated or if treatment is delayed [4]. On clinical examination, DFSP commonly appears as a salmon-colored erythematous plaque, extending into the subcutaneous tissue, fascia, and adjacent muscle with tendril-like growth and microscopic extensions, which can make complete surgical resection difficult [4].…”

“…DFSP is associated with a distinguishing chromosomal translocation, t(17;22). This results in a rearrangement and fusion of the type I alpha I collagen ( COL1A1 ) gene, which is widely expressed in many types of cells, and the beta chain of platelet-derived growth factor (PDGFB) [4]. This molecular aberration leads to the overstimulation of the PDGFB cell surface receptor kinase, subsequently causing tumorigenesis and cellular proliferation [5].…”

“…This molecular aberration leads to the overstimulation of the PDGFB cell surface receptor kinase, subsequently causing tumorigenesis and cellular proliferation [5]. Imatinib is a small molecule tyrosine kinase inhibitor with activity against platelet-derived growth factor receptor (PDGFR) and was approved for the treatment of unresectable and metastatic DFSP in 2006 [4]. Neoadjuvant use of imatinib may be effective in surgically challenging cases or in patients with DFSP tumors that are present in cosmetically sensitive areas [2].…”

Pharmacology and rationale for imatinib in the treatment of scleroderma

“…Imatinib has been approved for the treatment of several malignancies, ie, chronic myeloid leukemia (associated with the Philadelphia chromosome transformation; Bcr-Abl translocation), 29 myelodysplastic/myeloproliferative diseases associated with PDGFR gene rearrangements, 30 hypereosinophilic syndrome, 31 chronic eosinophilic leukaemia, 32 gastrointestinal stromal tumors, 33 , 34 aggressive systemic mastocytosis (with D816V mutation), 35 and nonresectable dermatofibrosarcoma protuberans. 36 …”

Successful treatment of unresectable dermatofibrosarcoma protuberans on finger with imatinib mesylate and Mohs microsurgery

“…1 Although wide excision can reduce its recurrence rate, treatment of large cutaneous malignancies on the digits by surgical excision may require amputation. With identification of the pathogenic role of PDGF signaling, target adjuvant therapy with imatinib has been shown to reduce tumor size and improve surgical resectability, 3 and DFSP treatment can be assisted by imatinib mesylate, especially in locally advanced, metastatic and inoperative patients.…”