Radiation Oncology/Sarcoma/DFSP

Dermatofibrosarcoma Protuberans

Epidemiology

 * Cutaneous, locally aggressive, primarily low grade sarcoma
 * ~10% may contain a high-grade fibrosarcoma component
 * Low rate (<5%) of metastasis; higher if fibrosarcoma component
 * Rare, 2-6% of soft tissue sarcomas
 * Adults in 30's
 * Risk factors: pregnancy, arsenic exposure, acanthosis nigricans

Clinical Presentation

 * Plaque-like areas of cutaneous thickening
 * Skin-colored, red-brown, or violaceous, particularly at the margins
 * May arise within pre-existing scar or tattoo
 * As it slowly enlarges, becomes raised ("protuberans"), firm, and nodular (fixed to dermis, but moves over deeper structures)
 * At diagnosis, >75% are superficial and <5cm diameter
 * Slow, indolent growth, such that the lesion may be present for years
 * Distribution:
 * Trunk ~50%
 * Lower extremity ~20%
 * Upper extremity 15%
 * Head and neck 15%

Work Up

 * MRI helpful to estimate extent of deep extent
 * CT not routinely necessary, unless bony invasion suspected
 * Metastatic workup not routinely necessary, unless suspicion from H&P

Histology

 * Cell of origina is not well understood
 * Histochemistry and electron microscopy suggest fibroblast lineage
 * However, the cells are CD34 positive, suggesting possibly dendritic lineage
 * In comparison, dermatofibromas and desmoid tumors are CD34-
 * The tumors show benign-appearing spindle cells, in an irregular patterns resembling a straw mat. In early lesions there is a tumor-free zone with epidermis
 * >90% have a t(17;22) translocation, resulting in a fusion of PDFG-B driven by a highly expressed collagen promoter (COL1A1)
 * Results in PDFGRb activation, which is tyrosine kinase receptor

Staging

 * AJCC 7th Edition (2010)
 * First edition to include DFSP
 * Please see the Soft Tissue Sarcoma staging page


 * American Musculoskeletal Tumor Society Staging for DFSP
 * Stage IA - Low or intermediate grade within the subcutaneous compartment
 * Stage IB - Low or intermediate grade extending outside anatomic compartment
 * Stage II - High grade histology

Natural History

 * Tends to recur locally after excision alone
 * Recur locally multiple times before metastasis; significant interval before development of metastases.
 * Fibrosarcomatous changes predict for metastatic potential.

Treatment Overview

 * Surgical resection is the primary treatment approach
 * Historically, wide local excision with 3cm margins was recommended, down to and including fascia
 * Mohs mapping reveals fine tentacles of tumor, and is becoming favored due to preservation of cosmesis
 * Some recommend modified Mohs to include a final path margin for permanent section
 * Pooled local recurrence rate with adequate margin WLE or Mohs' is <2%
 * Recurrences tend to occur within 3 years of surgery
 * Definitive RT not routinely; only couple reports available
 * Adjuvant radiation is typically indicated if positive or close margins, further resection anatomically not possible if recurrence happens, or recurrent disease
 * Given the high rate of t(17;22) leading downstream to a tyrosine kinase activation, efforts are under way to use Gleevec and other TKIs in this disease

Adjuvant Radiation Therapy

 * MD Anderson
 * 2013 (1972-2010) PMID 23628134 -- Dermatofibrosarcoma Protuberans: Long-term Outcomes of 53 Patients Treated With Conservative Surgery and Radiation Therapy. (Castle KO, Int J Radiat Oncol Biol Phys. 2013 Jul 1;86(3):585-90. doi: 10.1016/j.ijrobp.2013.02.024. Epub 2013 Apr 26.)
 * Retrospective. 53 consecutive patients. Surgery and preoperative (13%) or postoperative (87%) RT. Median tumor size 4 cm (1-25 cm). Preop dose 50 Gy, postop dose 60-66 Gy. Gross disease 7%, positive margin 30%. Median F/U 6.5 years
 * Outcome: Recurrence 4%. 5-year and 10-year OS 98%. Fibrosarcomatous change not associated with risk of LR or DM
 * Toxicity: 13%; moderate/severe complications 9% at 10 years
 * Conclusion: DFSP is radioresponse with excellent local control after surgery and RT. Adjuvant RT should be considered if large/recurrent tumor or where attempt at wide surgical margins would result in significant morbidity
 * 1998 PMID 9531366 -- "The role of radiation therapy in the management of dermatofibrosarcoma protuberans." (Ball MT, Int J Radiat Oncol Biol Phys. 1998 Mar 1;40(4):823-7.
 * Retrospective. 19 patients receiving adjuvant xrt. 60 Gy given for +microscopic margin; 65 Gy given for gross residual disease.  Local control at 10 yrs was 95%
 * Conclusion: adjuvant xrt should be considered for +margins or if adequate wide excision would lead to major cosmetic defect.


 * Soft Tissue Tumours Working Group, The Netherlands Cancer Institute; 1997 PMID 9376187 -- Haas RL et al. "The role of radiotherapy in the local management of dermatofibrosarcoma protuberans."
 * 38 consecutive pts w/ DFSP. 21 tx'd surgically, 17 tx'd w/ combined modality.
 * Surgery alone had local control of 67%
 * Combined modality had local control of 82% (many of these who had xrt already had multiple local recurrences.


 * Harvard; 1996 PMID 8708729 -- Suit H et al. "Radiation in management of patients with dermatofibrosarcoma protuberans."  J Clin Oncol. 1996 Aug;14(8):2365-9.
 * 18 patients treated with postop (n=15) or definitive (n=3) xrt. Population was +/close margins or xrt alone.
 * Local control at 10yrs was 88%.