Dermatofibrosarcoma Protuberans, Version 1.2014

Dermatofibrosarcoma protuberans (DFSP) is an uncommon soft tissue tumor characterized by a relatively high risk of local recurrence and low risk of metastasis. The NCCN Guidelines for DFSP provide multidisciplinary recommendations on the management of patients with this rare disease. These NCCN Guidelines Insights highlight the addition of the Principles of Pathology section, which provides recommendations on the pathologic assessment of DFSP. Because DFSP can mimic other lesions, immunohistochemical studies are often required to establish diagnosis. Cytogenetic testing for the characteristic translocation t(17;22)(q22;q13) can also be valuable in the differential diagnosis of DFSP with other histologically similar tumors.

Abstract

Dermatofibrosarcoma protuberans (DFSP) is an uncommon soft tissue tumor characterized by a relatively high risk of local recurrence and low risk of metastasis. The NCCN Guidelines for DFSP provide multidisciplinary recommendations on the management of patients with this rare disease. These NCCN Guidelines Insights highlight the addition of the Principles of Pathology section, which provides recommendations on the pathologic assessment of DFSP. Because DFSP can mimic other lesions, immunohistochemical studies are often required to establish diagnosis. Cytogenetic testing for the characteristic translocation t(17;22)(q22;q13) can also be valuable in the differential diagnosis of DFSP with other histologically similar tumors.

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This activity has been designated to meet the educational needs of physicians, nurses, and pharmacists involved in the management of patients with cancer. There is no fee for this article. The National Comprehensive Cancer Network (NCCN) is accredited by the ACCME to provide continuing medical education for physicians. NCCN designates this journal-based CE activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

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This activity is accredited for 1.0 contact hour. Accreditation as a provider refers to recognition of educational activities only; accredited status does not imply endorsement by NCCN or ANCC of any commercial products discussed/displayed in conjunction with the educational activity. Kristina M. Gregory, RN, MSN, OCN, is our nurse planner for this educational activity.

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All clinicians completing this activity will be issued a certificate of participation. To participate in this journal CE activity: 1) review the learning objectives and author disclosures; 2) study the education content; 3) take the posttest with a 66% minimum passing score and complete the evaluation at http://education.nccn.org/node/46935; and 4) view/print certificate.

Release date: June 16, 2014; Expiration date: June 16, 2015

Learning Objectives:

Upon completion of this activity, participants will be able to:

  • Integrate into professional practice the updates to NCCN Guidelines for Dermatofibrosarcoma Protuberans

  • Describe the rationale behind the decision-making process for developing the NCCN Guidelines for Dermatofibrosarcoma Protuberans

NCCN Categories of Evidence and Consensus

Category 1: Based upon high-level evidence, there is uniform NCCN consensus that the intervention is appropriate.

Category 2A: Based upon lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate.

Category 2B: Based upon lower-level evidence, there is NCCN consensus that the intervention is appropriate.

Category 3: Based upon any level of evidence, there is major NCCN disagreement that the intervention is appropriate.

All recommendations are category 2A unless otherwise noted.

Clinical trials: NCCN believes that the best management for any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.

F1NCCN Guidelines Insights: Dermatofibrosarcoma Protuberans, Version 1.2014

Version 1.2014 © National Comprehensive Cancer Network, Inc. 2014, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.

Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 12, 6; 10.6004/jnccn.2014.0081

Overview

Dermatofibrosarcoma protuberans (DFSP) is an uncommon, low-grade sarcoma of fibroblast origin with an incidence rate of 4.2 to 4.5 cases per million persons per year in the United States.1,2 Because of its slow-growing nature, definitive diagnosis is often delayed and large size at presentation is common. Although metastasis is rare, DFSP can be locally aggressive, resulting in significant morbidity. Local recurrence rates for DFSP in older studies range from 10% to 60%,3 whereas pooled data from more recent studies using wide surgical margins showed an overall recurrence rate of 7.3%.4

NCCN has assembled a multidisciplinary panel of leading experts from NCCN Member Institutions to develop and continually update guidelines for the treatment of nonmelanoma skin cancers. The NCCN Guidelines for DFSP are an extension of these guidelines that provide specific recommendations for DFSP management. The panel also received expert input from the NCCN Guidelines Panel for Soft Tissue Sarcoma during the initial development of this guideline. The latest full guideline, including a complete list of updates, is available on the NCCN Web site at NCCN.org. These NCCN Guidelines Insights highlight the addition of the “Principles of Pathology” section.

F2NCCN Guidelines Insights: Dermatofibrosarcoma Protuberans, Version 1.2014

Version 1.2014 © National Comprehensive Cancer Network, Inc. 2014, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.

Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 12, 6; 10.6004/jnccn.2014.0081

Principles of Pathology

Histologically, DFSP typically presents as a storiform or fascicular proliferation of bland spindled cells that extends from the dermis into the subcutis on a routine hematoxylin and eosin (H&E) stain.5,6 DFSP may be difficult to differentiate from other fibrous tumors, especially dermatofibroma; hence, immunohistochemical staining is frequently used to establish a definitive diagnosis. CD34, a glycoprotein expressed by bone marrow stem cells, is expressed in most cases of DFSP.7-10 In contrast, staining for the coagulation factor XIIIa is usually negative in DFSP.7,10 Positive CD34 and factor XIIIa staining is often sufficient for a DFSP diagnosis. Additional markers that are immunoreactive in DFSP include nestin, apolipoprotein D, and cathepsin K,11-13 which may be helpful in difficult cases.

DFSP is characterized by a t(17;22)(q22;q13) translocation or a supernumerary ring chromosome that results in the fusion of the platelet-derived growth factor B gene (PDGFB) on chromosome 22 to various exons of the collagen 1A1 (COL1A1) gene on chromosome 17.14 Found in more than 90% of DFSP tumors, this translocation upregulates PDGFB, a tyrosine kinase and key growth factor for connective tissue cells.15 Imatinib mesylate, a tyrosine kinase inhibitor, has shown clinical activity against localized and metastatic DFSP tumors containing the translocation.16-20 This agent has been approved by the FDA for the treatment of unresectable, recurrent, and/or metastatic DFSP in adult patients.

Whether high mitotic rate or evidence of fibrosarcomatous change (typically in >5% of the surgical specimen) has prognostic significance in DFSP remains unclear. Studies in the literature both support21,22 and refute23 this notion.

NCCN Recommendations

The NCCN Guidelines outline the initial workup for DFSP in the algorithm (see DFSP-1, page 865). Because metastatic disease is rare, an extensive workup is not routinely indicated unless suggestive aspects in the history and physical examination or adverse prognostic histologic features are present. Because misdiagnosis is common, the panel strongly recommends clinicians obtain sufficient tissue from a deep subcutaneous punch biopsy or incisional biopsy for accurate pathologic assessment. When the clinician’s suspicion for DFSP is high but the initial biopsy does not support the diagnosis, rebiopsy is recommended and may reveal tumor presence. Wide undermining of the skin is discouraged because it may potentially result in tumor seeding. It can also interfere with the pathologic examination of re-excisions.

The “Principles of Pathology” section is a new section providing additional guidance on the analysis, interpretation, and reporting of pathologic results (see DFSP-A, page 866). Currently, no synoptic reporting is recommended. In most cases, examination of H&E stains using light microscopy results in an unequivocal diagnosis. However, differentiation of DFSP from dermatofibroma and other fibrous tumors can be difficult at times. In these instances, immunostaining with CD34 and factor XIIIa can be valuable. Other tests that can be useful include nestin, apolipoprotein D, cathepsin K, and fluorescence in situ hybridization or polymerase chain reaction analysis for t(17;22)(q22;q13). The panel recommends that appropriate and confirmatory immunostaining be performed in all cases of suspected DFSP.

Fibrosarcomatous change and malignant transformations should be noted, because these are high-risk features that should prompt multidisciplinary consultation to optimize clinical and reconstructive outcomes.24 Clinicians should consult the NCCN Guidelines for Soft Tissue Sarcoma when fibrosarcomatous transformations are present (to view the most recent version of these guidelines, visit NCCN.org).

Conclusions

These NCCN Guidelines Insights highlight the addition of a “Principles of Pathology” section to the NCCN Guidelines for DFSP. The NCCN Guidelines are updated at least annually, and more often when new high-quality clinical data become available in the interim. The most up-to-date version of these continuously evolving guidelines is available online at NCCN.org. The recommendations in the NCCN Guidelines are based on evidence from clinical trials where available, combined with expert consensus of the panel. Independent medical judgment is required to apply these guidelines individually to provide optimal care. The physician and the patient have the responsibility to jointly explore and select the most appropriate option from among the available alternatives. When possible, consistent with NCCN philosophy, the NCCN panel strongly encourages participation in prospective clinical trials.

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    NCCN Guidelines Insights: Dermatofibrosarcoma Protuberans, Version 1.2014

    Version 1.2014 © National Comprehensive Cancer Network, Inc. 2014, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.

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    NCCN Guidelines Insights: Dermatofibrosarcoma Protuberans, Version 1.2014

    Version 1.2014 © National Comprehensive Cancer Network, Inc. 2014, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.

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