Fiona Zwald

Skin cancer in solid organ transplant recipients: Advances in therapy and management: Part II. Management of skin cancer in solid organ transplant recipients

The management of skin cancer in solid organ transplant recipients is a challenge to both the dermatologist and transplant physician. Part II of this continuing medical education review offers an approach to the management of this increasing problem. The importance of specialty dermatology clinics providing access to transplant patients, frequent skin cancer screening, patient education, and multidisciplinary care is discussed. The management of low risk squamous cell carcinoma with topical therapies, photodynamic therapy, systemic retinoids, and capecitabine is reviewed. Revision of immunosuppression in the management of high-risk patients is discussed in association with the potential role of sentinel lymph node biopsy for aggressive disease. Finally, management of in-transit and metastatic squamous cell carcinoma is reviewed, with a discussion of the role of more recent innovative therapies, including epidermal growth factor receptor inhibitors in advanced squamous cell carcinoma in solid organ transplant recipients.

Duration of Voriconazole Exposure: An Independent Risk Factor for Skin Cancer After Lung Transplantation

Objective To determine whether there is an association between duration of voriconazole therapy and number of nonmelanoma skin cancers (NMSC) after lung transplantation. Design A telephone‐based survey and chart review were performed for all living patients who received a lung transplant at Emory University from 1993 to 2009. Setting Academic medical center. Participants Lung transplant recipients. Main Outcome Measured Number of NMSC after lung transplantation. Results Sixty of 91 (65.9%) subjects were exposed to voriconazole for at least 3 months (11.2 ± 8.7 months, range 3–58 months) after lung transplantation, of whom 16 developed NMSC, with a mean of 38 months to first NMSC. Of 31 patients not exposed to voriconazole, 12 developed NMSC, with a mean of 52 months to first NMSC . By univariate analysis, time since transplant (correlation coefficient (r) = 0.514), age (r = 0.101), and high lifetime sun exposure (r = 0.211) were correlated with number of skin cancers after transplantation. Skin types V and VI were protective (r = −0.353). In multivariate regression, time since transplantation (0.061 per month), age (0.151 per year), skin type I or II (4.939), and months of exposure to voriconazole (0.149) were found to be independent risk factors for number of skin cancers after lung transplantation. Conclusion Duration of voriconazole exposure correlates with number of NMSC after lung transplantation. All patients exposed to voriconazole should be educated about their increased risk of skin cancer and should have regular dermatologic follow‐up for skin cancer screening. Physicians caring for lung‐transplant recipients should consider alternatives to voriconazole in patients at risk for skin cancer.

Management of Skin Cancer in Solid-organ Transplant Recipients: A Multidisciplinary Approach

Solid-organ transplant recipients are at increased risk for the development of skin cancers. A promising strategy for managing these complex patients involves a multidisciplinary approach that incorporates clinicians from various specialties, which provides the optimal milieu for patient education, treatment, and follow-up. The multidisciplinary clinic also facilitates communication between dermatologists and transplant physicians regarding such crucial concerns as revision of immunosuppression. This article reviews the problem of skin cancer in solid-organ transplant recipients, outlines preventive measures, discusses therapeutic modalities, and reinforces the advantage of a multidisciplinary approach in the management of this population.

Dermatopathology of skin cancer in solid organ transplant recipients.

Skin cancers occur more frequently in solid organ transplant recipients relative to the general population. Transplant recipients are at particularly high risk of squamous cell carcinoma, with up to a 100-fold increase in the relative risk when compared to the nontransplanted population. This compares with a 10- to 16-fold increase in basal cell carcinoma for renal transplant recipients. An increased incidence of melanoma in transplant patients has also been reported. Other types of skin cancer associated with immunosuppression in transplant patients include Kaposi sarcoma, Merkel cell carcinoma, and posttransplant lymphoproliferative disorder. This review discusses the epidemiology and pertinent pathologic features of each of these tumors. A brief clinical management strategy is outlined. In addition, the contribution of viral induced carcinogenesis with respect to Kaposi sarcoma, Merkel cell carcinoma, and posttransplant lymphoproliferative disorder is discussed.

Clinical Spectrum of Atypical Fibroxanthoma and Undifferentiated Pleomorphic Sarcoma in Solid Organ Transplant Recipients: A Collective Experience

BACKGROUND Atypical fibroxanthoma (AFX) and undifferentiated pleomorphic sarcoma (UPS) are uncommon, spindle cell cutaneous malignancies. Solid organ transplant recipients (SOTRs) are immunosuppressed and therefore have a higher incidence of cutaneous malignancies. OBJECTIVE We describe the clinical spectrum of AFX and a more‐aggressive, deeper variant, UPS, in SOTRs. MATERIALS AND METHODS A retrospective chart review of AFX and UPS in SOTRs was implemented. Cases from Vanderbilt University, Emory University, Mayo Clinic—Jacksonville, and University of Rochester were included. A literature search included previously published cases. RESULTS The average age of SOTRs at time of tumor presentation was younger than typically seen in immunocompetent patients for AFX. Rates of local recurrences and metastases were higher in the SOTRs than is noted in the immunocompetent literature. Rates of recurrence were higher in those treated with excision than in those treated with Mohs micrographic surgery (MMS). CONCLUSION AFX and UPS may have a greater risk for recurrence, metastases, and mortality in SOTRs, in whom early treatment with MMS may demonstrate certain advantages in terms of minimizing risk of recurrence and metastasis. UPS and recurrent tumors should be staged appropriately and may respond to adjuvant radiation therapy and reduction of immunosuppression. Immunohistochemical evaluation is recommended to exclude other spindle cell tumors. The authors have indicated no significant interest with commercial supporters.

Toward a Better Definition of High-Risk Cutaneous Squamous Cell Carcinoma: Comment on “Factors Predictive of Recurrence and Death From Cutaneous Squamous Cell Carcinoma”

Patient prognosis varies considerably among various types of skin cancer. Approximately 5% of cutaneous squamous cell carcinomas (CSCCs) metastasize, usually to regional nodes.1 A recent staging system has been developed for CSCC that combines tumor diameter with high-risk features, including primary tumor size greater than 2 cm, Breslow thickness greater than 2 mm, Clark level IV or greater, perineural invasion, poor differentiation, and primary site on the ear or lip, to classify tumors as T1 or T2. These high-risk factors have prognostic significance, particularly among immunocompromised patients. Immunosuppression contributes negatively to the prognosis and outcome of patients with CSCC; however, because strict TNM criteria exclude clinical risk factors in staging, immunosuppression was not included in the staging system.

Advances in transplant dermatology

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Chemoprevention of Skin Cancer

This chapter focuses on the use of systemic and topical retinoids in the chemoprevention of skin cancer and will aim to demystify their use in the clinical arena. The use of nonsteroidal anti-inflammatory agents, antioxidants, and tea polyploids will also be addressed. Topical imiquimod, 5-fluoruracil, and photodynamic therapy have been detailed elsewhere (see Chapters 2 and 4).