Management of Non-melanoma Skin Cancer in Transplant Recipients.

Transplant recipients have a significantly higher risk of developing non-melanoma skin cancers compared with the general population and squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) are the most common post-transplant malignancies. Although in the general population BCC outnumbers SCC 4:1, in transplant patients this ratio is reversed and SCC is more common, with a 65- to 250-fold increased incidence. As patients in immunosuppressed states are living longer after transplants, the incidence of skin cancer in this population continues to increase. The skin cancers in transplant patients also tend to be more aggressive, with higher morbidity and mortality. Preventive strategies play an important role in transplant recipients given their increased frequency of developing both premalignant and malignant skin lesions. Sun protection and regular skin cancer screening are critical. In addition, chemoprophylaxis with systemic retinoids, nicotinamide and capecitabine can significantly reduce the development of new skin cancers. Topical 5-fluorouracil, imiquimod, photodynamic therapy and cyclooxygenase inhibitors have all been investigated in transplant patients for the treatment of field cancerisation. Adjusting the immunosuppressive regimen is also an important adjuvant therapeutic strategy for managing skin cancers in transplant recipients and requires integrated multidisciplinary care with the entire transplant team. This article reviews the epidemiology of non-melanoma skin cancer in transplant patients, discusses the prevention strategies and highlights the management and treatment strategies of both field cancerisation and non-melanoma skin cancers.

Recommendations for Solid Organ Transplantation for Transplant Candidates With a Pretransplant Diagnosis of Cutaneous Squamous Cell Carcinoma, Merkel Cell Carcinoma and Melanoma: A Consensus Opinion From the International Transplant Skin Cancer Collaborative (ITSCC).

Advancements in solid organ transplantation successfully extend the lives of thousands of patients annually. The tenet of organ stewardship aims to prevent the futile expenditure of scarce donor organs in patient populations with high mortality risk, to the detriment of potential recipients with greater predicted life expectancy. The development of skin cancer posttransplantation portends tremendous morbidity, adversely affecting quality of life for many transplant recipients. This special article, provided by of members of the International Transplant Skin Cancer Collaborative (ITSCC), will provide the transplant professional with a consensus opinion and recommendations as to an appropriate wait period pretransplantation for transplant candidates with a history of either cutaneous squamous cell carcinoma, malignant melanoma, or Merkel cell carcinoma.

Management of skin cancer after organ transplantation.

Advances in transplant surgery and more effective immunosuppressive regimen have led to increased survival rates among transplant recipients. However, intense immunosuppression has led to increased rates of both internal and cutaneous malignancies, with skin cancer occurring as the most common cancer after transplantation. While many transplant recipients will develop mild and manageable cutaneous malignancies, some will develop potentially life-threatening disease. Dermatologists are an integral part in the care of organ transplant recipients. Therefore, it is important for dermatologists to be familiar with the available epidemiological data and management of skin cancers in this patient population. In this paper, we review the risk factors, prevention, recognition and effective intervention of skin cancers in organ transplant recipients.

Melanoma in solid organ transplant recipients.

This manuscript outlines estimated risk and clinical course of pretransplant MM, donor-transmitted MM and de novo MM posttransplantation and includes an analysis of risk factors for metastasis, data from clinical studies and current and proposed management. MM in situ and thin melanoma (<1 mm) in the transplant population has similar recurrence and survival estimates to those in the general population. A minimum wait time of 2 years prior to transplantation is suggested for MM with a Breslow depth <1 mm and no clinical evidence of metastasis. More advanced MM may adopt a more aggressive course in transplant recipients. Sentinel lymph node biopsy may be of additional prognostic benefit. Revision of immunosuppression in the management of de novo melanoma in collaboration with the transplant team should be considered. Larger studies utilizing uniform staging criteria or at minimum Breslow depth, are required to assess true risk and outcome of MM in the immunosuppressed transplant population. Emphasis remains on patient education and regular screening to provide early detection of MM.

Reduction of immunosuppression for transplant-associated skin cancer: thresholds and risks.

BACKGROUND: Although evidence supports the efficacy of reducing immunosuppression for transplant-associated skin cancer, clinical thresholds for and risks associated with reduction are not well defined. OBJECTIVES: In this study, experienced transplant physicians were surveyed regarding appropriate thresholds for consideration of reduction of immunosuppression and the likelihood of rejection and allograft compromise associated with various levels of reduction. PATIENTS AND METHODS: Fifty-two transplant physicians reviewed 13 hypothetical patient scenarios with graduated morbidity and mortality risk and provided opinions on the degree of reduction of immunosuppression that was warranted and the risks associated with various degrees of reduction. RESULTS: Renal, liver and cardiac transplant physicians generally concurred on the level of reduction of immunosuppression warranted by various degrees of skin cancer. As morbidity and mortality from skin cancer increased, physicians were more likely to accept risk to allograft function from more aggressive reduction. CONCLUSIONS: Reduction of immunosuppression is considered a reasonable adjuvant strategy in recipients of solid organ transplants who have substantial morbidity and mortality risk from skin cancer. Physicians are willing to accept an increased risk of allograft compromise when confronted by severe or extensive skin cancer. Further research is needed to define the precise correlation among levels of reduction of immunosuppression, therapeutic efficacy, and concomitant risks.

Oral retinoids for chemoprevention of skin cancers in organ transplant recipients: results of a survey.

Systemic retinoid therapy is thought to be beneficial for chemosuppression of skin cancers in solid organ transplant recipients. We present the results of a survey of 28 dermatologists with experience managing transplant recipients to clarify when and how systemic retinoids are used in this population. Almost 80% of respondents use retinoids in some transplant recipients. Factors influencing the use of retinoids include the incidence and aggressiveness of cutaneous squamous cell carcinomas and the extent of concomitant actinic keratoses. Patients are monitored more closely during periods of dose adjustment than during the maintenance phase of therapy. Adverse effects are variably managed symptomatically, with dose adjustment, by discontinuation of retinoids, or by referral to another specialist for further evaluation. In the absence of large randomized controlled trials, the practice habits of experienced physicians serve as a useful guide for the use of oral retinoids in transplant recipients.

Reduction of immunosuppression for transplant-associated skin cancer: expert consensus survey.

BACKGROUND: Reduction of immunosuppression is considered a reasonable adjuvant therapeutic strategy in solid-organ transplant recipients experiencing multiple or high-risk skin cancers. However, the literature provides no guidance about what threshold of cancer development would warrant initiation of reduction of immunosuppression. OBJECTIVES: To develop expert consensus guidelines for initiation of reduction of transplant-associated immunosuppression for solid-organ transplant recipients with severe skin cancer. METHODS: An expert consensus panel was convened by the International Transplant Skin Cancer Collaborative and Skin Care for Organ Transplant Patients Europe Reduction of Immunosuppression Task Force. Thirteen hypothetical patient scenarios with graduated morbidity and mortality risks were presented and mean and mode expert opinions about appropriate level of reduction of systemic immunosuppression (mild, moderate, severe) were generated. RESULTS: Mild reduction of transplant-associated immunosuppression was considered warranted once multiple skin cancers per year developed or with individual high-risk skin cancers. Moderate reduction was considered appropriate when patients experienced > 25 skin cancers per year or for skin cancers with a 10% 3-year risk of mortality. Severe reduction was considered warranted only for life-threatening skin cancers. CONCLUSIONS: Reduction of immunosuppression is considered a reasonable adjuvant management strategy for transplant recipients with numerous or life-threatening skin cancers. Proposed guidelines are presented for the graduated reduction of immunosuppression coincident with the increasing skin cancer risks.

Histologic features of actinic keratoses in solid organ transplant recipients and healthy controls.

BACKGROUND: Squamoproliferative lesions are common in patients who are immunosuppressed, particularly in recipients of solid organ transplants. Histologic features in such biopsy specimens may differ from those of otherwise healthy patients. Actinic keratoses (AKs) in transplant recipients may possess pathologic characteristics that suggest that they arose in an immunosuppressed host. OBJECTIVE: We evaluated 30 randomly selected AKs from 25 recipients of solid organ transplants and compared their histologic features to those of 50 AKs from 45 patients who were not immunosuppressed. METHODS: Tissue samples were categorized by sex, patient age, and site of biopsy. Sixteen separate histologic criteria were evaluated in a blinded fashion in each specimen. Statistical analysis was performed between the two groups with and without controlling for the age of the patient. RESULTS: The transplant group was significantly younger (54.8 years) than the nontransplant group (70.0) and contained more men (88%) than women (51%). AKs from transplant recipients were statistically more likely to demonstrate bacterial colonization, confluent parakeratosis, hyperkeratosis, increased mitotic activity, and verrucous changes. After controlling for age only, hyperkeratosis failed to be more prevalent in the transplant group. CONCLUSION: Certain histopathologic features are more common in AKs of immunosuppressed transplant recipients and may be used to distinguish between those removed from otherwise healthy persons.

Decreased skin cancer after cessation of therapy with transplant-associated immunosuppressants.

BACKGROUND: Immunosuppression for solid organ transplantation is associated with increased incidence of internal and cutaneous malignant tumors, among which skin cancer is the most common. OBJECTIVE: To determine the effects on cutaneous carcinogenesis when stopping therapy with immunosuppressive medications. OBSERVATIONS: We followed the clinical course of 6 solid organ transplant recipients after therapy with immunosuppressant medications was stopped because of allograft failure or unacceptable cutaneous carcinogenesis. Generally, we found that stopping therapy with immunosuppressive medications resulted in deceleration of cutaneous carcinogenesis, resolution of cutaneous verrucae vulgaris, and qualitative improvements in skin condition. Four patients experienced marked improvement; 2 did not. CONCLUSIONS: Cessation of transplant-associated therapy with immunosuppressive medications for patients in whom cutaneous carcinomas developed after transplantation may lead to deceleration of cutaneous carcinogenesis, decreased verrucae, and improved skin quality within 1 to 2 years. Because of the natural variation in skin cancer development and the small number of cases in this series, definitive conclusions require further study.

Cigarette smoking-associated elastotic changes in the skin.

BACKGROUND: Clinical features of the skin in persons who smoke include increased wrinkling, gauntness, and discoloration that has been termed smoker's face. The histologic changes in the sun-exposed skin of these patients have not been previously elucidated. OBJECTIVE: The purpose of this study was to assess the amount of elastosis in the sun-exposed skin of smokers and nonsmokers. METHODS: We evaluated the skin from the forehead and cheeks of 17 smokers and 14 nonsmokers for the presence of elastosis. With the use of a computer-generated analysis of tissue sections at 4 different levels, the amount of elastotic material was expressed as an average percent of the field staining for elastic tissue. Patients were also evaluated for the presence of other malignancies, arsenic and radiation exposure, and previous skin cancers. RESULTS: There was a significantly greater amount of elastosis (P < .05) in the skin of patients who smoked compared with those patients who did not. No significant differences were found between the 2 groups with regard to the other parameters evaluated. CONCLUSION: Cigarette smoking is associated with an increase in elastosis, which may contribute to the clinical features of "smoker's face."

Chromoblastomycosis in a patient with a cardiac transplant.

Cases of chromoblastomycosis have been reported in immunocompromised patients. However, chromoblastomycosis is rarely caused by Exophiala jeanselmei. While this organism has been reported to induce pheohyphomycosis in a recipient of a cardiac transplant, chromoblastomycosis has not been described. We present a case of chromoblastomycosis caused by Exophiala jeanselmei in a patient who had received a cardiac transplant.

Radiation-induced adiposis of the parotid gland.

Radiation-induced changes to the parotid gland may complicate later surgery for new or recurrent tumors of the area. Radiation commonly causes the replacement of parotid parenchyma by adipose cells as well as fibrosis and glandular atrophy. If the Mohs micrographic surgeon is not prepared for the gross and microscopic changes which may be present in the parotid gland, neighboring structures such as the facial nerve may be inadvertently encountered and tumor depth and extent may be poorly estimated. By discussing and illustrating this situation, we hope to make other surgeons aware of the difficulties which may be present after radiation to the parotid gland.

Clonal origin of dermatofibrosarcoma protuberans.

Dermatofibrosarcoma protuberans (DFSP) is a malignant tumor originating in the dermis. Although it is known to be locally aggressive, it only rarely metastasizes and will recur unless completely excised. The exact cell responsible for the development of a DFSP has been a matter of controversy for several decades; however, most histochemical and electron microscopic studies support a fibroblastic origin, with the tumor cells staining uniformly for vimentin and containing active endoplasmic reticulum synthesizing collagen. Cytogenetic analysis of some of these tumors has demonstrated at least two specific chromosomal abnormalities in DFSP and suggested that this tumor may be polyclonal in origin. To further address the clonal origin of this locally invasive, mesenchymal tumor, we analyzed DNA from two female patients by restriction fragment length polymorphisms and methylation analysis. Our data strongly support the concept that DFSP is monoclonal in origin and that this tumor mass reflects the clonal expansion of a single cell.

Hyperkeratotic mycosis fungoides restricted to the palms.

The case of a 45-year-old Latin American man, who presented to the Dermatology Clinic with a 6-month history of hyperkeratotic lesions confined to the palms and the palmar aspects of the digits of both hands, is discussed. Biopsy of these lesions revealed the classic histologic findings of mycosis fungoides. The clinical and histologic differential diagnosis of mycosis fungoides is considered.