Cancer Surveillance in Solid Organ Transplant Recipients With a Pretransplant History of Malignancy: Multidisciplinary Collaborative Expert Opinion.

With improved medical treatments, the prognosis for many malignancies has improved, and more patients are presenting for transplant evaluation with a history of treated cancer. Solid organ transplant (SOT) recipients with a prior malignancy are at higher risk of posttransplant recurrence or de novo malignancy, and they may require a cancer surveillance program that is individualized to their specific needs. There is a dearth of literature on optimal surveillance strategies specific to SOT recipients. A working group of transplant physicians and cancer-specific specialists met to provide expert opinion recommendations on optimal cancer surveillance after transplantation for patients with a history of malignancy. Surveillance strategies provided are mainly based on general population recurrence risk data, immunosuppression effects, and limited transplant-specific data and should be considered expert opinion based on current knowledge. Prospective studies of cancer-specific surveillance models in SOT recipients should be supported to inform posttransplant management of this high-risk population.

Outcomes in solid organ transplant recipients with a pretransplant diagnosis of melanoma.

Melanoma causes significant morbidity in solid organ transplant recipients (SOTRs). Melanomas diagnosed before transplantation can recur with intensive immunosuppression, but outcomes have not been well studied. We evaluated 901 non-Hispanic White SOTRs with a pretransplant melanoma identified using linked transplant and cancer registry data in the United States. Most pretransplant melanomas were invasive (60.7%), and the median time from diagnosis to transplantation was 5.1 years. After transplantation, 41 SOTRs developed a new invasive melanoma, corresponding to 9-fold increased risk compared with the general population (standardized incidence ratio, 9.2; 95% confidence interval [CI], 6.6-12). Twenty-two SOTRs died from melanoma after transplantation, corresponding to 52-fold increased risk (standardized mortality ratio, 52; 95% CI, 33-79). Risk factors for posttransplant melanoma included age at transplantation (adjusted hazard ratio [HR], 2.86; 95% CI, 1.24-6.60; for age 55+ vs <55 years) and maintenance immunosuppression with cyclosporine/azathioprine (adjusted HR, 2.53; 95% CI, 1.08-5.90). Melanoma mortality was strongly elevated after a posttransplant melanoma diagnosis (HR, 35.6; 95% CI, 14.0-90.4; adjusted for cyclosporine/azathioprine maintenance therapy and calendar year of transplantation). In conclusion, SOTRs with a pretransplant melanoma are at risk of adverse melanoma-related outcomes after transplantation. These findings support thorough dermatologic evaluation prior to transplantation and frequent posttransplant surveillance.

Consensus-Based Recommendations on the Prevention of Squamous Cell Carcinoma in Solid Organ Transplant Recipients: A Delphi Consensus Statement.

IMPORTANCE: There is a paucity of evidence to guide physicians regarding prevention strategies for cutaneous squamous cell carcinoma (CSCC) in solid organ transplant recipients (SOTRs). OBJECTIVE: To examine the development and results of a Delphi process initiated to identify consensus-based medical management recommendations for prevention of CSCC in SOTRs. EVIDENCE REVIEW: Dermatologists with more than 5 years' experience treating SOTRs were invited to participate. A novel actinic damage and skin cancer index (AD-SCI), consisting of 6 ordinal stages corresponding to an increasing burden of actinic damage and CSCC, was used to guide survey design. Three sequential web-based surveys were administered from January 1, 2019, to December 31, 2020. Pursuant to Delphi principles, respondents thoroughly reviewed all peer responses between rounds. Supplemental questions were also asked to better understand panelists' rationale for their responses. FINDINGS: The Delphi panel comprised 48 dermatologists. Respondents represented 13 countries, with 27 (56%) from the US. Twenty-nine respondents (60%) were Mohs surgeons. Consensus was reached with 80% or higher concordance among respondents when presented with a statement, question, or management strategy pertaining to prevention of CSCC in SOTRs. A near-consensus category of 70% to less than 80% concordance was also defined. The AD-SCI stage-based recommendations were established if consensus or near-consensus was achieved. The panel was able to make recommendations for 5 of 6 AD-SCI stages. Key recommendations include the following: cryotherapy for scattered actinic keratosis (AK); field therapy for AK when grouped in 1 anatomical area, unless AKs are thick in which case field therapy and cryotherapy were recommended; combination lesion directed and field therapy with fluorouracil for field cancerized skin; and initiation of acitretin therapy and discussion of immunosuppression reduction or modification for patients who develop multiple skin cancers at a high rate (10 CSCCs per year) or develop high-risk CSCC (defined by a tumor with approximately ≥20% risk of nodal metastasis). No consensus recommendation was achieved for SOTRs with a first low risk CSCC. CONCLUSIONS AND RELEVANCE: Physicians may consider implementation of panel recommendations for prevention of CSCC in SOTRs while awaiting high-level-of-evidence data. Additional clinical trials are needed in areas where consensus was not reached.

Cutaneous squamous cell carcinoma: Incidence, risk factors, diagnosis, and staging.

Cutaneous squamous cell carcinoma (cSCC), a malignant proliferation of cutaneous epithelium, represents 20% to 50% of skin cancers. Although the majority of cSCCs are successfully eradicated by surgical excision, a subset of cSCC possesses features associated with a higher likelihood of recurrence, metastasis, and death. The proper identification of these aggressive cSCCs can guide additional work-up and management. In the first article in this continuing medical education series, we discuss the incidence, recurrence rates, mortality rates, and risk factors associated with cSCC and review the staging systems used to stratify patients into high- and low-risk groups. The second article in this series reviews the treatment options for cSCC, with focused attention on the management of high-stage tumors.

Cutaneous squamous cell carcinoma: Management of advanced and high-stage tumors.

While the majority of cutaneous squamous cell carcinomas (cSCCs) can be treated surgically, the additional work-up and treatments indicated for high-risk cSCC remain undefined. In recent years, improvements in tumor staging systems have allowed for the more accurate stratification of tumors into high- and low-risk categories. This insight, along with the publication of cSCC guidelines, brings us closer to the development of a consensus approach. The second article in this continuing medical education series addresses in question and answer format the most common questions related to advanced and high-stage cSCCs, with a simplified flowchart. The questions include the following: 1) Does my patient have high-risk cSCC?; 2) What is the next step for patients with cSCC and palpable lymphadenopathy?; 3) In patients with no clinically evident lymphadenopathy, who are candidates for lymph node staging?; 4) What forms of radiologic imaging can help detect subclinical lymph node metastases?; 5) What is the role of sentinel lymph node biopsy in cSCC?; 6) Which patients with cSCC need adjuvant radiation therapy?; 7) Is adjuvant chemotherapy an option for patients with high-stage cSCC after surgery?; 8) Are targeted and immunologic therapies an option for advanced cSCC?; 9) How often should I follow up with my patient after he/she has been diagnosed with a high-risk cSCC?; 10) What are the options for chemoprophylaxis in a patient with an increased risk of cSCC?; and 11) What chemopreventive measures can be started in coordination with medical oncology or transplant physicians?

Aggressive Skin Cancers Occurring in Patients Treated With the Janus Kinase Inhibitor Ruxolitinib.

The Food and Drug Administration approved Ruxolitinib in 2011 for the treatment of primary myelofibrosis. Five-year safety data showed a higher incidence of skin cancer in patients treated with Ruxolitinib compared to best available therapy for myelofibrosis. This report presents a series of five patients with history of myelofibrosis treated with Ruxolitinib who subsequently developed numerous skin cancers with aggressive biological behavior. Each patient in this report was treated by a Mohs surgeon affiliated with an academic institution. All patients had a history of myelofibrosis and were exposed to Ruxolitinib. Some patients were exposed to other immunomodulatory medications such as Hydroxyurea and Rituximab. The total number of skin cancers and skin cancers with particularly aggressive behavior were noted. All five patients in this series developed numerous skin cancers with aggressive biological behavior during or after therapy with Ruxolitinib. Also, one patient developed lentigo maligna melanoma and another developed metastatic undifferentiated pleomorphic sarcoma. The repeat observation of skin cancers with aggressive features during JAK inhibitor treatment suggests that these medications may promote cutaneous malignant transformation in at risk patients. Further surveillance and testing of JAK kinases regarding the risk of skin cancers is indicated.

J Drugs Dermatol. 2017;16(5):508-511.

Retention of Mohs surgeons in academic dermatology.

BACKGROUND: Retention of academic Mohs surgeons is important for the growth of this specialty and teaching of residents and students. OBJECTIVE: To examine factors that influence retention of Mohs surgeons in academics and to better understand reasons for their departure. MATERIALS AND METHODS: A survey was electronically distributed to academic Mohs surgeons in the American College of Mohs Surgery, asking them to rate the importance of several variables on their decision to remain in academia. Private practice Mohs surgeons who had left academics were also surveyed. RESULTS: Two hundred thirty-six dermatologic surgeons completed the survey. Twenty-nine percent work full time in academics, and approximately 7% work part time. The top reasons for practicing in the academic setting are intellectual stimulation, teaching opportunities, and collaboration with other university physicians and researchers. Seventy-one percent of respondents reported they would stay in academics, 7% indicated they would not, and 22% were unsure. Unfair compensation, inadequate support staff, poor leadership, increased bureaucracy, and decreased autonomy were top reasons that may compel a Mohs surgeon to leave. CONCLUSION: Opportunities for intellectual stimulation, collaboration, and teaching remain the main draw for academic Mohs surgeons. A supportive environment, strong leadership, and establishing fair compensation are imperative in ensuring their stay.

Skin Cancer in the Crosshairs: Highlights from the Biennial Scientific Retreat of International Transplant Skin Cancer Collaborative and Skin Care in Organ Transplant Recipients Europe.

The International Transplant Skin Cancer Collaborative (ITSCC) is an organization comprising of physicians; transplant surgeons and basic science research scientists dedicated in providing optimal care and ongoing research advancements in solid organ transplant recipients to improve patient outcome and quality of life. As medical advances occur, it is anticipated that the sheer number of solid organ transplantations occurring worldwide will continue to increase. The long-term medication associated immunosuppression improves graft survival, but as a consequence, these individuals become increasingly susceptible to various cutaneous malignancies, lymphoproliferative disorders and infections. Squamous cell carcinoma is the most frequently encountered skin cancer and increases 65- to 250-fold [Jensen et al., Skin cancer in kidney and heart transplant recipients and different long-term immunosuppressive therapy regimens. J Am Acad Dermatol. 1999;40:177-186; Lindelöf et al., Incidence of skin cancer in 5356 patients following organ transplantation. Br J Dermatol. 2000; 143:513-519]. However, the rates of basal cell carcinoma, Merkel cell carcinoma and melanoma also increase in organ transplant recipients leading to significant morbidity as well as mortality [Berg and Otley. Skin cancer in organ transplant recipients: epidemiology, pathogenesis, and management. J Am Acad Dermatol. 2002; 47:1-20]. In October 2014, the International Transplant Skin Cancer Collaborative and its equivalent European counterpart, Skin Care in Organ Transplant Recipients Europe held its 10th biennial meeting in Essex, MA to discuss the clinical conundrums and the evolving research pertinent to the field. This meeting report provides a synthesis of all the clinical and research data presented at the 4-day meeting.

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.

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.

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.