Evaluation and Treatment of Skin Cancer in Patients With Immunosuppression

Clinical Significance

Prevention of Skin Cancers

Lifestyle

UV rays are the primary risk factor for skin cancer development, making proper sun protection education crucial for immunocompromised individuals. They should be advised to use broad-spectrum sunscreen with a sun protection factor (SPF) of 30 or higher, wear sun-protective clothing, avoid outdoor activities during peak UV hours (10 AM to 4 PM), and refrain from sun-seeking behaviors or tanning salons. A study highlights the effectiveness of sun protection in organ transplant recipients, showing that broad-spectrum sunscreen with an SPF greater than 60 significantly reduces the incidence of actinic keratosis, SCC, and BCC over a 24-week period.[8]

Actinic keratosis

Actinic keratosis results from the proliferation of abnormal keratinocytes caused by UV radiation damage. If left untreated, it carries the potential to progress to SCC.[9] In immunosuppressed patients, this progression occurs more rapidly and with a lower likelihood of spontaneous regression. The risk of invasive SCC increases with a higher burden of actinic keratosis. Therefore, proactive management is essential, using liquid nitrogen cryotherapy for a limited number of lesions, or photodynamic therapy and topical treatments for more extensive lesions.[10] Aggressive treatment of precancerous lesions is critical to preventing progression to invasive SCC.[11]

A systematic review found that liquid nitrogen cryotherapy as a standalone treatment achieves an average clearance rate of 72% at 1 to 3 months, 72% at 3 to 6 months, and 74% at 6 to 12 months, with improved efficacy when combined with 5-fluorouracil. Photodynamic therapy yields optimal results when incorporated into multifaceted treatment approaches, showing the lowest recurrence rates when combined with an ablative fractional laser and trichloroacetic acid. Photodynamic treatment has proven effective in treating diffuse actinic keratosis; however, its role in preventing actinic keratosis and keratinocyte skin cancers remains inconclusive.

A study found that despite prophylactic photodynamic therapy administered every 6 months over 5 years in renal transplant patients with normal skin, 63% still developed actinic keratosis.[12] Notably, actinic keratosis on the head and neck responds most effectively to topical 5-fluorouracil, either alone or combined with calcipotriol or photodynamic therapy. In contrast, topical diclofenac has demonstrated lower efficacy compared to these other treatment modalities.[9]

The National Comprehensive Cancer Network (NCCN) reported that recent prospective randomized controlled trials have demonstrated superior efficacy of various treatments for actinic keratosis compared to placebo. These treatments include topical 5-fluorouracil with or without calcipotriol, topical imiquimod, topical tirbanibulin, and photodynamic therapy. In high-risk patient groups such as transplant recipients, prophylactic use of oral retinoids such as acitretin has proven effective, reducing SCC and keratinocyte carcinoma incidence by 54% and 56%, respectively.[11]

An oral acitretin dose of 30 mg/d is effective in preventing keratinocyte carcinomas in renal transplant recipients in a 6-month period.[13] A 16-year retrospective study further demonstrated that solid organ transplant recipients experienced fewer cutaneous SCCs within 3 years of receiving 0.2 to 0.4 mg/kg/d of acitretin, with the prophylactic effect lasting up to 8 years.[14] However, the adverse effects of oral retinoids can be significant, and discontinuing acitretin therapy may lead to relapses of SCCs and actinic keratosis. Despite these concerns, the same retrospective study indicated that the adverse effects of acitretin were generally well tolerated.

The most commonly reported adverse effects of acitretin were mucocutaneous xerosis, hypertriglyceridemia, and hypercholesterolemia, often necessitating the use of lipid-lowering agents. However, no hepatic, renal, or skeletal toxicities were observed, and there were no cases of triglyceride-induced pancreatitis.[14] Due to its teratogenicity, oral retinoids must be used with extreme caution in individuals of childbearing potential. Acitretin should be discontinued for at least 3 years before conception. A retrospective study in Germany found that 1 in 5 children born to mothers with acitretin-exposed pregnancies within 3 years of stopping therapy had congenital malformations.[15]

Nicotinamide may help reduce the risk of cutaneous SCCs, but the evidence remains conflicting.[11] A study found that a dose of 500 mg of nicotinamide twice daily reduced the development of new nonmelanoma skin cancers by 23% in patients with at least 2 nonmelanoma skin cancers in the previous 5 years.[16] However, another 12-month trial showed that oral nicotinamide 500 mg twice daily did not reduce the development of keratinocyte cancers or actinic keratosis in solid organ transplant patients compared to a placebo group.[17]

Special Considerations

The incidence of skin cancer is significantly higher among organ transplant recipients due to the immunosuppressive medications required to prevent organ rejection. These drugs impair the immune system’s ability to detect and combat abnormal cell growth, substantially increasing the risk of skin cancer, particularly SCC. Studies indicate that SCC occurs 65 to 250 times more frequently in transplant recipients compared to the general population, while BCC is up to 10 times more common. Additionally, skin cancers in transplant recipients often develop earlier, are more likely to be multifocal, and tend to be invasive, presenting significant treatment challenges.[2][18]

Certain immunosuppressive medications are directly linked to an increased risk of skin cancer. For example, calcineurin inhibitors (eg, cyclosporine and tacrolimus) and azathioprine, commonly prescribed to organ transplant recipients, have been associated with a higher incidence of SCC. These medications suppress key immune responses that typically help control the malignant transformation of skin cells. In contrast, mammalian target of rapamycin (mTOR) inhibitors (eg, sirolimus and everolimus) may carry a lower risk of skin cancer and are being investigated as potential alternatives for high-risk patients. This differential risk underscores the importance of tailoring immunosuppressive regimens to balance the needs of preventing organ rejection while minimizing cancer risk.[19][20]

Immunosuppressed patients are also more susceptible to oncogenic viruses such as human papillomavirus (HPV), which can contribute to the development of SCC. As a result, the Advisory Committee on Immunization Practices recommends routine HPV vaccination for all immunocompromised individuals, including those with HIV who have not been previously vaccinated.[21] Notably, individuals with HIV infection have an elevated risk of developing anogenital SCC.[22] This risk is strongly associated with lower CD4 counts (<200 cells/mm³) and higher viral loads (>10,000 copies/mm³).[23] Thus, as a preventive measure, HPV vaccination is recommended for all HIV-positive individuals aged 26 or younger, as well as those engaging in high-risk sexual practices, regardless of CD4 count.[24]

Preventative strategies, along with regular dermatological surveillance, are crucial for reducing skin cancer risk in immunosuppressed individuals. Besides strict sun protection, early detection through regular skin exams, often performed by dermatologists experienced in treating immunosuppressed patients, allows for prompt intervention in treating precancerous lesions or early-stage cancers. A multidisciplinary approach involving dermatologists, oncologists, and transplant specialists is essential to optimize care and outcomes for this vulnerable population.[18]

Types of Skin Cancers

Squamous cell carcinoma

Evaluation and risk stratification: SCC is the most commonly diagnosed skin cancer in immunosuppressed populations. Management of SCC in these patients relies on risk stratification to assess the likelihood of local recurrence, metastasis, or disease-specific survival. Key risk factors for identifying high-risk individuals include the total number of SCCs, the frequency of new tumor formation, and the presence of aggressive tumor features. Aggressive characteristics may include tumor invasion beyond the skin, perineural involvement, and large or poorly differentiated tumors. Tumors exhibiting 3 or more risk factors for recurrence are of particular concern. These factors guide treatment decisions and help determine appropriate follow-up protocols.[11] 

In high-risk populations, clinical assessment of skin lesions can be challenging. Therefore, maintaining a low threshold for performing skin biopsies on suspicious lesions is essential to ensure timely diagnosis and treatment. Prompt diagnosis is critical, as delays can significantly worsen outcomes. For patients with an elevated risk of nodal metastases, imaging studies such as contrast-enhanced computed tomography (CT) or ultrasound may be used for nodal staging. In some instances, pathological evaluation of lymph nodes may also be necessary to assess for metastatic spread. Early detection and proactive management of both primary lesions and potential metastases are key to improving outcomes in these high-risk patients. Among organ transplant recipients and other immunosuppressed individuals, adjusting immunosuppressive therapy may be warranted in cases of rapid tumor progression or life-threatening skin cancer. Incorporating mTOR inhibitors may also be considered in select cases.[11]

Low-risk squamous cell carcinoma: According to the NCCN guidelines, low-risk SCC tumors are characterized by specific criteria—primary lesions 2 cm or smaller, located on the trunk or extremities, with well-defined borders, well or moderately differentiated, no deeper than 2 mm, and no invasion beyond the subcutaneous fat (see Table 1). Treatment options for low-risk SCC lesions include standard excision, electrodessication and curettage (E&C), shave excision, or topical application of 5-fluorouracil. Standard excision requires a margin of 4 to 6 mm, with postoperative margin assessment for clearance. Radiation therapy may be considered for nonsurgical candidates with low-risk tumors.[11]

Individuals with immunosuppression are at high risk for developing multiple skin cancers. As a result, rapid and effective treatment is crucial, given the potential for multiple tumors to form within a short time frame. Destructive therapies such as E&C and cryotherapy are often preferred for clinically low-risk tumors, as they allow for the treatment of multiple lesions in a single visit. However, when E&C is performed based solely on clinical assessment, it is essential to review pathology from a biopsy taken during the procedure to ensure no high-risk features are overlooked, which may necessitate further treatment. For patients with multiple adjacent tumors, surgical excision may leave behind surrounding in situ disease. In such cases, minimizing tissue rearrangement and treating in situ disease with topical therapies, similar to those used for actinic keratoses and field cancerization, is recommended.[11]

High-risk squamous cell carcinoma: High-risk SCCs include lesions that are larger than 2 cm, deeper than 2 mm, and located on the trunk or extremities, or any size lesions located on the head, neck, hands, feet, pretibial area, or anogenital regions. These tumors typically exhibit poorly defined borders, rapid growth, and a tendency to recur. They may arise in areas previously treated with radiation or in regions with chronic inflammation. Histologically, they may present with acantholytic, adenosquamous, or metaplastic subtypes, and/or demonstrate perineural, lymphatic, or vascular involvement. Neurological symptoms may also be present. In immunosuppressed patients, any lesion is considered high risk (see Table 1).

For SCC lacking high-risk features other than immunosuppression, excision with margins of at least 4 to 6 mm is recommended. Alternatively, Mohs micrographic surgery (MMS) may be considered. MMS is also preferred for low-risk skin cancers located in areas with terminal hair, lesions larger than 0.6 cm, or those in high-risk anatomical locations, especially in immunocompromised individuals, due to its lower recurrence rates. When MMS is not feasible, surgical excision with margins of 6 to 10 mm should be performed, accompanied by intraoperative or postoperative margin assessment. Reconstruction should be postponed until histological confirmation of negative margins.[11]

Moreover, immunosuppressed patients diagnosed with high-risk cutaneous SCC necessitate regular full-body skin examinations, encompassing evaluations of regional lymph nodes and evaluation of nerve function around the tumor site. These examinations should be performed every 3 to 6 months for the first 2 years, every 6 to 12 months for the following 3 years, and annually thereafter for life.[11] When clinical lymph node examination is positive, follow-up with fine needle aspiration, core biopsy, or excisional biopsy is essential for diagnostic evaluation. Preoperative staging using CT or ultrasonography is critical, followed by regional lymph node dissection as needed.[25] 

Currently, multiple staging guidelines exist for cutaneous SCC, with the most notable systems established by Brigham and Women’s Hospital (BWH) and the American Joint Committee on Cancer (AJCC; see Table 2). The NCCN also provides guidelines for risk stratification of keratinocyte carcinoma and treatment options based on risk. A study comparing the performance of the AJCC-8 and BWH staging systems found that BWH offers better specificity (93%) and positive predictive value (30%) for identifying tumors with poor outcomes, such as metastasis or death, thus reducing the risk of inappropriate upstaging of low-risk tumors.[26] 

In high-risk cutaneous SCC patients with no positive clinical nodal examination, imaging modalities such as CT, positron emission tomography (PET), or magnetic resonance imaging (MRI) may be considered. A study evaluating the impact of radiological imaging on outcomes in high-risk cutaneous SCC showed that nearly twice as many patients with BWH T2b/T3 tumors who underwent imaging received adjuvant therapy. This approach led to improved outcomes by enabling early detection and treatment of advanced-stage SCC, while also reducing the risk of nodal metastasis.[27] 

A cohort study conducted at BWH investigating the risk of nodal metastasis in cutaneous SCC patients indicated that BWH T1 tumors have a 0.1% risk of nodal metastasis, while BWH T2a, T2b, and T3 tumors carry risks of 1% to 5%, 21%, and 67%, respectively.[28] Additionally, a systematic review involving 130 patients undergoing sentinel lymph node biopsy (SLNB) revealed a statistically significant difference in the rate of positive SLNB between BWH T2a and T2b tumors (7% versus 29%).[29] Thus, nodal staging utilizing SLNB should be contemplated for tumors of BWH stage T2b or higher when clinical nodal examination yields negative results.

Radiation therapy: Although radiation therapy remains an option for nonsurgical candidates with low-risk SCC tumors, its efficacy diminishes in the context of high-risk SCC tumors, where the risk of recurrence exceeds 26% for T3 and T4 tumors. As such, in high-risk SCC cases, radiation therapy is best reserved for adjuvant or salvage treatment.[30] The NCCN recommends considering radiation therapy for immunosuppressed patients, especially as an adjuvant treatment for cases involving perineural disease. Additionally, satellite lesions and in-transit cutaneous metastases, which are more common in this population, should be managed aggressively with a multidisciplinary healthcare team.[11] Despite undergoing surgery and postoperative radiation therapy, immunosuppressed patients tend to have poorer outcomes in terms of recurrence-free and progression-free survival at 2 years compared to immunocompetent individuals.[31]

Systemic therapy: Systemic therapy for SCC is typically considered for individuals who are ineligible for curative surgery or radiation therapy, or those with metastatic, recurrent, or refractory disease. Immune checkpoint inhibitors (ICIs), such as programmed cell death protein 1 (PD-1) inhibitors such as cemiplimab and pembrolizumab, show response rates of 35% to 50% in locally advanced unresectable and metastatic SCC.[32][33] In indirect comparisons, cemiplimab has demonstrated superior overall survival and progression-free survival compared to pembrolizumab, epidermal growth factor receptor (EGFR) inhibitors, and platinum-based chemotherapy.[34] However, the efficacy of ICIs in immunocompromised patients remains largely unexplored due to their exclusion from clinical trials. Retrospective studies suggest that cutaneous SCC in solid organ transplant patients responds to ICI treatment at a lower rate compared to the immunocompetent population, with acute allograft rejection occurring in 10% to 65% of cases.[35][36]

A systematic review of 119 reported cases of ICI use in solid organ transplant recipients revealed that cutaneous SCC demonstrates a better response rate compared to other cancers, such as melanoma and hepatocellular carcinoma. Factors contributing to this improved response rate include a reduction in the dosage of immunosuppressive regimens and a longer time between transplant and ICI therapy. The rate of organ rejection was 41.2%, with graft failure occurring in 23.5% of cases. However, the most common cause of death was cancer progression (64%), followed by graft failure (24%). Allograft PD-L1 positivity and the absence of tacrolimus in the immunosuppressive regimen were correlated with an increased risk of allograft rejection.[37] Consequently, ICIs are relatively contraindicated in organ transplant recipients due to the risk of allograft rejection. This consideration must be carefully weighed against potential benefits through shared clinical decision-making between patients and clinicians, as organ rejection can be life-threatening.[36]

Chemotherapy has historically been used in the treatment of metastatic SCC, but it is associated with a higher incidence of adverse effects and a less favorable response rate. Platinum-based therapy, either alone or in combination with 5-fluorouracil, is a commonly utilized approach for managing metastatic SCC. However, combined chemotherapy and radiation therapy have not demonstrated superiority over radiation therapy alone in cases of advanced SCC. EGFR inhibitors, such as cetuximab and panitumumab, are used for unresectable cutaneous SCC and offer better tolerance compared to traditional cytotoxic chemotherapy. However, their therapeutic efficacy tends to be short-lived. Data regarding their use in solid organ transplant recipients are limited, and caution is warranted due to reports of fatal alveolar damage in lung transplant recipients.[38][39][40]

Basal cell carcinoma

Although BCC is not the most common skin cancer in the immunosuppressed population, individuals with immunosuppression are still at an increased risk of developing BCC. Studies show that the incidence of BCC in organ transplant recipients is 5 to 10 times higher than in the general population,[41][42][43] with up to 50% of patients experiencing BCC within 10 years posttransplantation.[44][45][46] Research has also indicated that BCCs in transplant recipients often present as superficial histological subtypes, typically occurring in younger individuals (onset approximately 15 years earlier) and in non-head and neck regions.[47][48][49] Despite similar recurrence rates between transplant recipients and the general population, the NCCN Guidelines Panel considers BCCs in immunosuppressed patients as potentially high-risk tumors based on clinical experience.[50]

Low-risk basal cell carcinoma: According to the NCCN, low-risk BCC is characterized by primary lesions measuring less than 2 cm on the trunk or extremities, with well-defined borders and histological features of superficial or nodular subtypes. These lesions should have a depth of around 6 mm and should not invade beyond the subcutaneous fat. For primary BCC lesions less than 1 cm on the trunk or extremities, E&C may be sufficient for treatment. However, for larger low-risk BCC lesions, excision with a standard margin of 4 mm is recommended, along with postoperative margin assessment. In the immunosuppressed population, wider margins may be necessary. MMS may be considered due to its higher cure rate and tissue-sparing properties. For patients with limited life expectancy, watchful waiting can be a viable option for asymptomatic superficial BCC and nodular BCC in low-risk anatomical locations.[50]

High-risk basal cell carcinoma: High-risk BCC is characterized by primary lesions on the trunk or extremities measuring 2 cm or larger, recurrent lesions, or lesions of any size located on the head, neck, hands, feet, pretibial, and anogenital regions. Histologically, these lesions exhibit poorly defined borders and aggressive growth patterns, such as mixed infiltrative, micronodular, morpheaform, basosquamous, sclerosing, or carcinosarcomatous features. High-risk lesions may also occur at sites of prior radiation therapy and in patients with immunosuppression. Treatment typically involves MMS or peripheral and deep en face margin assessment. When MMS is not feasible, standard excision with wider surgical margins and postoperative margin assessment is appropriate. Radiation therapy should be considered for nonsurgical candidates.[50]

Systemic therapy is indicated when curative radiation therapy is not an option. Hedgehog signaling pathway inhibitors, such as vismodegib and sonidegib, are oral treatments for advanced BCCs. Vismodegib is approved by the US Food and Drug Administration (FDA) for all advanced BCCs, while sonidegib is specifically approved for nodal and locally advanced BCCs. Although data on the use of systemic therapy in immunosuppressed populations are limited, case reports of organ transplant recipients suggest that these therapies can be both safe and effective.[51] However, prolonged treatment may induce resistance to smoothen inhibitors.[52] Cemiplimab is approved for the treatment of locally advanced and metastatic BCC that has failed smoothened inhibitor therapy. While ICIs are generally discouraged in solid organ transplant recipients, they may be considered in cases of lymphoproliferative and other acquired immunodeficiencies.[13][33]

Melanoma

The incidence of melanoma is notably higher in immunosuppressed individuals, approximately double that of those with a healthy immune system. After organ transplantation, melanoma is typically diagnosed within 1.5 to 2.5 years, with the highest risk of stages III and IV melanoma occurring within the first 4 years. However, the risk of melanoma in situ and localized melanoma remains elevated over time. Melanoma in transplant recipients tends to exhibit more aggressive behavior, leading to a higher mortality rate compared to non-recipients.[53] 

Following NCCN guidelines, melanoma treatment strategies are based on the stage of the disease. Melanoma in situ requires excision with a margin of 0.5 to 1 cm, while SLNB is recommended for stage T1b or higher. Excision margins range from 1 to 2 cm for stages T1a to T2, and at least 2 cm for stages T3 and T4 (see Table 3). Excision should extend to the depth of the superficial fascia without extensive undermining. Postoperative reconstruction should be delayed until histological confirmation of clear margins.[54] Immunotherapy is considered an adjuvant option for locally invasive melanoma in immunosuppressed patients, except for organ transplant recipients.[55] 

A comprehensive multidisciplinary approach is crucial in managing advanced stages III and IV melanoma, including a complete staging workup with baseline full-body imaging. Novel therapies, such as intralesional talimogene laherparepvec (T-VEC), a modified herpes simplex virus, show promise for nonsurgical treatment of unresectable cutaneous, subcutaneous, and nodal melanoma, as well as in-transit metastases. However, the efficacy of T-VEC in immunosuppressed populations remains uncertain, with limited data on potential graft failure complications in organ transplant recipients.[56][57] 

Immunotherapy, such as combination BRAF/MEK inhibitors, has shown efficacy in improving outcomes for advanced-stage melanoma patients with BRAF-activating mutations. However, their safety profile in organ transplant recipients requires further investigation.[55] Careful considerations should be made when using ICIs in organ transplant recipients due to the increased risk of graft rejection. Interestingly, for immunotherapy, the risk of graft failure correlates with higher cancer cure rates.[58]

Merkel cell carcinoma

Merkel cell carcinoma (MCC) poses an elevated risk in immunosuppressed populations due to its viral infection mechanism, with increased incidence observed in patients with conditions such as HIV, hematological malignancies, and organ transplants. MCC typically manifests as an aggressive malignancy, often diagnosed at advanced stages, and has a poorer survival rate for those with immunosuppression. As a result, immunosuppression is considered a high-risk factor associated with poor outcomes in MCC.[59] Consequently, a comprehensive management approach, involving a multidisciplinary healthcare team, is essential. When feasible, modifying immunosuppressive therapy should be considered. Notably, some immunosuppressive regimens, such as the combination of cyclosporine and azathioprine, are associated with a higher risk of MCC incidence compared to alternatives such as tacrolimus and mycophenolate.[60][61] 

Standard protocols for MCC management involve comprehensive assessments, including complete skin examinations, lymph node evaluations, and baseline imaging such as PET/CT or MRI. SLNB serves as a crucial staging tool for diagnosing subclinical nodal disease. Additionally, serological testing to quantify serum Merkel cell polyomavirus capsid (MCPyV) and oncoprotein antibodies is vital for prognosis and surveillance. Negative capsid antibodies suggest a higher risk of recurrence, while rising oncoprotein titers can signal early disease progression. Notably, immunosuppressed patients may exhibit lower baseline seropositivity compared to immunocompetent individuals.[62][63]

• For localized MCC without nodal involvement in immunosuppressed patients, the NCCN guidelines recommend surgical excision with a 1 to 2 cm margin, combined with adjuvant radiation therapy. Some studies suggest that MMS for MCC is associated with improved outcomes compared to standard surgical excision. However, other studies have shown that recurrence rates and overall survival outcomes are similar between MMS and wide local excision.[59]
• For localized MCC with regional lymph node involvement, postoperative radiation has been shown to improve overall survival compared to surgical excision alone (NCCN). Notably, patients with stage I or II MCC derive the most benefit from adjuvant radiation therapy, as it reduces the rate and time to local recurrence while improving survival outcomes.[59] 
• In metastatic MCC, a multidisciplinary approach involving surgery, systemic therapy, and radiation therapy is recommended. Systemic therapy options include ICIs and chemotherapy. However, in organ transplant recipients, caution is advised due to the risk of organ rejection, requiring consideration of alternative therapeutic strategies.[59]

The median time to recurrence in patients with MCC is approximately 8 to 9 months. Close clinical follow-up is recommended, with thorough skin and lymph node exams every 3 to 6 months for the first 3 years, followed by examinations every 6 to 12 months thereafter. Patients should be informed that a diagnosis of MCC increases their risk of developing other nonmelanoma skin cancers. Therefore, patient education on regular self-examination, alongside routine clinical follow-ups, is essential for early detection and ongoing surveillance. Regular monitoring of MCPyV oncoprotein antibody levels may be useful for seropositive patients, as an increase from baseline could indicate early recurrence.[59]

Kaposi sarcoma

Kaposi sarcoma encompasses 2 types associated with immunosuppression—endemic and iatrogenic. Endemic Kaposi sarcoma emerges as an AIDS-defining illness, particularly in individuals with low CD4 counts. The primary treatment involves combination antiviral therapy, which can induce regression of early-stage tumors. Chemotherapy may be considered for advanced AIDS-related Kaposi sarcoma or in cases of Kaposi sarcoma immune reconstitution inflammatory syndrome.[64] 

Iatrogenic or transplant-related Kaposi sarcoma typically manifests about 1 year after transplantation, with an average diagnosis age of 40. The condition primarily presents as cutaneous or mucosal lesions in 90% of cases, with 10% showing visceral involvement, which is more common among heart and liver transplant recipients. The incidence is highest in regions with a higher prevalence of human herpesvirus-8 (HHV-8), as posttransplant Kaposi sarcoma often results from HHV-8 reactivation.[65] 

The diagnosis of Kaposi sarcoma necessitates histological and immunological confirmation to differentiate it from disease mimickers such as bacillary angiomatosis, blastomycosis, and cryptococcus. Patients with iatrogenic Kaposi sarcoma often experience lesion regression upon discontinuation of immunosuppressive therapy.[66] Corticosteroids should be avoided due to their association with Kaposi sarcoma progression, while sirolimus may help inhibit disease advancement. In a study involving kidney transplant recipients who developed Kaposi sarcoma while on cyclosporine, switching to sirolimus resulted in the resolution of Kaposi sarcoma lesions.[66][67] For advanced disease with visceral involvement, chemotherapy regimens, such as doxorubicin and paclitaxel, are considered first-line treatments in immunocompetent patients. However, the risks and benefits must be carefully weighed in organ transplant recipients.

Table 1. NCCN Stratification for Squamous Cell Carcinoma

Abbreviations: NCCN, National Comprehensive Cancer Network; SCC, squamous cell carcinoma.

Reference for Table 1.[11]

Table 2. NCCN Stratification for Basal Cell Carcinoma

Abbreviation: NCCN, National Comprehensive Cancer Network.

Reference for Table 2.[50]

Table 3. Melanoma Staging and Wide Excision Margins

Reference for Table 3.[68]

Other Issues

Patient Education

In immunosuppressed patients, skin cancers often develop more rapidly and with greater severity, presenting unique challenges that require specialized management. Immunosuppression—whether resulting from organ transplantation, treatment of autoimmune diseases, or other underlying conditions—reduces the body’s ability to detect and eliminate cancer cells. As a result, these patients face not only a higher risk of developing skin cancer but also an increased likelihood of aggressive disease progression.

Prevention is therefore a key focus in managing these high-risk individuals, emphasizing strict sun protection and the initiation of early, frequent skin cancer screenings following the diagnosis of an immunosuppressive condition. Patients should also be educated about the potential adverse effects of prescribed medications. In particular, women of childbearing age should be informed of the teratogenic risks associated with certain drugs, such as retinoids, such as acitretin.

Enhancing Healthcare Team Outcomes

A multidisciplinary approach is essential to effectively prevent and manage skin cancer in immunosuppressed patients. This strategy involves the collaboration of a diverse team of healthcare professionals, including primary care providers, dermatologists, oncologists, transplant specialists, and other subspecialists who are involved in managing the underlying conditions that necessitate immunosuppression.

Dermatologists play a critical role in conducting regular skin examinations and in the early detection and treatment of precancerous lesions. Oncologists may be required to guide the treatment of more advanced cases. For patients with organ transplants, transplant specialists contribute by balancing immunosuppressive regimens to reduce cancer risk while ensuring transplant viability.

Coordination among healthcare providers is essential for a holistic approach that addresses both the patient’s cancer risk and underlying health needs. Frequent communication and shared decision-making enable timely adjustments to treatment plans, reducing the risk of early progression and effectively managing tumor burden. Additionally, a collaborative approach allows for personalized, proactive care strategies that can significantly enhance patient outcomes and quality of life. A comprehensive, collaborative team-based approach is essential for optimizing the management of skin cancer risk in immunosuppressed patients. This strategy aims to prevent complications and provide the highest level of care for this vulnerable population.