Optimal Management of Skin Cancer in Immunosuppressed Patients

Skin cancer is the most common malignancy in humans with basal cell carcinoma representing the majority of cases in the general population. The prevalence of skin cancer is increased amongst immunosuppressed patients such as those with lymphoproliferative disorders including non-Hodgkin lymphoma and chronic lymphocytic leukemia or those with iatrogenic immunosuppression following organ transplantation. In addition, these patients experience greater morbidity and mortality associated with skin cancers. The most common skin cancer in immunosuppressed patients is squamous cell carcinoma, which often presents with more aggressive features and has a greater rate of metastasis. This article reviews the risk factors, etiology, clinical presentation, and prevalence of skin cancer amongst immunosuppressed patients, including organ transplant, lymphoproliferative disorders, autoimmune disorders, and human immunodeficiency virus. We also provide a comprehensive review of treatment guidelines for immunosuppressed patients with cutaneous malignancy. Surgical therapy is the cornerstone of treatment; however, we also discuss pharmacologic treatment options, lifestyle modifications, and revision of immunosuppressive regimens.     

Human papilloma virus in skin, mouth and uterine cervix in female renal transplant recipients with or without a history of cutaneous squamous cell carcinoma

Some human papillomaviruses are thought to be associated with skin cancer. In this pilot study, 21 female renal transplant carriers, 10 with a history of skin squamous cell carcinoma and 11 without, together with 9 age-matched healthy women were investigated for human papillomavirus DNA in sun-exposed (forehead) and less sun-exposed (buttock) skin, mouth and uterine cervix. Paraffin-embedded tumours from 9 of the patients with a history of squamous cell carcinoma were analysed. Healthy skin from both the healthy and the immunosuppressed individuals harboured a wide variety of papillomaviruses. In the healthy individuals, samples from less sun-exposed skin showed a lower prevalence of human papillomavirus DNA than corresponding samples from the immunosuppressed patients (4/9 and 7/9, respectively). Among the immunosuppressed patients, human papillomavirus DNA was found as frequently in buttock samples (17/21) as in forehead samples (17/20). There was no increased prevalence of human papillomavirus in the cervix or mouth samples from the immunosuppressed patients.     

Human herpesvirus 8

Human herpesvirus 8 (HHV 8), also known as Kaposi's sarcoma-associated herpesvirus (KSHV) is a g2 herpesvirus and the most recently identified human tumor virus. HHV 8 has been consistently implicated in the pathogenesis of all clinical variants of Kaposi's sarcoma, as well as in the plasma cell variant of multicentric Castleman's disease and primary effusion lymphomas. Pathogenicity of the virus is increased in the host who is immunosuppressed, either iatrogenically or through H1V-1 infection. The HHV 8 genome contains several homologues of cellular genes that regulate cell growth and differentiation, and the exact mechanisms of the virus' oncogenicity using molecular piracy are still being investigated and elucidated. In this article, the authors review the epidemiology, transmission, clinical manifestations, and molecular genetics of HHV 8 infection and provide a summary of the current treatment modalities available to the clinician.     

Absence of human herpesvirus 8 and Epstein-Barr virus genome sequences in cutaneous epithelial neoplasms arising in immunosuppressed organ-transplant patients

Recent studies have implicated herpesvirus 8 and Epstein-Barr virus in the development of cutaneous malignancies in immunosuppressed patients. In order to examine the strength of this association, we examined 37 malignant, pre-malignant and benign cutaneous epithelial neoplasms removed from immunosuppressed organ recipients for the presence of human herpesvirus 8 and Epstein-Barr viral genome sequences using polymerase chain reaction (PCR) and in situ hybridization. We examined 2 actinic keratoses, 1 benign keratosis, 11 invasive squamous cell carcinomas, 17 squamous cell carcinomas in situ and 6 basal cell carcinomas. We also examined 4 basal cell carcinomas, 1 invasive squamous cell carcinoma and 3 squamous cell carcinomas in immunocompetent hosts. In contrast to findings reported by other investigators, we were unable to detect viral genome sequences in any of the biopsies examined. Our findings suggest that human herpesvirus 8 and Epstein-Barr virus likely do not play an etiologic cogenesis in immunocompromised patients.     

Merkel cell carcinoma arising in immunosuppressed patients treated with high-dose ultraviolet A1 (320-400 nm) phototherapy: a report of two cases

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine tumour of the skin. Though immunodeficiency is the most relevant risk factor, ultraviolet (UV) radiation is also involved, but as of yet we do not know the action spectrum, pattern or dose which would produce a dangerous exposure. A retrospective study of two immunosuppressed patients who developed MCC during, or soon after a treatment cycle with high dose UVA1 exposures was conducted, in order to understand wether repeated exposures to suberythemogenic UVA1 radiation may have a cancerogenic activity provoking MCC in immunosuppressed patients.     

Mycobacterium haemophilum in an immunosuppressed child

Mycobacterium haemophilum is an emerging cutaneous and systemic pathogen in immunosuppressed adults. Reports in the pediatric literature prior to 2004, limited to immunocompetent children with lymphadenitis, offer a different clinical presentation from that of the immunosuppressed adult. We report an instance of this atypical mycobacterial infection occurring in an immunosuppressed boy with clinical findings similar to those described in immunosuppressed adults.     

Phaeohyphomycosis in renal transplantation: report of two cases

Phaeohyphomycosis is an infection caused by a filamentous fungus that contains pigment melanin in its cell wall. We report two cases caused by Exophiala sp. emphasizing the clinical variability of the disease, as well as diagnostic and therapeutic difficulties of this opportunistic infection in immunosuppressed patients (kidney transplant).     

Fatal squamous cell carcinoma arising from transplant-associated porokeratosis

Porokeratosis is a disorder of epidermal keratinization characterized by variably sized plaques with central depression and a well-demarcated keratotic border. Associations of porokeratosis with immunosuppression and of porokeratosis with malignancy have been observed. The authors report a case of fatal metastatic squamous cell carcinoma arising from porokeratosis in an immunosuppressed patient.     

Primary effusion lymphoma presenting as a cutaneous intravascular lymphoma

Primary effusion lymphoma (PEL) is a rare and aggressive lymphoma that arises in the context of immunosuppression and is characterized by co‐infection with Epstein–Barr virus (EBV) and human herpesvirus‐8/Kaposi sarcoma‐associated herpesvirus (HHV‐8/KSHV). It was originally described as arising in body cavity effusions, but presentation as a mass lesion (extracavitary PEL) is now recognized. Here, we describe a case of PEL with an initial presentation as an intravascular lymphoma with associated skin lesions. The patient was a 53‐year‐old man with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) who presented with fevers, weight loss and skin lesions concerning for Kaposi sarcoma (KS). A skin biopsy revealed no evidence of KS; however, dermal vessels contained large atypical cells that expressed CD31 and plasma cell markers but lacked most B‐ and T‐cell antigens. The atypical cells expressed EBV and HHV‐8. The patient subsequently developed a malignant pleural effusion containing the same neoplastic cell population. The findings in this case highlight the potential for unusual intravascular presentations of PEL in the skin as well as the importance of pursuing microscopic diagnosis of skin lesions in immunosuppressed patients.     

Human papillomavirus type 2-associated basal cell carcinoma in two immunosuppressed patients

Human papillomavirus-2 genomes were detected by molecular hybridization in two cases of basal cell carcinomas that developed in immunosuppressed individuals. This form of human papillomavirus is usually responsible for common warts in the general population. Although it does not appear to have oncogenic potential, it may be, in some cases, associated with cutaneous malignancy.     

T6+ and HLA-DR+ cell numbers in epidermis of immunosuppressed renal transplant recipients

The increased susceptibility of the skin of chronically immunosuppressed individuals to viral infections and sunlight-induced malignancies suggests specific drug-induced, dysfunction of local immune mechanisms within the sun-exposed skin of these individuals. To help understand the effect of immunosuppressive therapy alone in the absence of ultraviolet light on the immune system of skin, biopsies were collected from non-sun-exposed buttock skin of control, healthy volunteers and kidney transplant recipients immunosuppressed with either azathioprine/prednisone or cyclosporin A/prednisone and examined for incidences of T6+, and HLA-DR+ cells. No significant differences in the incidences of these 2 cell types were found (a) between control individuals and transplants recipients, (b) between transplant recipients receiving either of the immunosuppressive drug regimes, or (c) between transplant recipients who either had or had not developed skin cancer.     

Exserohilum Infection in an Immunocompromised Neonate

Abstract: Invasive fungal infections in children have increased in recent years, coinciding with greater survival of preterm neonates and children with immunodeficiencies, more intense chemotherapy regimens, and greater use of stem cell and solid organ transplantation. We describe a case of an immunosuppressed neonate who developed cutaneous Exserohilum rostratum infection.     

Merkel cell carcinoma in the setting of HIV infection.

Merkel cell carcinoma has been found to have an increased incidence among immunosuppressed patients, specifically organ transplant recipients receiving immunosuppressive therapy. HIV similarly depresses the immune response of infected persons. We report a case of Merkel cell carcinoma (MCC) in an HIV-infected patient who died from liver metastases 2 years after his tumor was diagnosed. The purpose of this report is to describe the possible relationship between HIV and MCC and to emphasize the importance of early diagnosis and aggressive management of MCC.     

Merkel cell carcinoma arising after therapeutic immunosuppression

Azathioprine and cyclosporin have been used as immunosuppressants for many years, but long-term use has also been associated with neoplasia. We report three cases of rapidly fatal Merkel cell carcinoma in patients who had been treated with azathioprine for many years either for rheumatoid arthritis or following organ transplantation. Two of these patients had also received cyclosporin. We suggest that Merkel cell carcinoma may be seen more commonly in immunosuppressed patients than in the normal population and that the oncogenic potential of azathioprine and cyclosporin should be borne in mind when prescribing these drugs.     

Leukaemic dissemination of Merkel cell carcinoma in a patient with systemic lupus erythematosus

We describe an unusual bone‐marrow metastasis of Merkel cell carcinoma (MCC) arising in the right cheek of a 73‐year‐old woman with systemic lupus erythematosus (SLE) and Sjögren’s syndrome, who had been treated with oral prednisolone and methotrexate for 10 years. Seven months after wide local excision followed by local irradiation, the patient presented with thrombocytopaenia. Her bone marrow had been completely replaced by metastatic MCC cells, and metastatic cytokeratin 20‐positive cells were also identified in the peripheral blood. To our knowledge, in the English literature, only six cases have been described previously of MCC bone‐marrow involvement. Of these six cases, four were immunosuppressed, similar to our case. The high incidence of MCC in immunosuppressed patients such as those with SLE has been discussed previously. We consider that immunosuppression might be associated with bone‐marrow metastasis, which is a rare form of MCC.     

Human papillomavirus type 16 in bowenoid papulosis, intraoral papillomas, and squamous cell carcinoma of the tongue

A 33-year-old immunosuppressed man developed bowenoid papulosis on his genitalia, velvety papules and plaques in his mouth, and invasive squamous cell carcinoma of his tongue. All three lesions were positive for human papillomavirus type 16 (HPV-16). The case provides further circumstantial evidence for a role of HPV-16 in epithelial neoplasia. The possible roles of a second HPV infection and of immunosuppression are also discussed.     

华芙消毒液治疗免疫抑制小鼠皮肤癣菌病的研究

目的建立免疫抑制小鼠皮肤癣菌病模型,探讨华芙消毒液对免疫抑制小鼠皮肤癣菌病的疗效.方法60只小鼠分别予腹腔注射氢化可的松30 mg/kg,隔日1次,共3次,然后在小鼠皮肤上接种须癣毛癣菌,建立免疫抑制小鼠皮肤癣菌病模型;皮损局部外涂华芙消毒液和3%克霉唑液,观察二者对免疫抑制小鼠皮肤癣菌病疗效.结果华芙消毒液及3%克霉唑液对免疫抑制小鼠皮肤癣菌病治疗的总有效率分别为80%和75%,真菌学治愈率分别为85%和80%,两者之间无显著性差异(P＞0.05).结论华芙消毒液对免疫抑制小鼠皮肤癣菌病具有良好的疗效.     

Multiple basal cell carcinomas in a patient with acute myeloid leukaemia and chronic lymphocytic leukaemia

Skin cancer is a well-recognized risk of prolonged immunosuppression, for example, following renal transplantation. These tumours contrast with idiopathic lesions in that squamous cell, rather than basal cell carcinomas usually predominate. We report a Caucasian female who developed multiple basal cell carcinomas following protracted cytotoxic therapy for acute myeloid leukaemia and subsequently chronic lymphocytic leukaemia. No other clinical risk factors nor relevant polymorphisms of genes encoding for detoxifying enzymes were identified. Immune suppression is a well-recognized cause of multiple skin tumours, the most striking increase usually being of squamous cell carcinomas. We believe this woman is representative of a subgroup of immunosuppressed patients who, for as yet poorly understood reasons, have a predisposition to basal cell, rather than squamous cell carcinoma accrual.     

Clinical patterns of cutaneous nontuberculous mycobacterial infections

BACKGROUND: Cutaneous nontuberculous mycobacterial infections result from external inoculation, spread of a deeper infection, or haematogenous spread of a disseminated infection. There are two species-specific infections (fish-tank or swimming-pool granuloma, due to Mycobacterium marinum, and Buruli ulcer, caused by M. ulcerans). Most infections, however, produce a nonspecific clinical picture. OBJECTIVES: To define clinical patterns of cutaneous disease in nontuberculous mycobacterial infections. METHODS: Fifty-one patients with cutaneous nontuberculous mycobacterial infections were reviewed. Clinical and histopathological features of normal hosts and immunosuppressed patients were compared. Two subgroups of immunosuppressed patients were distinguished: patients with cutaneous infection and patients with a disseminated infection and cutaneous involvement. RESULTS: In immunosuppressed patients the number of lesions was significantly higher. Abscesses and ulceration were also more frequently observed. Different species were found in normal hosts and immunosuppressed patients. Several clinical patterns of cutaneous infection were defined: lymphocutaneous or sporotrichoid lesions; nonlymphocutaneous lesions at the site of trauma; folliculitis and furunculosis involving the lower extremities; disseminated lesions on the extremities in immunosuppressed patients. Two patterns were observed in patients with a disseminated infection: localized cutaneous lesions and disseminated cutaneous and mucosal lesions. CONCLUSIONS: Cutaneous manifestations of nontuberculous mycobacterial infections may be classified according to criteria such as cutaneous lesions and immune status.     

Intralesional vitamin D immunotherapy for recalcitrant molluscum contagiosum

Molluscum contagiosum (MC) is a benign viral infection, which may have florid manifestations in immunosuppressed patients. Moreover, the treatment is often unsatisfactory in these patients and it maybe recalcitrant. We hereby report the use of intralesional vitamin D immunotherapy in two immunosuppressed patients with persistent widespread MC lesions.