High frequency and diversity of cutaneous appendageal tumors in organ transplant recipients

BACKGROUND: Recipients of organ transplant who are immunosuppressed are at greatly increased risk of nonmelanoma skin cancers compared with the general population, but their risk of appendageal tumors is unknown. OBJECTIVE: Our aim was to conduct a systematic examination of cutaneous appendageal tumors arising in recipients of organ transplants compared with individuals who were immunocompetent (ICP). METHODS: We conducted a retrospective, clinicopathologic analysis of consecutive appendageal tumors arising in 650 recipients of organ transplants and in the general population of approximately 605,000 people served by our institution. RESULTS: Between 1993 and 1998, 231 appendageal tumors were identified in 211 individuals; 23 tumors were found in 21 of 650 patients undergoing transplant (3%), 10 in individuals with other immunosuppressive conditions, 3 in 2 patients with Muir-Torre syndrome, and 195 in 178 apparently ICP. In addition to the increased frequency of appendageal tumors among recipients of transplants, malignant tumors were overrepresented (43% of transplant tumors vs 4% in ICP; P <.0001) as were tumors of sebaceous origin (30% vs 6%; P <.0001). CONCLUSIONS: Recipients of organ transplant who are immunosuppressed have a greatly increased risk of cutaneous appendageal tumors compared with apparently ICP. In addition, their tumors are more likely to be malignant and of sebaceous origin.     

Special concern about squamous cell carcinoma of the scalp in organ transplant recipients

BACKGROUND: Several risk factors are generally accepted to portend more aggressive behavior of cutaneous squamous cell carcinoma. These include tumor size, tumor depth, histologic subtype, location on the lip or ear, tumor arising in scar, recurrent tumor, and tumor demonstrating perineural invasion. Organ transplant recipients can have significant morbidity and mortality from squamous cell carcinoma. OBSERVATIONS: Four organ transplant recipients developed metastatic disease from squamous cell carcinoma of the scalp. CONCLUSIONS: Squamous cell carcinoma of the scalp in organ transplant recipients should be considered a high-risk tumor because of its anatomic location. Margin-controlled tumor extirpation, sentinel lymph node biopsy, and adjuvant radiation therapy should all be considered in the organ transplant recipient population.     

Skin cancer in organ transplant recipients: Epidemiology,pathogenesis, and management

In the United States more than 100,000 people are living with solid organ transplants. The intense immunosuppressive regimens necessary for prolonged survival of allografts significantly increase the rates of both internal and cutaneous malignancies in recipients of solid organ transplants. Skin cancer is the most common cancer in patients after transplantation. Because of the early onset and high tumor burden in transplant recipients, dermatologists have significant challenges in managing the treatment of these patients. This article describes the epidemiology and clinical presentation of skin cancer during posttransplantation immunosuppression, discusses pathogenic cofactors, and reviews the optimal management for mild and severe skin cancer in transplant recipients.     

Basal cell carcinomas developing in solid organ transplant recipients: clinicopathologic study of 176 cases

OBJECTIVE: To assess the clinicopathologic features of basal cell carcinomas developing in organ transplant recipients. DESIGN: Case series. SETTING: University department of dermatology. PATIENTS: One hundred forty-six (7.2%) of 2029 transplant recipients followed up in our department who developed 176 histologically proven basal cell carcinomas. One hundred fifty-three random samples of basal cell carcinomas excised from nonimmunosuppressed patients served as controls. MAIN OUTCOME MEASURES: Clinical data were gathered from the medical records. Histologic slides were retrospectively reexamined. RESULTS: Basal cell carcinomas developed an average of 6.9 years after transplantation, sooner after heart than kidney transplantation, and showed a relative predilection for heart allograft recipients. The mean age of transplant recipients with basal cell carcinomas was significantly lower than that of controls (54.6 vs 69.8 years), especially for recipients of renal transplants, and a male preponderance was found (male-female ratio, 4.8:1 vs 1.3:1). In both groups, basal cell carcinomas were predominantly found on the head and neck, but extracephalic locations were significantly more frequent in transplant recipients (37.5%) than controls (24.5%). Histologically, superficial basal cell carcinomas were more frequent in transplant recipients than controls (33.6% vs 14.4%). The density of the peritumoral cell infiltrate was lower in tumors from transplant recipients compared with controls. The tumor thickness and the presence of epidermal ulceration did not differ significantly between the 2 groups. CONCLUSIONS: Basal cell carcinomas in transplant recipients show some clinicopathologic differences from their "ordinary" counterparts, namely, a younger age at development, male preponderance, more frequent distribution in extracephalic sites, and higher frequency of superficial subtypes.     

Iatrogenic skin cancer: induction by psoralen/ultraviolet A and immunosuppression of organ transplant recipients

Photochemotherapy (psoralen/UVA (PUVA)) is an efficient therapeutic tool for a wide range of skin diseases. Concern, however, exists regarding the long-term carcinogenic effects of this treatment modality and, as a consequence, is being used less frequently. PUVA remains an important treatment in our therapeutic armamentarium but must be used with caution in those patients with risk factors and cumulative dose exposure must be limited. PUVA-induced cancers show features in common with skin cancers induced by immunosuppressed organ transplant recipients. Tumours in the latter group of individuals are, however, much more aggressive and difficult to manage.     

Skin cancer and other cutaneous disorders in liver transplant recipients

Patients who have received liver transplant are at increased risk of skin complications due to long-term immunosuppression regimen. The aim of this study was to analyze the incidence and risk factors of skin complications in liver transplant patients. We analyzed 161 liver transplant recipients. The mean age at transplantation was 47.4 years. Mean follow-up was 6 years. Seventy-one percent of patients presented with skin complications, including aestethic alterations, infections, precancerous lesions and malignancies, which represented 57%, 43%, 18% and 9%, respectively. Risk factors were: age at transplantation ≥ 45 years, immunosuppressive therapy with cyclosporine, and phototype II and III. Our study indicates that although liver transplant recipients are at greater risk of developing skin complications compared to the general population, the risk is lower than for other solid organ transplants, particularly for premalignant and malignant lesions.     

Oral retinoids for the prevention of skin cancers in solid organ transplant recipients: a systematic review of randomized controlled trials

BACKGROUND: The increased incidence of skin cancers after solid organ transplantation is well recognized. Skin cancers developing in transplant recipients are more aggressive in behaviour. Therapeutic options to reduce and/or delay the development of cutaneous neoplasms are therefore of interest. OBJECTIVES: The objective of this review was to summarize the available medical literature from randomized controlled trials on the use of oral retinoids as a preventive agent for skin cancers in the solid organ transplant population. METHODS: Three electronic databases were searched for relevant trials: MEDLINE (1966-October 2003), EMBASE (1980-week 44, 2003) and the Cochrane Controlled Trials Register (third quarter 2003). Randomized or quasi-randomized controlled clinical trials on subjects of any age or ethnic background who had received a solid organ transplant (cardiac, renal, liver, etc.) were evaluated. All titles and abstracts found by the search strategy were independently reviewed by two researchers for inclusion into the review. RESULTS: Eighty-one abstracts were identified through the electronic databases for consideration. Review of the abstracts identified three eligible trials. One cross-over trial involving 23 subjects treated with acitretin 25 mg daily for 12 months reported 46 squamous cell carcinomas (SCCs) developing in six subjects during acitretin treatment vs. 65 SCCs developing in 15 subjects during the drug-free period. Another trial involving 44 subjects treated with acitretin 30 mg daily or placebo for 6 months reported two of 19 subjects developing two SCCs in the treatment group vs. nine of 19 subjects developing 18 new skin cancers (15 SCCs, one Bowen's disease, two basal cell carcinomas) in the placebo group. One dose comparison trial involving 26 renal transplant recipients treated with acitretin did not find a significant difference in numbers of skin cancers developing at the doses examined. The major limitation to the use of acitretin was poor tolerance due to adverse events. Headaches, rash, musculoskeletal symptoms and hyperlipidaemia were the most common causes of withdrawal from treatment. No alterations in renal or liver function were detected during the periods of treatment or follow-up. CONCLUSIONS: The available data from a small number of randomized controlled trials suggest that acitretin may have a role in the management of solid organ transplant recipients with skin cancers. Tolerability of the drug is a major factor limiting its use. Appropriate selection of patients may help improve the risk-benefit ratio.     

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.     

Non-melanoma skin cancer risk in the Queensland renal transplant population

BACKGROUND: Non-melanoma skin cancer (NMSC) is an important complication of solid organ transplantation, especially in areas of high ultraviolet light exposure. Registry data may underestimate the scale of the problem. OBJECTIVES: A single-observer study of a Queensland renal transplant population was conducted between July 1999 and April 2000 utilizing both cross-sectional and retrospective data. The aims were to determine accurately the risk of NMSC following renal transplantation and compare this with currently available registry data. PATIENTS AND METHODS: A structured interview and full skin examination was completed by 398 renal transplant recipients. Case notes and histology reports were examined for details of previous skin tumours. Independently collected data on 341 subjects from the Australia and New Zealand Dialysis and Transplantation Registry (ANZDATA) were also examined. RESULTS: One hundred and eighty-seven of 361 (51.8%) transplant recipients of Fitzpatrick skin types I-IV had developed 3979 histologically diagnosed NMSCs since first transplantation. The ratio of SCC/BCC was reversed from 1 : 3.7 before transplantation to 2 : 1 after transplantation. NMSC increased with duration of immunosuppression; 29.1%, 52.2%, 72.4% and 82.1% of those immunosuppressed for < 5, 5-10, 10-20 and > 20 years, respectively, had developed at least one tumour. The ANZDATA registry under-recorded the numbers of patients with NMSC by 28.4% and gave no indication of tumour numbers. CONCLUSIONS: NMSC is a greater clinical problem in renal transplant recipients living in subtropical Queensland, Australia, than is shown by currently available registry data. This has implications for the development of prevention and surveillance strategies.     

Merkel cell carcinoma in organ-transplant recipients: report of two cases with unusual histological features and literature review

BACKGROUND: Non-melanoma skin cancers are the commonest malignancies after organ transplantation and are often associated with human papillomavirus (HPV). Merkel cell carcinoma is an uncommon neuroendocrine skin tumor, of which 67 cases have been reported up till now, usually briefly, in organ transplant patients. METHODS: Among a cohort of 2340 organ-transplant recipients, two patients (one renal, one heart) developed cutaneous Merkel cell carcinomas 5 and 12 years of post graft, respectively. These were studied histologically and immunohistochemically, as well as virologically for the presence of HPV. A thorough literature review of all reported cases of Merkel cell carcinoma following solid organ transplantation was performed. RESULTS: Despite a typical immunophenotype, the tumors showed unusual histological features: both were epidermotropic, and one was intermingled with a bowenoid squamous cell carcinoma. Search for HPV by immunohistochemistry and PCR proved negative in both cases. CONCLUSION: In the setting of organ transplantation, Merkel cell carcinoma is much rarer than other non melanoma skin cancers but may show unusual histologic features. HPV do not seem to be involved in its pathogenesis.     

Prevention of non-melanoma skin cancers with nicotinamide in transplant recipients: a case-control study

Background

Nicotinamide is the precursor of nicotinamide adenine dinucleotide (NAD+), an essential cofactor for adenosine triphosphate (ATP) production. It has recently been reported to be effective in reducing the rates of new non-melanoma skin cancers (NMSCs) and actinic keratosis (AKs).

Objectives

We studied the efficacy of oral nicotinamide as treatment for AKs in transplant recipients.

Materials & methods

We recruited 38 transplant (eight liver and 30 kidney) patients with single or multiple AKs. Nineteen patients were randomly assigned to Group 1 and took nicotinamide 500 mg/daily (cases); the other 19 patients were randomly assigned to Group 2 without nicotinamide (controls). At base-line, AKs were identified, measured, and photographed for follow-up. Five patients underwent an AK biopsy for histopathology. Statistical analyses were performed using the Student t test.

Results

At baseline, no statistically significant differences were observed regarding AK size between the two groups. After six months, among the cases, AKs had significantly decreased in size in 18/19 patients (88%). Among these 18 patients, seven patients (42%) had shown complete clinical regression and no patient developed new AKs. Conversely, among the controls, 91% showed an increase in AK size and/or developed new AKs. Seven pre-existing AKs progressed to squamous-cell carcinoma.

Conclusion

Nicotinamide appears to be effective in preventing and treating AKs, although the mechanisms are still unclear. Further studies with a larger sample of organ transplant recipients and a longer follow-up period are needed to further support our conclusions.

     

Skin surveillance of a U.K. paediatric transplant population

BACKGROUND: Solid organ transplant recipients are at increased risk of skin cancer. Melanoma is less common than nonmelanoma skin cancer (NMSC) although the relative proportion of melanoma among skin cancers has been shown to be higher in paediatric than adult recipients. Multiple melanocytic naevi and/or atypical naevi may be a risk factor for the development of melanoma. The relationship between naevus counts and phenotypic characteristics, disease-related variables and sun exposure has not been explored in paediatric transplant patients. OBJECTIVES: To determine the prevalence of premalignant and malignant skin lesions and to identify known risk factors associated with benign and atypical melanocytic naevi in a U.K. paediatric transplant population. METHODS: Paediatric (< or = 19 years) renal and liver transplant patients, who were 5 or more years post-transplantation, were reviewed over 12 months. Lifetime history of sun exposure, episodes of sunburn, sunny holidays, sunscreen use, sun bed use, demographic and transplantation details were collected using interview, questionnaire and case note review. A skin examination was performed for regional counts of malignant lesions, benign and atypical naevi. RESULTS: Ninety-eight patients (82 liver, 13 renal, three multiorgan) with a median follow up of 9 years (range 5-16) were reviewed. Neither skin cancer nor premalignant lesions for NMSC were detected in this group. Eighty-five patients had benign naevi (median 6, range 1-57). Clinical risk factors for increased counts of benign naevi included increasing age (P = 0.03), more episodes of sunburn (P = 0.003) and prolonged treatment with cyclosporin (P = 0.009). The presence of atypical naevi in six patients was significantly associated with more episodes of sunburn (P = 0.006) and more transplants (P = 0.04). Other variables including phenotype, skin type, sun exposure, holidays abroad, residence abroad and total duration of immunosuppression did not correlate with benign or atypical naevus counts. CONCLUSIONS: Skin cancer was not observed in paediatric solid organ transplant recipients who were 5-16 years post-transplantation. Both benign and atypical naevus counts were higher in children with frequent episodes of sunburn. As both naevi and sunburn are risk factors for melanoma, we should target fair-skinned transplant recipients with naevi for intensive sun avoidance education. A prospective, longitudinal follow-up study should determine the onset of skin cancer post-transplantation and the significance of benign and atypical naevus counts in this cohort.     

Clinical recognition of actinic keratoses in a high-risk population: how good are we?

BACKGROUND: Actinic keratoses (AKs) are dysplastic epidermal lesions considered to be potential precursors of squamous cell carcinoma. Most AKs are diagnosed clinically and are rarely confirmed histologically. High interobserver variation exists among dermatologists for the diagnosis of AKs. Previous studies of the positive predictive value of the diagnosis of AKs have yielded rates as high as 94%. This study evaluates the rate at which histologic analysis confirms the clinical impression (positive predictive value) of AKs in patients with a history of skin cancer. OBSERVATIONS: Seventeen (74%) of 23 lesions with classic features of AKs, as determined by 3 dermatologists, were confirmed as AKs histologically. These were lesions that would ordinarily not be biopsied. Of the 6 misdiagnoses, 5 (83%) were skin cancer, most often squamous cell carcinoma. CONCLUSIONS: The positive predictive value of 74% for the diagnosis of AKs in this study is substantially lower than that of 2 previous studies, suggesting that physicians may be misdiagnosing many patients with classic features of AKs. Most misdiagnosed cases were forms of skin cancer. These preliminary data suggest that the threshold for biopsy of suspect lesions in patients with a history of skin cancer should be low and warrant further evaluation.     

Cutaneous squamous cell carcinoma: an epidemiological review

Cutaneous squamous cell carcinoma (SCC) is a common cancer in white populations and its disease burden is often substantially underestimated. SCC occurs more often in men than women and increases dramatically with age; those affected often develop multiple primaries over time, which increases the burden. The main external cause is solar ultraviolet radiation (UVR), with immunosuppression being the other established risk factor, shown by the high SCC rates in organ transplant recipients. Sunbed use and certain genetic disorders and medical conditions are also associated with SCC, while associations with human papillomavirus infection and high bodyweight are not established. The presence of actinic keratoses (AKs) on sun‐damaged skin is one of the strongest predictors of SCC in unaffected people and a very small proportion of AKs are SCC precursors, although the true rate of malignant transformation of AKs is unknown. The mainstay of SCC prevention is protection of the skin from undue sun exposure by use of clothing cover and sunscreen during summer or in sunny places. Educational, behavioural and multicomponent interventions directed at individuals ranging from parents of newborns, to school children and adolescents, to outdoor workers, have repeatedly been shown to be effective in improving sun‐protective behaviours. Health policies can facilitate SCC prevention by setting standards for relevant behaviours to reduce UVR exposure, for example, by legislated restriction of the tanning industry. Skin cancer prevention initiatives are generally highly cost‐effective and public investment should be encouraged to control the growing public health problems caused by SCC.     

Skin diseases in children with organ transplants

BACKGROUND: Skin diseases are frequent in organ transplant recipients, but studies concerning children are sparse. OBJECTIVE: We assessed skin diseases in children who had received organ transplants. METHODS: A total of 145 children referred to our dermatologic consultation were studied. RESULTS: Steroid-induced striae distensae and acne occurred only in adolescents; severe cyclosporine-related side effects were more frequent in younger children. The most common findings were warts (53.8%), tinea versicolor (14.5%), herpes simplex/zoster (9.6%), molluscum contagiosum (6.9%), and impetigo contagiosum and folliculitis (6.2%). Other notable disorders included a diffuse hyperpigmentation with a "dirty" appearance of the skin, pyogenic granulomas, melanocytic nevi proliferation, and skin tags. Two of 20 further adult patients who received transplants during childhood had squamous cell carcinomas. CONCLUSION: Children who have received organ transplants frequently present side effects of immunosuppressive drugs and infectious diseases. Most disorders are related to the age of the patients rather than to the length of immunosuppression, whereas others are favored by the reinforcement of immunosuppression. Skin cancers were not encountered, but the risk of carcinomas in early adulthood should be considered.     

Incidence and clinical predictors of Kaposi's sarcoma among 1721 Italian solid organ transplant recipients: a multicenter study

Kaposi's sarcoma (KS) can be a complication of solid organ transplantation, but with an important incidence rate variability in different geographical areas. Here we analyzed the incidence rate, timing and clinical correlates of KS, in a cohort of Italian solid organ transplant recipients from four distinct transplantation centers. A total of 1721 renal, heart and liver transplant recipients were recruited between 1997 and 2004. KS was diagnosed in 40 patients, after a median follow up of 1 year (range 0.8-5.1). Visceral involvement was detected in 7/40 patients. Incidence rate of KS in the whole population was 2.3 cases per 1000 individuals per year. The standardized incidence rate (SIR) for KS in renal transplant recipients was 149.9 (95% CI 103.0-212.0), with the excess risk greater among women (SIR 316.0) than among men (SIR 133.6). In a Cox proportional hazard regression model, age at transplantation equal or older than 30 years and only combined immunosuppressive therapy with mycophenolate mofetil + cyclosporine + prednisolone were independently associated with KS. Italian organ transplant recipients have an increased risk (about 100 times greater) for KS compared to the general population, especially during the first two years after transplantation. Age older than 30 years at transplantation and a more aggressive immunosuppressive regimen were both independent risk factors for the disease.     

Basal cell carcinoma in a series of renal transplant recipients: epidemiology and clinicopathologic features

Background Basal cell carcinoma (BCC) is the most common malignancy among Caucasians worldwide. The risk of BCC is 10–16 times higher among immunosuppressed transplant recipients compared with the general population. Objective To analyze the incidence, clinical presentation, histologic features, treatment and recurrence rate of BCC in a cohort of 69 renal transplant recipients (RTRs; 53 male). Methods Retrospective population‐based cohort study of immunosuppressed RTRs. Results Ten of 69 patients (14.5%, five male) developed a total of 17 BCCs, mostly on the head. Mean age at first diagnosis of BCC was 65.5 ± 8.5 years, and latency between kidney transplantation and diagnosis of the first BCC was 11.1 ± 6.3 years (mean ± SD). The risk of female RTRs to develop BCCs appeared to be three times higher than the risk of male RTRs, and female RTRs developed BCCs earlier after transplantation. Nodular BCC was the most common histologic subtype. Most BCCs in these RTRs were treated by complete surgical excision. Recurrence after surgical excision was observed in one of the 10 patients (10%). Conclusion Our results suggest female RTRs to be at higher risk to develop cutaneous BCCs than male RTRs. There are no differences in localization and clinicopathologic presentation of BCCs developing in RTRs compared with immunocompetent patients. Therefore, BCCs in RTRs do not require different treatment than in other patient groups. As patients tend to develop a second BCC, close follow‐up is mandatory.     

Altered density,composition and microanatomical distribution of infiltrating immune cells in cutaneous squamous cell carcinoma of organ transplant recipients

Organ transplant recipients (OTR) who require the long‐term use of immunosuppressant medications to prevent organ rejection are more than 65 times more likely than the general population to develop squamous cell carcinoma of the skin (SCC), which is a type of skin cancer and the most frequent malignant tumor after organ transplantation. Allegedly, the immune system in the skin may influence the disease as SCCs tend to behave more aggressively in immunosuppressed patients. The aim of this study was to gain an insight into the distribution patterns of different immune cells in SCCs arising in immunosuppressed OTR and non‐transplant patients. The researchers from Heidelberg, Germany, stained different immune cell subsets in 20 SCCs from kidney transplant recipients and SCCs from thoroughly matched immunocompetent non‐transplant patients (IC). They compared quantities and tissue distribution of immune cells in tumors and surrounding skin in both groups by using a novel semi‐automatic technology and computerized microscopy. The investigators found that the density of immune cells in SCC and surrounding skin from OTR was overall reduced compared to IC, particularly at the tumor borders. In addition to reduced CD4+ immune cells at the tumor borders the density of CD8+ T cells (a subset of immune cells thought to help fight tumours), within the SCCs and tumor‐surrounding skin of OTR was significantly diminished. One possible explanation may be that immunosuppressants (drugs that suppress the immune system to stop the body rejecting the new, transplanted organ) influence the ability of immune cells to accumulate in the skin and position themselves at the site of a growing SCC in order to detect and defend against cancer. The authors note that additional studies must be done to learn more about the functional relevance of the particular immune cell subsets for the control of skin cancer.     

Successful treatment of multiple actinic keratoses in organ transplant patients with topical 5% imiquimod: a report of six cases

BACKGROUND: Nonmelanoma skin cancer represents a significant cause of morbidity in organ transplant recipients (OTRs). Cutaneous malignancies, mainly invasive squamous cell carcinoma and its precursor actinic keratosis (AK), appear approximately 5-10 years after organ transplantation. Impaired wound healing and high recurrence rates in immunocompromised patients treated with destructive therapies such as cryosurgery or topical 5-fluorouracil represent frequently known complications. OBJECTIVES: To evaluate the safety and efficacy of imiqimod 5% in the treatment of AKs in OTRs. METHODS: Six OTRs (two kidney, two heart, one lung and one liver) with extensive AKs were treated with imiquimod 5% cream two to three times weekly in an open-label uncontrolled, nonrandomized pilot study. RESULTS: In five of six patients treated with imiquimod 5% cream all AK lesions were cleared after 12-16 weeks. One patient showed partial response. Local adverse events at the site of application included erythema, oedema and mild erosion. No wound infection or scarring was observed in any of these patients. All graft-related laboratory parameters were stable during and after treatment. Immunosuppressive therapy remained unchanged throughout the treatment. CONCLUSIONS: These results suggest that imiquimod 5% cream may be useful for the local treatment of precancerous AK lesions in OTRs.     

Lichenoid graft vs. host disease following liver transplantation

BACKGROUND: Graft vs. host disease (GVHD) is a common complication of bone marrow transplantation (BMT) but is rarely seen after solid organ transplantation. METHODS: We report a case of lichenoid GVDH arising in a 60-year-old man 10 weeks after orthotopic liver transplantation. RESULTS: Skin biopsies revealed changes suggestive of lichenoid GVHD, but histological features differed from those described in post bone marrow (stem cell) transplant GVHD, in that a dense lymphoid infiltrate was present. The brisk infiltrate contained eosinophils that initially led to concern for a lichenoid drug eruption. The patient developed multiorgan GVHD after reduction in immunosuppression. The diagnosis of chronic GVHD was confirmed by the demonstration of chimerism in the patient's peripheral blood. The generalized cutaneous eruption and systemic manifestations responded to salvage therapy including intravenous immunoglobulin infusion, increased immunosuppression with high-dose steroids, mycophenolate mofetil, and systemic and topical tacrolimus. CONCLUSIONS: In interpreting skin biopsies, it is important to recognize that brisk inflammation may be seen in GVHD in the setting of solid organ transplantation, in contrast to the more sparse inflammation typical of GVHD following BMT. The clinical and histologic differential diagnosis included the eruption of lymphocyte recovery, drug reaction, and viral exanthem. We provide a conceptual framework for evaluating generalized cutaneous changes that may occur post transplantation.