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Visible actinic keratosis (AK) lesions and subclinical (non-visible) sun damage in the field of cancerization are associated with risk of both non-melanoma skin cancer, including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), and, more rarely, melanoma. As the incidences of AK and skin cancer are increasing, effective prevention and treatment of AK is essential to minimize disease burden and improve patient quality of life. Currently, AK lesions are often left untreated and field therapies are underused. Patient-centred care, with a focus on the patient-physician relationship, has proven cost-effective, and improved clinical outcomes and patient satisfaction in a number of therapy areas. Strategies for applying patient-centred care to AK are warranted. Existing barriers to the effective treatment of AK were identified and patient-centric strategies to overcome each barrier were discussed. Barriers to effective AK treatment include poor disease awareness (for both patient and physician), concerns associated with the cosmetic effects of treatment, treatment-related side effects, cost perceptions for lesion-directed vs field-directed therapies, and inadequate adherence, particularly with long treatment duration. Overcoming these barriers will involve patient and physician education that promotes: disease prevention and awareness; the importance of self-examination; an understanding of treatment options; and the importance of adherence to treatment. To maximize its effectiveness, education should be delivered within a patient-centric framework, where the relationship between patient and physician is built on effective communication, empathy and a feeling of partnership. Patient-centric care, including patient education, is key to overcoming the barriers associated with effective AK treatment.

Porokeratosis is a clonal epidermal disorder of keratinization characterized by annular lesions with an atrophic centre and a hyperkeratotic edge. The cornoid lamella is the histopathological hallmark. Six clinical variants are recognized: porokeratosis of Mibelli; disseminated superficial porokeratosis; disseminated superficial actinic porokeratosis (DSAP); porokeratosis plantaris et palmaris disseminata; punctate porokeratosis and linear porokeratosis. Linear porokeratosis is the type most frequently associated with malignant transformation into squamous cell carcinoma (SCC). It is thought to represent a mosaic form of DSAP and has an incidence of less than 1 in 200 000; treatment options are limited. We describe a patient with systematized linear porokeratosis and multiple SCCs who was successfully treated with bleomycin electrochemotherapy (ECT), a form of intralesional chemotherapy. In view of their large number, the individual SCCs were treated with bleomycin ECT. One year post-treatment the patient remains tumour free. To our knowledge, this is the first case of multiple SCCs treated by ECT in the context of systematized linear porokeratosis. Our case highlights the challenges associated with diagnosing and managing this unusual form of porokeratosis.

A common debate among dermatopathologists is that prior knowledge of the clinical picture of melanocytic skin neoplasms may introduce a potential bias in the histopathologic examination. Histologic slides from 99 melanocytic skin neoplasms were circulated among 10 clinical dermatologists, all of them formally trained and board-certified dermatopathologists: 5 dermatopathologists had clinical images available after a 'blind' examination (Group 1); the other 5 had clinical images available before microscopic examination (Group 2). Data from the two groups were compared regarding 'consensus' (a diagnosis in agreement by ≥4 dermatopathologists/group), chance-corrected interobserver agreement (Fleiss' k) and level of diagnostic confidence (LDC: a 1-5 arbitrary scale indicating 'increasing reliability' of any given diagnosis). Compared with Group 1 dermatopathologists, Group 2 achieved a lower number of consensus (84 vs. 90) but a higher k value (0.74 vs. 0.69) and a greater mean LDC value (4.57 vs. 4.32). The same consensus was achieved by the two groups in 81/99 cases. Spitzoid neoplasms were most frequently controversial for both groups. The histopathologic interpretation of melanocytic neoplasms seems to be not biased by the knowledge of the clinical picture before histopathologic examination.

We report the case of a 24-year-old woman with an 8-month history of deep pelvic pain and postcoital bleeding. Examination revealed desquamation of the vaginal epithelium with tender fissured plaques in the vagina, initially thought to be vaginal intraepithelial neoplasia. Histology showed squamous mucosa with suprabasal acantholysis and hyperkeratosis, and no evidence of viral infection, dysplasia or malignancy. These findings were consistent with acantholytic dermatosis (AD), a rare lesion that resembles Hailey-Hailey and Darier disease histopathologically, but can be distinguished on a clinical basis. Vulval cases of AD are well recognized, but to our knowledge, this is the first reported case involving the vaginal epithelium alone.

Objective: Several questionnaires have been developed to screen for psoriatic arthritis (PsA) but head to head studies have found limitations. This study aimed to develop new questionnaires encompassing the most discriminative questions from existing instruments. Methods: Data from the CONTEST study, a head to head comparison of three existing questionnaires, were used to identify items with a Youden's index of ?0.1. These were combined using four approaches: CONTEST- simple additions of questions; CONTESTw- weighting using logistic regression; CONTESTjt- addition of a joint manikin and CONTESTtree- additional questions identified by CART analysis. These candidate questionnaires were tested in independent datasets. Results: 12 individual questions with a Youden's index of ?0.1 were identified but 4 of these were excluded due to duplication and redundancy. Weighting for two of these questions, was included in CONTESTw. Receiver operating characteristic (ROC) curve analysis showed that involvement in six joint areas on the manikin was predictive of PsA for inclusion in CONTESTjt. CART analysis identified a further 5 questions for inclusion in CONTESTtree. CONTESTtree was not significant on ROC analysis and discarded. The other three were significant in all datasets, although CONTESTw was slightly inferior to the others in the validation datasets. Potential cut points for referral are discussed. Conclusion: Of four candidate questionnaires combining existing discriminatory items to identify psoriatic arthritis in people with psoriasis three were found to be significant on ROC analysis. Testing in independent datasets identifies two questionnaires: CONTEST and CONTESTjt that should be pursued for further prospective testing. � 2014 American College of Rheumatology.

Background To report our experience with sentinel lymph node biopsy for staging patients with conjunctival melanoma. Methods A prospective review of patients with conjunctival melanoma who underwent sentinel lymph node biopsy at St Bartholomew9s Hospital from May 2008 to May 2012. The selection criterion for sentinel node biopsy depended on the tumour thickness (≥2 mm) and location of the conjunctival melanoma. The main outcome measures were the incidence of sentinel lymph node positivity and the procedure-related complications. Results In 4 years, 26 out of 70 patients met the selection criteria for sentinel lymph node biopsy. 4 patients declined and 22 patients consented for the procedure. Technetium-99m failed to identify a sentinel lymph node in four of the 22 patients (18%). Of the remaining 18 patients, two were found to have subclinical micrometastasis in regional lymph nodes. Median follow-up was 20 months (range 6–36 months). No false-negative events were observed. Complications of the procedure included transient blue staining of the epibulbar surface in five patients and transient facial nerve palsy in one patient. Conclusions Sentinel lymph node biopsy is a safe procedure with minimal complications. It should be considered for the staging of conjunctival melanomas, especially melanomas in non-limbal location or conjunctival melanomas ≥2 mm thick.

Summary Background Multiple questionnaires to screen for psoriatic arthritis (PsA) have been developed but the optimal screening questionnaire is unknown. Objectives To compare three PsA screening questionnaires in a head-to-head study using CASPAR (the Classification Criteria for Psoriatic Arthritis) as the gold standard. Methods This study recruited from 10 U.K. secondary care dermatology clinics. Patients with a diagnosis of psoriasis, not previously diagnosed with PsA, were given all three questionnaires. All patients who were positive on any questionnaire were invited for a rheumatological assessment. Receiver operating characteristic (ROC) curves were used to compare the sensitivity, specificity and area under the curve of the three questionnaires according to CASPAR criteria. Results In total, 938 patients with psoriasis were invited to participate and 657 (70%) patients returned the questionnaires. One or more questionnaires were positive in 314 patients (48%) and 195 (62%) of these patients attended for assessment. Of these, 47 patients (24%) were diagnosed with PsA according to the CASPAR criteria. The proportion of patients with PsA increased with the number of positive questionnaires (one questionnaire, 19·1%; two, 34·0%; three, 46·8%). Sensitivities and specificities for the three questionnaires, and areas under the ROC curve were, respectively: Psoriatic Arthritis Screening Evaluation (PASE), 74·5%, 38·5%, 0·594; Psoriasis Epidemiology Screening Tool (PEST), 76·6%, 37·2%, 0·610; Toronto Psoriatic Arthritis Screen (ToPAS), 76·6%, 29·7%, 0·554. The majority of patients with a false positive response had degenerative or osteoarthritis. Conclusion Although the PEST and ToPAS questionnaires performed slightly better than the PASE questionnaire at identifying PsA, there is little difference between these instruments. These screening tools identify many cases of musculoskeletal disease other than PsA.

Expression of Axl, a receptor tyrosine kinase, is increased in cutaneous squamous cell carcinoma (SCC). Examination of a series of cutaneous SCC tumors revealed positive phospho-Akt (P-Akt) staining accompanied by weak TUNEL staining in Axl-positive tumors, suggesting an anti-apoptotic role for Axl in SCC survival. The role of Axl in UV-induced apoptosis was investigated in a cutaneous SCC cell line using retroviral short hairpin RNA sequences enabling stable Axl knock-down. We show that, although Axl knock-down has no effect on cell proliferation, it sensitizes cells to UV-induced apoptosis through increased activation of the pro-apoptotic protein Bad, a change in the conformation of Bax and Bak, release of cytochrome c into the cytosol, and activation of caspases. These events are accompanied by faster Akt dephosphorylation in UV-treated Axl knock-down cells and correlate with the degree of Axl knock-down. Treatment with the pan-caspase inhibitor zVAD-fmk partially rescued cells from UV-induced apoptosis but did not affect Bid cleavage or cytochrome c release, suggesting that cells die via the mitochondrial-mediated pathway. Thus, Axl confers resistance of SCC cells to apoptosis and displays potential as a target for therapeutic intervention in cutaneous SCC.

Background Clinical information on histologic referral sheets is usually very limited, and particularly for inflammatory skin disorders, dermatopathologists often ask referring physicians for clinical correlation. Objective In this study we tested the value of clinicopathologic correlation in the histopathologic diagnosis of inflammatory skin disorders. Methods One-hundred biopsy specimens were digitalized and stored on 3 DVDs along with the clinical images. All cases were evaluated by 9 independent full-time dermatopathologists, initially without looking at the clinical pictures and subsequently after checking them. All diagnoses were finally compared with the "reference" diagnosis established in Graz, Austria, and the results were statistically analyzed. Results After evaluation of the clinical images, the number of dermatopathologists making a correct diagnosis was increased in 70 cases, unchanged in 25 cases, and decreased in 5 cases. The total number of correct diagnoses increased from 332 (diagnoses before evaluation of clinical pictures) to 481 (diagnoses after evaluation of clinical pictures), with a 16.6% increase in the total. Limitations The computerized setting is different from real-life dermatopathology and physical examination of patients. Conclusion Our study clearly shows that clinical pictures should be added to biopsy request slips of inflammatory skin disorders whenever possible, as they allow a better interpretation of histopathologic findings.

Palisaded neutrophilic granulomatous dermatitis is a rare but increasingly recognized cutaneous manifestation of connective tissue disorders. It is reported most commonly with rheumatoid arthritis but also occasionally in association with systemic lupus erythematosus, inflammatory bowel disease, lymphoproliferative disorders, and systemic vasculitides. The clinicopathological presentation is highly variable, which has led to suggestions that it encompasses a number of distinct diseases. Most previous cases have reported only a single clinical and histologic manifestation of the condition within an individual. Here, we present a case of systemic lupus erythematosus-associated palisaded neutrophilic granulomatous dermatitis in which a striking evolution of both clinical and histologic features was observed during the course of 7 years, providing compelling evidence for the proposal that palisaded neutrophilic granulomatous dermatitis represents a disease spectrum rather than separate disease entities.

Actinic keratoses are areas of abnormal epidermal growth that usually form on sun-exposed skin, and may lead to carcinomas if left untreated. Here, Professor Cerio discusses the clinical features of actinic keratoses and describes the various treatment options. Copyright © 2007 Wiley Interface Ltd

We present a case of an intriguing mesenchymal neoplasm of the scalp that recurred several times over 10 years before a final diagnosis was possible. The case was sent for expert opinions to various international dermatopathological authorities and was, for a long time, unanimously interpreted as malignant melanoma. This diagnosis was supported by immunohistochemical examinations demonstrating S-100 positivity. Nevertheless, the clinical behaviour, as well as some histopathological features raised doubt regarding the diagnosis. Only after the last recurrence, followed by a repeat extensive immunohistochemical study, the diagnosis of epithelioid angiosarcoma was made. Histologically malignant melanoma can be highly misleading and in literature, reports of misinterpreted cases of melanoma are published. In contrast, tumours that can simulate melanoma are also not infrequent and it is essential to perform immunohistochemistry to confirm diagnosis and exclude a melanocytic lesion.

In recent years improved knowledge of the mechanisms of intercellular and cell-matrix adhesion has led to better understanding of the blistering process in many bullous dermatoses. The wide characterisation of adhesion molecules has partially changed some traditional views and invariably has made the routine work of the pathologist more complex. If understanding cell-cell cohesion structures such as desmosomes and adherens junctions is complex enough, the cell-matrix adhesion structures, such as hemidesmosomes and their structural analogues on the basement membrane and superficial dermis, are even more complex. Defects of such structures cause the subepidermal bullous diseases in which there has been most characterisation of the adhesion molecules and has also led to the discovery of new diseases (e.g. p200 pemphigoid). Most of the antigens are also the targets for mutations seen in patients with the inherited type of epidermolysis bullosa, a group of rare blistering genodermatoses. Another important aspect of bullous skin conditions is the more accurate definition of the role of the different inflammatory cells involved in triggering, development and maintenance of these diseases. Recent studies have outlined the important role of T-cell lymphocytes and their cytokines in their pathogenesis. All these studies, based mainly on highly sophisticated ultrastructural and molecular biology techniques, have updated our knowledge of the pathogenesis of blistering diseases. Nevertheless, the diagnostic characterisation of bullous diseases remains sometimes difficult, and some pathological features and mechanisms still represent an enigma. Diseases such as bullous pemphigoid and cicatricial pemphigoid, or anti-laminin cicatricial pemphigoid and acquired bullous epidermolysis share the same molecular target but have very different clinical manifestations. Explaining this phenomenon, probably linked to different expressions of MHC, is one of the challenges for the future.

The incidence of malignant melanoma (MM) is continuing to rise, although childhood MM remains rare. We describe an 8-year-old Afro-Caribbean girl who developed a non pigmented lesion on the tip of her left thumb, which persisted despite treatment in primary care with cryotherapy. At biopsy she was found to have an acquired acral MM. She underwent amputation of the distal phalanx of her thumb, together with positive sentinel lymph node (SLN) biopsy and subsequent axillary lymph node clearance and adjuvant chemotherapy. MMs are very rare in this age and skin-type group, therefore requiring strict diagnostic criteria. These criteria include the distinction from MM mimics, especially Spitz tumours, and an appropriate use of staging techniques such as SLN biopsy to influence management.

Over the past decade there have been several reports in the literature of atypical forms of granuloma annulare (GA) occurring in HIV positive patients. We now report a case of diffuse granuloma annulare in an HIV positive patient with unusual clinical and immunohistological features. Our patient presented with a persistent extensive macular erythematous eruption on his face and upper trunk with bizarre sparing around the nipples and axillae. The histology showed an interstitial pattern of GA, with a predominance of CD8 positive cells, in contrast to the usual CD4 positive infiltrate typically seen in GA.

We report a 22-year-old woman who developed systemic lupus erythematosus (SLE) immediately after an Epstein-Barr virus (EBV)-induced mononucleosis infection. The link between these two conditions has long been suspected. The close temporal relationship, the course of the pathological events and the development of immunological changes in this case provide further evidence supporting the hypothesis that EBV infection could work as a trigger in some cases of SLE, particularly if the patient is genetically susceptible.

Normal human skin is remarkably resistant to infection from the large numbers of microorganisms that routinely colonize its surface. In addition to the role of skin as a mechanical barrier, it has long been recognized that skin and other epithelia can produce a range of anti-microbial chemicals that play an important part in eliminating potential cutaneous pathogens. Anti-microbial peptides are an important evolutionarily conserved innate host defense mechanism in many organisms. Human beta defensin-1 and -2 are cysteine-rich, cationic, low molecular weight anti-microbial peptides that have recently been shown to be expressed in epithelial tissues. In this study, we describe the characterization of human beta defensin-1 and -2 mRNA and peptide expression in normal human skin. Using reverse transcription-polymerase chain reaction we demonstrate that human beta defensin-1 is consistently expressed in skin samples from various body sites. Human beta defensin-2 demonstrates expression that is more variable and is more readily detectable in facial skin and foreskin compared with skin from abdomen and breast. In situ hybridization localizes the human beta defensin-1 and -2 transcripts to keratinocytes within interfollicular skin. Using specific antibodies, we have shown that human beta defensin-1 and -2 peptides are localized to the Malpighian layer of the epidermis and/or stratum corneum and that there are interindividual and site-specific differences in intensity of immunostaining and the pattern of peptide localization. The localization of human beta defensins to the outer layer of the skin is consistent with the hypothesis that human beta defensins play an essential part in cutaneous innate immunity.

A 36-year-old Asian man with von Hippel-Lindau syndrome was referred to the dermatology clinic in January 2005 with stiff fingers and ankles of 3 months' duration. He had undergone bilateral nephrectomy for renal squamous cell carcinoma in 2002 and had started hemodialysis. Multiple cerebellar hemangiomata were resected in 1991, 2001, and 2003, and consequently he underwent multiple magnetic resonance imaging (MRI) scans with gadolinium-based contrast agents whilst on hemodialysis. The serum creatinine level and calculated glomerular filtration rate (GFR) at the time of his first exposure to gadolinium were 584 micromol/L and 13.31 mL/min, respectively. The patient recalled his symptoms worsening dramatically immediately after he had undergone two MRI scans on a day on which he was not dialyzed. On examination, he had thickening and edema on the hands and feet with significant pain and loss of range of movement. Autoantibodies for connective tissue disorders and thrombophilia screen were negative. Histology showed a proliferation of fibroblasts and dendritic cells, thickened collagen bundles, increased elastic fibers, and mucin deposition, consistent with the diagnosis of nephrogenic fibrosing dermopathy (NFD) (Figs 1 and 2). A trial of thalidomide for several months was unhelpful. He received a live, unrelated renal transplant in August 2005 but, despite excellent renal function and early conversion to sirolimus, his symptoms continued to progress. He now has contractures of all the limbs (Figs 3 and 4) and great difficulty with the activities of daily living. He is receiving physiotherapy and being considered for extracorporeal photophoresis therapy.

Lichen Sclerosus (LS), also known as Lichen Sclerosus et Atrophicus, or, in other literature as, Balanitis Xerotica Obliterans, is a chronic inflammatory skin disease which manifests in both males and females, affecting primarily the genitourinary area. The exact pathogenesis of LS is unknown and several hypotheses have been proposed, including autoimmune pathology, infective triggers, trauma (such as surgical interventions and sexual abuse) and genetic predisposition (rather than a direct genetic [...]

Summary Kaposi's sarcoma may occur in transplant recipients on immunosuppressive regimens, but is not well recognized in association with treatment for dermatological disease. We report two cases where multifocal Kaposi's sarcoma developed following iatrogenic immunosuppression with prednisolone and azathioprine for bullous pemphigoid. Both patients were HIV negative and, in one case, lesions regressed both clinically and histologically when immunosuppressive therapy was withdrawn.

Background Appropriate management of patients with atopic dermatitis must depend primarily on early, accurate diagnosis and allergen avoidance in infants. Patients with less typical lesions, such as extensor involvement, may be mis-diagnosed. Aim Dermatologists should try to ensure that correct management is initiated in the primary care setting and maintained by patients and parents. Guidelines for the management of both paediatric and adult patients with atopic dermatitis have been drawn up by an international panel of dermatologists. For patients with mild disease, elaborate investigations to identify the trigger factors are unnecessary. Management should include general measures (skin hydration, irritant and allergen avoidance), provision of information to parents and intermittent use of low potency topical corticosteroids when necessary. For patients with mild to moderate disease, investigations may require assessment of food allergies in paediatric cases and of contact allergens and irritants in adult cases. Identification of Staphylococcus aureus and herpes simplex virus secondary infection is also important. Conclusions General measures remain important in mild to moderate atopic dermatitis, with appropriate education and support for parents. Topical corticosteroids play an important role, possibly with antihistamines to help alleviate the pruritus. In certain situations, systemic treatment with antibiotics, corticosteroids and other agents may be indicated.

Summary Clear cell acanthoma (CCA) is a benign epidermal tumour with distinctive and uniform clinical and histological features. Although solitary lesions are the rule, some cases of multiple CCA, rarely with more than 10 lesions, have been previously reported. Only 22 cases of multiple CCA have been described in the English literature to date. A healthy 32-year-old woman is reported, with approximately 400 asymptomatic rounded papules, on the upper and lower extremities. Multiple skin biopsies showed the typical histological pictures of CCA. This case appears unusual because of the presence of numerous lesions scattered on the upper and lower extremities. For this reason it could be classified as disseminated eruptive CCA.

Summary A 39-year-old woman is reported who developed numerous confluent yellowish semitranslucent papules of the face over 8 months. The patient habitually exposed herself to UVA-radiation twice a week for 7 years for aesthetic reasons. Histological, histochemical and immunohisto-chemical examinations were consistent with the diagnosis of adult colloid milium. A review of the literature is discussed. This case emphasizes the close relationship between long-term sun exposure, solar elastosis and adult colloid milium.

Contact Dermatitis

Summary We report a case of Jessner's lymphocytic infiltrate of the skin in an 11-year-old boy. This benign lymphocytic infiltrate was originally described in 1953, and classically occurs in middle-aged men. Its occurrence in children appears to be very rare, and there are only two other case reports in the literature.

Using monoclonal antibodies in immunofluorescence techniques, the subclass distribution of anti-basement membrane zone IgG antibodies was studied in the skin, placenta, and serum of patients with pemphigoid (herpes) gestationis. IgG1 was found to be the major IgG subclass in both serum and tissue, being detected in the sera of all pemphigoid gestationis patients studied.In pemphigoid and pemphigus, however, the distribution of IgG subclasses was heterogeneous, with IgG4 being the dominant autoantibody.Pemphigoid (herpes) gestationis factor, the circulating anti-basement membrane zone autoantibody thought to be pathogenic in pemphigoid gestationis, is therefore, an IgG1 antibody, with inferred complement binding capacity. Tissue damage in pemphigoid gestationis is apparently mediated by complement fixation which is detected via the classical complement cascade.

Cutaneous squamous cell carcinomas (cSCCs) are the second most frequent cancers in fair-skinned populations; yet, because of their genetic heterogeneity, the key molecular events in cSCC tumorigenesis remain poorly defined. We have employed single nucleotide polymorphism microarray analysis to examine genome-wide allelic imbalance in 60 cSCCs using paired non-tumour samples. The most frequent recurrent aberrations were loss of heterozygosity (LOH) at 3p and 9p, observed in 39 (65%) and 45 (75%) tumours respectively. Microdeletions at 9p23 within the protein tyrosine phosphatase receptor type D (PTPRD) locus were identified in a total of 9 (15%) samples, supporting a tumour suppressor role for PTPRD in cSCC. In addition, microdeletions at 3p14.2 were detected in 3 (5%) cSCCs, implicating fragile histidine triad (FHIT) gene as a possible target for inactivation. Statistical analysis revealed that well-differentiated cSCCs demonstrated significantly fewer aberrations than moderately and poorly differentiated cSCCs; yet, despite a lower rate of allelic imbalance, some specific aberrations were observed equally frequently in both groups. No correlation was established between the frequency of chromosomal aberrations and immune or human papillomavirus status. Our data suggest that well differentiated tumours are a genetically distinct subpopulation of cSCC.

Sebaceous carcinomas are rare cutaneous appendageal tumors that may occur sporadically or in association with an internal malignancy in Muir-Torre syndrome. In Muir-Torre syndrome microsatellite instability can often be demonstrated in tumor DNA as a result of an inherited mutation in one of several known mismatch repair genes; however, the role of microsatellite instability in sporadic sebaceous carcinomas has not been previously studied. In this report we describe the clinicopathologic characteristics of a series of unselected sebaceous carcinomas and examine them for the presence of microsatellite instability. Of 10 consecutive tumors identified over a 10 y period, only one was from a patient known to have Muir-Torre syndrome. Of the nine presumed sporadic cases, five were from four renal transplant recipients and four from otherwise healthy individuals. Microsatellite instability was demonstrable in three cases: in the Muir-Torre syndrome-associated tumor and in two tumors from transplant patients. Microsatellite instability was subsequently also found in a sebaceous carcinoma from a further transplant patient prospectively sought from another institution. The presence of microsatellite instability in post-transplant sebaceous carcinomas was associated with loss of expression of the mismatch repair protein hMSH2. In summary, sebaceous gland carcinomas, while characteristic of Muir-Torre syndrome, are commonly found outside this context. Among presumed sporadic cases, our data suggest they may be over-represented in immunosuppressed renal transplant recipients. The presence of microsatellite instability in transplant-associated lesions, together with loss of hMSH2 expression suggests that immunosuppression might unmask a previously silent Muir-Torre syndrome phenotype in some cases. Alternatively, there is experimental evidence to suggest that immunosuppressive drugs, most plausibly azathioprine, could select for the emergence of a mutator phenotype and thus predispose to the development of sebaceous carcinomas. The role of mismatch repair defects in other post-transplant skin malignancies remains to be established.

The influence of the sequential stages of conventional formaldehyde fixation and paraffin embedding of cutaneous tissue on monoclonal antibody labeling of cell surface antigens is described. The effects of variation in fixation time, dehydration, clearing, wax embedding, and enzyme treatment of cutaneous sections were examined. By curtailing fixation time, using cold ethanol dehydration, and limited cold clearing with xylene, immunoreactivity of several important monoclonal antibodies was retained. Wax embedding could be achieved at 58 degrees C for 1 h or by using low-melting-point wax at 42 degrees C for 3 h. Thus was derived an optimal processing procedure which afforded good tissue morphology and allowed reliable reproducible labeling by monoclonal antibodies to cell surface antigens.