Verruciform xanthoma of the penis: a rare Australian case.

We present a case of verruciform xanthoma ((VX) of the penis in an elderly man in whom an asymptomatic papule on his foreskin was noted during a routine clinical examination. VX is a rare, benign condition with a predilection for the oral cavity and clinically presents as isolated, painless mucosal lesions with a verrucoid surface. Accurate diagnosis is important in avoiding aggressive surgical management of this relatively rare condition.

Noninvasive methods for the assessment of photoageing.

Although histopathological dermal elastosis is the current gold standard for the diagnosis of photoageing, noninvasive methods for quantifying the amount of photodamage to skin are clearly preferable. This study is the first to survey five noninvasive methods of assessing photoageing (clinical examination, spectrophotometry, skin surface topography, reflectance confocal microscopy and fluorescence lifetime imaging microscopy) in the same individual. Measurements for each noninvasive method were compared across nine individuals from three participant groups ('younger', 'older' and 'photodamaged') in UV-protected volar and UV-exposed dorsal forearm skin. Overall, participants in the younger group had the lowest measures of photodamage, while those in the photodamaged group had the highest, as indicated by each modality. The five noninvasive strategies surveyed in this study may demonstrate potential as a suitable methodology for the quantification of photoageing. The advantage of such noninvasive methods is that they allow for skin visualisation in vivo and repeated assessments of the same site. The main limitation of this study was its small sample size, which may have precluded many findings of statistical significance.

RNA-seq reveals more consistent reference genes for gene expression studies in human non-melanoma skin cancers.

Identification of appropriate reference genes (RGs) is critical to accurate data interpretation in quantitative real-time PCR (qPCR) experiments. In this study, we have utilised next generation RNA sequencing (RNA-seq) to analyse the transcriptome of a panel of non-melanoma skin cancer lesions, identifying genes that are consistently expressed across all samples. Genes encoding ribosomal proteins were amongst the most stable in this dataset. Validation of this RNA-seq data was examined using qPCR to confirm the suitability of a set of highly stable genes for use as qPCR RGs. These genes will provide a valuable resource for the normalisation of qPCR data for the analysis of non-melanoma skin cancer.

Prevalence of Skin Cancer and Related Skin Tumors in High-Risk Kidney and Liver Transplant Recipients in Queensland, Australia.

The increased skin cancer incidence in organ transplant recipients is well-known, but the skin cancer burden at any one time is unknown. Our objective was to estimate the period prevalence of untreated skin malignancy and actinic keratoses in high-risk kidney and liver transplant recipients and to assess associated factors. Organ transplant recipients underwent full skin examinations by dermatologically trained physicians. The proportion of examined organ transplant recipients with histopathologically confirmed skin cancer in the 3-month baseline period was estimated. Prevalence ratios with 95% confidence intervals indicated significant associations. Of 495 high-risk organ transplant recipients (average age = 54 years, time immunosuppressed = 8.9 years), 135 (27%) had basal cell carcinoma, squamous cell carcinoma or Bowen's disease (intraepidermal carcinoma) present and confirmed in the baseline period, with respective prevalence proportions of 10%, 11%, and 18% in kidney transplant recipients and 10%, 9%, and 13% in liver transplant recipients. Over 80% had actinic keratosis present, with approximately 30% having 5 or more actinic keratoses. Organ transplant recipients with the highest skin cancer burden were Australian born, were fair skinned (prevalence ratio = 1.61, 95% confidence interval = [1.07, 2.43]), reported past skin cancer (prevalence ratio =3.39, 95% confidence interval = [1.93, 5.95]), and were receiving the most frequent skin checks (prevalence ratio = 1.76, 95% confidence interval = [1.15, 2.70]). In conclusion, high-risk organ transplant recipients carry a substantial measurable skin cancer burden at any given time and require frequent review through easily accessible, specialized services.

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

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

High incidence of primary melanomas in an MC1R RHC homozygote/CDKN2A mutant genotype patient.

Melanoma incidence in Australia remains the highest in the world; hence understanding its causation is paramount for future therapeutic developments. Multiple primary melanomas are also common occurrences among the Australian population with identified risk factors such as personal and family history of melanoma, fair skin type, dysplastic naevus syndrome and history of significant ultraviolet exposure. The roles of both environmental and genetic factors have been elucidated in melanoma development, but the synergy of interactions between the two remains complex given the heterogeneous nature of the disease. We present a rare case of a 57-year-old female with 20 cutaneous melanomas and review the role of genetic and environmental factors in development of her multiple primary melanomas.

Automated detection of actinic keratoses in clinical photographs.

BACKGROUND: Clinical diagnosis of actinic keratosis is known to have intra- and inter-observer variability, and there is currently no non-invasive and objective measure to diagnose these lesions. OBJECTIVE: The aim of this pilot study was to determine if automatically detecting and circumscribing actinic keratoses in clinical photographs is feasible. METHODS: Photographs of the face and dorsal forearms were acquired in 20 volunteers from two groups: the first with at least on actinic keratosis present on the face and each arm, the second with no actinic keratoses. The photographs were automatically analysed using colour space transforms and morphological features to detect erythema. The automated output was compared with a senior consultant dermatologist's assessment of the photographs, including the intra-observer variability. Performance was assessed by the correlation between total lesions detected by automated method and dermatologist, and whether the individual lesions detected were in the same location as the dermatologist identified lesions. Additionally, the ability to limit false positives was assessed by automatic assessment of the photographs from the no actinic keratosis group in comparison to the high actinic keratosis group. RESULTS: The correlation between the automatic and dermatologist counts was 0.62 on the face and 0.51 on the arms, compared to the dermatologist's intra-observer variation of 0.83 and 0.93 for the same. Sensitivity of automatic detection was 39.5% on the face, 53.1% on the arms. Positive predictive values were 13.9% on the face and 39.8% on the arms. Significantly more lesions (p<0.0001) were detected in the high actinic keratosis group compared to the no actinic keratosis group. CONCLUSIONS: The proposed method was inferior to assessment by the dermatologist in terms of sensitivity and positive predictive value. However, this pilot study used only a single simple feature and was still able to achieve sensitivity of detection of 53.1% on the arms.This suggests that image analysis is a feasible avenue of investigation for overcoming variability in clinical assessment. Future studies should focus on more sophisticated features to improve sensitivity for actinic keratoses without erythema and limit false positives associated with the anatomical structures on the face.

Expression of Bcl-xL and Mcl-1 in the nonmelanoma skin cancers of renal transplant recipients.

OBJECTIVES: This study aims to investigate how immunosuppression influences the protein expression of antiapoptotic members of the Bcl-2 family-namely, Bcl-xL and Mcl-1-in nonmelanoma skin cancer (NMSC) and the peritumoral epidermis of renal transplant recipients. METHODS: NMSC and peritumoral epidermis protein expression of Bcl-xL and Mcl-1 were assessed by immunohistochemistry in renal transplant recipients receiving tacrolimus or sirolimus and the general population not receiving immunosuppression. RESULTS: NMSC from renal transplant recipients compared with patients not receiving immunosuppressant medications had a reduced Bcl-xL expression intensity (P = .042). Mcl-1 expression intensity in NMSC was decreased in tacrolimus-treated patients compared with sirolimus-treated patients and the nonimmunosuppressed population (P = .024). Bcl-xL expression intensity was increased in peritumoral epidermis compared with NMSC (P = .002). CONCLUSIONS: It was shown for the first time that Bcl-xL and Mcl-1 expression are widespread in the peritumoral epidermis and NMSC of renal transplant recipients. Importantly in NMSC, Bcl-xL expression was reduced with immunosuppression exposure, and Mcl-1 expression was reduced in tacrolimus-treated compared with sirolimus-treated patients.

Stress and melanoma: increasing the evidence towards a causal basis.

Melanoma is a multifactorial disease with a strong genetic component and known risk factors such as excessive ultraviolet exposure, intermittent sunburns and fair skin type. The prognosis is poor if diagnosis is delayed, in spite of recent treatment advances. Evidence is mounting that the incidence of melanoma is higher in the immunosuppressed and individuals with highly stressful occupations. We present a case series of individuals diagnosed with multiple cutaneous melanomas over a few months to 1 year. All had encountered psychological stressors in their lives, and the melanomas were diagnosed briefly after encountering these stressors. No known causes of immunosuppression were detected to explain the sporadic occurrence of melanomas in these individuals. There is evidence in the current literature that stress can lead to immune disregulation, predisposing an individual to various disease states including melanoma. Stress hormones such as norepinephrine have been shown to cause upregulation of cytokines such as Interleukin 6 and 8, which are proangiogenic and support tumour progression. Coupled with genetic and environmental factors, stress appears to play a role in melanoma formation and progression. Large prospective studies are required to study the link between stress and melanoma and gain further insight into the etiology of melanoma.

Pyoderma gangrenosum of the breast treated with intravenous immunoglobulin.

BACKGROUND: Pyoderma gangrenosum is a rare neutrophilic dermatosis which leads to necrotic and painful skin ulceration. PG of the breast is extremely rare with 32 documented cases in the current literature. Delay in diagnosis worsens scarring as the ulcers are rapidly expanding, painful and usually slow to heal. CASE PRESENTATION: We present a case of pyoderma gangrenosum of the breast in a patient with associated rheumatoid arthritis which was initially diagnosed as an infected breast ulcer and later successfully treated with systemic steroids and intravenous immunoglobulin (IVIG). CONCLUSION: Even though PG of the breast has been gaining increased recognition over the past two decades, this has been more common in the post-surgical setting. This case highlights the need to consider PG as a differential diagnosis when faced with unsual cases of breast ulceration and the importance of multidisplinary approach for effective treatment of this condition.