TIL grade is an independent predictor of survival and SLN status in patients with melanoma. Patients with a pronounced TIL infiltrate have an excellent prognosis.

Background Nonmelanoma skin cancer is caused by exposure to ultraviolet radiation within sunlight. Actinic keratoses (AKs) are benign precursor lesions that can develop into invasive squamous cell carcinoma (SCC). Little is known about the molecular events that lead to human skin cancer progression from benign to invasive. Objectives To determine novel genes that may be involved in skin cancer progression based on data from an initial microarray screen of human skin cancers. Methods The SWI/SNF chromatin remodelling ATPase subunit BRM was identified as being downregulated in SCC but not AK compared with normal skin in our microarray screen. Therefore reverse transcription-polymerase chain reaction, gene methylation and protein expression was used to study BRM and its alternative ATPase subunit BRG1 in a range of human skin cancers. Results We found reduced levels of mRNA coding for BRM but not BRG1 in SCC. BRM mRNA levels in AK were similar to those in normal skin. Deregulation of BRM did not result from hypermethylation of CpG regions in the promoter of these genes. Both BRM and BRG1 protein was reduced by about 10-fold in 100% of SCC and basal cell carcinoma, but not in AK specimens examined. Conclusions BRM protein may be decreased due to low levels of mRNA, while BRG1 protein loss appears to be post-translational. BRM and BRG1 may be novel tumour suppressor genes for human skin cancer. They appear to be involved after development of benign lesions, and are downregulated during progression towards invasion.

Recently, a CTLA-4 antibody and BRAF inhibitors showed survival benefits in advance melanoma treatment. The documentation of immune infiltrates in melanomas early during BRAF inhibitor therapy provides a scientific rationale for combination therapy with both treatments with possible synergistic benefits. This commentary reviews immune responses induced by BRAF inhibitors.

The cellular composition of primary DM correlates with that of metastatic DM and with outcome. It is important to consider the possibility of primary or metastatic DM when examining tumours composed of spindle cells.

There is little doubt that excessive consumption of alcohol over a considerable period of time leads to an impairment of cognitive function. Specific alcohol-related disorders such as the Wernicke–Korsakoff syndrome, hepatic encephalopathy, and pellagra cause clinical dementia syndromes but when these have been excluded there is still a considerable number of alcoholics who can be classified as demented. The Liverpool Longitudinal Study of mental health of the elderly residing in a community dwelling found that dementia was 4.6 times more likely to occur in men aged 65 and older who had a lifetime history of heavy drinking (Saunders et al., 1991). A more recent epidemiological study of older African-American men found that increasing alcohol consumption was associated with a worsening performance on dementia screening scales (Hendrie et al., 1996). In a sample of 130 cognitively impaired residents of long-term care facilities, alcohol-related dementia comprised 24% of this population compared with Alzheimer's disease (35%), vascular dementia (19%), and other causes (22%) (Carlen et al., 1994). The most commonly used clinical definition of alcohol-related dementia is given in the Diagnostic and Statistical Manual Version IV (DSM IV) (Frances, 1994). This definition requires the presence of dementia that, in the opinion of the clinician, is intrinsically linked to the abuse of alcohol. The diagnostic criteria are vague and subjective and there have been no published validation or reliability reports using these criteria. Two recent papers dealing with operational diagnostic criteria in alcohol-related disorders might help clarify the issue.

For disseminated melanoma, new prognostic biomarkers and therapeutic targets are urgently needed. The organization of protein-protein interaction networks was assessed via the transcriptomes of four independent studies of metastatic melanoma and related to clinical outcome and MAP-kinase pathway mutations (BRAF/NRAS). We also examined patient outcome-related differences in a predicted network of microRNAs and their targets. The 32 hub genes with the most reproducible survival-related disturbances in co-expression with their protein partner genes included oncogenes and tumor suppressors, previously known correlates of prognosis, and other proteins not previously associated with melanoma outcome. Notably, this network-based gene set could classify patients according to clinical outcomes with 67-80% accuracy among cohorts. Reproducibly disturbed networks were also more likely to have a higher functional mutation burden than would be expected by chance. The disturbed regions of networks are therefore markers of clinically relevant, selectable tumor evolution in melanoma which may carry driver mutations.

An unusual case of subcutaneous panniculitis-like T-cell lymphoma is presented involving multiple organ systems, which eventually culminated in rapid demise from the haemophagocytic syndrome, after an initial protracted course. A 44-year-old man presented in April 2001 with bronchiolitis obliterans organising pneumonia that initially responded well to corticosteroids. However, the condition relapsed on attempted prednisone withdrawal in January 2002 and the patient was noted to have developed truncal subcutaneous nodules. Initial skin biopsy revealed lobular panniculitis, with negative microbiological culture. In July 2002, mononeuritis multiplex was diagnosed after the patient presented with paresthesiae and was treated with pulse cyclophosphamide therapy. By November 2002 there was ulceration of the subcutaneous nodules. Repeat skin biopsy revealed subcutaneous panniculitis-like T-cell lymphoma. The clinical manifestations were supportive of an unifying diagnosis of malignancy involving pulmonary, cutaneous and nervous systems. Combination chemotherapy with fludarabine, mitoxantrone and dexamethasone was commenced. However, the patient deteriorated, with fevers, weight loss, pancytopenia and laboratory features consistent with the haemophagocytic syndrome. Despite maximal supportive therapy the patient succumbed to his disease.

Different genotypes exist within BRAF-mutant metastatic melanoma, representing biologically and clinically discrete subtypes, suggesting distinct etiology and behavior.

The use of clinical, primary tumor, and SN tumor characteristics shown to be independent predictors of clinical outcomes in melanoma patients will assist in accurate prediction of prognosis and optimize clinical management.

Higher stromal expression of NOS in phyllodes tumours is associated with malignancy, suggesting a possible role in malignant progression, particularly metastasising potential.

Expression of activated ERK1/2 in melanocytic lesions appears to be related to malignant potential so that activation of ERK1/2 may be important in melanoma progression. These results provide important histological support for the proposal that inhibition of this signalling pathway may be useful in treatment of melanoma.