It is well appreciated that melanocortin 1 receptor variants can produce a fair skinned and red-haired phenotype that has a strong association with increased melanoma risk. These patients are easily recognised and given appropriate attention. What may not be appreciated is that darker-skinned individuals may also carry melanocortin 1 receptor variant alleles and that they can also be at increased risk of melanoma. Considering that melanocortin 1 receptor is crucial for melanocyte proliferation, regulation and differentiation do the naevi of these darker-skinned individuals have specific features that help identify them as carrying one of these melanocortin 1 receptor variants and do melanomas that develop in dark-skinned melanocortin 1 receptor variant carriers have particular characteristics?

No abstract

We live with solar radiation from birth to death and have since the emergence of life on earth. Why then does skin cancer diagnosis remain so disturbingly high in Australia? Part of the problem is the majority of the population are of Northern European ancestry. Moving closer to the equator on mass we have carried with us a polymorphic melanocortin receptor gene on our melanocytes responsible for an incomplete tanning response. We attempt to protect ourselves with clothing and creams or remain indoors but this does not seem to be stemming the tide. Occupation, recreation or both drive us outside and into the sun. We need to be more successful at negotiating the potentially harmful effects by relooking at solar radiation and instead of focusing on the most harmful wavelengths look at the overall effect of the whole spectrum. We also need to re-examine our behaviour and exposure patterns. Prolonged periods indoors under artificial light punctuated with short bursts of intense irradiation is maladaptive. Creams aim to block the ultraviolet component, ignoring 90% of solar photons, the protective effect is incomplete, yet their use encourages more prolonged exposure. Protective behaviours are necessary for the most sensitive skin types but they are still at risk. For the rest of the population evolutionarily developed natural protective mechanisms can be employed. Regular moderate sun exposure, below the burn threshold, ideally aimed at early morning or late afternoon. Augmented with clothing, hats and creams with an appreciation of the incomplete protective effect of these measures.

Cryptochromes, evolutionally conserved and retained in mammals as transcriptional regulators having a repressive role in the transcription-translation feedback loop, the molecular mechanism behind the control of the endogenous mammalian circadian clock. This clock mechanism regulates the oscillation of a huge number of clock-controlled output genes. This in turn is responsible for modification of the physiological response of most organs and tissues, to coordinate with diurnal and seasonal changes in light and nutrient availability. Cryptochromes have also been found to participate in additional signalling cascades, outside of the circadian system, forming supplementary feedback loops that initiate cross-talk between systems influencing metabolism, inflammation and DNA damage response to maintain cellular homeostasis. This physiological organisation system has developed from Palaeolithic man but is still relevant in our modern world.

This is a report of a metastatic melanoma presenting clinically as a soft tissue mass and histologically being diagnosed as a malignant peripheral nerve sheath tumour. In this case the metastatic melanoma was preceded by a primary cutaneous melanoma in a similar anatomical region. Histologically the tumour was characterised by a malignant-appearing Spindle cell proliferation, arranged in fascicules. There was no evidence of connection to a nerve, co-existent neurofibroma or stigmata of neurofibromatosis. This presentation is only infrequently mentioned in the literature and heterogeneity can make clinical and histological diagnosis of metastatic melanoma problematic. It can easily be misinterpreted without effective clinico-histological correlation, making a good working relationship between Clinician and Histopathologist essential for correct diagnosis.