Amelanotic and hypomelanotic skin lesions can be difficult to diagnose clinically and dermoscopically.1-3 Evidence is emerging that optical coherence tomography (OCT) can detect superficial basal cell carcinoma (sBCC) with good sensitivity (79-95.7%) and specificity (75.3-96%).4 Given that sBCC is a common problem4, and that it may be treated noninvasively5, the potential benefits from using OCT as an adjunct to clinical diagnosis are high. However, if OCT is used without histopathological confirmation in this setting, there is a risk that more clinically aggressive malignant pathology, such as amelanotic /hypomelanotic melanoma (AHM), may be misdiagnosed and left to progress if it is inadequately treated. Indeed, this research was prompted after experiencing a clinical case where a lesion had typical clinical-dermoscopic and OCT features for sBCC, but histopathology revealed an amelanotic melanoma. This article is protected by copyright. All rights reserved.

Non-melanoma skin cancer (NMSC) is the most common malignancy in fair-skinned populations. In Australia, NMSC is four times as common as all other cancers combined, with an incidence of ~1000 per 100 000 person-years. The incidence of NMSC has been gradually rising among Caucasian/white populations over the last few decades. The vast majority of NMSCs are basal cell carcinomas (BCCs), which rarely metastasize, or squamous cell carcinomas (SCCs), which do have metastatic potential, especially in immune-suppressed individuals. Because of their high frequency in the general population, and particularly in older people, NMSCs are likely to occur in many general oncology patients. Skin cancer risk can be additionally increased in oncology patients as a result of disease-induced immune suppression (e.g., non-Hodgkin’s lymphoma) or by a range of cancer treatments including iatrogenic immune suppression, radiation therapy arsenic, and BRAF inhibitors (if not given with a MEK inhibitor). In this chapter the aetiology, pathology, prognosis, and management of NMSCs are discussed.

Introduction: The most appropriate protocol for biopsying musculoskeletal tumours is controversial. Some authors advocate the use of CT-guided core biopsy. At the Royal Prince Alfred Hospital, Sydney, Australia, initial biopsies of most musculoskeletal tumours involve a surgeon-led operative core biopsy technique with frozen section evaluation. The latter is used to determine whether diagnostic tissue has been obtained and, if possible, to establish a definitive diagnosis. Aims: To determine the accuracy and cost effectiveness of a surgeon-led biopsy protocol for biopsying musculoskeletal tumours. Methods: A retrospective audit of biopsies of musculoskeletal tumours performed in the bone and soft tissue sarcoma unit at the Royal Prince Alfred Hospital over a two year period was performed. Results: One hundred and four patients had biopsies performed under the protocol. There were no non-diagnostic biopsies and one minor error resulting in no change in the patient’s management. There was no requirement to re-biopsy any of the patients. A surgeon-led operative core biopsy with frozen section evaluation was 38% more costly than a CT-guided core biopsy (AU$1804 versus AU$1308). Conclusions: Surgeon-led biopsy with intra-operative frozen section evaluation is effective and accurate and, despite being labour intensive, the reduction in the need for repeat biopsies justifies its use. Whilst the technique is approximately 38% more costly, there is no requirement for re-biopsy and anxiety associated with the need for this is allayed.

Immunotherapy of advanced melanoma with CTLA-4 or PD-1/PD-L1 checkpoint blockade induces in a proportion of patients long durable responses. In contrast, targeting the MAPK-pathway by selective BRAF and MEK inhibitors induces high response rates, but most patients relapse. Combining targeted therapy with immunotherapy is proposed to improve the long-term outcomes of patients. Preclinical data endorsing this hypothesis are accumulating. Inhibition of the PI3K-Akt-mTOR pathway may be a promising treatment option to overcome resistance to MAPK inhibition and for additional combination with immunotherapy. We therefore evaluated to which extent dual targeting of the MAPK and PI3K-Akt-mTOR pathways affects tumor immune infiltrates and whether it synergizes with PD-1 checkpoint blockade in a BRAF^V600E/PTEN^-/--driven melanoma mouse model. Short-term dual BRAF + MEK inhibition enhanced tumor immune infiltration and improved tumor control when combined with PD-1 blockade in a CD8⁺ T cell dependent manner. Additional PI3K inhibition did not impair tumor control or immune cell infiltration and functionality. Analysis of on-treatment samples from melanoma patients treated with BRAF or BRAF + MEK inhibitors indicates that inhibitor-mediated T cell infiltration occurred in all patients early after treatment initiation but was less frequent found in on-treatment biopsies beyond day 15. Our findings provide a rationale for clinical testing of short-term BRAF + MEK inhibition in combination with immune checkpoint blockade, currently implemented at our institutes. Additional PI3K inhibition could be an option for BRAF + MEK inhibitor resistant patients that receive targeted therapy in combination with immune checkpoint blockade.