Merkel cell carcinoma (MCC) is an aggressive tumour with neuroendocrine differentiation. Clinically significant differences within the entity we know as MCC are apparent. This review aims to evaluate the evidence for differences in tumours within Merkel cell carcinoma and to stratify these. A literature search of research pertaining to various characteristics MCC was undertaken from 1972, when Merkel cell carcinoma was first described, to 2018, using PubMed and similar search engines. A total of 41 papers were analysed, including clinical trials, laboratory‐based research and reviews. A proportion of MCC has Merkel cell polyomavirus genome integrated (MCPyV+) while others do not (MCPyV−). Both types have a different mutation burden. MCPyV+ tumours are likely true neuroendocrine carcinomas, with a dermal origin, probably from fibroblasts which have been transformed by integration of the viral genome. MCPyV−tumours are likely derived from either keratinocytes or epidermal stem cells, are probably squamous cell carcinomas with neuroendocrine differentiation, and are related to sun damage. Prognostic factors (apart from tumour stage) include the MCPyV status, with MCPyV+ tumours having a better prognosis. P63 expression confers a worse prognosis in most studies. CD8+ lymphocytes play an important role, providing a possible target for PD1/PD‐L1 blockade treatment. The incidence of MCC varies from country to country. Countries such as Australia have a high rate and a far greater proportion of MCPyV− tumours than places such as the United Kingdom. MCC doubtlessly encompasses two tumours. The two tumours have demonstrated differences in prognosis and management. One is a neuroendocrine carcinoma related to MCPyV integration likely derived from fibroblasts, and the other is a UV‐related squamous cell carcinoma with neuroendocrine differentiation, presumptively derived from either keratinocytes or epidermal stem cells. We propose naming the former Merkel type sarcoma and the latter squamous cell carcinoma, Merkel type.

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SummaryA fixed drug eruption (FDE) is a common cutaneous adverse drug reaction which occurs following administration of an offending drug. The aim of this review is to provide an update on the list of drugs causing FDE, with a focus on emerging drug culprits reported since the start of the century. Across published literature, triggers for FDE are widely varied. The most frequently implicated drugs include analgesics (nonsteroidal anti‐inflammatory drugs [NSAIDs] and paracetamol) and antibiotics. Co‐trimoxazole is perhaps the most well described single agent. Since the start of the century there have been over 200 drugs named in case reports on FDE. Newer, novel agents of note include cyclooxygenase‐2 specific inhibitors, fluconazole, and phosphodiesterase 5 inhibitors. Other implicated drugs include vaccines, such as various SARS‐CoV‐2 vaccines.Drugs incriminated in FDE vary based on the geographical region studied and prescribing patterns at a given time. Newer drugs continue to enter the market and are playing an increasing role in the field of FDE. Awareness of rarer culprits and emerging novel agents can help identify a trigger, allowing for prompt withdrawal of the causative agent, preventing recurrence.

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Improved methodology in determining melanoma mortality and selecting patients for immunotherapyDear Editor, Sentinel lymph node biopsy (SLNB) benefits are said to include identifying the presence and degree of micrometastases, improving staging, predicting prognosis and determining eligibility for adjuvant drug therapy. Sentinel lymph node biopsy is an invasive procedure, which needs nuclear medicine and operating room facilities. Neither SLNB nor early identification of micrometastases provides an overall survival benefit for melanoma patients. 1,2 Adverse events in the order of 11% are expected. 3 Predicting the likelihood of mortality can assist patient selection for adjuvant drug therapy. Breslow thickness, ulceration status and other clinical and pathologic predictors (CAPP) assist predicting melanoma survival. 4 Sentinel lymph node biopsy status (SLNBS) might contribute only a marginal survival predictability above that of an algorithm of CAPP. 5,6 Until recently, no quality research has been available to test this hypothesis.El Sharouni et al (ESS) 7 recently detailed the prognostic value of CAPP, with or without SLNBS, for calculating overall survival (OS) for melanoma patients. Predictors including Breslow thickness, tumour, ulceration, patient age, sex, mitotic activity, regression, tumour subtype and location were evaluated in 9272 Dutch patients. The findings were validated in 5644 Australian patients. 7 El Sharouni et al evaluated the accuracy of each CAPP in predicting OS using appropriate Area Under Curve (AUC) cstatistic methodology. 7 The higher the C-statistic, the better the model separates patients who will die from those who will not die. Combined CAPP was significantly superior to SLNBS at predicting OS. Combining SLNBS with CAPP increased c-statistic for OS by only 3%, with overlapping confidence intervals indicating an absence of statistical significance (Figure 1).El Sharouni et al found Breslow thickness to be the most accurate OS predictor followed by patient age. Subsequently, SLNBS and ulceration were similar. Mitotic activity and regression fell below 0.54, suggesting they might not provide relevant information 7 (Figure 2).El Sharouni et al also reported that SLNBS detected 1.4 more net high-risk melanoma patients (HRMP) for every 100 patients experiencing recurrence within 3 years when used in combination with CAPP. 7 Recurrence rates of approximately 13%-15% have been reported in HRMP. 8 Assuming

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FIGURE 1. Low-power microscopic view of a keratoacanthoma.FIGURE 2. Clinical photograph of keratoacanthoma.

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