Immunotherapy-induced sarcoidosis in patients with melanoma treated with PD-1 checkpoint inhibitors: Case series and immunophenotypic analysis.

AIM: Sarcoidosis is a multisystem granulomatous disease. This condition has a documented association with the diagnosis of melanoma and can be induced in melanoma patients receiving anti-neoplastic therapy. We evaluated a case series of melanoma patients who developed immunotherapy-induced sarcoidosis. METHODS: Three patients with melanoma (n = 1 resected Stage III, n = 2 metastatic) treated with anti-programmed cell death (PD)-1 antibody therapy at two institutions developed biopsy-proven sarcoidosis. We used mass cytometry to determine expression of the relevant chemokine receptors (CR) by peripheral blood mononuclear cells for two of the three patients who developed sarcoidosis and 13 melanoma patients who did not. Blood samples were collected before receiving PD-1 checkpoint inhibitor therapy. RESULTS: Immunophenotypic analysis demonstrated abnormally high numbers of circulating Th17.1 (CCR6+ CCR4- CXCR3+ CCR10- ) cells prior to commencing PD-1 checkpoint inhibitor therapy in five of 15 melanoma patients, including both the patients who developed sarcoidosis during the course of therapy. CONCLUSION: Our findings support prior literature implicating Th17.1 cells in the pathogenesis of sarcoidosis. However, we demonstrate these findings in patients with melanoma prior to administration of checkpoint therapy and before the onset of clinically symptomatic sarcoidosis. The identification of elevated Th17.1 cells in melanoma patients who have not developed sarcoidosis may reflect the established association between melanoma and sarcoidosis. With some patients receiving these agents over a prolonged period, the clinical course of immunotherapy-induced sarcoidosis is uncertain.

Reversing the slow death of the clinical necropsy: developing the post of the Pathology Liaison Nurse.

The adult clinical necropsy has been declining for many years and is nearing extinction in many hospitals. In Norwich, to prevent this from occurring, a Pathology Liaison Nurse (PLN) was appointed, resulting in a modest reversal of the trend. In 2005, the number of adult clinical necropsies increased to 58 (clinical necropsy rate = 2.4%) from its nadir of 34 (clinical necropsy rate = 1.4%) in 2003. Moreover, consent is now much more likely to be full and to allow histopathological and other studies. The PLN ensures that consent is properly and fully obtained, in line with current legislation. She also plays an important role in arranging for feedback to be given by clinicians to the families after the examination, and in teaching and training Trust staff about death, bereavement, and related matters. This paper describes how the role of PLN was established and evaluated, and gives details of the current state of the adult clinical necropsy in Norwich.

The slow death of the clinical post-mortem examination: implications for clinical audit, diagnostics and medical education.

The adult clinical post-mortem examination has seriously declined in Norwich recently, with only 34 of them (representing 1.4% of deaths in hospital) having been undertaken in 2003. Moreover, the next-of-kin are increasingly restricting the extent of the examination when they give consent. Analogous but less severe changes have occurred in the post-mortem examination of stillbirths and perinates. Many clinicians are unaware of these events, which may come to have wide-ranging detrimental effects. One possible cause is the lack of training of junior medical staff in obtaining consent for post-mortem examination, though other factors are also important.