title: Histopathological aspects of cutaneous erythematous-papular eruptions induced by immune checkpoint inhibitors for the treatment of metastatic melanoma.
abstract: BACKGROUND
  Immune checkpoint blockade therapy (ICBT) for the treatment of melanoma has led to an important improvement of overall survival in advanced stage patients. However, secondary cutaneous maculopapular eruptions (CMPEs) are frequent and remain poorly characterized.
  
  
  METHODS
  We performed a retrospective analysis of melanoma patients from our institution who developed CMPEs during ICBT. Clinical information was retrieved, and histopathological and immunohistochemical characterization was performed by two pathologists. For comparison, a group of biopsies from CMPE caused by anti-v-raf murine sarcoma viral oncogene homolog B1 (BRAF) therapy was analyzed.
  
  
  RESULTS
  Eleven patients met the inclusion criteria. On clinical grounds, CMPE developed mainly on early onset of immunotherapy and were of low grade. Typical lesions included erythematous papules and macules affecting the trunk and/or extremities with associated pruritus. The histopathological patterns consisted of a superficial perivascular lymphocytic dermatitis (SPLD) with eosinophils followed by a granulomatous dermatitis. Other patterns included lichenoid, spongiotic, and a case of Grover's disease. The inflammatory infiltrate consisted of T lymphocytes (CD3+) with a predominance of CD4+over CD8+cells; isolated Foxp3+cells were invariably present, and PD-1 was not expressed. Biopsies from CMPE caused by anti-BRAF therapy showed an SPLD and a similar lymphocytic immunophenotype.
  
  
  CONCLUSIONS
  Our study showed the clinical features of a group of melanoma patients with CMPE for ICBT and emphasized the wide spectrum of histological findings as well as their immunohistochemical profile. Differential diagnosis can be difficult with CMPE provoked by other therapies as was seen in our comparison group of anti-BRAF-induced eruptions.
authors.affiliation: Oncodermatology department, CIC, CHU, Nantes, France.
authors.forename: Raul E
authors.initials: RE
authors.lastname: Perret
authors.affiliation: Histopathology Institute, Nantes, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Josselin
authors.affiliation: Immunodermatology lab, CHU, Nantes, France.|U 892, INSERM, Nantes, France.
authors.forename: Anne-Chantal
authors.initials: AC
authors.lastname: Knol
authors.affiliation: Oncodermatology department, CIC, CHU, Nantes, France.|Immunodermatology lab, CHU, Nantes, France.|U 892, INSERM, Nantes, France.
authors.forename: Amir
authors.initials: A
authors.lastname: Khammari
authors.affiliation: Oncodermatology department, CIC, CHU, Nantes, France.|Immunodermatology lab, CHU, Nantes, France.|U 892, INSERM, Nantes, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Cassecuel
authors.affiliation: Oncodermatology department, CIC, CHU, Nantes, France.|Immunodermatology lab, CHU, Nantes, France.|U 892, INSERM, Nantes, France.
authors.forename: Lucie
authors.initials: L
authors.lastname: Peuvrel
authors.affiliation: Oncodermatology department, CIC, CHU, Nantes, France.|Immunodermatology lab, CHU, Nantes, France.|U 892, INSERM, Nantes, France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Dreno
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000009:adverse effects*; D003875:Drug Eruptions / Q000209:etiology / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007167:Immunotherapy / Q000009:adverse effects; D000074324:Ipilimumab / Q000009:adverse effects; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000556:secondary; D008875:Middle Aged; D000077594:Nivolumab; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000074324:Ipilimumab; D000077594:Nivolumab; C582435:pembrolizumab