title: Malignant melanoma with neuroendocrine differentiation: clinical, histological, immunohistochemical and ultrastructural features of three cases.
abstract: OBJECTIVE
  To document the clinical, histological, immunohistochemical and ultrastructural features of three malignant melanomas showing neuroendocrine differentiation.
  
  
  RESULTS
  Three patients, two with primary cutaneous melanoma and one with nasal mucosal melanoma, subsequently developing or simultaneously presenting with metastatic malignant melanoma, were studied by conventional histological technique, immunohistochemistry of formalin-fixed paraffin-wax embedded tissues, and electron microscopy of epoxy-resin-embedded tumour tissue. Tumours showed either small cell or conventional malignant melanoma cell morphology. One of the three primary melanocytic lesions (the nasal melanoma) exhibited neuroendocrine differentiation immunohistochemically. All three metastatic malignant melanomas showed, in varying combinations, immunohistochemical and ultrastructural evidence for neuroendocrine differentiation: they were positive for the melanocytic markers, S100 protein, HMB-45, Melan-A and tyrosinase, and the neuroendocrine markers chromogranin, synaptophysin and neurofilament protein. Ultrastructural study in two of the metastases revealed neuroendocrine granules but no lattice-bearing melanosomes.
  
  
  CONCLUSIONS
  The cases described are the most comprehensively investigated malignant melanomas showing neuroendocrine differentiation to date, and the first to document neuroendocrine differentiation ultrastructurally in these tumours. Malignant melanoma with neuroendocrine differentiation therefore needs to be recognized among the other, better known variants of malignant melanoma.
authors.affiliation: Department of Histopathology, Christie Hospital NHS Trust, Manchester, UK. brian.eyden@christie-tr.nwest.nhs.uk
authors.forename: B
authors.initials: B
authors.lastname: Eyden
authors.forename: D
authors.initials: D
authors.lastname: Pandit
authors.forename: S S
authors.initials: SS
authors.lastname: Banerjee
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000556:secondary; D008207:Lymphatic Metastasis / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D008545:Melanoma / Q000378:metabolism / Q000473:pathology* / Q000556:secondary; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D009669:Nose Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure
chemical_list: D014408:Biomarkers, Tumor