A localized variant of paraneoplastic pemphigus: acantholysis associated with malignant melanoma

Abstract

We report a 72-year-old male patient with a nodular malignant melanoma that was associated with focal suprabasal acantholysis (FSA). This phenomenon, which is regarded as an incidental finding by dermatopathologists, may be associated with inflammatory and also neoplastic skin diseases. Haematoxylin and eosin stained sections from an erythematous plaque surrounding the patient's tumour showed FSA, direct immunofluorescence (DIF) and indirect immunofluorescence (IIF) on normal human skin, monkey oesophagus and rat urinary bladder were negative. On electron microscopy few desmosomes could be detected in the basal cell layer of the acantholytic areas and there was a nearly complete loss of these structures in the spinous cell layer. Only remnants of cytoplasmic plaques and keratin filaments could be observed in those areas. In contrast, adherens junctions appeared to be well preserved. An enzyme-linked immunosorbent assay (ELISA) using recombinant fusion proteins as antigens did not show circulating autoantibodies against desmoglein 1 (Dsg1) or desmoglein 3 (Dsg3). In contrast, immunoblotting revealed autoantibodies directed against keratinocyte antigens with a molecular weight of 85 kDa and 250 kDa, the first band corresponding to the molecular weight of comigrating plakoglobin. Immunoprecipitation with patient serum also revealed a 85-kDa band. We conclude that these autoantibodies, probably in conjunction with cofactors produced by the tumour, could play a part in the pathogenesis of this variant of FSA, for which we propose the term 'localized paraneoplastic pemphigus.'

Paraneoplastic autoimmune multiorgan syndrome: Review of the literature and support for a cytotoxic role in pathogenesis

“…One case of malignant melanoma associated with localized acantholysis and autoantibodies to 85-and 250-kDa proteins was suggested to be a "localized PNP" [29], but this case may not represent true PAMS as defined by the diagnostic criteria of Anhalt et al [1,30]. One case of PAMS was reported in a patient without identifiable neoplasia [31], but the rapid death of the patient and lack of an autopsy in this case may have precluded discovery of an underlying neoplasm.…”

Cleft formation and consumption of the epidermis in cutaneous melanocytic lesions—reply

“…Schaeppi et al [2] thought of an immunologic cause of CF in MM, comparable with the pathomechanism of localized paraneoplastic pemphigus with autoantibodies against keratinocyte antigens.…”

Paraneoplastic pemphigus presenting with a single oral lesion

“…PNP is a particular form of blistering disease typically associated with extraoral neoplasms (in 84% of cases haematologically related neoplasms, mostly non-Hodgkin's lymphoma4 16 17 and chronic lymphocytic leukaemia,16 18 less frequently Waldenstrom's macroglobulinaemia, Castleman's disease, thymoma and Hodgkin's lymphoma1 and in 16% of cases non-haematological neoplasms such as carcinoma, sarcoma16 18 and malignant melanoma19). …”