Solitary melanoma confined to the dermal and/or subcutaneous tissue: evidence for revisiting the staging classification.

BACKGROUND: Several patients presented with a single focus of presumed cutaneous metastatic melanoma with an unknown primary tumor based on clinical and histologic staging criteria of the American Joint Committee on Cancer (AJCC). This population is classified as having stage IV disease by the current AJCC staging system, which carries a dismal prognosis (5%-18% 5-year survival). Our clinical observation was that these patients had a higher survival rate than would be expected for stage IV disease. We believe this population represents a subgroup of primary dermal- and or subcutaneously-derived melanoma that simulates cutaneous metastatic melanoma in histologic and clinical presentation but may differ in behavior. OBSERVATIONS: The database records of 1800 patients from the University of Michigan Melanoma Clinic, Ann Arbor, were retrospectively reviewed to identify the prevalence and survival for patients diagnosed with a single focus of presumed metastatic melanoma to the skin based on accepted histologic and clinical parameters. The prevalence of this population was 0.61% (11 of 1800 patients). The Kaplan-Meier 8-year survival estimate was 83% (95% confidence interval, 58%-100%). CONCLUSIONS: By AJCC convention, these cases are classified as stage IV metastatic disease. Our data suggest that these presumed metastatic tumors do not behave like stage IV metastatic disease to the skin via lymphatic or hematogenous spread from an unknown primary site; rather, they are behaving like primary tumors originating in the dermal and/or subcutaneous tissue.

Lichenoid dermatitis in paraneoplastic pemphigus: a pathogenic trigger of epitope spreading?

BACKGROUND: In select cases, lichen planus has been observed to be a paraneoplastic condition sometimes associated with paraneoplastic pemphigus, a disease featuring autoantibodies directed against plakin proteins, desmogleins 3 and 1, and a still uncharacterized 170-kd antigen. Epitope spreading describes the phenomenon where underlying chronic inflammation leads to the sequential recognition of new epitopes on self-proteins over time. OBSERVATIONS: Five of 6 patients diagnosed as having paraneoplastic pemphigus had concomitant clinical and histological features of lichen planus. In 1 patient, results of the initial indirect immunofluorescence on rat bladder were negative and only 2 of the 5 antigens were identified by immunoprecipitation. After 1 year of worsening disease, repeated testing confirmed the presence of antibodies directed against all 6 of the implicated antigens, supportive of our hypothesis that epitope spreading may occur in paraneoplastic pemphigus. CONCLUSIONS: Lichenoid eruptions may predispose to an early evolutionary stage of paraneoplastic pemphigus. Cell-mediated autoimmunity at the dermoepidermal junction may promote the exposure of self-antigens and the development of subsequent and progressive humoral autoimmunity. As such, paraneoplastic pemphigus may demonstrate epitope spreading in a human, humoral-mediated autoimmune disease.