Paraneoplastic pemphigus (PNP) is a rare and life-threatening autoimmune bullous disease that classically occurs in the setting of an underlying neoplasm. PNP is also known as paraneoplastic autoimmune multiorgan syndrome (PAMS) because of its varied mucocutaneous and systemic deleterious effects. Due to the variable disease characteristics and lack of formally accepted diagnostic criteria, PNP remains a diagnostic challenge for clinicians.
Original diagnostic criteria for paraneoplastic pemphigus by Anhalt
| Clinical | Painful mucosal erosions with or without accompanying polymorphous cutaneous lesions in the setting of an underlying malignancy |
| Histopathology | Suprabasal (intraepidermal) acantholysis, interface dermatitis, and keratinocyte necrosis |
| Direct immunofluorescence (DIF) | Intercellular and basement membrane zone deposition of IgG and complement (C3) |
| Indirect immunofluorescence (IIF) | Detection of autoantibodies targeting intercellular proteins found in transitional or stratified squamous epithelia |
| Immunoprecipitation | Precipitation of characteristic proteins desmoplakin 1 (250 kD), Bullous pemphigoid antigen (230 kD), desmoplakin 2 (210 kD), periplakin (190 kD), alpha-2-macroglobulin-like-1 antigen (170 kD) |
Diagnostic guidelines by Camisa and Helm requiring three major criteria, or two major and two minor criteria, for the diagnosis of paraneoplastic pemphigus
Major criteria
- Polymorphic mucocutaneous eruptions
- Concomitant internal neoplasm
- Serum antibodies with a specific immunoprecipitation pattern
Minor criteria
- Acantholysis observed histopathologically
- DIF displaying intercellular and basement membrane staining
- IIF staining positive on rat bladder epithelium
Revised Diagnostic Criteria for Paraneoplastic Pemphigus
Revised diagnostic criteria for paraneoplastic pemphigus requiring three major criteria, or two major and both minor criteria
Major criteria
- Mucous membrane lesions with or without cutaneous involvement
- Concomitant internal neoplasm
- Evidence of anti-plakin antibodies,a including but not limited to IP, IB, ELISA, IIF on transitional epithelium
Minor criteria
- Acantholysis and/or lichenoid interface observed on histopathology, ± necrotic keratinocytes
- DIF displaying intercellular and/or basement membrane staining
Abbreviations: DIF, direct immunofluorescence; ELISA, enzyme-linked immunosorbent assay; IP, immunoprecipitation; IB, immunoblot; IIF, indirect immunofluorescence.
aIncludes antibodies to alpha-2-macroglobulin-like-1.
References:
- Svoboda SA, Huang S, Liu X, Hsu S, Motaparthi K. Paraneoplastic pemphigus: Revised diagnostic criteria based on literature analysis. J Cutan Pathol. 2021 Sep;48(9):1133-1138. [Medline]
- Kim JH, Kim SC. Paraneoplastic Pemphigus: Paraneoplastic Autoimmune Disease of the Skin and Mucosa. Front Immunol. 2019 Jun 4;10:1259. [Medline]
Created Oct 21, 2021
