ReviewNeoplasms associated with paraneoplastic pemphigus: a review with emphasis on non-hematologic malignancy and oral mucosal manifestations
Introduction
Paraneoplastic pemphigus (PNP), an autoimmune blistering and erosive mucocutaneous disease associated with neoplasia. It was first defined as a separate entity in 1990 by Anhalt et al.1 Since then, at least 150 additional cases have been reported in the literature. Since oral involvement is reported in 100% of cases, PNP is particularly important in oral pathology and medicine.2 Characteristically, it manifests with diffuse erosions and shallow ulcerations of the oral mucosa extending to the vermillion surface of the lips. Isolated oral lesions, as the first sign, are present in 45% of cases.3 The oropharynx and nasopharynx, tonsils, anogenital mucosa, and esophagus may also be affected.2 Conjunctival lesions, which may be severe and resemble those seen in cicatricial pemphigoid, are present in about two-thirds of the patients.2 Cutaneous manifestations have been reported in all but one case, in which there was only oral involvement.4 Cutaneous lesions with polymorphic manifestation have recently been divided into five variants: pemphigus-like, pemphigoid-like, erythema multiforme-like, graft versus host disease-like and lichen planus-like.5 Different morphologic patterns of skin lesions may be present concomitantly in a patient or vary during the disease course. The trunk and proximal extremities are usually affected. Palmoplantar and paronychial involvement are also frequent.2
Most PNP cases are associated with a hematologic malignancy. However, there are cases of solid non-hematologic neoplasms of different origins. Because of the relatively infrequent association of PNP with non-hematologic malignancy, awareness towards the clinical signs may be low, leading to a delay in correct diagnosis and treatment.
The purpose of the present report is to review the spectrum of different neoplasms associated with PNP, with emphasis on the group of non-hematologic malignancy, and the manifestations of PNP in the oral mucosa. A unique case of PNP associated with occult breast cancer and an ovarian cyst of borderline malignancy is presented, and the potential diagnostic pitfalls in PNP discussed.
Section snippets
Initial presentation
A 62-year-old woman presented with the chief complaint of pain and burning in the oral cavity which started the previous week. Her medical history was positive for mild hypertension and lower back pain, for which she had been prescribed Rofecoxib, a non-steroidal anti-inflammatory drug (NSAID). Oral symptoms became apparent within a week of treatment and increased in severity during the following week.
At presentation, diffuse, irregular shallow ulcerations involving the tongue, floor of mouth,
Literature review
The first definition of PNP as a distinct entity was introduced by Anhalt et al.,1 and included the following clinical, histologic, DIF, IIF and immunoprecipitation tests as diagnostic criteria:
- 1.
Painful mucosal erosions and polymorphous skin eruptions.
- 2.
Histopathologic features of intraepidermal acantholysis, dyskeratosis and vacuolar interface dermatitis.
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DIF findings of intercellular epidermal IgG and complement, with or without granular linear complement deposition along the basement membrane
Discussion
Ulcerative lesions of the oral mucosa could be the presenting symptom of several diseases or conditions, including viral and bacterial infections, reactions to drugs or local irritants, as well as auto-immune diseases. Association with malignant diseases is rare, and probably is the least frequent etiology for oral ulcerative lesions. Therefore, it is rare for PNP to be included in the differential diagnosis of oral ulcerative lesions unless the existence of a primary tumor is known before the
Conclusion
The presence of diffuse and persistent oral ulcerations, which fail to meet the clinical, histologic and DIF criteria for any specific disease, should be highly suspicious for PNP, even in the absence of an overt malignancy, The full spectrum of signs described as diagnostic for PNP may not be initially present in all cases. It could take several months until the disease progresses and all characteristic signs “unveil” for the correct diagnosis to be made. In the absence of a clear diagnosis
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