CAN YOU MAKE THE DIAGNOSIS?
A. Squamous cell carcinoma( SCC) B. Paraneoplastic pemphigus C. EBV-positive mucocutaneous ulcer D. Traumatic ulcerative granuloma with stromal eosinophilia( TUGSE) E. Persistent pemphigus vulgaris
THE DIAGNOSIS: E. Persistent Pemphigus Vulgaris
The histopathologic features of the lesion are consistent with pemphigus vulgaris. The histologic hallmarks of this condition, particularly suprabasilar clefting and separation with the presence of free-floating epithelial cells( also referred to as Tzanck cells), are observable at low power magnification( Figure 2). Visible at higher magnification is the phenomenon known as“ tombstoning,” a process by which the basal cells that remain anchored to the connective tissue assume a rectangular shape, reminiscent of a tombstone( Figure 3). The biopsy for direct immunofluorescence( DIF) studies failed because the epithelium was separated from the connective tissue and was lost, precluding diagnosis using this technique. The patient’ s initial biopsy submitted for direct immunofluorescence in 2020 had a similar issue. DIF characteristically highlights autoantibodies deposited within intercellular spaces of the epithelium. This presents as a so-called“ chicken wire” or“ fishnet” pattern on fluorescence microscopy. Successful biopsy of intact mucosa in vesiculobullous diseases, such as pemphigus vulgaris, for DIF studies is a challenging task due to the fragility of the epithelium. Nonetheless, the clinical features of mucosal desquamation and ulceration, the patient’ s prior history of pemphigus vulgaris, and the histopathologic presentation observed on H & E allow for a confident diagnosis of pemphigus vulgaris.
Pemphigus vulgaris is the most common variant of pemphigus diseases, a family of rare autoimmune bullous diseases. [ 1 ] The exact cause of pemphigus vulgaris has not been elucidated, however, the pathogenesis of this condition is well characterized. Specifically, immunoglobulin G( IgG) autoantibodies target desmoglein 1 and desmoglein 3, glycoproteins that are components of epithelial desmosomes. [ 1 ] Desmosomes are responsible for providing cohesion between epithelial cells. With destruction of desmoglein 1 and 3, fragile intraepithelial bullae form and subsequently rupture, resulting in desquamation and ulceration. Pemphigus affects both the oral mucosa and the skin. [ 1 ] Pemphigus vulgaris manifests in the oral cavity as desquamation of the attached and non-attached oral mucosa. Gingival desquamation is not specific to pemphigus and can be observed in other autoimmune conditions, including mucous membrane pemphigoid and erosive lichen planus. Pemphigus vulgaris exhibits a positive Nikolsky sign clinically – a moderate amount of pressure on the mucosa can induce bulla formation. Although a useful diagnostic test, this property is not specific to pemphigus vulgaris and can be seen in other vesiculo-erosive conditions, including mucous membrane pemphigoid, erosive lichen planus, and even herpes simplex virus infection. [ 2 ] Due to the overlap of clinical features amongst both autoimmune and infectious diseases that affect the oral cavity, performing biopsies for both light microscopy and direct immunofluorescence studies are essential for an accurate diagnosis. In the instance of a solitary ulcerative lesion, trauma, infection, and malignancy should also be considered in the differential diagnosis, all of which necessitate biopsy.
JANUARY / FEBRUARY 2026 | PENNSYLVANIA DENTAL JOURNAL 19