Oral and Maxillofacial Pathology Case: Persistent ulcer of the alveolar mucosa
DIFFERENTIAL DIAGNOSIS
A. Oral Squamous Cell Carcinoma( OSCC)
OSCC is the most common primary malignancy of the oral cavity, often manifesting as a persistent ulcer with irregular borders and induration on palpation. [ 3 ] Although the alveolar mucosa and gingiva can be affected, the floor of the mouth, ventral, and lateral tongue are the most common sites of involvement. [ 3 ] Additionally, a history of alcohol and / or tobacco use are well-established risk factors for OSCC pathogenesis. [ 4 ] In this particular case, OSCC is a reasonable clinical differential, particularly in light of the patient’ s former smoking history. Additionally, OSCC may bear clinical resemblance to autoimmunedriven oral ulcerations, but this malignant neoplasm is histopathologically characterized by invasive tumor nests composed of malignant keratinocytes that demonstrate cellular and nuclear pleomorphism( i. e., variation in size and staining and increased nuclear: cytoplasmic ratios), increased mitotic activity, prominent cellular nucleoli, and keratin pearl formation. [ 3 ] None of these features were observed in the submitted biopsy.
B. Paraneoplastic Pemphigus
Paraneoplastic pemphigus is a rare autoimmune blistering disorder associated with an underlying neoplastic process, most commonly hematologic malignancies( e. g., lymphoma and leukemia). [ 5 ] Clinically, this condition presents with fragile bullae of the skin and mucosa that rupture and form erosions or ulcers, similar to pemphigus vulgaris. Likewise, paraneoplastic pemphigus histologically demonstrates suprabasilar epithelial separation with free-floating keratinocytes, although the keratinocytes may occasionally exhibit dyskeratosis( increased keratin production, causing the cellular cytoplasm to stain darker). However, on direct immunofluorescence studies, paraneoplastic pemphigus demonstrates linear deposits of IgG and C3 along the basement membrane zone, in contrast to the“ chicken wire” or“ fishnet” intraepithelial pattern seen with pemphigus vulgaris. Pertaining to the mechanism of paraneoplastic pemphigus, it has been proposed that this condition is caused by an antitumor response; particularly, tumor-specific neoantigens( i. e., proteins produced by the neoplasm) elicit a host immune response resulting in an autoantibody-mediated attack on epithelial desmosomes and hemidesmosomes. [ 5 ] Clinically, this manifests as the formation of cutaneous and mucosal bullae. Though a direct immunofluorescence assay could not be performed to determine the pattern of autoantibody distribution in our case, the patient had no history of a current or prior neoplastic process.
C. EBV-Positive Mucocutaneous Ulcer( EBV-MCU)
EBV-positive mucocutaneous ulcer( EBV-MCU), a recently recognized entity, is an Epstein-Barr virus( EBV)-positive B-cell lymphoproliferative disorder. [ 6 ] The oral cavity, as a portal of entry, is especially vulnerable to infectious agents, such as viruses, and the pathoses they cause. EBV-MCUs may be a result of senescence or are iatrogenic in nature. In particular, iatrogenic lesions are a result of a state of immunosuppression, such as in individuals using systemic steroids. Within the oral cavity, the gingiva is the most frequently encountered site; however, lesions have also been reported to involve the non-attached mucosa.
[ 7 ]
These ulcerations clinically present as erythematous and pseudomembranous with a rolled border and induration. Histopathologically, EBV-MCUs demonstrate occasional pseudoepitheliomatous hyperplasia with necrosis of the ulcer base admixed with granulation tissue that harbors granulocytes, histiocytes, plasma cells, and atypical cells. These atypical cells are of variable size, have bare, irregularly shaped nuclei, and distinct nucleoli. Additionally, these atypical cells exhibit immunoreactivity with B-cell markers, including CD20 and PAX5. [ 7 ] Staining for immunoreactivity to EBV latent membrane protein-1( LMP-1) and EBV-encoded small RNA in situ hybridization
20 JANUARY / FEBRUARY 2026 | PENNSYLVANIA DENTAL JOURNAL