Oral Lichen Planus With Malignant Transformation to Invasive Squamous Cell Carcinoma

To the Editor:

A 62-year-old woman with an extensive history of cutaneous and oral lichen planus (OLP) presented with gradual worsening of oral pain refractory to previously successful treatment regimens. The pains were described as sharp sensations originating in the right superior oral cavity, occurring almost constantly over the course of 2 months. On examination, the oral mucosa on the right side showed lacy, white, hyperkeratotic buccal lesions, as well as superficial erythematous erosion on the right upper alveolar ridge mucosa (Figure 1). On the left side, lacy, white, reticular patches were noted along the buccal mucosa. Gingival desquamation with superficial erosions were observed bilaterally, extending to the upper alveolar ridge in some locations. The skin examination revealed resolving, nonirritated, violaceous, flat-topped papules with a white-gray hue on the upper back and vulva.

^{Figure 1. Erosive oral lichen planus of the right maxillary alveolar ridge.}

The rest of the physical examination was benign, including a lack of appreciable lymphadenopathy, a cranial nerve examination without focal deficit, and the presence of fluent unaffected speech. On review of systems, the patient denied fevers, chills, weight loss, or night sweats. She had no history of skin cancer or oropharyngeal cancer. Family history revealed that her father had nonmelanoma skin cancer of the head and neck. She denied heavy alcohol use as well as history of smoking or other oral tobacco products. Laboratory tests revealed a complete blood cell count and comprehensive metabolic panel that was within reference range. Due to the refractory nature of the pain, which was out of character for OLP, the patient was referred to an oral maxillofacial surgeon who extracted right maxillary teeth adjacent to the erosion to obtain an adequate specimen for surgical biopsy of the lesion itself. Histopathology confirmed the diagnosis of chronic erosive OLP with malignant transformation to localized squamous cell carcinoma (SCC) of the right maxilla.

While awaiting treatment, she began to develop unremitting headaches and painful shooting sensations beginning in the right superior oral mucosa, radiating to the ipsilateral naris, nasolabial folds, malar cheek, and temple region. This clinical picture was consistent with neuralgia occurring along the maxillary nerve. A subsequent computed tomography scan revealed local bony destruction of the primary tumor and likely perineural involvement (Figure 2), without notable nodal involvement or metastasis (stage III: T4aN0M0). An otolaryngologist performed a wide alveolar and maxillary excision with lymph node dissection. Surgical margins were deemed as negative and there was no evidence of nodal disease. She was later seen by the oncology and radiation oncology teams and received several courses of chemoradiotherapy.

Figure 2. Coronal (A) and axial (B) computed tomography demonstrated right maxillary bony destruction.

Seven months later, a new indurated ulcer was noted on the left lateral tongue. Biopsy revealed a new primary oral SCC (OSCC), which also was excised by an otolaryngologist. Recent computed tomography did not detect any recurrence or potential metastases, but the patient subsequently was lost to follow-up.

Lichen planus is an idiopathic inflammatory disease most commonly affecting the cutaneous skin as well as the oral mucosa, genital mucosa, nails, and scalp. Oral lichen planus is a relatively common manifestation, found in approximately 1% to 2% of individuals older than 15 years.¹ Epidemiologic studies revealed that OLP is uncommon in children,^2,3 it affects women more frequently than men (approximately 3:1 ratio),³ and its incidence peaks between 30 and 60 years of age.⁴ The literature on malignant transformation of OLP is varied and controversial, with some early investigations such as Krutchkoff et al⁵ concluding that the reported cases often fall short of supporting OLP as a premalignant source of OSCC due to insufficient evidence in claimed case reports supporting the diagnosis of OLP histopathologically, the occurrence of OSCC in sites where OLP lesions did not previously exist, and uncertainty regarding confounding factors such as carcinogen exposure.⁵ In contrast, a longitudinal cohort study reported malignant transformation in 2.4% of 
OLP cases (N=327), with a standardized incidence ratio of 17.7 (95% confidence interval, 8.8-35.3) when compared to a control group.⁶ Current literature has predominantly sided with the notion that OLP, especially the erosive variant, carries the risk for malignant potential⁶ as well as the World Health Organization’s classification of the disorder as precancerous.³

The pathophysiology of OLP and its potential for malignant transformation are unknown. It is believed that cell-mediated immunity, specifically CD8⁺ lymphocytes targeting stratum basale keratinocytes for apoptosis via the caspase cascade, plays a major role in the development of OLP, beginning with Langerhans cell recognition of an unknown basal cell antigen.³ Moreover, it is postulated that antigen expression is induced by certain drugs, infections, and contact allergens such as dental amalgams, explaining their known associations with OLP initiation and exacerbation. The etiology behind OLP developing into OSCC also is poorly understood and many different hypotheses have been suggested. Modified expression of p53, a 53-kd protein, in OLP patients has been demonstrated.⁶ Some investigators propose that a lack of the expected keratinocyte apoptotic response to the cell-mediated attack may be etiologic in cancerous transformation.³ Given their utility in treatment of OLP, there also has been apprehension over the potential for immunosuppressant medications leading to decreased expression of antitumor regulators and development of malignant cells, though it has not been substantiated by current literature.⁶ Finally, some cases of OSCC are believed to have been linked to N-nitrosobenzylmethylamine, a known carcinogen produced by colonized Candida albicans, which also may play a role in OLP treated with immunosuppressants.⁷