Introduction

Oral papillary hyperplasia (OPH) is a benign lesion of the oral mucosa that is characterized by the presence of numerous wart-like, red nodular growths of the affected mucosa. Papillary lesions include a variety of reactive, developmental, and neoplastic conditions and are histopathologically described as papillary projections that are covered by stratified squamous epithelium with or without chronic inflammation. The clinical features of this lesion are well-established. The histologic samples of the lesion are currently believed to have a predominantly inflammatory nature, although fewer pathologists are familiar with its malignancy potential (1).

The etiopathogenesis is unclear; however, OPH is associated with the long-term use of removable dentures, poor oral hygiene, age, human papillomavirus (HPV), and systemic disorders but can also be found in patients with dentures without a history of removable prostheses (2). OPH is also associated with Candida colonization due to poor oral hygiene, but Candida is solely not a factor for the onset of symptoms. The lesion almost exclusively involves the hard palate, as well as the upper and lower lips, alveolar crest, gingiva, and tongue in rare circumstances. The lesion is generally asymptomatic (3).

This report aimed to present a case of a rarely encountered multifocal non-HPV inflammatory papillary hyperplasia and discuss other differential diagnoses, which represent similar clinical and histopathological conditions.

Case Report

A 44-year-old male patient was referred to the Department of Oral and Maxillofacial Surgery, at the faculty of dentistry, Bezmialem Vakıf University with a chief complaint of papillary lesions on the lips and tongue. The medical history of the patient revealed that wart-like lesions on the lips and hands were first diagnosed 15 years ago and were treated with cryotherapy. The patient had two heart attacks at intervals of 3 months in 2015 and underwent stent operations after the coronary angiography. The pre-prandial blood glucose level of the patient was recorded as 130 mg/dL. The patient receives metformin hydrochloride of 1,000 mg per day for diabetes mellitus treatment and acetylsalicylic acid of 100 mg per day for stent thrombosis prophylaxis.

The patient mainly complained about esthetic and function. Clinical examination revealed no history of wearing a removable prosthesis and multifocal papillary projections on the lips, tongue, and alveolar mucosa. Radiological examination revealed no bony involvement of nearby lesions. Multifocal lesions were asymptomatic. Clinical manifestations of the lesion are presented in Figure 1.

Histopathologic Examination

The biopsy specimen with the provisional diagnosis of HPV-induced OPH was obtained and sent for histopathologic examination. The microscopic features of the inflammatory papillary hyperplasia were verified. The lesion showed numerous papillary growths of the oral mucosa that were covered by parakeratotic stratified squamous epithelium. The connective tissue forms the cores of the papillary growths presented edema, vascular proliferation, and low-grade chronic inflammatory cell infiltration (Figure 2). Candida colonization was investigated using Grocott-Gomori’s Methenamine Silver Staining (Figure 3), which identified no signs of Candida infection. The diagnosis of HPV-induced lesion was also eliminated by in situ hybridization (Figure 4).

The patient has undergone excisional biopsy and then, laser therapy was applied to the base of the lesion for stable and healthy mucosa for the prosthetic rehabilitation of the jaws. The hyperemic and papillary formations were resolved within a month (Figure 5). Removable prosthetic rehabilitation of the upper and lower jaw was achieved after a 2-month healing period.

Discussion

The treatment type for OPH is associated with clinical manifestation and histopathological verification. A concern arises regarding the malignancy potential of OPH; however, the treatment modalities mostly include denture removal as conservative therapy, as well as electrocauterization, cryotherapy, surgical removal of the lesion, or complete excision. The denture removal can eliminate the edema and hyperemia; however, the connective tissue cannot be removed with conservative treatment (4). Non-invasive and superficial lesions can be treated with mouth rinse or denture removal. Clinicians have recommended that aggressive and extensive papillary lesions can be treated with excision, laser, electrosurgery, or cryotherapy (4,5).

The etiologic factors revealed several causes that are associated with OPH. Night-time use of ill-fitting dentures and poor oral hygiene has been reported as frequent causes, but OPH has also been found in patients with no history of wearing a removable denture (6). Some authors have reported HPV-driven infections of the oral mucosa, which represent a similar clinical appearance with OPH (7).

In addition to HPV-induced and removable denture-related lesions, oral papillary lesions also include a variety of developmental and neoplastic origins. Differential diagnoses are made with verruciform xanthoma, Costello syndrome, and paraneoplastic conditions as malignant acanthosis nigricans (8). The histological features of verruciform xanthoma are similar to OPH. A papillary proliferation of stratified squamous epithelium that is associated with hyperparakeratosis is usually encountered. The outstanding characteristic feature of these lesions includes the presence of xanthoma-like cells (foamy lipid-laden histiocytes) and the biopsy specimen shows cytoplasmic immunopositivity (CD69, CD63, and CD163) (9,10).

Hyperemic papillary growths usually begin on the palatal surface, and then extend to the entire hard palatal mucosa. However, perioral involvement of papillary lesions can be found in neoplastic or syndromic conditions. Acanthosis nigricans, which is a variety of paraneoplastic conditions associated with gastrointestinal malignancy, shows a characteristic of florid papillomatosis of the lips, labial commissures, or oral mucosa. Perioral papillomatosis was also reported in patients with Costello syndrome (8).

Multifocal inflammatory papillary hyperplasia is a rare condition and its pathogenesis remains unclear. Multifocal localization of papillary lesions in non-denture wearers can be a challenging issue in disease diagnosis and patient management. Clinicopathologic correlation and collaboration can prevent diagnostic pitfalls. Differential diagnosis should be rendered by the pathologist and clinicians based on the histopathologic and clinical presentations of the lesion. In this patient, malignant conditions and HPV-induced lesions were excluded via histopathologic and immunohistochemical analysis. The patient will undergo further genetic investigations.

Ethics

Informed Consent: Obtained.

Peer-review: Externally peer reviewed.

Authorship Contributions

Surgical and Medical Practices: Ö.D., T.K., D.D.,  Concept: Ö.D.,  Design: D.D., Data Collection or Processing: T.A.,  Analysis or Interpretation: Ö.D., D.D., Literature Search: Ö.D.,  Writing: Ö.D.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study received no financial support.