Oral Verrucous Hyperplasia: A Case Report

INTRODUCTION

Oral Verrucous Hyperplasia (OVH) indicates a clinico-pathological descriptive term used to describe a rare histopathological entity that is occult and hard to define and has unclear etiology. This slow growing, progressive soft tissue lesion was definedby Shear and Pindborgwho were the first to report it in 1980.¹Such lesions can occur in both smokers as well non-smokers and also are common in elderly patients. Studies have reported that placement of tobacco-betel-lime quid in vestibule or chewing areca nut quid as most predominant habits associated with OVH growth, while smokinghas been reported as the second most common associated etiological factor.^{2, 3}It has been documented that Human papilloma virus (HPV) is also associated with development of OVH.⁴However someliteraturehassuggestedthat there is no putative link between HPV andtobacco product use. Theselesions are predominantly seen on buccal mucosa and tongue. Initially the lesionstarts as a white hyperkeratoticplaque whichsooner or later becomes multifocal, exophytic, proliferative and has a papillary surface.⁵

Case Report

A 62-year-old male reported with a primary complaint of a white rough patch on edentulous alveolar ridge in right upper back tooth region of jaw and occasional burning sensation while having spicy food in same area since 2months. Initially patient noticed a small white patch in the region of missing 16 on alveolar ridge mucosa 6 months ago which slowly increased in size. But patient had ignored it as it was asymptomatic. The patient had visited a general dentist a few times 3-4 months ago for replacement of missing teeth in the same region. The general dentist had given a removable partial denture over the lesion 3 months ago.

Patient history for deleterious habits like smoking or tobacco chewing was negative and he had no contributing medical history.

On Intra-oral examination, mucosa over crest of the edentulous alveolar ridge in missing 16 region revealed a non-scrapableexophyticand warty white patch with irregular borders measuring about 1x1cm (Fig 1). Lesion was firm in consistency.

The growth was provisionally diagnosed as Squamous papilloma with differential diagnosis of Proliferative VerrucousLeukoplakia (PVL) and Oral Verrucous Carcinoma (OVC). It was planned that the lesion be excisedand the biopsy examined microscopically. Literature on treatment of verrucous hyperplasia suggests that it is mandatory that the tissue biopsy must include adjoining normal epithelium and a wide excision with 3mm-5mm of surrounding normal tissue be done.

Case Management:

After informed consent and evaluation of blood hemogram, full mouth oral prophylaxis was performed. One week after oral prophylaxis, the lesion was excised under local anaesthesia. The area to be excised which also included 5mm of surrounding clinically normal tissue was marked. Local anaesthesia was administered. Incision was given using a No.15 blade with a Bard Parker handle. The incision was given at angle at 450 to the surface of the tissue such that the maximum depth of the incision would be in the centre of the lesion. The lesion was then separated from the underlying tissue by sharp dissection. The excised lesion left behind a wedge shaped trough. Bleeding from the site was controlled by pressure pack with moist gauze for 5-6 min. Once the bleeding was arrested the area was covered with periodontal pack (CoePack).Theexcised tissue specimenwas advanced for histopathological examination. One week post excision, surgical site showed satisfactory healing. No signs of recurrence were observed at one month follow up visit (Fig 2). 5 months follow-up visit also showed no signs of recurrence. The patient has been scheduled for periodic follow up.

Histopathological Examination:

The tissue section which was stained with Hematoxylinand eosin (Fig3) showed marked hyperorthokeratotic stratified squamous epithelium which appeared acanthotic and hyperplastic with keratin plugging. The epithelium in the basal one third regionshowed mild dysplastic features and surface epithelium showed fibrinous exudate. The underlying connective tissue was composed of dense bundles of collagen fibers, fibroblasts, diffuse inflammatory cell infiltrate of lymphocytes and plasma cells. The photomicrograph was indicative of OVH

Discussion:

It has been envisaged that OVH is a plausible malignant disorder. Shear and Pindborg clinically classified Verrucoushyperplasias into two types, one being a sharp type which consists of narrow, long andheavily keratinized verrucousprocesses which appear white and a second blunt variety consisting of broader and flatterminimally keratinized verrucous processes.1 Later Wang et al dependingupon the histological features reclassifiedthese lesions into (1) plaque-type and (2) mass type.³ They concluded that the terminology OVH should be used to denote both clinically and histologically the mass-type lesions andthe plaque-type lesions should be classified clinically as oral verruciformleukoplakia and histologically as verruciform hyperplasia.² Theconsensus report by the working committee of the first Asian Regional Meeting on the Terminology and Criteria for Verruco-papillary Lesions of the Oral Cavity held in Kuala Lumpur, Malaysia (2013) proposed certain guidelines for clinical and histological diagnosis of OVH.⁶ They proposed the term “ExophyticVerrucous Hyperplasia” (EVH) to denote the clinical entity that represents the microscopic diagnosis of OVH. The proposed diagnostic criteria for OVH are:

Clinical Criteria:

1. Lesions clinically present in two forms: 1) as an exophytic, fleshy verruco-papillary outgrowth with a white and/or pink surface colour and 2) as a white, plaque-like exophyticverrucous lesion which may mimic verrucousleukoplakia. In both instances the clinical term ‘exophyticverrucous hyperplasia’ should be used.

2. May occur at any anatomical sitein oral cavityand in general would be >1 cm in size.

3. Unlike PVL, EHV is a discrete and solitary lesion.

4. Absence of induration is a cardinal feature.

Histological Criteria:

1. Keratinized exophyticverruco-papillary processes are seen. Keratin plugging may be present.

2. Epithelium is hyperplastic with both basal cell hyperplasia and acanthosis.

3. The hyperplastic epithelial down growth into the lamina propria was absent when correlated to the basement membranelevel of the adjoining normal epithelium.

4. Epithelial dysplasia with subepithelial lymphocytic infiltration as host response may be present or absent.

Furthermoreit was recommended that, the pathology report include a statement describing degree of dysplasia if present, a cautionary note on recurrence following excision and potential for malignant transformation thus making careful surveillance mandatory.

In the present case patient reported with a solitary elevated or exophytic white mass which had a typical papillary surface which was in agreement with the clinical description of OVH. Although buccal mucosa is the most common site followed by tongue for occurrence of such lesions^2,3, studies have shown that less commonly it can also occur on the gingiva^1,7 and are 1 cm or more in size6 like was observed in the present case.Literature also shows male predilection (2:1) with mean age between 30-60 years or 4th decade of life.^2,8 The present case agrees with literature in terms of age and gender. Placement of tobacco-betel-lime quid in vestibule or chewing areca nut quid and smoking have been reported as associated etiological factors.^2,3 However in the present case the patient did not give any history of such deleterious habits. Absence of induration in the surrounding tissue which is a cardinal feature of OVH was also positive in the present case. Thus the present case fulfils most of the clinical criteria specified in the consensus report on the Terminology and Criteria for Verruco-papillary Lesions of the Oral Cavity.⁶

The consensus report also specified that of the many histological criteria enumerated earlier in the present report, keratinized exophyticverrucopapillary processes, keratin plugging, epithelialcell hyperplasia and acanthosis must be present when tissue specimen is observed microscopically.⁶ Also there should be absence of downward growth of hyperplastic epithelium into lamina propria when compared to the level of basement membrane of adjacent epithelium.^6,7 In the present case all these histological changes were observed. Also epithelial dysplasia with subepithelial lymphocytic infiltration was observed. Thus histopathological examination of the lesion in the present case, identified the lesion as Oral Verrucous Hyperplasia.

Clinically as well as pathologically OVH closely resembles OVC is contemplated to be a morphological variation of the OVC with similar biologic potential.⁵ Since bothentities present with comparable clinical features, they have to be differentiated histologically.^1,3,5 They are distinguished by the observation of lack of invasive growth with OVH. OVH is completely superficial to the adjoining normal epithelium.On the other hand OVC shows a downward growth pattern.⁷ Henceits mandatory that the tissue biopsy must include adjoining normal epithelium for distinguishing the two lesions.In the present case there was absence of downward growth of hyperplastic epithelium into lamina propria, hence the diagnosis tipped in favour of OVH and OVC was ruled out.OVH commonly exhibits dysplasia(approx 66%)^1,3 which was also observed in the present case although the dysplasia observed in the present case was to a lesser extent i.e. mild dysplasia. OVH can be alsomistakenfor PVL, a type of non-homogenous leukoplakiawhich may presentin a similar mannerwith aexophyticverrucous appearance and has increased tendency for malignant transformation.⁵ OVH refers to the clinical features as well ashistopathological features, while PVL is a purely clinical descriptive term representing a specific type of leukoplakia with verrucous surface.PVL refers to a pathologic lesion which has potential to transform to OVC or SCC and OVH is a part of its developmental spectrum.⁹Squamous papillomawhich is anoral epithelial soft-tissue lesion, has characteristicmultiple finger-like projections extending above the mucosal surface and is caused by infection with the Human papillomavirus (HPV) 6 and 11.⁴ The finger‑like projections are havea stratified squamous epithelial lining and contain a central connectivetissue core and HPV altered epithelial cells, i.e. Koilocytes, which affects the intermediate layers may be obserbved.⁴The provisional diagnosis of Squamous papilloma although was clinically valid because both Squamous papilloma andOVH have similar clinical picture was ruled out histologically due to absence ofKoilocytes and others histologic features of Squamous papilloma.

OVH is a plausible malignant condition thatcan transform into either OVC or oral SCC.⁷ A studyreported that C-erb B-3 protein expressionduring advancement from OVH to OVC and SCC was denotative of malignancy¹⁰ and thatexpression of P53 and epidermal growth factorreceptor (EGFR) levels can be used as marker todifferentiateverrucous hyperplasia from to OVC and SCC.¹¹

This apparently innocuous white lesion has poor prognosis and the diagnostic significance of OVH lies primarilyin the factuality that the clinician should be aware thatdysplasiapresent may in due course progress into OVC or SCC. Hence patients who have a suspected diagnosis of OVH should be managedaggressively with a wide surgical excision of the primary verrucous lesion with adequate excision of surrounding mucosal and soft-tissue margin. The lesion should be completely excised with a margin of atleast5 mm.And its recommended that these patients be closely followed owing to the high probability of recurrence of such lesions and also high tendencytowards malignant transition of these lesions.^6,7 Other modalities of treatment which have beendescribed for the managementof such lesions include radiation therapy, chemotherapy, cryotherapy, laser therapy, photodynamic therapy, and treatment with recombinant alpha–interferon. However surgical excision still remains the preferred treatment modality for the primary lesion.^6,7 The malignant transformation rate of OVH has been documented as ranging from 3.1% and 20% to as high 70.3 % in various studies.^5,6 The recurrence rate is about 26% with a median follow-up period of 92.5 months.¹²

In the present case the patient had visited a general dentist a few times earlier but lesion was not diagnosed and the general dentist had given a removable partial denture over the lesion. But when the patient reported to a specialist periodontist, the lesion was detected and diagnosed. Oral Verrucous hyperplasia has been conceived to be a potentially malignant disorder. In the present case the epithelium in the basal one third region showed mild dysplastic features. Had it not been diagnosed and detected it could have undergone malignant transformation especially after continued chronic irritation from the removable partial denture. Since as periodontists we closely examined the gingiva, the lesion was diagnosed at an early stage. It was missed by the general dentist simply because of lack of awareness of such conditions.Thus this case report implicates the significance of early detection and intervention. It’s important that the clinicians be aware of this potentially malignant condition as lack of awareness coupled with delay in diagnosis generally results in these lesions being detected in their advanced stages.It can be stressed that a specialist referral when deemed necessary is import and should be considered for such conditions.