Malignant Transformation Potential of Oral Lichen Planus: A Case Series
Article by :
P. R. Sawant
The World Health Organization has classified oral lichen planus as a potentially malignant disorder. The malignant transformation rates, although meagre, requires noteworthy recognition that this immune mediated disease is a potentially lethal lesion. The etio-pathogenesis of oral lichen planus remains elusive and contributes to the confounding nature of the progression of this lesion into oral squamous cell carcinoma. This article aims to highlight the importance of both clinical and histopathological parameters, in the early detection of the malignant transformation potential of oral lichen planus.
Oral lichen planus (OLP) is the most common immune mediated lesion affecting the general population. Prevalence rates in Indian studies (2.6%) exceed those seen in other Asian studies (1-2%). It is considered to be an oral, potentially malignant disorder as it can undergo malignant transformation resulting in oral squamous cell carcinoma. The clinical pathological parameters which govern the malignant transformation rate need evaluation to furnish close follow-up regimes as part of treatment protocol. This article aims to review a series of four cases demonstrating the varying clinical and pathological spectrum of OLP so as to better understand the etio-pathogenesis of this disease entity and thus potentiate a more effective management to prevent its progression to frank carcinoma.
A 54-year-old female patient presented with a chief complaint of burning sensation of the oral mucosa since past 6 months, which was associated with periods of exacerbations and remissions. Patient was operated for oral squamous cell carcinoma of the left lateral border of the tongue 10 years back. Intraoral examination revealed the characteristic interlacing white striae with peripheral erythematous zone bilaterally involving the buccal mucosa. Other areas of the mouth were apparently normal.
A 36-year-old male patient reported to the Department of Oral & Maxillofacial Pathology with a chief complaint of a vesicle formation involving the right buccal mucosa for 4 days. The patient gave a history of insidious onset of burning sensation in the buccal mucosa particularly on having spicy food with no relieving factors.
Intraorally, a single round tense vesicle measuring approx. 2.5 x 1.5 cm with surrounding mucosa showed whitish striae (reticular pattern) was noted in the right buccal mucosa along the line of occlusion. A punch biopsy was taken from the margin of the vesicular lesion and was sent for histopathological examination.
A 40-year-old female patient reported to the Department of Oral & Maxillofacial Pathology with the chief complaint of burning sensation of oral cavity since past 2 months. Burning sensation was insidious in onset, aggravated on having spicy food substances and had no relieving factors. On intra-oral examination, mixed red and white lesions were observed on the right and left buccal mucosa. The lesion appeared atrophic, irregular in shape with white interlacing striae. The surrounding mucosa was normal.
A 58-year-old female patient reported to the Department of Oral & Maxillofacial Pathology with the chief complaint of burning sensation of oral cavity over past one year. Patient complained that the burning sensation was insidious in onset and gradually aggravated over the past one year. The patient expressed inability to have spicy food, due to severe burning in the oral cavity, particularly of the right buccal mucosa. On intra-oral examination, mixed red and white lesions was observed on the right buccal mucosa. The lesion had a smooth surface, irregular borders with few white interlacing striae. The surrounding mucosa was normal. Generalized desquamative gingivitis with superficial erosion was noted.
For each of the above cases, the medical history was non-contributory and general examination did not reveal any skin changes. None of the cases had a history of any deleterious habit such as tobacco chewing or smoking. Each case underwent the following investigations: complete haemogram, blood sugar estimation and incisional biopsy from the corresponding representative site. All blood parameters were normal for every case and the histopathological features of each case have been tabulated (Table 1) & photomicrograph illustrations are shown in Figure 1.
The Austrian dermatologist Ferdinand von Hebra was the first to describe ‘Lichen Planus’ and he had termed the disease ‘Lichen Ruber’. However, the first clinical description of lichen planus was reported in 1866 by an English surgeon and dermatologist, Erasmus Wilson. It most commonly affects the oral mucosa (oral lichen planus), but can rarely involve other sites such as skin, genital mucosa, scalp and nails. Fifty percent of patients with cutaneous lesions have oral involvement whereas only 25% of patients with oral lesions also have skin involvement.
The potentially malignant nature of oral lichen planus (OLP) has been a subject of concern since 1910, when Hallopeau reported a case of carcinoma arising in OLP. Literature states that with respect to the malignant transformation of OLP, the following controversies have been discussed: 1) OLP transforms into carcinoma, 2) OLP affected epithelium is more vulnerable to carcinogens, 3) carcinoma could appear in coincidence with OLP.
It has been suggested that OLP lesions that were originally diagnosed with epithelial dysplasia could be termed as ‘Lichenoid’ in clinical appearance. Van der Meij and Van der Waal in 2003 modified the WHO criteria and introduced the term Oral Lichenoid Lesion (OLL), with histopathological epithelial dysplasia as a distinct entity from OLP (Table 2).
One distinguishing feature which has been consistently observed in most of the studies on OLP/OLL is the type of the inflammatory cell infiltrate. It has been stated that plasma cells, eosinophils and neutrophils in inﬂammatory infiltrate can be distinctive for OLL compared to OLP. However, to accept this finding as a standard protocol, a larger number of patients need to be examined. Since the qualification of the inflammatory cell infiltrate has not been included in the 2003 WHO criteria for the diagnosis of OLP/OLL, the discussion of the same has not been elaborated by this article.
Evaluating the four cases with respect to the modified WHO diagnostic criteria, Case 1 and Case 3 showed typical clinical and histopathological criteria and thus fulfilled the diagnosis of OLP. Case 2 proved to be histopathologically typical of OLP, but clinically only compatible and thus fell in the category of OLL type 2. By virtue of epithelial dysplasia elaborated by Case 4 as well as the presentation restricted to the right buccal mucosa, this case would be termed as OLL type 3.
Even though the exact etiopathogenesis of the malignant transformation of OLP and OLL has not yet been specifically elucidated, many hypotheses have been put forth.
The malignant potential in lesions showing epithelial dysplasia has been assessed by comparing the degree of genetic instability and found that chromosome 9 monosomy could have an important role in oral cancer initiation. It is also believed that the p53 protein, which is increasingly expressed in keratinocytes undergoing apoptosis seen in the basal layer in both OLP and OLL cases resulted in oral carcinogenesis. It is suggested that chronic inflammation results in a cytokine based micro environment that affects keratinocyte growth, proliferation, differentiation and cell survival characteristics which could contribute to cancer initiation, promotion and progression.
Gandolfo et al (2004) evaluated 402 cases of OLP lesions and found that the cases which had undergone malignant transformation showed a positive correlation with Hepatitis A infection, hypothesizing a possible role of Hepatitis A virus in cancer development. Studies have evaluated and investigated the influence of cell cycle interrupting mechanisms by evaluating the immunohistochemical expression of Bax, Caspase 3 and p21 proteins and concluded that the low response of oral keratinocytes to apoptosis could result in their malignant transformation. Others have demonstrated a higher CD 133 positivity in OSCC developing in lesions previously diagnosed as OLP than in cases of OLP without malignant transformation.
The incidence of neoplasia in OLP with respect to gender is usually found more in females than in males, however Meij et al stated the opposite and Irani et al found no gender predilection. Some authors report that malignant transformation of OLP and OLL occurs between the sixth and seventh decade of life, though lower mean ages have been documented. Multiple studies have shown that the tongue is the most common site for the appearance of oral cancer. Most studies report that the atrophic/erosive is the most likely to undergo transformation to carcinoma. However, a few studies have reported frank carcinoma development in reticular and plaque like forms. No consensus has been reached with smoking and alcohol as risk factors for OSCC developing in patients with OLP/OLL.[1,3]
The absence of strict diagnostic criteria is the culprit behind the controversy regarding the premalignant nature of OLP. Although the incidence of malignant transformation of OLP/OLL remains controversial, careful regular and long term follow up will allow for the early detection of malignant transformation. Several authors have suggested follow up intervals which range from two months to annually (Table 3).
Some authors suggest that the follow-up interval should be based on the clinical form as well as histopathological criteria i.e. reticular form should be assessed annually, while dysplastic changes should be treated aggressively and followed up at every 2-3 months interval. If erosive changes are evident during follow-up visits, additional biopsies should be advocated and the subsequent follow-up intervals should be shortened.
Assessing the true malignant potential of OLP/OLL will require prospective long-term follow-up studies which use strict clinical and histopathological diagnostic criteria.
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