A case of well-differentiated squamous cell carcinoma in an extraction socket.

Squamous cell carcinomas of the gingiva make up a significant percentage of oral squamous cell carcinomas and are one of the most common causes of death worldwide. Cancers of the gingiva often escape early detection, and hence an early intervention, since their initial signs and symptoms resemble common dental and periodontal infections. This article presents a case of a 29-year-old female patient who presented with a non-healing wound for about 1.5 months post-extraction. The wound was associated with pain and suppuration. A provisional diagnosis of alveolar osteitis was derived at with a differential diagnosis of osteomyelitis and carcinoma of the alveolus. The patient was advised a complete hemogram, orthopantomograph, and intra-oral periapical radiograph of the extraction socket. An incisional biopsy was carried out. Radiographs revealed extensive bone loss, and the biopsy report confirmed the diagnosis of well-differentiated squamous cell carcinoma of the alveolus. Carcinoma of the gingiva often mimics inflammatory lesions and hence is often misdiagnosed. Therefore, any oral lesion should strike a chord of suspicion, and practitioners should base their diagnosis on careful examination, and valid evidence.

INTRODUCTION

Oral carcinomas are among the most prevalent cancers in the world and one of the 10 most common causes of death. Of these, squamous cell carcinomas (SSC) form the majority bulk of cases of oral cancers. Squamous cell carcinoma has been defined as, ‘a malignant epithelial neoplasm exhibiting squamous differentiation as characterized by the formation of keratin and/or the presence of intercellular bridges.’

In parts of Asia, including India, where the use of tobacco, betel nuts, or lime to form a quid is widespread, the incidence of oral cancer is high. In India, oral cancer ranks first among all cancer cases in males, and third among females in many regions. In a 10-year follow-up study, over 30,000 individuals in 3 distinct geographic regions of India were selected because of specific forms of tobacco habits practiced there. And the annual incidence rates of development of potentially malignant disorders were found to be 1.1-2.4/1000 in males and 0.2-1.3/1000 in females.[1]

Carcinoma of the gingiva constitutes an extremely important group of oral neoplasms as the incidence of carcinomas of gingiva is quite high.[2] Alveolar ridge SSC comprised 9% of all patients with oral SCC according to a report by Ildstad et al.[3] About 70% of the carcinomas arise from the mandibular gingiva and 30% from the maxillary gingiva. The fixed gingiva is more often involved than the free gingiva and edentulous areas more than dentate areas. The similarity of early cancerous lesions of the gingiva to common dental infections has frequently led to delay in diagnosis or even misdiagnosis. Hence, institution of treatment has been delayed, and the ultimate prognosis of the patient is poorer.

Occasionally, cases of carcinoma of the gingiva appear to arise following extraction of a tooth. However, if such cases are carefully examined, it can usually be ascertained that the tooth was extracted because of gingival lesion or disease or mobility which in fact was a tumor, which at the time of treatment (surgery) went unrecognized or undiagnosed.

CASE REPORT

A 29-year-old female reported to the Department of Periodontics of M.A. Rangoonwala College of Dental Sciences and Research Centre, in the month of January 2010, with a complaint of pain and bleeding gums in the right side of the lower jaw since 1.5 months. A detailed case history revealed that the pain started 8 days following extraction of a mobile tooth in the same region. The pain was localized and continuous in nature. She experienced difficulty during mastication and while brushing. The pain also disturbed her sleep. The pain was only transiently relieved on taking analgesics. The patient complained of bleeding on and off from the extraction site. The patient also complained of halitosis. On receiving no permanent relief despite repeated visits to her dentist, she approached M.A. Rangoonwala Dental College for her problem.

Her past medical history didn’t reveal anything of significance. The patient gave a history of use of mishri (a roasted, powdered preparation made by baking tobacco on a hot metal plate until it is uniformly black and later on powdered)[45] 4-5 times a day for the past 15 years. The patient would place the quid of mishri in the vestibule on the right side. She cleaned her teeth once-a-day with a toothbrush and toothpaste but had stopped brushing following the onset of pain after the extraction.

General examination revealed that the patient was of moderate height and built, and her vital signs were within the normal range. She, however, had pallor.

Extra-oral examination revealed a diffuse swelling along the lower border of the mandible on the right side extending from the angle of the mandible to the lip commissure. The overlying skin appeared normal with no sinus or color changes or temperature changes. The swelling overall was soft and tender on palpation, except in the submandibular region where it was indurated. The swelling didn’t exhibit any bruit or egg-shell crackling. The patient had partial trismus with mouth opening of 2.5 – 3.0 cms.

Intra-oral examination revealed an ulcero-proliferative reddish pink colored growth measuring 2.5×1.5 cms. in the alveolar socket of extracted 46 [Figures 1 and 2]. The gingiva in relation to 45, 46, 47 appeared reddish-pink, edematous, and swollen. The intra-socket growth was soft in consistency and extremely tender and bled on the slightest provocation. 47 was grade I mobile, and pus exudation was seen from mesial aspect of 47. A white non-scrapable patch was seen on the right buccal mucosa in the premolar- molar region. The patch extended inferiorly into the vestibule and involved the attached gingiva. The surface was wrinkled and irregular with diffuse margins. There was no difficulty in the movements of the tongue.

Figure 1

Ulcero-proliferative reddish pink-colored growth in the right mandibular posterior region

Figure 2

Ulcero-proliferative reddish pink-colored growth in the right mandibular posterior region

A provisional diagnosis of Alveolar osteitis was arrived at with the differential diagnosis including:

Osteomyelitis

Carcinoma of the alveolus.

INVESTIGATIONS

A complete hemogram, blood glucose estimation, intra-oral periapical radiographs (IOPA), orthopantomogram (OPG), and biopsy were advised.

All the parameters of the hemogram and blood glucose estimation were within the normal range.

The IOPA revealed diffuse, poorly-defined radiolucency with ragged margins in the region associated with 46 and vertical and horizontal bone loss with distal aspect of 45 and mesial aspect of 47, respectively [Figure 3].

Figure 3

Intra-oral periapical radiograph

The OPG revealed a diffuse, poorly-defined radiolucency with ragged borders in relation to the region of 46, extending inferiorly up to the mandibular canal and laterally on either side involving surrounding alveolar bone associated with 45 and 47 on the distal and mesial aspects, respectively [Figure 4].

Figure 4

Orthopantomogram

The biopsy report revealed that the section showed the presence of connective tissue stroma showing epithelial pearls and keratin pearls and dysplastic features such as altered nuclear cytoplasmic ratio and prominent nucleoli. A moderate to dense amount of chronic inflammatory infiltrate could be appreciated, and a few dilated blood vessels could be noted [Figure 5].

Figure 5

H and E section showing epithelial and keratin pearls, altered cytoplasmic ratio, and prominent nuclei

The final diagnosis arrived at was well-differentiated squamous cell carcinoma of the alveolus (Right). The stage of the tumor was estimated to be cT4aN0M0.

The patient was referred to the Department of Oncology, Command Hospital, Pune, where hemimandibulectomy with radical neck dissection and mandibular reconstruction using free fibular microvascular graft was carried out. The patient was kept on a regular follow-up. Recurrence was noticed 2 months following surgery in the area adjacent to the surgical site. The base of the tongue was also found to be involved. Since surgery was not an option, the patient was put on chemotherapy and radiotherapy and is being followed up.

DISCUSSION

The majority of oral cancers involve the tongue, oropharynx, and the floor of the mouth. The lips, gingiva, dorsal tongue, and palate are less common sites. Primary squamous cell carcinoma of bone is rare.

In India, the majority of oral cancers are unequivocally associated with tobacco-chewing habits, and are usually preceded by pre-malignant lesions, most often a persistent leukoplakia or oral submucous fibrosis. The use of tobacco in its various forms, including smokeless tobacco, is regarded as the main cause of oral cancers, particularly when associated with the use of excess alcohol. Tobacco and alcohol are acknowledged risk factors for oral and oropharyngeal cancer.[6-9] Tobacco contains potent carcinogens including nitrosamines (nicotine), polycyclic aromatic hydrocarbons, nitrosodicthanolamine, nitrosoprotine, and polonium. Nicotine is a powerful and addicting drug.

The etiology of carcinoma of gingiva appears to be no more specific or defined than that of carcinomas of other areas of the oral cavity. Since the gingiva is a site of chronic irritation and inflammation, because of calculus formation and collection of micro-organisms in many individuals, one may speculate on the possible role of chronic irritation in the development of cancer of the gingiva. The carcinomas can be insidious in onset and progression and can be mistaken for persistent gingivitis, periodontal disease, or abscess. Focus on these masquerades without thorough examination and appropriate investigations like radiographs can lead to extraction of these teeth. Many cases of carcinoma of gingiva occurring following extraction of teeth have been reported.[10] But this could be explained by the fact that the gingival lesion or disease led to mobility of the tooth and subsequent extraction rather than vice versa.

In some instances, after extraction of a tooth, the carcinoma appears to develop rapidly and proliferate up out of the socket, which could probably be due to the unobstructed growth of the neoplastic tissue along the periodontal ligament and then sudden proliferation after extraction.

Carcinoma of the mandibular gingiva is more common than the maxillary.[11] Carcinoma of the gingiva usually manifests initially as an area of ulceration, which may be a purely erosive lesion or may exhibit an exophytic, granular, or verrucous type of growth. Many times, carcinoma of the gingiva does not have the clinical appearance of a malignant neoplasm. It may or may not be painful. The tumor arises most commonly in edentulous areas, although it may develop in a site in which teeth are present. The fixed gingiva is more frequently involved primarily than the free gingiva.[3]

The proximity of the underlying periosteum and bone usually invites early invasion of these structures. Although many cases exhibit irregular invasion and infiltration of the bone, superficial erosion arising apparently as a pressure phenomenon sometimes occurs. In the maxilla, gingival carcinoma often invades into the maxillary sinus, or it may extend onto the palate or into the tonsillar pillar. In the mandible, extension into the floor of the mouth or laterally into the cheek as well as deep into the bone is rather common. Pathologic fracture sometimes occurs in the latter instance.

Metastasis is a common sequel of gingival carcinoma. Carcinoma of mandibular gingiva metastasizes more frequently than cancer of the maxillary gingiva. Metastasis from carcinoma of the mandibular gingiva have a predilection for the cervical lymphnodes of the submandibular triangle and the upper jugular regions.[12] This is especially true for subclinical neck disease, while those patients with clinically positive neck disease are more likely to have involvement of additional nodal levels.

Approximately 13% of the carcinomas are associated with 2nd primaries even though the majority are early stage lesions. Ilstad et al. reported a 66% 2-year and 49% 5-year overall survival.[3]

Treatment of carcinomas of gingiva is generally a surgical problem. Radiation therapy of carcinoma of gingiva is fraught with hazards because of damaging effect of X-rays on bone. Prognosis of cancer of gingiva is not particularly good, and lymph node metastasis worsens prognosis. This again emphasizes the need for early diagnosis, appropriate investigations, and treatment of these neoplasms.