Gingival squamous cell carcinoma: A diagnostic impediment.

Oral squamous cell carcinomas represent 3% of cancers in men and 2% of cancers in women. More than 90% of oral cancer occurs in people older than 45 years Lesions of gingiva account for approximately 10% of the oral squamous cell carcinomas and may present clinically as an area of ulceration, exophytic mass, or red/white speckled patches. The proximity to the underlying periosteum may invite early bone invasion. Carcinoma of gingiva constitutes an extremely important group of neoplasms as the lesion frequently mimics the reactive and inflammatory conditions affecting the periodontium, delaying the diagnosis and making the prognosis of the patient poorer. A rare case of gingival squamous cell carcinoma has been reported here, in a 40 Year old male patient. Careful recording of the case history and results of clinical examination, radiographic, and laboratory investigations, along with a critical review of similar conditions led to the diagnosis, and treatment was initiated.

INTRODUCTION

In India, oral cancer may account for more than 50% of all cancer cases[1] Gingival squamous cell carcinoma (GSCC) group accounts for 6.3% of all the oral carcinomas between the ages of 36 and 65 years and up to 91.4% in patients older than 66 years. Gingival involvement with SCC is the most prevalent one, followed by verrucous carcinoma and adenocarcinoma, with lymphoma and Kaposi sarcoma being far less prevalent.[2] Males are affected more by this form of carcinoma than females.[3] This lesion affecting the gingiva is very often confused with inflammatory conditions affecting the periodontium; hence, it is of paramount importance that the lesion should be diagnosed early to initiate treatment, prevent metastasis, and thereby improve the prognosis.

CASE REPORT

A 40-year-old male patient reported to the Department of Periodontics, Panineeya Dental College, Hyderabad, with the chief complaint of pain and burning sensation in the right back region of the lower jaw since 1 month, which was preceded by toothbrush trauma 1½ months back. Pain was severe and continuous that aggravated on taking food. Since then, the patient stopped brushing on the affected side, which led to poor oral hygiene. He consulted a dentist 15 days back and was diagnosed as having a traumatic ulcer. He was put on painkillers (patient was not aware) and amoxicillin 500 mg t.i.d. for 5 days. However, no change was observed, except for mild reduction in pain. His medical history was non-contributory although he was a chronic smoker (4–5 cigarettes daily) for almost 20 years. Extraoral examination revealed solitary, palpable, firm, nodular, non-tender, and mobile submandibular lymph nodes of the right side. Intraoral examination revealed moderate gingival inflammation [Figure 1] with clinical attachment loss of approximately 4 mm (buccally) in relation to 45, 46, 47, and 48. An irregular ulcerative lesion with raised edges was seen on buccal gingivae i.r.t. 46, 47 near the mucogingival line. It had a central yellowish core with reddish periphery, sprinkled with white necrotic areas, and was covered with yellowish white slough indicating food debris. The lesion extended 8 mm mesiodistally and 4 mm buccolingually. Whole of the buccal gingiva in the 4th quadrant was bright red in appearance [Figure 2] . All the observed findings were confirmed with palpation regarding the site, shape, size, and extent of the lesion. Borders were raised and firm on palpation with a firm, fixed, and broad base. There was no bleeding or exudation on palpation. The surrounding gingiva in the 4th quadrant along with the alveolar mucosa was inflamed and tender on percussion. Gingiva in relation to 47 and 48 showed absence of stippling and grade II recession with insufficient attached gingiva and obliterated vestibule. Other mucus membranes were under normal range and grade I recession of marginal gingiva was present i.r.t. 12, 13, and 42. The lesion was provisionally diagnosed as a nonhealing ulcer and the differential diagnosis included SCC, metastatic carcinoma (from the lungs and vestibule), speckled erythroplakia, deep fungal infection, and chronic traumatic ulcer. Patient was advised intraoral periapical radiograph [Figure 3] initially, followed by an orthopantomogram [Figure 4] which showed no bony involvement. He underwent a preliminary phase of therapy on the day he reported to us with supragingival debridement and was put on etoricoxib + serratiopeptidase 10 mg b.i.d. for 5 days, chlorhexidine mouthwash twice daily for 1 week, and Hexi-M gel 3–4 times daily for 1 week. However, healing was not satisfactory after 1 week recall [Figure 5]. All biochemical investigations (complete blood picture, random blood sugar, human immunodeficiency virus I and II – tridot method) were normal except for HbsAg which was reactive. Hence, excisional biopsy of the lesion was performed and the patient was put on amoxicillin 250 mg + clavulanic acid 125 mg t.i.d. for 5 days post biopsy [Figure 6]. On histopathologic examination, the sample presented with islands of epithelial cells, altered nuclear–cytoplasm ratio, cellular and nuclear pleomorphism, hyperchromatism, abnormal mitotic figures within the subepithelial connective tissue which showed epithelial cells arranged in chords and strands, infiltrating muscle, and blood vessels. The surface epithelium showed normal stratification with absence of rete ridges [Figure 7]. On the basis of histopathologic examination of the tissue and lymph node biopsy (revealed a stage I involvement of right submandibular lymph nodes), it was diagnosed as moderately differentiated SCC of the gingiva (T1N1M0). To rule out secondaries from lung, chest X-ray was taken [Figure 8] and was found to be clear. Patient was then shifted to a cancer research institute where he underwent marginal mandibulectomy with level 5 radical neck dissection of the involved side.

Figure 1

Preoperative facial view

Figure 2

Preoperative view of the lesion

Figure 3

Intraoral periapical radiograph

Figure 4

Orthopantomogram

Figure 5

Post preliminary therapy

Figure 6

Post biopsy

Figure 7

Histopathologic section: Dashed arrow denotes attempted keratin pearl formation, black colored arrow denotes absence of epithelial rete pegs, and red colored arrow denotes altered nuclear/cytoplasmic ratio

Figure 8

Chest radiograph

DISCUSSION

SCC is defined as a malignant epithelial neoplasm exhibiting squamous differentiation characterized by the formation of keratin and/or the presence of intercellular bridges.[4] A review shows that the most common etiologic factors associated with SCC are smoking, which carries a 2–3 times greater risk than that in the general population (only 0.03% to begin with), smokeless tobacco use which increases the general risk fourfold, and chewing pan (a combination which includes calcium hydroxide, areca nut, and betel leaf) which increases the general risk by a factor of 8. People who consume alcohol and use tobacco are at a greater risk as are people with syphilis. Phenol use, exposure to ultraviolet radiation, iron deficiency, candidal infections, oncogenic viruses, and immunosuppression play much smaller roles.[5]

SCC is often asymptomatic, and the initial symptoms are usually an intraoral mass or swelling, ulceration, pain, ill-fitting dentures, mobility of teeth, or unhealed extraction wounds. These tumors frequently resemble inflammatory lesions affecting the periodontium like pyogenic granuloma, gingivitis, periodontitis, and benign conditions like verrucous xanthoma. In early stages, the lesion often closely simulates advanced periodontitis, associated with minimal pain, and may lead to a diagnostic delay.[26] Because of the proximity of the underlying alveolus, early bone invasion is a frequent occurrence.

Our differential diagnosis included erythroplakia, deep fungal infections, metastatic carcinoma, and chronic traumatic ulcer. Chronic traumatic/reactive ulcers are covered by a yellow membrane and are surrounded by elevated margins that may show hyperkeratosis or induration due to scar formation. However, they are more frequently seen on tongue and show chronic cell infiltration on histopathologic evaluation.

Deep fungal infections (blastomycosis, histoplasmosis, coccidioimycosis, and cryptococcosis) may also present as chronic nonhealing ulcers with indurated margins, but they are characterized by primary involvement of lungs and microscopic examination revealing granulomatous inflammation with organism, which was ruled out in our case.[1]

The present case mimicked clinically an erythroleukoplakic lesion, which is a premalignant condition, and it was ruled out after histopathologic examination. Metastatic carcinoma of lung was ruled out after examination of the lungs.

Clinically, early SCC is leukoplakic, erythroplakic, or erythroleukoplakic in nature, and advanced cases are endophytic or exophytic. There is minimal pain leading to a delay of 4–8 months in seeking treatment.

Total diagnostic delay in oral cancer is defined as the time from the first onset of signs and symptoms (which included any anatomic changes or discomfort at the site of diagnosis) up to the definitive diagnosis. This term includes the concepts of delay by patients, scheduling delay caused by delayed access to the healthcare system, and delay by the clinicians.[27]

In a study reported by Juan Seoane et al. in 2006, this diagnostic delay for GSCC was quantified as <1.5 months for 75% of the cases and >1.5 months for the rest of 25% cases of GSCC. This delay was frequently found to be associated with invasion of adjacent structures than other oral cancers.[2]

Early detection of SCC is vital as the prognosis is directly related to the size of the lesion. Lesions measuring less than 1 cm are amenable to cure and have a long-term prognosis. Thus, it is prudent to biopsy any unexplained lesion which remains after 2 weeks following removal of any suspected etiologic agent to avoid unnecessary delay in diagnosing such conditions. The overall survival rate for GSCC is about 54%.[18]

CONCLUSION

Many a times, we are too quick to dismiss persistent lesions without further investigations and doing so could result in failure of diagnosis of a potentially life-threatening disease like squamous cell carcinoma as the worldwide survival rate of this condition is rather disappointing.