Challenges in Early Diagnosis of Oral Cancer: Cases Series

Abstract

Oral cancer has an overall survival rate of only 50%. This prognosis is significantly improved when this disease is diagnosed and treated in its early stages. Oral cancer is usually associated with classical clinical features associated with malignancy resulting in accurate diagnosis. However, certain cases of oral cancer, especially in its early stages, can be clinically deceptive and can be misdiagnosed. There is a recent trend of changing demographics and etiology associated with oral cancer adding to the diagnostic challenges faced by the clinician. The awareness of these changing trends is needed to aid in early diagnosis of oral cancer. In this case series, we have presented three cases of patients with challenging aspects.

Introduction

Oral squamous cell carcinoma (OSCC) is the sixth most common cancer with the five-year survival rate of 50% and a dismal prognosis. The morbidity and mortality rates associated with this aggressive condition significantly improve with early diagnosis (1).The delay in diagnosis may be related to the patient (patient delay) or clinician (professional delay) (2). Although patient awareness is essential for early diagnosis of OSCC, a clinician’s acumen is crucial. The clinical presentation of OSCC is usually characteristic, thus aiding in early diagnosis. In addition, OSCC is most often associated with known risk factors such as tobacco usage or it may be preceded by potentially malignant disorders¹, which raises a clinician’s suspicion of malignancy. However, certain cases can be challenging to diagnose as they may have an uncommon presentation. In this case series we have presented three such cases.

CASE 1

A 30 years year old female patient with no abusive habits presented with burning sensation on the left side of the tongue which had been persisting for past 4 years. She gave a history of a lesion in the same region 4 years back, which was surgically excised by a dentist. On histopathological examination, the lesion was reported to be dysplastic. Post excision, the area had healed completely, however, occasional mild localized burning sensation persisted. Although she wasn’t clearly able to describe her symptoms, she reported of a change in intensity of the burning sensation since past 2 weeks which prompted her to seek medical attention. On examination, there was a blanched area on the ventrolateral surface of the tongue (Figure 1), the borders of which were blending imperceptibly with the surrounding mucosa. On palpation, the consistency was normal and there was no induration. No sharp teeth were associated with the lesion. The cervical lymph nodes were non-palpable. Although her previous history of dysplastic lesion raised our suspicion of malignancy, the clinical findings were not consistent with it and a provisional diagnosis of a hypersensitive scar tissue with a differential diagnosis of scar tissue superinfected with candida infection was made. The patient was prescribed Candid® mouth paint application and a monthly follow up was recommended. Over the course of the follow up there was no discernable change clinically or symptomatically. After 6 months, a slightly raised, firm, circular area was noted in the same region (Figure 2). To better delineate the lesion, advanced imaging was advised prior to incisional biopsy. MRI revealed a well-defined oval lesion along the left lateral border of the tongue at the level of 1st and 2nd molar which was hyperintense on T1weighted images (WI) and showed heterogeneous hyperintensity on T2WI. The incisional biopsy was reported to be well differentiated squamous cell carcinoma (T₁N₀M₀). The patient was referred to another center on request where she underwent partial glossectomy with removal of level I-IV lymph nodes which were benign. Surgical treatment was followed by brachytherapy. There is no evidence of recurrence after the first year of follow up.

Figure 1.

Case 1 first visit

Figure 2.

Case 1 follow up visit

CASE 2

A 30 year old female patient with no abusive habits reported of a traumatic lesion on the right lateral aspect of her tongue which had been persisting for past 3 months. She gave a history of chronic trauma (> 6 months) due to sharp cusps of teeth with which she associated the lesion. She reported persistence of the lesion despite undergoing coronoplasty with posterior teeth in the first and fourth quadrant 2 months prior to coronoplasty. On examination, a firm nodule of approximately 0.5 cm x 0.5 cm was noted on the right lateral aspect of her tongue. Anterior to the lesion, the mucosa showed mild atrophy with white non scrapable lesion (Figure 3). A provisional diagnosis of traumatic fibroma with frictional keratosis was made. Excisional biopsy of the fibrotic lesion was advised which was reported to be well differentiated squamous cell carcinoma (T₁N₀M₀). The patient subsequently underwent partial glossectomy with removal of level I-IV lymph nodes and is currently on 4th month of follow up.

Figure 3.

Case 2

CASE 3

A 56 year old medically fit female patient with no abusive habits reported of a painful growth on the right lateral aspect of her tongue which had been persisting for past 3 months. She noticed the growth after the replacement of missing 46 with a fixed partial denture (FPD) 3 months prior to the replacement and she attributed it the initiation of the lesion to chronic trauma caused by the FPD. On examination, a nodular lesion of approximate dimension 1.5 cm X 2cm cm was detected on the right lateral aspect of the tongue. The surface of the lesion was granular and the surrounding mucosa was erythematous. On palpation, the lesion was firm, tender and there was a mild induration. The FPD did not show any gross abnormalities. However, the lesion seemed to impinge in the area of the FPD (Figure 4). Also a single right submandibular lymph node was palpable which was oval, firm, mobile and tender, suggestive of a reactive lymphadenitis. A provisional diagnosis of traumatic fibroma was given. A differential diagnosis of squamous cell carcinoma was also given owing to the induration associated. An incisional biopsy was done and the lesion was reported to be well differentiated squamous cell carcinoma (T₁N₀M_0). The patient subsequently underwent partial glossectomy with removal of level I-IV lymph nodes recently and is on follow up.

Figure 4.

Case 3

Discussion

Early diagnosis of OSCC significantly affects the associated morbidity and mortality and currently is the best method to improve patient prognosis. Risk factors associated with OSCC help the clinician to identify the patients prone to malignancy. OSCC is most commonly seen in older age group and is often associated with tobacco usage (1). In the first 2 cases mentioned above the women belonged to a much younger age group with no history of abusive habits, a population with traditionally reduced expectation of OSCC. A recent review of the literature on this topic found that there has been an increase in prevalence of oral cancer among younger individuals with no traditional risk factors (1, 3), pointing to the need to screen even young individuals for OSCC. There is also an increase in incidence of OSCC of the tongue, with it being the most common site of involvement in younger individuals. The prognosis of OSCC of the tongue is poor with the 5 year survival rate being only 33%. This can be attributed to the fact that nearly 50% of tongue malignancy would have metastasized at the time of diagnosis. For this reason, early diagnosis is extremely critical for improving the prognosis of tongue malignancies (1).

The presence of potentially malignant disorders has always helped the clinician to identify high risk individuals in whom OSCC is more likely to occur. In the first case, the patient had a history of a dysplastic lesion; therefore, the suspicion of malignancy was imperative. The second and third cases were associated with chronic dental irritation. Although it has been implicated in few epidemiologic studies on the etiopathogenesis of OSCC, confounding by alcohol and tobacco has limited its credibility (4). A recent study concludes that OSCC occurs predominantly at sites of potential dental trauma, especially in patients without other risk factors (5). In this way, chronic traumatic lesions which persist even after removing the causative agent should be subjected to histopathologic evaluation.

Molecular mechanisms of OSCC in young have been found to be similar to that of the normal variants. However, the mechanisms by which these alterations are acquired in young non-habituated individuals may be different. Some of the emerging risk factors include human papilloma virus, diet and nutrition, hormonal and immunologic modulations, and genetic susceptibility (1, 4). An assessment of these factors, although may not be feasible in routine dental practice, has gained a lot of importance in oral cancer research.

The clinical features associated with malignancy although varied, tend to be characteristic, thus making clinical diagnosis apparent. OSCC can present as a red or white lesion, chronic solitary ulcer, proliferative growth or a fissure. These lesions usually are non-tender, indurated and bleed easily on manipulation. The initial stages of malignancy are usually painless and severe pain may be associated with advanced stages of malignancy as the lesion invades into the deeper tissues.¹ These lesions may also be associated with enlarged, fixed, stony hard lymph nodes which are typical of malignancy. The clinical presentation in the above cases lacked the obvious signs of malignancy making early diagnosis challenging. In the first case, the lesion was not clinically evident during the initial presentation and eventually during a follow up visit a raised lesion was seen. The suspicion of malignancy was high owing to the patient’s previous history of dysplastic lesion and lack of an evident etiologic agent rather than the clinical features alone. The second case also lacked the characteristic malignant features and was evident only on histopathological examination. In the third case, although malignancy was suspected, a provisional diagnosis of chronic traumatic fibroma was given as the lesion was extremely painful with no associated bleeding and mild induration which were evident and could be associated with chronic lesions.

Various noninvasive clinical test have been introduced to aid in establishing early clinical diagnosis of such incipient lesions. These tests include vital staining, cytological studies, tissue fluoresce and other cytochemical and molecular studies. Apart from the additional cost involved, especially in the case of molecular studies, none of the techniques have shown 100% sensitivity limiting these techniques being employed for routine clinical use (6). Current evidence suggests that visual and tactile examination with biopsy is the best method for early detection of OSCC (7). This stresses the importance on the clinician’s acumen as professional delays in diagnosis can occur if clinicians are unaware about the risk factors and different clinical presentations. In contrast, another factor causing professional delay is the familiarity associated with the most common presenting characteristics of OSCC, which may make the clinician likely to expect this among elderly patients with a positive habit history. Pitiphat et al (8) have shown in their study that there was a less professional delay among patients with history of smoking. Another study by Kerdpon et al (9) found no such association with abusive habits and professional delays. OSCC in young individuals with no abusive habits and with such an innocuous clinical presentation as reported here is rare. Such cases are more likely to be misdiagnosed and inappropriately managed leading to poor prognosis unless clinicians are aware of the possibility of malignancy.

The timing and technique of biopsy and its histopathological evaluation is an integral part of early detection of OSCC. Gao et al (10) in their study found that biopsy taken at the initial clinical visit or at the earliest from the initial presentation significantly reduced professional delay. However, the patients with high risk of malignancy who are on long term follow up may have to undergo multiple biopsies before definitive diagnosis can be made. It is the clinician’s responsibility to identify the correct timing and correct site of biopsy in such cases. In the first case, identifying the timing and site of biopsy proved challenging and required close follow up with application of advance imaging to make a favorable decision. There is some debate involved regarding the timing of biopsy with respect to referrals. It has been pointed out that biopsy done prior to specialist referral may result in underestimation of the staging of malignancy. The study by Kaing et al showed no significant difference in professional delay among patients biopsied prior to referral and those who underwent biopsy after specialist referral. They suggested that it is suitable to carry out biopsy and imaging at the tertiary center where definitive treatment will be done (11). This issue was noted in the first case, as excisional biopsy was done as a part of the investigative procedure after which the patient was referred to another center for treatment. Due to this, the specialist was not able to discern the exact clinical extent of the lesion even though MRI images were available. When this was communicated to us, the clinical photographs were promptly sent which aided the specialist to understand the extent of the lesion. Hence, in such cases it is always advisable to supplement meticulous clinical notes with clinical photographs (obtained with patient consent). These cases also emphasize the importance of regular recall & follow up. A study by Groome et al (12) has shown that early diagnosis of OSCC is more likely in patients on regular dental check-ups. Follow up of patients with risk factors and patients who present with atypical symptoms with low suspicion of malignancy is necessary and can be lifesaving. Studies have shown that professional delay in diagnosis can vary from 4 days to 3.5 months (13). Some of the factors associated with professional delay include small tumor size, treatment given prior to definitive diagnosis, increase in number of referrals prior to definitive diagnosis and referrals by general practitioners to specialist without clear description of malignancy or suspicion of malignancy (10, 14).

Studies have shown that most often delays in diagnosis of oral malignancies are due to patient delays. One of the most common causes for delay by patients to seek medical consult is lack of awareness. Patients do not realize the seriousness of the initial symptoms. This may be related to smaller size of the initial lesion. Young patients, and those with lessened tobacco use may have lowered expectation of malignancy, thus considering initial symptoms to be harmless (14, 15). Also certain sites in the oral cavity may not be visually accessible to the patients and lesions may go unnoticed in their incipient stage. Other causes may be psychological stress or denial among patients that may result in delay to seek medical advice (15). This can be dealt with by formulating effective population awareness programs related to oral cancer. Clinicians also have an opportunity to provide patient education and habit counselling when required in their routine dental practice.

The aim of this case series was to highlight the fact that with changing population and uncommon clinical presentations of OSCC, the clinicians should remain alert for lesions of suspicious etiology since early detection of malignancy and intervention can go a long way in the management of this physically and psychologically scarring condition.