Evaluation of Metastatic Lymph Nodes in Oral Squamous Cell Carcinoma: A Comparative Study of Clinical, FNAC, Ultra Sonography and Computed Tomography with Post Operative Histopathology

Abstract

All the head and neck tumours, more than 90% are squamous cell carcinomas (SCC). The presence of metastatic cervical lymph nodes histologically positive for SCC provides one of the simplest and most important prognostic factor in patients with head and neck cancer. In this study, all patients were examined clinically for, location, number, size, shape, consistency and fixation of cervical neck nodes to the underlying structure, and the same was carried out by FNAC, USG and CT. Findings of these modalities and histopathological results were compared for the overall metastases of lymph nodes in the neck. The accuracy of clinical examination was 87.77% and sensitivity only 41.66%. FNAC has the greatest specificity, 98.71% and least sensitivity, 33.33%. The accuracy of FNAC was 90%. The positive predictive value and negative predictive value of FNAC were 80.0% and 90.58% respectively. USG revealed 50% of sensitivity. Specificity of USG was 93.58% and accuracy 87.77%. CT scan have the highest sensitivity among all other tests, 66.66%.The negative predictive value for CT scan was also the highest, 94.59%. Specificity and accuracy of CT scan was 89.74% and 86.66% respectively. This study concludes that USG with FNAC is the most accurate in evaluating metastatic lymph nodes in oral squamous cell carcinoma patients along with other investigations like CT scan for staging of the oral squamous cell carcinoma.

Introduction

All the head and neck tumours more than 90% are squamous cell carcinomas (SCC) [1]. Globally oral squamous cell carcinoma ranks sixth most common cause of cancer relate mortality [2]. The presence of metastatic cervical lymph nodes histologically positive for SCC provides one of the simplest and most important prognostic factor in patients with head and neck cancer [3]. A single ipsilateral node reduces survival by 50%; a contralateral node, additional 50%. Consequently, bilateral nodal involvement actually by 75% and extra nodal involvement by another 50%. Not only affecting the survival, but nodal spread also increases the chance of distant metastases, thereby affecting overall quality of life [4].

The neck has traditionally been assessed by clinical examination, but the studies that compared clinical examination with histology have shown that clinical examination of the neck lymph nodes has a low sensitivity and specificity with false negative results that range from 15 to 25%. For the detection of a mass, if cells 1 cm³ in size (the size of palpable nodes) one billion tumour cells have to be present. Small lymph nodes (less than 1 cm in diameter) with metastatic disease easily missed on clinical examination [5]. The high false-positive rate (low specificity) of palpation causes over treatment in many patients. It is possible to reduce the risk of undiagnosed metastasis with accurate imaging techniques and thus probably reduce the number of elective neck treatments [6].

Management in patients presenting with lymph node metastases could consist of a neck dissection. This could be followed by radiation therapy depending on histological findings like extra nodal spread or presence of multiple metastases. Neck dissection as well as radiation therapy have a considerable morbidity and mortality. Therefore, accurate assessment of the lymph node status is important for the criteria of treatment [1].

Currently, several methods are available for investigating the presence and extent of nodal metastasis including physical palpation, contrast- enhanced computed tomography (CT), magnetic resonance imaging (MRI), ultra-sonography, (USG), ultrasound (US) with fine-needle aspiration cytology (FNAC), fluoro-2-deoxy-glucose positron emission tomography (PET), and lymphoscintigraphy. However, none of these investigative modalities shows 100% accuracy in identifying neck node metastasis [7]. The present study was conducted to compare the effectiveness of Clinical, FNAC, ultra sonography and computed tomography with post-operative histopathology in detection of metastatic lymph nodes in oral squamous cell carcinoma.

Material and Methods

Ten consecutive patients who were diagnosed histo-pathologically with oral squamous cell carcinoma et Al-Badar Dental college and Hospital, Kalaburagi, Karnataka were taken up for study. Patients with previous primary surgery, radiotherapy, chemotherapy, non-operable cases-involvement of internal carotid artery, deep neck muscles, base of the skull etc., Any systemic condition contraindicating general anaesthesia were excluded. All the patients were examined clinically and then examination of neck nodes was carried out by FNAC, USG and CT.

Clinical examination: all the patients were clinically examined for location, number, size, texture, consistency and fixation to the underlying structure, of the lymph nodes. Nodes that were greater than 10 mm and hard, especially those on the same side of the primary tumour, and the presence of fixation accepted as evidence of metastasis according to palpation criteria [8].

FNAC: A 10 cc syringe and a 0.6 mm × 25 mm needle was used. Lymph nodes detected with or without USG with a minimal diameter of 10 mm were subjected for aspiration. The most suspicious nodes (largest in the drainage region of the primary tumour) on one or both sides of the neck were aspirated. Most smears consisted of two or three aspirations. Smears were air dried and reviewed by one pathologist [4].

USG: patient was kept in supine position with neck hyper-extended and turned to the opposite side of examination during scanning to optimally visualize the lymph nodes. The levels and number of lymph nodes for each level were recorded similar to the clinical examination. The lymph node levels: level 1 (sub-mental, sub-mandibular region), level 2 (upper jugular), level 3 (middle jugular), level 4 (lower jugular), level 5 (posterior triangle region) and level 6 (upper mediastinal) nodes were assessed. The criteria used to define a node as metastatic in ultrasound was as follows: size: a short axis diameter greater than 8 mm; shape: round; echogenicity: central hypoechogenecity; hilus: loss of hilus; necrosis; extracapsular spread: irregular margin; roundness index: less than 2 cm were considered malignant [6].

Contrast CT: the criteria for determination of metastasis with CT scanning were: heterogeneous density in the node, presence of central necrosis and conglomerate lymph nodes, irregularity of the border accepted as extra capsular invasion, and presence of contrast material surrounding lymph node. Criteria for malignancy for CT according to the size varied according to the location of node in different studies. We considered the size criterion to vary between 10 and 15 mm [8].

Patients were operated; all the neck specimens along with the primary tumour were sent to the same pathologist and examined with meticulous histopathology. All nodes confirmed by clinical, FNAC, USG, and CT scan in the specimen removed for microscopic examination. Of all the macroscopically positive nodes, two or more representative sections were made [4]. Findings of these modalities and histopathological results were compared for the overall numbers of metastased lymph nodes in the neck. Tukey HSD Post Hoc test was used to compare Clinical, FNAC, USG and CT. A ‘P’ value of 0.05 or less was considered as statistically significant.

Results

The results presented in terms of true positive (TP), true negative (TN), false positive (FP), false negative (FN). True positive (TP) results were metastasis carrying nodes detected by any method.

True negative (TN) results were unaffected by nodes demonstrated by any method. False positive (FP) results were unaffected nodes demonstrated as carrying metastasis by any method. False negative (FN) results were metastasis carrying nodes demonstrated as unaffected by any method. Table 1 shows comparison of clinical examination, FNAC, USG and CT with histopathology report. Table 2 shows ‘P’ values using TUKEY HSD POST HOC TEST to compare clinical, CT scan, USG and FNAC and is statistically insignificant.

Table 1.

shows comparison of clinical examination, FNAC, USG and CT with histopathology report

Investigations	Findings	Histopathology report
		Positive	Negative
Clinical	Positive	True positive (n = 5)	False positive (n = 4)
	Negative	False negative (n = 7)	True negative (n = 74)
FNAC	Positive	True positive (n = 4)	False positive (n = 1)
	Negative	False negative (n = 8)	True negative (n = 77)
USG	Positive	True positive (n = 6)	False positive (n = 5)
	Negative	False negative (n = 6)	True negative (n = 73)
CT scan	Positive	True positive (n = 8)	False positive (n = 8)
	Negative	False negative (n = 4)	True negative (n = 70)

Table 2.

shows ‘P’ values using Tukey HSD post hoc test to compare clinical, CT scan, USG and FNAC and is statistically insignificant

Comparison between	TP	TN	FP	FN
Clinical and FNAC	0.8999 (NS)	0.8999 (NS)	0.7135 (NS)	0.8999 (NS)
Clinical and USG	0.8999 (NS)	0.8999 (NS)	0.8999 (NS)	0.8999 (NS)
Clinical and CT SCAN	0.7937 (NS)	0.8361 (NS)	0.5248 (NS)	0.7327 (NS)
FNAC and USG	0.8999 (NS)	0.8361 (NS)	0.5248 (NS)	0.8999 (NS)
FNAC and CT SCAN	0.6317 (NS)	0.5034 (NS)	0.0966 (NS)	0.5504 (NS)
USG and CT SCAN	0.8999 (NS)	0.8999 (NS)	0.7135 (NS)	0.8999 (NS)

Diagnostic validity tests for different methods to assess the nodal metastasis was performed again and the results were presented in terms of sensitivity, specificity, predictive values and accuracy. Histopathological examination was considered gold standard for comparing these methods. Sensitivity was computed as the number of true-positive lymph nodes/(number of true-positive + false-negativelymph nodes) × 100. Specificity was computed as the number of true-negative lymph nodes/(number of true-negative + false-positive lymph nodes) × 100. Positive predictive value was computed as the number of true-positive lymph nodes/(number of true-positive + false-positive) × 100. Negative predictive value was computed as the number of true-negative lymph nodes/(number of true-negative + false negative lymph nodes) × 100. Accuracy was computed as (true-positive + true-negative/total) × 100. Table 3 shows sensitivity, specificity, accuracy, positive and negative predictive values of methods used.

Table 3.

shows sensitivity, specificity, accuracy, positive and negative predictive values of methods used

Statistical test	Palpation	FNAC	USG	CT Scan
Sensitivity	41.66	33.33	50.0	66.66
Specificity	94.87	98.71	93.58	89.74
Positive predictive value	55.55	80.0	54.54	50.0
Negative predictive value	91.35	90.58	92.40	94.59
Accuracy	87.77	90.0	87.77	86.66

The accuracy of palpation was 87.77% and sensitivity 41.66%. It has the highest positive predictive value 55.55%. FNAC has greatest specificity, 98.71% and least sensitivity, 33.33%. The accuracy of FNAC was 90%. The positive predictive value and negative predictive value of FNAC were 80.0% and 90.58% respectively. USG revealed 50% of sensitivity, which is better than Clinical and FNAC but less than that of CT scan. Specificity of USG was 93.58%, higher than that of CT scan. Accuracy of USG was 87.77%, same to that of clinical method. CT scan have the highest sensitivity among all other tests, 66.66%.The negative predictive value for CT scan was also the highest, 94.59%. Specificity and accuracy of CT scan was 89.74% and 86.66%.

Discussion

Lymphatic metastasis is the most important mechanism in the spread of head and neck squamous cell carcinomas. The rate of metastasis probably reflects the aggressiveness of the primary tumour and is an important prognosticator. Treatment and prognosis of patients with head and neck malignant neoplasms is mainly determined by nodal disease. Not only the presence but also the number, size, level in the neck, and the presence of extra nodal spread are important prognostic features [6, 9].

Leemans et al. demonstrated that the number and size of lymph node metastases relates directly to the probability of death attributable to cancer [10]. Assessment of the cervical lymph nodes for metastases is a critical component of this process [11]. Although, several staging techniques have already been studied and compared, the evaluation of cervical lymph nodes in patients with primary head and neck cancer remains a challenge [3]. Radiological imaging modalities such as X-rays, computed tomography (CT), magnetic resonance (MR) imaging, ultrasonography (USG) and Positron emission tomography (PET) have been widely used for the assessment of the cervical lymph node status [12].

Clinical examination is the routine first line in evaluating metastatic cervical lymphadenopathy in oral squamous cell carcinoma [4]. It is generally accepted that palpation alone is insufficient to evaluate whether a lymph node is positive for metastasis because of its low sensitivity. Lymph nodes can easily be misinterpreted, because of possible reactive changes due to malignancy or infection. On the other hand, even small lymph nodes, not clinically distinguishable from normal lymph nodes, can contain malignant cells at histopathologic examination [3]. Deep-seated nodes, short, thick and fatty neck and occult metastases gives false negative results in clinical palpation [2]. It is totally operator dependent and follows a learning curve with experience [7].

In our study, clinically examined the neck nodes for number, size, texture, consistency and fixity and got a low sensitivity (41.66%) and a high specificity (94.87%). Other studies conducted by Rottey et al. [3] and Shetty et al. [7], got sensitivity 48.7%, 36.6% and specificity of 95.5%, 86.61% respectively. Study conducted by Mishra et al. [2] also got similar sensitivity (66.7%) and specificity (95.2%). The positive predictive value of palpation was 55.55%. The negative predictive value of palpation in the present study was better than that of FNAC, which was 91.35%. The accuracy of palpation (87.77%) could be explained by the large number of true negative neck regions (74 vs 16 as a summary of all the other values), which was similar to the study conducted by Anand et al. [8]

FNAC of the suspicious lymph nodes is the superior method for detection of cervical metastases rather that CT or MRI [11]. Cytologic evidence on the nature of a lymph node is more convincing to clinicians than arbitrary radiologic criteria and it can usually be repeated during patients follow up visits. False negative results with fine needle aspiration cytology caused by either puncturing the wrong nodes, obtaining insufficient material, or puncturing the wrong part of a node with a very small metastasis [13].

In the present study, we got highest specificity (98.71%) and positive predictive value (80.0%). The overall accuracy of FNAC was better than that of any other test, which was 90.0%). Study conducted by Van Den Brekel et al. [14] shows similar specificity (100%) and accuracy (92%) except to that of sensitivity (83%). Similar accuracy was found in a study conducted by Knappe et al. [15] with accuracy of 94.5% for USG guided FNAC. In our study, FNAC got less sensitivity (33.33%) and negative predictive value (90.58%).

USG is at least as accurate as CT for cervical lymph node identification [16]. The lower cost, relative ease of application, possibility of frequent repetition without radiation exposure is in favour of USG [2]. The disadvantages of USG is that, it will not detect micro-metastases or lymph node metastases less than 10 mm. False negative results also be caused by a fusion of several small affected lymph nodes [2, 10].

USG in our study shows sensitivity of 50.0%, specificity of 93%, positive predictive value 54.54%, negative predictive value 92.40% and accuracy of 87.77% respectively. Study conducted by Sugawara et al. [17] shows similar findings with respect to specificity (92%), negative predictive value (85.2%) and accuracy (88.2%). Our study also shows similar results in terms of specificity (92.5%) and accuracy (85.9%) with the study conducted by Anand [8] In the literature, USG investigation of lymph-node metastases in oral cancer shows a sensitivity ranging from 78 to 97% [10].

Use of CT imaging for evaluating metastatic cervical lymphadenopathy in patients with oral cancer reported since 1981 [4]. It is less operator dependent than USG [8]. CT imaging is more than ten times expensive than USG. It is contra-indicated in patients who are allergic to contrast medium and patients with high serum creatinine levels.

Our study Contrast CT examination conclude highest sensitivity of 66.66%, lowest specificity of 89%, lowest positive predictive value of 50.0%, and highest negative predictive value of 94.59% and accuracy of 86.66%. Similar results found in the study conducted by Haberal et al. [8] in terms of specificity (96%), negative predictive value (85.0%) and accuracy (87%). In their study, findings like conglomeration and central necrosis made sensitivity and specificity higher and thus increasing the accuracy of CT scan. Study conducted by Bergman et al. [18] also shows similar findings with respect to sensitivity (55%) and specificity (90%). Other study conducted by Takes et al. [19] shows similar results with sensitivity of 54%, specificity of 92%, and overall accuracy of 77%. The results of sensitivity for CT scan for diagnostic of head and neck lymph nodes in patients with oral cancer range from 78 to 97% while specificity described with a range from 30 to 84% [10].

FNAC and clinical examination gave a less sensitivity compared to other two methods. The accuracy of palpation (87.77%) was more when compared to CT scan (86.66%) and less compared to FNAC (90.0%) but similar with that of USG (87.77%). The specificity (98.71%), positive predictive value (80.0%) and accuracy (90.0%) of FNAC was more when compared to palpation (94.87%, 55.55% and 87.77%), USG (93.58%, 54.54% and 87.77%) and CT scan (89.74%, 50.0% and 86.66%). FNAC is a safe, accurate, and valuable investigation evaluating cervical adenopathy [20].

The sensitivity of USG (50.0%) was better than that of clinical examination (41.66%) and FNAC (33.33%) but less than that of CT scan (66.66%). It has a higher specificity (93.58%) and positive predictive value (54.54%) than CT scan (89.74% and 50.0%). CT scan has the highest sensitivity (66.66%) and negative predictive value (94.59%) when compared to clinical examination (41.66% and 91.35%), FNAC (33.33% and 90.58%) and USG (50.0% and 92.40%). It has the least accuracy (86.66%) and positive predictive value (50.0%) among all the four methods. CT scan in spite of high false negative results for detecting metastatic disease is advantageous because of its accuracy in detecting bony erosion of mandible, base of skull invasion, laryngeal cartilage invasion, and extra capsular spread of tumour or carotid encasement by tumour [8].

It is apparent from this and other studies that clinical examination is poor, unreliable, inaccurate method to determine the presence of occult cervical lymph node involvement [7]. USG with FNAC is the most accurate in evaluating metastatic lymph nodes in oral squamous cell carcinoma patients along with other investigations like CT scan for staging of the oral squamous cell Carcinoma.

Conclusion

This study concludes that USG with FNAC is the most accurate in evaluating metastatic lymph nodes in oral squamous cell carcinoma patients along with other investigations like CT scan for staging of the oral squamous cell Carcinoma.

In view of our small sample size, further study is essential to establish the reliability of the criterion in a large sample of cervical lymph nodes.

Funding

None.

Declarations

Conflicts of interest

None.

Ethical approval

No. IEC/ 2017-18/16.

Patient consent

Taken.