evaluation of metastatic lymph nodes in head and neck cancer

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EVALUATION OF METASTATIC LYMPH NODES IN HEAD AND NECK CANCER

Original articles

EVALUATION OF METASTATIC LYMPH NODES IN HEAD AND NECK CANCER: A COMPARATIVE STUDY BETWEEN PALPATION, ULTRASONOGRAPHY, ULTRASOUND-GUIDED FINE NEEDLE ASPIRATION CYTOLOGY AND COMPUTED TOMOGRAPHY S. Rottey1, M. Petrovic², W. Bauters³, K. Mervillie4, E. Vanherreweghe³, K. Bonte5, S. Van Belle1, H. Vermeersch5. Key Words : Head and Neck Cancer, Lymph Nodes, Palpation, Diagnosis

ABSTRACT Study design. In head and neck cancer patients, diagnosis of metastatic lymph nodes of the neck is essential for treatment planning and prognosis assessment. In a retrospective study, we compared palpation, ultrasonography, ultrasound-guided fine needle aspiration and computed tomography in patients with head and neck cancer.

––––––––––––––– 1 Department of Medical Oncology, Ghent University Hospital 2 Department of Internal Medicine, Ghent University Hospital 3 Department of Radiology, Ghent University Hospital 4 Department of Pathological Anatomy, Ghent University Hospital 5 Department of Head and Neck Surgery, Ghent University Hospital Address for correspondence : Dr. Sylvie Rottey De Pintelaan 185 9000 Gent Belgium Tel: 0032 9 240 28 11 Fax: 0032 9 240 38 43 [email protected]

Acta Clinica Belgica, 2006; 61-5

Methods. Results of palpation, ultrasonography and computed tomography were available in 78 out of 110 patients diagnosed with head and neck cancer. Ultrasound-guided fine needle aspiration cytology was performed in 26 of these patients. Patients with suspected lymph node(s) observed in one or more techniques underwent neck dissection. Results. Twenty seven patients underwent neck dissection, studying 150 lymph node regions. The sensitivity, specificity, positive predictive value, negative predictive value and efficacy were calculated for palpation (48.7 %, 95.5 %, 79.2 %, 84.1 %, 83.3 % respectively), ultrasonography (65.8 %, 83.0 %, 56.8 %, 87.7 %, 78.7 % respectively), ultrasound-guided fine needle aspiration cytology (86.7 %, 87.5 %, 81.3 %, 91.3 %, 87.2 % respectively) and computed tomography (52.5 %, 83.6 %, 53.9 %, 82.9 %, 75.3 % respectively). Conclusions. In the assessment of lymph node metastases of the neck in patients with primary head and neck cancer, we found a high specificity for palpation of the neck and an acceptable efficacy for both ultrasonography and computed tomography being comparable between the two methods. Efficacy of ultrasound-guided fine needle aspiration cytology was high approaching the value of 90 %.


INTRODUCTION

MATERIALS AND METHODS

Head and neck cancer is the fifth most common cancer worldwide. Males are affected significantly more than females with a ratio ranging from 2:1 to 4:1. The incidence rate in males exceeds 20 per 100.000 in regions of central and Eastern Europe (1, 2, 3). Five-year survival data for all patients with locally advanced head and neck cancer are still less than 50 % and have changed little in the past 30 years despite significant medical and surgical advances (4). Correct treatment of patients suffering from head and neck cancer requires an accurate risk stratification to determine the specific therapy needed, and to predict the clinical outcome. The presence of metastatic cervical lymph nodes histologically positive for squamous cell carcinoma provides one of the simplest and most important prognostic factors in patients with head and neck cancer. A retrospective study of 914 patients who underwent cervical lymph node dissection as a component of initial therapy for oral cavity, oropharyngeal, hypopharyngeal and laryngeal squamous cell carcinoma has shown that the number of positive nodes was a significant, independent predictor of survival (5). The importance of positive cervical lymph nodes has been confirmed in several other studies and appears to correlate with risk for regional recurrence as well as with risk for distant metastases (5-10). An accurate detection of lymph node metastases in the neck has implications on therapeutic approaches. Moreover, a multidisciplinary approach, using different diagnostic strategies to ameliorate lymph node detection in the neck regions from head and neck cancer patients can increase survival and quality of life. In our hospital, a multidisciplinary working group of representatives of different disciplines involved in head and neck cancer treatment functions since many years: head and neck surgery, radiotherapy, medical oncology, radiology, ultrasonography, anatomopathology, dentistry, plastic surgery, dermatology, ophthalmology, oral surgery and logopedics. In patients councelled by our group between 2001-2003, diagnostic tools for detection of cervical lymph node invasion were evaluated retrospectively. The findings of palpation, ultrasonography (US), ultrasound-guided fine needle aspiration cytology (FNAC) and computed tomography (CT) were compared with histopathologic results in patients undergoing neck dissection for clinically positive lymph nodes.

Patients Between January 2001 and January 2003, 110 patients presented with a primary head and neck cancer at the department of head and neck surgery at the Ghent University Hospital, Belgium. Results of palpation, US and CT of the neck region were available for 87 patients out of 110 (in 16 patients no ultrasonography was performed and CT scans of 7 patients were not available for evaluation). Disease stage was determined according to the classification system of the International Union Against Cancer (11). Investigations Palpation of the neck was performed by a head and neck surgeon. Ultrasonography and FNAC were performed by a clinician experienced in US of the neck. FNAC was performed in one or two lymph node regions per side of the neck, only in case of presence of suspected lymph nodes on ultrasonography. Computed tomography was performed by a skilled radiologist. Palpation was performed at diagnosis, preoperatively. The number of lymph nodes, location, size and fixation were reported. Lymph nodes that were greater than 10 mm, hard and fixed to surrounding tissue were accepted as metastatic. Ultrasonography was performed using a Pro Sound SSD-5000, ALOKA Co., Ltd., Tokyo, Japan with a probe UST-5545 (frequence 5-13MHz). Size criteria for lymph nodes proposed by van den Brekel, concerning minimal axial diameters, were applied. Optimal size criteria could be considered as follows: a minimal diameter of 9 mm for subdigastric nodes and 8 mm for all other nodes of the neck (12). Ultrasound-guided fine needle aspiration cytology was performed using a 10 cc syringe and a 0.9 mm x 70 mm needle. Smears were air-dried and stained with May-Grünwald-Giemsa. The smears were all reviewed by the same pathologist. Computed tomography was performed using a MDCT scanner (Volume Zoom, Siemens Medical Solutions). Contrast-enhanced CT scans (collimation 4x2.5 mm; reconstruction section thickness 3 mm, reconstruction intervals 3 mm) were obtained 40 sec after IV administration of 90 mL of iopromide 300 mg I/mL ( Ultravist 300, Berlex Laboratories), injected at a rate of


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2.0 mL/sec using a mechanical power injector. Lymph nodes were considered malignant when central necrosis was present, independent of the size of the lymph node or when this diameter was 10 mm or more in region I-V and 5 mm or more for retropharyngeal lymph nodes (13). Neck dissection specimens were fixed in formalin for a minimum of 24 hours. After fixation, dissection specimens were divided according to different levels of the lymph node regions of the neck. Each lymph node was cut in two parts and embedded in paraffin. Two sections of each lymph node were performed and stained with Haematoxylin and Eosin. According to the guidelines of the multidisciplinary working group of our hospital, neck dissection was part of the operative procedure if malignant invasion of lymph nodes was suspected by at least one of the investigations. If no surgery for primary tumour was planned (to preserve organ function and to guarantee a better quality of life f.i. for small lesions of the sinus piriformis), neck dissection was performed for a TNM classification ≥ N2a. The standard procedure of neck dissection was an ipsilateral neck dissection if only unilateral lymph nodes of the neck were suspected by investigations. This was extended to an ipsilateral neck dissection plus contralateral elective neck dissection in the presence of T4 primary tumours, midline tumours, tumours of the soft palate, pharyngeal wall and base of the tongue (14). According to the results of clinical stage of the primary tumour and pathological stage of the surgical specimen, postoperative treatment was determined. For each lymph node region, palpation, US and CT findings were compared with histopathologic findings, which were accepted as the standard. Lymph node regions evaluated by FNAC were also compared with histopathologic findings of the neck dissection. The results were evaluated statistically and the sensitivity, specificity, predictive value and accuracy of preoperative methods were estimated. Sensitivity was computed as the number of truepositive lymph nodes/(number of true-positive + falsenegative lymph nodes) X 100. Specificity was computed as the number of truenegative lymph nodes/(number of true-negative + false-positive lymph nodes) X 100. Positive predictive value was computed as the number of true-positive lymph nodes/(number of truepositive + false-positive) X 100. Negative predictive value was computed as the number of true-negative lymph nodes/(number of true-


negative + false negative lymph nodes) X 100. Efficacy was computed as (true-positive + truenegative + false-negative + false-positive) X 100. This study was approved by the ethical comittee of our university hospital.

RESULTS Sixty of 87 patients had no suspected lymph nodes on palpation, US and CT. Twenty seven patients were diagnosed as clinically node positive and as a consequence, they were selected for neck dissection. This resulted in 6 bilateral neck dissections and 21 unilateral neck dissections, providing 150 lymph node regions. Clinical N stage of all 27 node positive patients could be defined as: N1 (n=6), N2a (n=2), N2b (n=13), N2c (n=6). This N stage was determined by taking the highest of the 3 N stages obtained by the different clinical investigations (palpation, US and CT). In more detail, clinical N stage determined by palpation of the neck was: N0 (n=13), N1 (n= 8), N2a (n=1), N2b (n=3), N2c (N=2). Clinical N stage independently determined by US was: N1 (n=5), N2b (n=16), N2c (n=6). Clinical N stage independently determined by CT was: N0 (n=2), N1 (n=11), N2a (n=2), N2b (n=7), N2c (n=5). Of the 27 patients with primary cancer of the head and neck, which underwent neck dissection, 22 were male and 5 female. The mean age was 61 years (range 44 to 77 years). Thirteen of these patients were diagnosed with carcinoma of the pharynx: cT1 (n=3), cT2 (n=3), cT3 (n=2), cT4 (n=5); 7 patients were diagnosed with cancer of the oral cavity: cT4 (n=4), cT3 (n=1), cT2 (n=2); 4 patients were diagnosed with carcinoma of the larynx: cT3 (n=2), cT4 (n=2); 2 patients were diagnosed with carcinoma of the maxillary sinus: cT4 (n=2) and in 1 patient, a benign tumour of the parotid gland was found: cTxN+. Eighteen of 33 neck dissection specimens showed metastatic lymph node involvement, 16 of them were positive for squamous cell carcinoma and 2 of them showed adenocarcinoma (derived from both carcinomas of the maxillary sinus). Forty six FNAC samples were evaluated from 26 patients. Seven samples (15.2 %) contained no lymph node material and were considered not representative. The other 39 samples were interpretable for presence of malignant cells and were compared to neck dissection specimens.


The sensitivity, specificity, positive predictive value, negative predictive value and efficacy for palpation were 48.7 %, 95.5 %, 79.2 %, 84.1 % and 83.3 %. The sensitivity, specificity, positive predictive value, negative predictive value and efficacy for US were 65.8 %; 83.0 %, 56.8 %, 87.7 % and 78.7 %. The sensitivity, specificity, positive predictive value, negative predictive value and efficacy for FNAC were 86.7 %, 87.5 %, 81.3 %, 91.3 % and 87.2 %. The sensitivity, specificity, positive predictive value, negative predictive value and efficacy for CT were 52.5 %, 83.6 %, 53.8 %, 82.9 % and 75.3 %. Table 1 summarizes these data in combination with the true positive, false positive, true negative and false negative values of the different diagnostic methods. Further interpretation of the findings shows that palpation revealed no suspected lymph nodes in 13 of the 27 node positive patients that underwent neck dissection (palpation-negative-patients). US showed suspected lymph nodes in all of these 13 patients and CT in 12 of these 13 patients, doubling the number of patients undergoing a neck dissection. Pathological investigation of the neck dissection specimen revealed malignancy in 5 of these13 palpation-negative-patients (38.5 %). FNAC could demonstrate malignant invasion of cervical lymph nodes in 1 of these 5 palpation-negative-patients (20 %) with proven lymph node metastases in the neck by histopathologic investigation.

DISCUSSION Accurate initial assessment of nodal involvement is crucial for staging, treatment planning and prognosis estimation in patients with head and neck cancer. Although, several staging techniques have already been studied and compared, the evaluation of cervical lymph nodes in patients with primary head and neck cancer still remains a challenge. Lymph nodes can be easily misinterpreted because of possible reactive changes due to malignancy or infection (15). On the other hand, even small lymph nodes, not clinically distinguishable from normal lymph nodes, can contain malignant cells at histopathologic examination (16). Moreover, a needless neck dissection increases the morbidity and must be avoided if possible. The number of patients that are over- or undertreated with regard to the neck can be decreased by an accurate staging method that is able to reliably detect or exclude metastatic cervical lymph nodes.

Table 1 : Comparison of palpation, ultrasonography (US), fine needle aspiration cytology (FNAC) and computed tomography (CT). Sensitivity and specificity rates and positive and negative predictive values of used methods are given. Palpation

US

FNAC

CT

True positives (TP)

19

25

13

21

False positives (FP)

5

19

3

18

True negatives (TN)

106

93

21

92

False negatives (FN)

20

13

2

19

sum TP+FP+TN+FN

150

150

39

150

Sensitivity (%)

48,7

65,8

86,7

52,5

Specificity (%)

95,5

83,0

87,5

83,6

Positive predictive value (%)

79,2

56,8

81,3

53,9

Negative predictive value (%)

84,1

87,7

91,3

82,9

Efficacy (%)

83,3

78,7

87,2

75,3

It is generally accepted that palpation alone is insufficient to evaluate whether a lymph node is positive for metastasis. The low sensitivity of palpation is the source of continuing controversy if prophylactic neck dissection is to be preferred over a wait-and-see policy. In our study, we found a low sensitivity (48.7 %) and a high specificity (95.5 %) of palpation. Only 38.5 % of palpation-negative-patients showed malignant invasion of lymph nodes. These findings reflect the impossibility to detect an important part of metastatic lymph nodes by palpation. On the contrary, if lymph nodes are detected by palpation, there is a very high probability for the presence of metastatic disease (only 5/150 false positive lymph node regions in this study). The high efficacy for palpation (83.3 %) could be explained by the large number of true negative neck regions (106 versus 44 as a summary of all the other values). The large number of true negative palpations in this study is expected: to detect involved nodes with a small diameter, total neck dissection is performed for all regions, from which most will be negative. Most studies agree on the efficacy of additional staging modalities like CT and US. Jank et al. found a sensitivity of 71 % and a specificity of 87 % for US next to a sensitivity of 32 % and a specificity of 96 % for CT (17). Sumi et al. found US better than CT in depicting cervical metastatic nodes (18). Haberal et al. reported for palpation a sensitivity of 64 %, a specificity of 85 %, a negative predictive value of 74 %, a positive predictive value of 78 %, and an accuracy of 78%. In the same


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study, respective values for US and CT concerning sensitivity, specificity, negative predictive value, positive predictive value, and accuracy were 72 %, 96 %, 80 %, 94 %, and 85 % and 81 %, 96 %, 85 %, 90 %, and 87 % (19). Close et al. found a significant relationship between CT findings and pathological status of the neck (20). In our study, US reached an efficacy of 78.7 %. This is slightly higher than the efficacy of CT in this study (75.3 %). Specificity was equal for US and CT (83.0 and 83.6 % respectively) whereas sensitivity was higher for US (65.8 %) than for CT (52.5 %). The role of FNAC in diagnosis of metastastic lymph nodes of head and neck cancer patients was investigated by Atula et al. FNAC was found to offer additional information about enlarged lymph nodes and was able to show malignancy in small lymph nodes (21, 22). Data of Knappe et al. showed a sensitivity of 89.2 %, specificity of 98.1 %, and accuracy of 94.5 % of FNAC (23). In our study, FNAC reaches high sensitivity, specificity and accuracy although values above 90 % were not reached. The goal of this study was to evaluate the different diagnostic tools used for the staging of patients presenting with a primary head and neck cancer in our hospital. This study evaluated efficacy, sensitivity and specificity of different diagnostic procedures in clinically positive necks in head and neck cancer patients. The evaluation of the palpation-negative-neck in patients with head and neck cancer is of the utmost importance. We demonstrated that US and CT are important in the detection of invaded lymph nodes, doubling the number of patients withdrawn for neck dissection. Whether both CT and US are needed is not clear. US reached a better sensitivity than CT did in this study, while specificity was comparable. We could state that, according to our results, US could be the first choice to evaluate the lymph node regions in head and neck cancer patients. However, CT of the primary tumour region is often needed for staging of the primary tumour and preoperative evaluation. As a consequence, CT of the lymph node regions is almost always available. FNAC is the most accurate technique for detecting or excluding the presence of metastasis preoperatively, but the risk for occult metastases remains. In our opinion, FNAC is indicated for this patient population only if there remains any doubt about the status of the neck nodes after US and/or CT. Although the study was performed in a retrospective manner, we believe that the results represent an important reflection of the current standard of care of the


experienced multidisciplinary working group on head and neck cancer in our hospital. Moreover, this study offers an answer to the questions clinicians are dealing with when confronted with head and neck cancer patients in every-day practice. We conclude that no pre-treatment evaluation method can accurately assess the need for neck dissection. In this study, US revealed higher efficacy and sensitivity and equal specificity compared to CT, when evaluating the regional lymph nodes in head and neck cancer patients.

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