Abstract
To analyse the distribution of Neck metastases (NM) and to study frequency of skip metastases in oral squamous cell carcinoma (SCC) of oral cavity. From September 2012 to April 2013, 30 previously untreated patients with SCC of oral cavity underwent primary surgical treatment in our institution. From pathological report of Neck dissection specimen prevalence and distribution of NM were ascertained. All patients were classified according to American Joint Committee on Cancer 2005 TNM classification. Overall frequency of NM was 36.7%. Frequency of occult metastases was 33.3%. N+ metastases found in 37% cases. The overall frequency of NM in level IV and V was 9.5%. Isolated level III involvement was found in 3.3%. No isolated level IV and V involvement was found. Skip metastases to level III LN was 6.7%. We did not find any skip metastases to level IV in our study. Neck nodes at greater risk for metastases were level I and II (50 and 28.6%). Level III (11.9%), IV (7.14%), V (2.38%). The risk of skip metastases to level IV was nil in our study.
Keywords: Oral cavity, Squamous cell carcinoma, Lymph nodes, Skip metastasis
Introduction
Intraoral sites are having very rich lymphatic supply and is the usual pattern of metastases in oral cancer. Cervical NM is the most important prognostic factor in oral cancer. A predictable pattern of spread from upper to lower node level exist, from submental (IA), submandibular (IB),upper jugular (II),middle jugular(III),lower jugular (IV) and posterior cervical (V) in the order described. However occurence of occult metastases and also skip metastases bypassing upper node level and going directly to level IV, V also observed by Byers et al. [1]. So knowledge of pattern of NM is a crucial element to plan a proper management strategy of neck. The ignorance will lead to incomplete clearance of disease.
In this study we analysed the pattern of lymphatic spread in 30 cases of oral cancer underwent surgery in our in our institution. This will help in proper management of neck and avoid under treatment in future.
Materials and Methods
From september 2012 through April 2013, 30 previously untreated patients with oral cavity cancer underwent primary surgical treatment at otorhinolaryngology, Head & Neck Surgery Department of Maulana Azad Medical College, New Delhi, India. All patients were diagnosed with SCC of oral cavity. Out of total 34 neck dissection(ND), 24 (70.6%) modified radical neck dissection (MRND),7 (20.6%) supraomohyoid neck dissection (SOHND),and 3 (8.8%) radical neck dissection (RND) were done. In 4 patients, (13.3%) bilateral ND was done as shown in (Fig. 1).
Fig. 1.
Algorithm for management of oral cancer with N0 and N + neck in the study
Each patient was analysed by specific primary site. Population distribution by primary site, T stage (Fig. 2). Staging of tumour was done according to 2005 AJCC and International Union Against Cancer TNM staging system. We analysed ND specimen by histopathological examination (HPE) for levels of nodes involvement and to ascertain any occult and skip metastases. Statistical analysis was performed by SPSS software.
Fig. 2.
Showing sites of oral cancer
Results
Most common age group was 51–60 years. Male: female ratio being 4:1. Urban: rural ratio was 2:1. Majority of the patients i.e. 18 out of 30(60%) were from lower socioeconomic class. Tobacco chewing addiction was present in 80% of cases followed by alcohol, betel nut and smoking in decreasing order. Buccal mucosa cancer was the most common site in 11 out of 30 cases (36.7%), followed by tongue in 9 out of 30 cases (30%), and lower alveolus in 6 out of 30 cases (20%) (Fig. 2). Most common type on HPE was MDSCC in 18(60%). WDSCC was found in 12(40%) cases (Fig. 3). Nodal status of the patients at the time of presentation was 3 (10%), 13 (43.3%), 14 (46.6%) and 0 (0%) for N0, N1, N2 and N3 stage. T stage of the tumour at the time of presentation was 2 (6.7%), 10 (33.3%), 4 (13.3%) and 14 (46.6%) for T1, T2, T3 and T4 respectively. Large number of patients 19 (63.3%) presented in stage IV. All the patients presented with mass in oral cavity. Pain was the next most common symptom (67% cases), followed by trismus (17%), cheek swelling (13%) and neck swelling (10%). Rate of lymph node metastases in stage I, II, III and IV of OSSC were 0, 9, 27 and 64% respectively. The site wise distribution and clinical T and N staging of tumour is shown in Tables 1, 2, 3.This shows majority of patients (18 out of 30) presented in advanced T3, T4 stage of the disease, comprising of 60% of total cases. A significant number of patients (14 out 30) presented with N2 stage, comprised of 46.7% of total cases (Table 3). Nodal metastatic disease was diagnosed histologically in 11 (36.7%) out of 30 patients (Table 4).
Fig. 3.
Showing pathologial differentiation
Table 1.
Site wise distribution and clinical T and N staging of tumour
| Site | N0 Neck | N + Neck | Total | ||||
|---|---|---|---|---|---|---|---|
| T1 | T2 | T1 | T2 | T3 | T4 | ||
| Buccal | 0 | 0 | 2 | 3 | 3 | 3 | 11 |
| Tongue | 0 | 3 | 0 | 3 | 1 | 2 | 9 |
| Alveolus | 0 | 0 | 0 | 1 | 0 | 5 | 6 |
| Buccoalveolus | 0 | 0 | 0 | 0 | 0 | 3 | 3 |
| Lip | 0 | 0 | 0 | 0 | 0 | 1 | 1 |
| Total | 0 | 3 | 2 | 7 | 4 | 14 | 30 |
Table 2.
Distribution of patients according to T stage
| T stage | No of patients | Percentage | |
|---|---|---|---|
| T1 | 2 | 6.7 | |
| T2 | 10 | 33.3 | |
| T3 | 4 | 13.3 | |
| T4 | T4a | 13 | 43.3 |
| T4b | 1 | 3.3 | |
Table 3.
Distribution of patients according to nodal staging
| N stage | No. of patients | percentage | |
|---|---|---|---|
| N0 | 3 | 10.0 | |
| N1 | 13 | 43.3 | |
| N2 | N2a | 1 | 3.3 |
| N2b | 7 | 23.3 | |
| N2c | 6 | 20.0 | |
| N3 | 0 | 0.0 | |
Table 4.
Cervical metastases in relation to T stage and clinical nodal status
| T-stage | N0 Cases | N + cases | ||
|---|---|---|---|---|
| No.of patient | PN+ | No.of patient | PN+ | |
| T1 | 0 | 0 | 2 | 0 |
| T2 | 3 | 1 | 7 | 5 |
| T3 | 0 | 0 | 4 | 1 |
| T4a | 0 | 0 | 13 | 4 |
| T4b | 0 | 0 | 1 | 0 |
| Total | 3 | 1 | 27 | 10 |
pN+ is pathologically positive nodes
So metastatic disease was diagnosed histologically in 11 (36.7%) out of 30 patients
The rate of metastases in relation to T stage was
T1 stage-0%
T2 stage-60%
T3 stage-25%
T4a stage-30.8%
T4b stage-0%
The rate of metastases in relation to T stage was
T1 stage-0%
T2 stage-60%
T3 stage-25%
T4a stage-30.8%
T4b stage-0%
So majority of the patients (63.3%) presented in stage IV of the oral cancer, and rate of metastases to neck nodes goes on increasing as the stage advances (Table 5). Occult metastases found in 1 case (33.3%) in N0 group in which both level I and II were positive (Tables 6, 7). Results shows 42 nodes out of 704 nodes (5.96%) were having metastases. Among all the pathologically positive nodes, 21 out of 42(50%) were level I, 12 (28.57%) were level II, 5 (11.9%) were level III, 3 (7.14%) were level IV, 1 (2.38%) was level V (Table 8). Comparison between HPE and radiology (CT scan) showed sensitivity, specificity, positive predictive value, negative predictive value and accuracy of radiology is 90.9, 15.8, 38.5, 75 and 43.3% respectively (Table 9, Fig. 4). Comparison between HPE of sampled nodes and combined clinical and radiological examination showed sensitivity, specificity, PPV,NPV and accuracy of combined methods is 90.9, 0, 34.5, 0 and 33.3% respectively (Table 10, Fig. 5). In our stdudy, frequency of skip metastases to level III is 6.7%. No skip metastases to level IV found (Fig. 6).
Table 5.
Rate of node metastases in relation to stage of tumour
| Stage | No. of cases | Percentage of total cases (%) | No. of cases with pN+ | Rate of metastases to neck nodes (%) |
|---|---|---|---|---|
| I | 0 | 0 | 0 | 0 |
| II | 3 | 10 | 1 | 9 |
| III | 8 | 26.7 | 3 | 27 |
| IV | 19 | 63.3 | 7 | 64 |
Table 6.
Distribution of pathologically positive nodes in clinically N0 neck
| Distribution of lymph nodes | No of cases |
|---|---|
| Level I | 0 |
| Level I, II | 1 |
| Level II | 0 |
| Level II, III | 0 |
| Level III | 0 |
| Level III, IV | 0 |
Table 7.
Frequency of occult metastases in N0 neck
| Node level | No. of cases involved |
|---|---|
| Level I, II | 1 (33.3%) |
| Level III | 0 |
| Level IV | 0 |
| Level V | 0 |
Table 8.
Frequecy of specific lymph nodes level found to be positive by HPE
| Level of nodes | No. of nodes removed | No. of nodes positive by HPE | Percentage (%) |
|---|---|---|---|
| I | 166 | 21 | 50 |
| II | 263 | 12 | 28.57 |
| III | 133 | 5 | 11.9 |
| IV | 108 | 3 | 7.14 |
| V | 34 | 1 | 2.38 |
| Total | 704 | 42 | 5.96 |
Table 9.
Correlation between histopathology of sampled node and CT scan finding
| LN level in CT scan | Lymphnode level +ve | P value | |||
|---|---|---|---|---|---|
| No | % | Yes | % | ||
| No | 3 | 15.8 | 1 | 9.1 | 1.00 |
| Yes | 16 | 84.2 | 10 | 90.9 | |
| Total | 19 | 100 | 11 | 100 | |
| Senstivity | 90.9% | 60.1–99.9% |
|---|---|---|
| Specificity | 15.8% | 4.7–38.4% |
| PPV | 38.5% | 22.4–57.5% |
| NPV | 75.0% | 28.9–96.6% |
| Accuracy | 43.3% | 27.4–60.8% |
Fig. 4.
Correlation between histopathology of sampled node and CT scan finding
Table 10.
Correlation between histopathology of sampled node and both clinical and CT scan finding
| Clinical + CT | Lymphnode level +ve | P value | |||
|---|---|---|---|---|---|
| No | % | Yes | % | ||
| No | 0 | 0.0 | 1 | 9.1 | 0.367 |
| Yes | 19 | 100.0 | 10 | 90.9 | |
| Total | 19 | 100 | 11 | 100 | |
| Sensitivity | 90.9% | 60.1–99.9% |
|---|---|---|
| Specificity | 0.0% | – |
| PPV | 34.5% | 19.8–52.7% |
| NPV | 0.0% | – |
| Accuracy | 33.3% | 19.1–51.3% |
Fig. 5.
Correlation between histopathology of sampled node and both clinical and CT scan finding
Fig. 6.
Showing frequency of skip metastases to level III
Discussion
Oral cancer is one of the most common cancers in the world, with approximately 274,300 new cases and 127,500 deaths occurring each year. Two-third of those cases occur in developing countries. The highest incidence rate has been observed in the Indian sub-continent. Five-year relative survival for oral cancer patients is approximately 30% in India. The poor overall survival reflects the advanced stage at diagnosis for the vast majority of these patients. Nevertheless, when first seen, many patients present with advanced tumour, owing to variety of reasons including socioeconomic factor, illiteracy, long distances and attending doctor’s lack of expertise in early diagnosis of oral cancer [2].
In our study most common site affected was buccal mucosa, with 36.7% of cases (11 out of 30).This is in conformity with studies showing which mention 40% of oral cancer of this site in South East Asia. This contrasts with North America and Western Europe where it accounts for 2–10% of cases.80 Cases of tongue cancer in our study was 30% (9 out of 30). Other studies show 22–39% of oral cancer developing at this site [3–5]. Lower alveolus was involved in 20% (6 out of 30) in our study. Previous studies showed 7.5–17.5% of oral cancer involving lower alveolus [4, 6, 7]. Although it represents 30% cases in Japanese population [8]. Mishra et al. [9] has reported 42, 23.5, 13.5, 12.3, 5 and 3.7% of tongue, buccal mucosa, floor of mouth, lower alveolus, retro molar trigone and lip cancer respectively. These are somewhat similar to what we have observed.
Clinically positive lymphadenopathy at presentation can be in 21–34% in tongue cancer and 57% in advanced buccal mucosa cancer [10].
In our study a significant number of patients presented in stage IV of the disease (63.3%). Stage III included only 26.3% and stage II included 10%. Deo et al. has reported 74% of patients in their study presented in an advanced stage (stage III and IV A) of the disease [15]. The cause of the delay is directly related to low socioeconomic status, low education level, unawareness of the disease and long distance of their residence from our centre and in 20% of cases the cause was our professional delay of approximately 10–18 weeks. The largest contributing factor to delay in treatment of head and neck cancers continues to be patient driven, with the average delay of 3.5–5.4 months. The average professional delay is approximately 14–21 weeks [11].
Considering the TNM staging in our study, majority of our patients presented in advanced T stage. Two patients presented (6.7%) in T1 stage, 7 in T2 (23.3%), 4 in T3 (13.3%) and 14 in T4 (46.7%). Three out of 30 patients (10%) presented in N0 stage, 13 (43.3%) in N1 stage, 14 patients (46.6%) presented in N2 stage. Nithya et al. [12] has reported 13, 33, 15 and 14% of cases for T1, T2, T3 and T4 stage and 41, 26, 6 and 2% for N0, N1, N2b and N2c nodal stages.
Balasubramanian et al. [13] reported 46, 36.5, 15.3 and 2% of their cases for T1, T2, T3 and T4 stage and 67.2, 25 and 3.8% in N0, N1 and N3 stages. Lodder [14] has reported 12.5, 49, 23.5, 28% of stage T1, T2, T3 and T4 cancer and 63.5,24,23 and 2.5% of N0, N1, N2 and N3 stages. Our observations are consistent with others observations.
Each of the patient in this study underwent a neck dissection along with excision of primary with or without reconstruction. Twenty out of 30 patients (66.7%) underwent MRND. Four underwent SOND (13.3%).Three underwent RND (10%).Three (10%) underwent both SOND and MRND on either side. In 30 patients 34 neck dissection were performed. Four patients underwent bilateral neck dissection. In total 3 (9%) of 34 operated neck were preoperatively staged N0. Thirty-one necks (91%) were staged N+ .Of the neck dissection, 12 (35.3%) dissections proved to be pN+ on histological examination. Of these 12 pN+ necks, 1 has been staged N0 preoperatively. This gives sensitivity of our clinical staging 90.9% (range 60.1–99.9%), and positive predictive value of 37.0% (range 21.5–55.8%). Among the 3 clinically N0 neck, 2 were pN0, resulting in a specificity of 10.5% (range 1.7–32.6%) with a accuracy of 40% (range 24.6–57.7%). Previous study showed sensitivity of clinical staging of 81% and specificity of 91% [3]. Deo et al. reported the sensitivity of clinical examination for detection of neck nodes as 86.7% but the specificity was 30.5% [15]. However clinical examination is unreliable for detection of nodes and incidence of occult nodal metastases even in early oral cancer varies from 16% to 40% in tongue cancer [16]. In our study for CT scan the sensitivity, specificity, positive predictive value, negative predictive value and accuracy 90.9% (60.1–99.9%), 15.8% (4.7–38.4%), 38.5% (22.4–57.5%), 75% (28.9–96.6%), and 43.3% (27.4–60.8%) respectively.
Previous study reported, CT has a sensitivity varying from 55 to 95% and a specificity of 39–96% for assessing neck node metastases [17]. Woolgar et al. [18] reported CT scan with sensitivity and specificity of 49 and 87% respectively and clinical examination 49 and 87% respectively.
In our study, when clinical examination was supplemented by CT scan, the accuracy was 33.3% (range 19.1–51.3%).The result of our study shows that the accuracy of preoperative assessment of metastatic status of cervical lymph nodes remains poor even when clinical examination is supplemented by CT. Furthermore the detailed HPE finding provided plausible explanation of pre operative misdiagnosis of many cases. One of the reason may be, some metastatic deposits has developed or increased in size in intervening period between presentation and surgery.
In this study ND specimens were anatomically divided into separate levels. Standard H&E stain was used for HPE. In total 704 nodes were removed in 34 neck dissections (mean of 20 nodes per specimen) comparable to previous study showed mean of 30 nodes per specimen [14].Out of 704 nodes we found 42 lymph nodes having tumour deposits (6%), giving a result of approximately median number of positive nodes is 4 in pN + group. Deo et al. reported a median number of 2 in his pN+ group [15]. Woolgar et al. [18] has reported in 104 patients 3764 nodes (36 nodes per specimen) were removed, out of which 169 (4.5%) were found to be positive for metastatic disease.
Our study showed 27 patients (90%) of N+ and 3 patients (10%) with N0 stage. Deo et al. [15] has reported majority (7 5.9%) of his patients were N+ with only 24.1% being N0.
In our study, we found that the lymph node metastases was sequential and predictable in N0 neck cases. The rate of occult metastases was 33.3%. This observation is comparable with previous studies where occult metastases was 26% [9, 19]. Dias et al. [20] showed incidence of occult neck disease, 17.4% in stage I and 27.6% in stage II of OSCC patients. Kim et al. [21] observed occult metastases in 15% cases out of which 26.3% in T2 patients and 12.5% in T4 cases. Deo et al. [15] reported, 20.5% cases in N0 group had occult neck secondary. The rate of occult neck secondary was 17.6 and 23% in early and advanced T stages, respectively. In our study metastases were confined to level I–II. Only one patient with occult neck disease found on END. We did not find any occult metastases to level III and IV. The reported incidence of occult regional lymph node metastases from such tumours varies from 6 to 46% [22]. According to Robbins et al. for the treatment of N0 neck of the oral cancer, the procedure of choice is SOHND comprising level I–III [23]. Byers [1] Ferlito [22] and Robbins [23] proposed an extended SOHND (including level IV) because of skip metastases at level IV in N0 cases of oral cancers. In our study in those necks preoperatively staged N0, no skip metastases was seen in contrast to other study where 4% of operated neck contained skip metastases. Two percent found in level III, and 2% contained skip metastases in level IV or both level III and IV [14]
In the cN0 neck, elective ND was proposed when incidence of nodal metastases was greater than 15–20% [17].
In our study the prevalence of level-specific nodal metastases in the N+ neck was 54.5, 27.3, 18.2, 9 and 9% at level I, II, III, IV and V, respectively. This finding differs from previous study which showed 53, 70, 30, 13 and 0% of metastases to level I, II, III, IV and V respectively [9]. Jamsed et al. analysed a total of 1056 cervical lymph nodes. The number of nodes in level I, II, III, IV and V was 261, 295, 230, 250 and 20 respectively. The result was 53% (16/30) of the patients had positive cervical nodal disease. The distribution of positive nodes in neck was 40, 40, 20, 10 and 0% in level I, II, III, IV and V respectively. Skip metastases in level III and IV were seen in 10% (3/30) of the patients. No patient had isolated level IV involvement in their study [16]. Deo et al. has reported, Level I was the most common level involved in pN+ group (67.8%). Level II was involved in 17.5% of pN+ patients. The overall involvement of level IV and V was 9.4 and 4.7% respectively [15].
In our study overall incidence of neck metastases was 36.7% (11 out of 30 patients) Magremanne et al. [24] showed a metastases of 30% in their study. Balasubramanian et al. [13] observed an incidence of 32.6% metastases in OT cancer. Pandey et al. [25] reported a incidence of 36%. Nithya et al. [12] has reported a incidence of 44% of metastases to neck nodes in tongue cancer. Woolgar et al. [18] diagnosed metastatic disease histologically in 47 (45%) out of the 104 patients. Berg et al. [26] reported, the incidence of lymph node metastases in patients with squamous cell carcinoma of the oral cavity was 20–30%. Deo et al. [15] Reported that 37.2% had positive lymph nodes on pathologic analysis of the neck dissection specimen (pN+).Our observation is similar to others.
Our study shows rate of lymph nodes metastases in stage I, II, III and IV was 0, 9, 27 and 64% respectively. This study showed incidence of metastases to neck nodes in relation to T stage was 0, 60, 25, and 30.8% with T1, T2, T3 and T4 respectively. Mishra et al. [9] reported the rate of metastases in relation to T stage was 20.8% (5/24) with T1 stage, 41.4% (17/41) with T2 stage and 75% (12/16) with T3 stage. Deo et al. [15] reported metastases of 33.3 and 44.7% in early (T1 and T2) and late T stages (T3 and T4), respectively.
The “T” stage of a tumour is an accepted prognostic and therapeutic indicator. Study of patients with cancer of anterior tongue showed that a tumour thickness greater than 5 mm was the only predictor of recurrence in the regional nodes [27]. It has been shown that threshold was breached for tumours with thickness of 2–4 mm depth of invasion and then LN are at risk of metestasis [27]. Ajith et al. [28] reported, treatment of neck nodes in early (T1, T2) SCC of the oral tongue can be expectant in cases where tumour thickness is less than 04 mm, but where it is more than 04 mm elective treatment of the neck is recommended. In our study lymph node metastases has been found in case where tumour thickness was ≥ 3 mm and maximum diameter of ≥ 2 cm. So we can conclude that selective neck dissection remains the standard of care for T1–T2N0 oral cancer. Even for T1, and tumour thickness >2 mm are risk factors for occult neck metastases.
In our study isolated level III involvement was seen in 1 patient out of 30 patients (3.3%). Balasubramanian et al. [13] reported isolated level III involvement in 3.8%. No isolated level IV involvement was seen in our study. Another one patient (3.3%) showed both level III and level IV involvement without involving the upper level nodes. Level IV and level V was involved in the same patient but in continuity with level III involvement. Iqbal et al. [29] has reported 7.6% patients had positive lymph nodes in level IV but no isolated level IV involvement. They found one patient had skip metastases with pathologically positive node in level III, escaping levels I and II. In our study the incidence of skip metastases to level III was 6%. Deo et al. [15] has reported incidence of skip metastases to level III was 3.9% There was no case of skip metastases occurring to either level IV or level V. In our study patients with skip metastases were tongue and a lower alveolus cancer, though studies says skip metastases is rare in gingivobuccal cancer [30]. Julio et al. [31] found 20.8% of cases node levels I-II were skipped. Satish et al. and Kazuaki et al. did not find any skip metastases to level III, IV or V in their study [32, 33].
We found the rate of involvement of level IV and level V in 9% of N+ cases. Although we did not find any skip metastases to level IV, many authors reported very high rate of skip metastases to level IV. Byers et al. [1] reported 15.8% skip metastases to level IV in oral tongue cancers; 15.8% skip metastases to level IV is a very high rate by any standard. Other studies showed incidence of skip metastases to level IV in 4.8% [19]. Dias et al. [20] reported a total of 0.9% of skip metastases in level IV. Woolgar [34] found 10% skip metastases in level IV . However, even examinations using imaging techniques such as CT, MRI and USG are still not reliable for detection of micrometastases because of the high incidence of occult neck disease [35]. Our observation is similar to others.
The relevance of skip metastases to level IV specifically lies in the choice of ND for treatment. It is generally accepted that level III should be included in all therapeutic and END, therefore the chance of skip metastases to level III are of little importance in clinical decision making. Level IV is commonly involved in a stage of T4. The conclusion of this study is to surgically remove the lower jugular group of nodes (level IV) in every patient with squamous cell carcinoma of the oral tongue of stage T3 and T4.
Conclusions
Frequency of neck node metastases diagnosed histologically is 11 out of 30 (36.7%). Six percent of neck nodes (42 out of 704) were found to have tumour deposit on HPE. Most common level involved was level I (50%), and for level II, III, IV and V it was 28.6, 12, 7 and 2.4% respectively. Frequency of occult metastases in N0 cases was 1(33.3%) case. Isolated lymph nodes level involved were level I in 45.5%, II in 18.2%, III in 9% in N+ cases. Among all the study population, in 2 patients level III was found to be involved without involvement of level I and II. No patients with isolated level IV or V node involvement was found. Frequency of skip metastases to level III in N+ cases was found to be 7.4% and overall in the study population it was 6.7%. No skip metastases to level IV was found in our study.We did not observe ‘‘skip metastases’’ at level IV in N0/N+ neck. Metastases may occur at level I–IV in N + neck. SOHND and MRND are appropriate standard management for neck in N0 and N + cases of oral cancer.
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