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 Table of Contents  
ORIGINAL ARTICLE
Year : 2022  |  Volume : 6  |  Issue : 2  |  Page : 37-41

Clinicopathological factors affecting lymph node yield in patients undergoing surgery in head-and-neck squamous cell carcinoma in a tertiary care center of North East India


1 Department of Oncopathology, State Cancer Institute, Guwahati, Assam, India
2 Department of Head and Neck Oncology, State Cancer Institute, Guwahati, Assam, India
3 Department of Radiation Oncology, State Cancer Institute, Guwahati, Assam, India

Date of Submission27-Jan-2022
Date of Decision10-Aug-2022
Date of Acceptance15-Aug-2022
Date of Web Publication29-Aug-2022

Correspondence Address:
Manisha Salvi
No. 412, Shri Bhomiya Ji Nagar, North Sundarwas, Udaipur - 313 001, Rajasthan
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/oji.oji_2_22

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  Abstract 


Background: Lymph node yield (LNY), number of lymph nodes recovered after neck dissection has been identified as a prognostic indicator for several cancers of non-head and neck sites as well as head-and-neck squamous cell carcinoma (HNSCC). Accurate estimation of LNY has been less evaluated in Indian settings. The purpose of this study was to estimate LNY in HNSCC patients, and to find out their association with clinicopathological factors. Materials and Methods: This was a single-center prospective study conducted on patients diagnosed with HNSCC who had undergone neck dissection with or without primary surgery. Grossing of all surgical specimens was done by guidelines under the College of American Pathologists (November 2021). LNY with their association with other clinic-pathological parameters were analyzed using SPSS software version 21.0. Results: A total of 2692 lymph nodes yielded from 112 samples of neck dissection with the mean LNY of 24.02 ± 9.69. A total of 192 lymph nodes were found to be positive with the mean lymph node ratio of 0.07 ± 2.96. Modified radical neck dissection versus selective node dissection performed cases, poor differentiation of tumor, higher tumor stage, more tumor thickness, and positive nodes for metastasis of squamous cell carcinoma were factors that contributed to higher mean LNY over 24. Conclusions: In an Indian setting, the mean LNY for HNSCC patients undergoing lymph node dissection is 24.02 and the factors such as node positivity, tumor differentiation, tumor stage, and higher tumor thickness affect the estimation of LNY.

Keywords: Extracapsular spread, head-and-neck squamous cell carcinoma, lymph node ratio, lymph node yield


How to cite this article:
Salvi M, Bharadwaj BS, Deka M, Sharma M, Goswami B C. Clinicopathological factors affecting lymph node yield in patients undergoing surgery in head-and-neck squamous cell carcinoma in a tertiary care center of North East India. Oncol J India 2022;6:37-41

How to cite this URL:
Salvi M, Bharadwaj BS, Deka M, Sharma M, Goswami B C. Clinicopathological factors affecting lymph node yield in patients undergoing surgery in head-and-neck squamous cell carcinoma in a tertiary care center of North East India. Oncol J India [serial online] 2022 [cited 2022 Sep 30];6:37-41. Available from: https://www.ojionline.org/text.asp?2022/6/2/37/354901




  Introduction Top


Head-and-neck squamous cell carcinomas (HNSCC) are the sixth-most common cancer worldwide. There is a persistently increase in incidence of HNSCC and is anticipated to increase by 30% (that is, 1.08 million new cases annually) by 2030 (Global Cancer Observatory).[1],[2],[3]

Lymph node involvement is common in HNSCC at the time of diagnosis. However, the presence of occult lymph node metastasis (LNM) is seen in up to 20% of cases.[4] The presence of LNM is one of the important prognostic factors of HNSCC presenting at the time of diagnosis. Recent studies stated that other than tumor node metastasis, the exact number of positive nodes, the total number of dissected nodes, and the presence of extracapsular spread (ECS) are also the determinants of prognosis in oral squamous cell carcinomas (SCC).[5]

Lymph node yield (LNY) and lymph node ratio (LNR) are the measurable factors that may have a potential prognostic implication. LNY is defined as the number of lymph nodes retrieved after neck dissection, whereas LNR is defined as the ratio of pathologically positive lymph nodes out of the total number of retrieved lymph nodes. It is likely that a higher LNY means that more potential, occult, pathological tissue has been removed and this should be a favorable prognostic factor. Decreased LNY may result in a decreased likelihood of removing occult nodal disease which may lead to poorer survival.[6] LNY is used for accurate LNR estimation. However, LNY may vary due to anatomical, surgical, and pathological factors.[7] The importance of LNY and LNR is established in malignancies such as colorectal and breast cancer, yet there has been no definitively established general consensus on a specific yield or ratio in HNSCC.[8],[9],[10],[11],[12],[13],[14],[15]

Moreover, accurate estimation of LNY in HNSCC patients and the clinicopathological factors in association with LNY are less evaluated in Indian settings. HNSCC is one of the common malignancies at our institute. The present prospective study was conducted on surgical specimens of HNSCC patients to determine the LNY and to study the association of LNY with different clinicopathological parameters.


  Materials and Methods Top


This was a single-center prospective study conducted over a period between January 2021 and September 2021. The study was approved by Institutional Ethics Committee via letter number SCI/ECR/2020/44. The biopsy-proven HNSCC patients who had undergone neck dissection at our center were included. The patients with distant metastasis, recurrence, previous therapy, tuberculosis, or chronic inflammatory diseases of the head and neck and those with non-SCC were excluded from the study.

The surgical specimens for neck node dissection and/or specimens for primary disease received in the Department of Onco-pathology were enrolled in the study. The specimens having bilateral neck dissection were considered as two samples one for each site and were individually counted for LNY.

The surgical specimens were oriented by the operating surgeon, and nodal levels were identified. Dissection of each nodal level was done by a single oncopathologist to avoid the biasness. These dissected nodes were transferred to separate labeled bottles, completely immersed in 10% of buffered formalin solution.

Grossing of all surgical specimens was done by guidelines under the College of American Pathologists (November 2021). The specimens were sectioned after 24 h of fixation, and all the lymph nodes in the specimens were processed. The lymph nodes >2 mm in size were sectioned along the long axis. Four-μm sections of all the lesions and lymph node sections were stained by routine eosin and hematoxylin and eosin staining and microscopic examination were done. All slides were reviewed by senior oncopathologist.

Pathological details included were pathological tumor-node-metastasis status, histological differentiation, gross tumor thickness, skin infiltration by the tumor, perineural invasion, the total number of lymph nodes harvested per specimen, and the number of positive nodes and nodes with ECS.

Statistical analysis

The data were entered in Microsoft Excel sheet and analyzed using IBM SPSS software (version 21, IBM Corp., 2021. Armonk, New York, USA). Continuous variables were evaluated as mean and standard deviation (SD), whereas nominal/categorical variables were summarized as proportions in terms of percentage. The difference in LNY in different groups of clinicopathological variables was analyzed using the mean value (±SD).


  Results Top


Specimens for neck dissection included either modified radical neck dissection (MRND) or selective node dissection (SND). Specimens for primary disease included either segmental mandibulectomy, marginal mandibulectomy, bite resection, wide local excision, maxillectomy, hemiglossectomy, or laryngectomy.

In this prospective analysis, a total of 100 specimens (patients) of neck node dissection and/or specimens for the primary disease were received by the department of Onco-pathology during the study period. Twelve out of 100 cases had bilateral neck dissection specimens and the surgical specimens of primary disease for these 12 cases were eight cases of laryngectomy and one case each for subtotal mandibulectomy, anterior segment mandibulectomy, bilateral segmental mandibulectomy, and right segmental mandibulectomy. Hence, according to site wise, a total of 112 neck dissection specimens were enrolled as the final study sample size for the analysis.

The patient and surgical variables studied are mentioned in [Table 1]. The mean age of the patients was 56.44 years and ranged between 32 and 76 years. Sixty-six patients were males and 34 were female. Most of the patients were T3 and T4a which together constituted 75% of cases. Skin involvement was seen in seven cases. The mean tumor thickness was 1.8 cm and was divided into two groups such as thickness from 0.2 to 0.9 cm (n = 23), and thickness of ≥1 cm (n = 77).
Table 1: The basic characteristics of the patient profiles (n=100)

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According to the type of neck dissection (n = 112) performed, 77 neck dissections were of MRND type and 35 neck dissections were of SND type. Overall, 2692 lymph nodes were dissected, and the mean LNY was 24.02 ± 9.69.

Pathological node-positive (pN+) status was seen in 45 out of 100 patients. However, according to neck dissection sites, pN+ was seen in 49 out of 112 neck dissections (43.75%). A total of 192 lymph nodes were detected positive out of 2692 lymph nodes retrieved. ENE positive was seen in 30 out of 112 neck dissection sites (26.79%).

The relation of different clinicopathological factors with LNY was evaluated. The distribution of demographic and primary tumor characteristics with LNY is highlighted in [Table 2]. The demographic parameters evaluated for the association are age and sex of the patients, and it was shown no difference in mean LNY ± SD Among tumor characteristics for primary disease, poor tumor differentiation, tumor thickness of ≥1 cm, and higher tumor stage (T4a) showed a distribution with higher LNY. The distribution of lymph node characteristics with LNY is depicted in [Table 3]. The patients with a greater number of positive lymph nodes had higher mean LNY. In our study, the presence of extracapsular extension did not associate with higher LNY.
Table 2: Distribution of lymph node yield with demographic and primary tumour characteristics

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Table 3: Distribution of lymph node characteristics with lymph node yield

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When LNY was compared with the type of neck node dissections performed, we found a higher mean LNY of 25.10 ± 2.82 for MRND cases (n = 77) when compared to SND cases (n = 35) where the mean LNY was 21.68 ± 9.19.

The mean LNR in our study was 0.07 ± 2.96.


  Discussion Top


The present study estimates LNY from surgical specimens of HNSCC patients and determines the association of LNY with clinicopathological factors such as histological differentiation, tumor thickness, tumor status, skin infiltration by tumor, number of positive nodes, and ECS.

We found the mean LNY of 24.02 ± 9.69 in our patients which was comparable with the published studies. Muttagi et al.[7] reported a mean LNY of 21.97 from surgical specimens of 106 locally advanced SCC of mandibular gingiva-buccal sulcus in an Indian setting.

The total number of LN dissected from specimens depends on the training of pathologists, surgeons, and pathology technicians, affecting the overall LNY. However, in our study, the lymph node dissection and their retrieval from specimen were done by the most experienced single surgeon and single pathologist, to prevent the biasness. Variations in the neck dissection fields by the surgeon depend on consensus-based definitions of various neck dissection procedures, individual judgment, expertise, and decision-making. Lower LNY may be found in HNSCC patients who has undergone elective neck dissections than therapeutic neck dissections due to higher proportions of elective dissections are expected to be selective rather than comprehensive. In our study, the mean LNY was found to be 25.10 ± 2.82 in MRND performed cases, whereas the mean LNY was 21.68 ± 9.19 in SND performed cases. Hence, a strong comparison of LNYs obtained by a uniform, standard neck dissection procedure from different centers will help in determining the factors responsible for variation in yields.

The pathological node-negative status in our study was seen in 63 out of 112 neck dissection sites (56.25%) of cases which was higher than reported by Sheppard et al. which was 41%.[4] However, mean LNY increased with an increase in the number of positive nodes. The immunological response in the regional lymph nodes could contribute to the overall increase in the LNY.[16] Kuo et al.[17] performed a database registry study and established better survival advantage in patients for more extensive neck dissection such as ≥16 lymph nodes in cN0, and ≥26 lymph nodes in cN+.

In our study, increased LNY was associated with tumor thickness ≥1 cm which was supported by the published literature.[7] Muttagi et al.[7] reported a slightly higher mean LNY in patients with tumor thickness >1 cm; although the difference is not statistically significant.

In our study, mean LNY was associated with tumor differentiation and pathological T stage. While it was not associated with age, sex, and extracapsular extension of patients as distribution of patients with respect to these factors was not uniform. Muttagi et al.[7] found no significant association of LNY with factors such as age, sex, and tumor differentiation.

LNY and LNR may be used as prognostic factors of survival as discussed in many studies.[6] The literature reported that patients with higher LNYs for neck node dissection had improved long-term outcomes. Moreover, increased LNY may lead to improved survival even in cases of all dissection nodes are negative.[18] Ebrahimi et al.,[5] in a landmark retrospective study reported higher 5-year overall survival and 5-year disease-specific survival for LNY of ≥18 than <18. They suggested a minimal LN to be harvested for patients who underwent SND in oral SCC is 18. This data were further validated prospectively by 2 NRG oncology trials (RTOG 9501 and RTOG 0234), and suggested improved survival and lower loco-regional failure rates with removal and identification of ≥18 lymph nodes.[19]

LNR is an interesting variable for risk assessment in HNSCC patients. LNR or lymph node density as a valuable prognostic indicator is less studied. Several studies reported a cut-off value for LNR within a range from 0.13 to 0.02 for stratifying oral SCC patients into low-risk and high-risk groups.[13],[14],[20],[21],[22],[23],[24] Patel et al.[13] in a large multicentric study reported a cutoff value of 0.07 for NLR and stated the need of more aggressive adjuvant treatment beyond this. Reinisch et al.[11] stated LNR as a predictor of survival in oral SCC patients affected with ipsilateral neck node, and also suggested that LNR is invalid if contralateral neck node is affected and/or conglomerate lymph nodes. In our study, we aimed to analyze the association of LNY with clinicopathological factors and we estimated only a mean LNR of 0.07 ± 2.96.

Limitations

The present study has some limitations. This is a single-center-based study. Moreover, the study analyses only LNY and their association with clinicopathological factors. The study does not evaluate the survival outcomes with respect to the LNY threshold. Hence, survival predictiveness cannot be determined. The study does not evaluate the importance of LNR.


  Conclusions Top


In patients with HNSCC, the mean LNY was 24.02 ± 9.69. The poor differentiation of tumor, tumor thickness, higher T stage, and positive nodes for metastasis of SCC were significant factors that contributed to higher LNY. Further studies with a larger sample size, incorporating multivariate statistical analysis, are required to validate the findings of this study.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Ferlay J, Colombet M, Soerjomataram I, Mathers C, Parkin DM, Piñeros M, et al. Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. Int J Cancer 2019;144:1941-53.  Back to cited text no. 1
    
2.
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018;68:394-424.  Back to cited text no. 2
    
3.
Johnson DE, Burtness B, Leemans CR, Lui VWY, Bauman JE, Grandis JR. Head and neck squamous cell carcinoma. Nat Rev Dis Primers 2020;6:92.  Back to cited text no. 3
    
4.
Sheppard SC, Frech L, Giger R, Nisa L. Lymph node yield and ratio in selective and modified radical neck dissection in head and neck cancer-impact on oncological outcome. Cancers (Basel) 2021;13:2205.  Back to cited text no. 4
    
5.
Ebrahimi A, Zhang WJ, Gao K, Clark JR. Nodal yield and survival in oral squamous cancer: Defining the standard of care. Cancer 2011;117:2917-25.  Back to cited text no. 5
    
6.
Cheraghlou S, Otremba M, Kuo Yu P, Agogo GO, Hersey D, Judson BL. Prognostic value of lymph node yield and density in head and neck malignancies. Otolaryngol Head Neck Surg 2018;158:1016-23.  Back to cited text no. 6
    
7.
Muttagi SS, Patil BR, Godhi AS, Arora DK, Hallikerimath SR, Kale AD. Clinico-pathological factors affecting lymph node yield in Indian patients with locally advanced squamous cell carcinoma of mandibular gingivo-buccal sulcus. Indian J Cancer 2016;53:239-43.  Back to cited text no. 7
[PUBMED]  [Full text]  
8.
Mechera R, Schuster T, Rosenberg R, Speich B. Lymph node yield after rectal resection in patients treated with neoadjuvant radiation for rectal cancer: A systematic review and meta-analysis. Eur J Cancer 2017;72:84-94.  Back to cited text no. 8
    
9.
Zhang MR, Xie TH, Chi JL, Li Y, Yang L, Yu YY, et al. Prognostic role of the lymph node ratio in node positive colorectal cancer: A meta-analysis. Oncotarget 2016;7:72898-907.  Back to cited text no. 9
    
10.
Lykke J, Jess P, Roikjær O, Danish Colorectal Cancer Group. A high lymph node yield in colon cancer is associated with age, tumour stage, tumour sub-site and priority of surgery. Results from a prospective national cohort study. Int J Colorectal Dis 2016;31:1299-305.  Back to cited text no. 10
    
11.
Reinisch S, Kruse A, Bredell M, Lübbers HT, Gander T, Lanzer M. Is lymph-node ratio a superior predictor than lymph node status for recurrence-free and overall survival in patients with head and neck squamous cell carcinoma? Ann Surg Oncol 2014;21:1912-8.  Back to cited text no. 11
    
12.
Liu D, Chen Y, Deng M, Xie G, Wang J, Zhang L, et al. Lymph node ratio and breast cancer prognosis: A meta-analysis. Breast Cancer 2014;21:1-9.  Back to cited text no. 12
    
13.
Patel SG, Amit M, Yen TC, Liao CT, Chaturvedi P, Agarwal JP, et al. Lymph node density in oral cavity cancer: Results of the International Consortium for Outcomes Research. Br J Cancer 2013;109:2087-95.  Back to cited text no. 13
    
14.
Shrime MG, Bachar G, Lea J, Volling C, Ma C, Gullane PJ, et al. Nodal ratio as an independent predictor of survival in squamous cell carcinoma of the oral cavity. Head Neck 2009;31:1482-8.  Back to cited text no. 14
    
15.
Prandi M, Lionetto R, Bini A, Francioni G, Accarpio G, Anfossi A, et al. Prognostic evaluation of stage B colon cancer patients is improved by an adequate lymphadenectomy: Results of a secondary analysis of a large scale adjuvant trial. Ann Surg 2002;235:458-63.  Back to cited text no. 15
    
16.
Nakamura K, Ninomiya I, Oyama K, Inokuchi M, Kinami S, Fushida S, et al. Evaluation of immune response according to the metastatic status in the regional lymph nodes in patients with gastric carcinoma. Oncol Rep 2010;24:1433-41.  Back to cited text no. 16
    
17.
Kuo P, Mehra S, Sosa JA, Roman SA, Husain ZA, Burtness BA. Proposing prognostic thresholds for lymph node yield in clinically lymph node-negative and lymph node-positive cancers of the oral cavity. Cancer 2016;122:3624-31.  Back to cited text no. 17
    
18.
Lemieux A, Kedarisetty S, Raju S, Orosco R, Coffey C. Lymph node yield as a predictor of survival in pathologically node negative oral cavity carcinoma. Otolaryngol Head Neck Surg 2016;154:465-72.  Back to cited text no. 18
    
19.
Divi V, Harris J, Harari PM, Cooper JS, McHugh J, Bell D, et al. Establishing quality indicators for neck dissection: Correlating the number of lymph nodes with oncologic outcomes (NRG Oncology RTOG 9501 and RTOG 0234). Cancer 2016;122:3464-71.  Back to cited text no. 19
    
20.
Liao CT, Hsueh C, Lee LY, Lin CY, Fan KH, Wang HM, et al. Neck dissection field and lymph node density predict prognosis in patients with oral cavity cancer and pathological node metastases treated with adjuvant therapy. Oral Oncol 2012;48:329-36.  Back to cited text no. 20
    
21.
Kim SY, Nam SY, Choi SH, Cho KJ, Roh JL. Prognostic value of lymph node density in node-positive patients with oral squamous cell carcinoma. Ann Surg Oncol 2011;18:2310-7.  Back to cited text no. 21
    
22.
Ebrahimi A, Clark JR, Zhang WJ, Elliott MS, Gao K, Milross CG, et al. Lymph node ratio as an independent prognostic factor in oral squamous cell carcinoma. Head Neck 2011;33:1245-51.  Back to cited text no. 22
    
23.
Urban D, Gluck I, Pfeffer MR, Symon Z, Lawrence YR. Lymph node ratio predicts the benefit of post-operative radiotherapy in oral cavity cancer. Radiother Oncol 2013;106:74-9.  Back to cited text no. 23
    
24.
Gil Z, Carlson DL, Boyle JO, Kraus DH, Shah JP, Shaha AR, et al. Lymph node density is a significant predictor of outcome in patients with oral cancer. Cancer 2009;115:5700-10.  Back to cited text no. 24
    



 
 
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