Central Annals of Otolaryngology and Rhinology

Cite this article: Marzullo A, Lettini T, Fiorella ML, Di Nicola V, Arborea G, et al. (2017) Sentinel Node Detection Using Rouviere’s Scheme Dissection in Laryngeal Cancer. A Retrospective Analysis of 170 Cases. Ann Otolaryngol Rhinol 4(3): 1170.

*Corresponding author

Andrea Marzullo, Department of Emergency and Organ Transplantation, Division of Pathology, Medical School of Bari, University of Bari, p.za G. Cesare, 11, 70125 Bari, Italy, Tel 39-080-5478267; Fax: 39-080-5478280; Email:

Submitted: 20 April 2017

Accepted: 03 May 2017

Published: 05 May 2017

ISSN: 2379-948X

Copyright© 2017 Marzullo et al.

OPEN ACCESS

Keywords•Larynx•Cancer•Sentinel node

Research Article

Sentinel Node Detection Using Rouviere’s Scheme Dissection in Laryngeal Cancer. A Retrospective Analysis of 170 CasesAndrea Marzullo1*, Teresa Lettini1, Maria Luisa Fiorella2, Vincenzo Di Nicola2, Graziana Arborea1, Federica Pezzuto1, Francesco Fortarezza1, Leonardo Resta1 and Gabriella Serio1

1Department of Emergency and Organ Transplantation, University of Bari, Italy2Department of Medical Basic Sciences, University of Bari, Italy

Abstract

Advanced head and neck squamous cell carcinoma (SCC) is a disease that metastasizes predominantly to the locoregional lymph nodes. The presence of regional metastases is crucial for staging, therapeutic decision making and prognosis. For patients with clinically negative neck nodes, there are two major management strategies: elective neck dissection or follow-up. Sentinel lymph node biopsy (SLNB) using radioisotope injection has been developed for breast cancer and cutaneous melanoma, and this method is considered the gold standard for SLNB, although in head and neck cancer, the method is not widely accepted because the radioisotope injection has to be performed under general anesthesia. This study aimed to evaluate the diagnostic reliability of sentinel lymph node biopsy in SCC of the larynx, identified using Rouvière’s scheme dissection, and that can be routinely excised without contrast-enhancement.

A systematic clinical and pathological review was performed of 1500 cases of laryngectomy subjected to radical or functional neck dissection. Most patients had a tumor with negative (pN0) lymph nodes. Among 170 patients with neck metastases there were 125 cases with 1 or 2 positive nodes and 45 cases with 3 or more metastatic nodes. The most frequent loci of metastasis were the Kuttner, the omohyoid or the prelaryngeal lymph nodes; in 159 cases one or more of these were involved. In 11 cases the metastasis affected other different nodes. The possible causes of these exceptions are also investigated. In conclusion, the Kuttner, omohyoid and prelaryngeal lymph nodes are eminently suitable for use as sentinel lymph nodes.

ABBREVIATIONS SCC: Squamous Cell Carcinoma; SLNB: Sentinel Lymph Node

Biopsy

INTRODUCTIONHypopharyngeal and laryngeal squamous cell carcinomas

(SCCs) metastasize principally to the regional lymph nodes, while distant metastases are rare or occur at a late stage. Neck dissection with preservation of one or more lymph nodes is therefore the standardized procedure so as to maintain the highest possible quality of life for the patient. The treatment of patients without clinical or radiographic evidence of regional metastasis is still under debate, but the application of sentinel lymph node biopsy (SLNB) is encouraged to limit dissection and harm to vital structures [1-3]. The sensitivity reported for CT scan, MRI, PET scan and ultrasonography (US) in terms of positive predictive value for latero cervical metastasis is 50-70%, while the negative predictive value for nodal metastasis is 80-

95%. The rate of occult cervical nodal metastases is at least 30% after clinical and radiological examination.

In breast cancer and melanoma, to obtain a functional lymph node map, lymphoscintigraphy is often performed, whereby a radioactive substance is injected near the tumour to identify the sentinel lymph nodes (SLN), namely the first node or nodes group that drains the cancer. This technique has also been successfully applied in head and neck epidermoid carcinoma, especially for oral cancer. However, in pharyngeal and laryngeal cancer, the radioisotope method requires accurate injection of the tracer into the pharyngeal or supraglottic areas, which is highly likely to evoke the pharyngeal reflex; thus, this method must be done under general anesthesia and involves prolonged operating room time [1,4]. Using the classic Rouvière’s scheme for functional cervical neck dissection in hypopharyngeal and laryngeal SCCs [5-7], we examined the lymphatic drainage of the neck to identify those lymph nodes most frequently the site of metastases that could be removed without the need for prior lymphoscintigraphy.

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MATERIALS AND METHODS We identified a group of about 1,500 patients who underwent

subtotal or total laryngectomy with radical or functional neck dissection over the period 1981-2001 at the Otolaryngology Section of Bari University Hospital, Bari in southern Italy. From this group we selected 170 patients with pN+ neck dissection, and excluded patients with pN0 tumours. Clinical and radiological data were available in all cases. The tumour stage was T1 [62 cases (36.5%)], T2 [15 cases (8.4%)], T3 [47 cases (27.6%)], T4 [46 cases (27.5%)]. The lymph node chains were identified using the procedure described by Pinel et al. [5].

In the neck, apart from the submandibular nodes, the other lymphatic chains are located in Rouvière’s original schematic representation that includes the anterior jugular lymphatic chain, the spinal accessory lymphatic chain and the transverse cervical lymphatic chain, positioned as in the sides of a triangle. The one or two nodes found behind the posterior belly of the digastric muscle were identified as Kuttner lymph nodes, while those in front were identified as submandibular and those behind the posterior side of Rouvière’s triangle as spinal lymph nodes. Along the anterior border of the jugular chain, at the point of superposition of the sternocleidomastoid and supraomohyoid muscles, the omohyoid lymph node was identified. After their isolation from the supraclavear chain, the jugular lymph nodes were identified, and finally those in front of the larynx, when present, were identified as prelaryngeal nodes. Thus, for each functional dissection (Figure 1) the following lymph nodes were identified as:

1. Kuttner

2. Submandibular

3. Spinal

4. Omohyoid

5. Other Jugular (not Kuttner nor Omohyoid)

6. Supraclavear

7. Prelaryngeal

In one case only, a paratracheal node was identified; this is not usually present in functional neck dissection. For each case, clinical and pathological data were evaluated: histological type, degree of differentiation, primary site, local extension, stage (according to whole-organ dissection), survival time and site of recurrence.

RESULTSIn our population, of the 170 cancers, there were 125 with 1

or 2 positive nodes and 45 cases with 3 or more positive nodes. The lymph nodes most frequently found with metastasis were the Kuttner, the omohyoid or the prelaryngeal nodes, one or more of them being involved in 159 cases. There were thus only 11 cases with lymph node metastasis not involving these nodes. As can be seen from (Tables 1,2) when 1 or 2 lymph nodes are involved the most frequent sites for metastasis in head and neck cancer are the Kuttner (69/125), omohyoid (53/125) and prelaryngeal (6/125) nodes. In 25/69 cases of tumour with positive Kuttner nodes the metastases measured 1 cm or less. Supra-omohyoid lymph nodes were the site of isolated tumoral cells identified by immunohistochemistry in 12 cases with two positive metastatic nodes (Figure 2).

In the 45 cases with three or more positive metastatic nodes, either the Kuttner or omohyoid was always positive, Kuttner (23 cases), omohyoid (3 cases), both (19 cases). In these cases, the tumour stage was pT3. Metastasis not involving the Kuttner, the omohyoid or the prelaryngeal node was found in 11 of the

Figure 1 Functional dissection of right latero-cervical lymph nodes: schematic representation of laterocervical lymph nodes (left); surgical specimen viewed from the internal surface (right). The lymph nodes are indicated in both pictures as follows: 1. Kuttner; 2. Submandibular; 3. Spinal; 4. Omohyoid; 5. Other Jugular (not Kuttner nor Omohyoid); 6. Supraclavear.

Table 1: Lymph node location in cases with 1 metastasis.

Lymph node with metastasis Number out of 85 cases

Kuttner 39

omohyoid 32

prelaryngeal 5

supraclavear 3

submandibular 3

jugular 2

paratracheal 1

Table 2: Lymph node location in cases with 2 metastases.

Lymph nodes with metastasis Number out of 40 cases

Kuttner + Kuttner 7

Kuttner + omohyoid 14

Kuttner + supraclavear 1

Kuttner + submandibular 1

Kuttner + jugular 5

Kuttner + Spinal 2

omohyoid + omohyoid 1

omohyoid + submandibular 1

omohyoid + jugular 5

prelaryngeal + jugular 1

submandibular + submandibular 1

submandibular + jugular 1

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170 cases examined. Table 3 shows the clinical and pathological data of these 11 cases: type of resection, histotype, tumour grade, stage of the primary tumour, site and number of metastatic lymph nodes and follow-up.

The first 4 cases involved metastases only in the submandib-ular lymph nodes deriving from a squamous cell carcinoma of the glottis (case 4) or supraglottic larynx with diffusion to the glosso-epiglottic fold (case 1), to the aryepiglottic fold (case 2) or with transglottic diffusion (case 3), involving the lateral part of the organ, with predominantly vertical lymph node chains. It seems that the branch of the superior peduncle, the “Farabeuf confluence”, instead of leading to the Kuttner lymph nodes, led directly to the submandibular lymph nodes, following the thyro-linguofacial venous trunk. Patient 4, in 1995, underwent a subto-tal laryngectomy with cricohyoidopexy and, 15 months later, was reoperated for relapse, with resection of the residual larynx and right latero-cervical dissection. It is certainly possible that in this patient a variation in lymphatic draining of the neck developed.

Cases 5 and 6 presented pyriform sinus cancer with infiltration of the paraglottic regions, a transglottic tumour and

metastases in only the jugular lymph nodes. These cases did not follow a classic anatomic drainage but skipped the two principal lymph nodes, Kuttner and omohyoid, and therefore are real exceptions.

Case 7 showed a combination of the two previous situations with a more voluminous tumour (pT3) infiltrating the glosso-epiglottic fold, with both submandibular and jugular metastases.

Cases 8, 9 and 10 involved metastases only in the supraclavear lymph nodes deriving from a very large (pT3/pT4) squamous cell carcinoma of the larynx involving the anterior and middle parts of the organ, and in case 9 there was a large hypoglottic extension. Here it is reasonable to presume that drainage was through the anterior lymphatic peduncle, involving the prelaryngeal lymph nodes (not always observable in the pathological specimen) leading to the supraclavear lymph nodes. In case 10, the patient had undergone a left latero-cervical dissection two months previously, metastases being found in the omohyoid and jugular lymph nodes.

Case 11 was an isolated case of metastasis in the paratracheal lymph node. This exceptional finding in such a deep-seated lymph node was probably due to direct perivisceral lymphatic drainage.

Analysis of the follow-up did not show a different disease evolution of those cases with anomalous lymph node metastases. Those cases with extensive larynx disease showed a normal disease progression as compared to those with limited damage.

DISCUSSIONThe use of the sentinel lymph node procedure has been

proposed also for tumours of the head and the neck [9,10] but has yielded controversial results and a mixed success [11-15]. There are objective difficulties in injecting a colloid or dye into the primary tumour site, especially at or close to the midline [16], which limits the possible surgical techniques. An analysis of more recent studies revealed limited series with insufficient follow-up, employing different techniques and procedures, not necessarily validated, and showing a diagnostic accuracy varying from 95%

Figure 2 Lymph node with Isolated Tumor Cells (Haematoxylin-Eosin; 200 X Magnification). In the insert, positive immunostaining for CK-pool.

Table 3: Exceptions to the expected lymph node locations of metastases.

Patient Site Type Grade Dissection MET LN pTNM FOLLOW-UP

CASE 1 Supraglottic SCC G3 Left 1SM pT4aN1M0 D other reason

CASE 2 Supraglottic SCC G1 Right 1SM pT1N1M0 MET N 1 yearNED 8 years

CASE 3 Transglottic SCC G1 Right 1SM pT2N1M0 Lost to follow up

CASE 4 Glottic SCC G1 Right/P.L. 2SM pT4aN2M0 NED 8 years

CASE 5 Pyriform sinus SCC G1 Right 1J pT1N1M0 NED 60 months

CASE 6 Pyriform sinus SCC G2 Right 1J pT1N1M0 MET N 1 yearNED 7 years

CASE 7 Supraglottic SCC G1 Left 1J+1SM pT3N2M0 D other reason

CASE 8 Supraglottic SCC G2 Right 1SC pT3N1M0 D 17 months Relapse

CASE 9 Tranglottic SCC G1 Right 1SC pT4aN1M0 Relapse 5 months

CASE 10 Transglottic SCC G3 Right 1J + 1O pT3N1M0 NED 18 months

CASE 11 Glottic-supraglottic SCC G2 Left 1 PT pT1N1M0 NED 36 monthsAbbreviations: MET LN: Lymph Node Metastases; SCC: Squamous Cell Carcinoma; SM: Submandibular. J: Jugular; SC: Supraclavear; PT: Paratracheal; PL: Prelaryngeal; O: Omohyoid; D: Death; NED: No Evidence of Disease

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to 98% [17-22]. In our series only in 12 out of 170 selected cases (7%) were isolated tumour cells found at immunohistochemistry and in all cases the site was the omohyoid station. These cN0 cases were classified as pN+ after pathological examination.

Our previous work [23], based on a large case file, has shown that metastases derived from laryngeal and hypopharyngeal carcinoma principally reach the Kuttner, supraomohyoid and prelaryngeal lymph nodes, as would be expected from the known anatomic structure of the lymphatic drainage of these organs. In contrast with Welsh’s findings [8], lymphatic drainage did not seem to be substantially modified by the neoplasia in our experience, as there were only 11 exceptional cases among the 170 (6.5%).

The cases of isolated submandibular lymph node metastases are to be expected due to the presence of the Farabeuf confluence, a branch deriving from the superior laryngeal peduncle which then follows the thyro-linguofacial venous trunk to the submandibular lymph nodes. Also, in ¾ of the cases involved there was diffusion to the glossoepiglottic and/or aryepiglottic folds, so invading the oropharyngeal region. Additionally, the extensive operations in patient 4 could certainly have stimulated the formation of new drainage. Metastases in the supraclavear lymph nodes can be explained by the involvement of the glottic-hypoglottic region where an isolated mid-anterior peduncle can be found, that crosses the cricothyroid membrane and leads to the prelaryngeal lymph node and from there to the inferior mediastinal lymph nodes. In a previous work on data from the Gustave Roussy Institute [23], we showed that the prelaryngeal lymph node is not constantly present, being found in only 30% of laryngectomies, and therefore any possible metastases can spread from the anterior laryngeal peduncle into the deep-seated lymph nodes, and so the involvement of this lymph node cannot be demonstrated. The same mechanism could perhaps explain the observation of paratracheal lymph node metastasis.

Our observations cannot explain the real exceptions of the metastases in the jugular lymph nodes, but we can hypothesise:

1) that metastases in Kuttner or in supraomohyoid nodes were not evident;

2) skipping of the principal lymph node due to a pre-existing inflammatory condition;

3) the development of new drainage after surgical operations;

4) Individual variability in lymphatic drainage.

Our conclusion is that the Kuttner, supra-omohyoid and prelaryngeal lymph nodes are eminently suitable to be designated as sentinel lymph nodes. The error rate of only 6.5% for metastasis and of less than 1% in the general cases is very much lower than the rates reported in the literature for attempts to identify SLNs, and can be equated to the error rates found in SLN analysis in breast cancer.

Our intention was not to demonstrate the reliability of the sentinel node technique in the treatment of laryngeal cancer, but to identify a possible “natural” sentinel lymph node whose recognition does not require a delicate pre-operative procedure.

Only in those 11 cases that we considered exceptions are all clinical and follow-up data reported (Table 3), to support possible explanations for the unexpected site of metastasis. We performed a retrospective analysis on a large series of laryngeal cancers submitted to laterocervical node dissection, independently of the type of surgical procedure adopted, in order to include the largest possible number of lymph nodes in the study. Nowadays, the adoption of less invasive treatment is, in our view, in line with the need to find a less aggressive approach to the study of laterocervical lymph nodes, as proposed in this paper.

Furthermore, the possibility of metastasis in anomalous sites can be taken into account in cancer of the vestibule, in cases of invasion of the glossoepiglottic fold or midline glosso-epiglottic invasion or in patients subjected to prior cervical operations.

CONCLUSIONThe designation of the Kuttner, supraomohyoid and

prelaryngeal lymph nodes as sentinel lymph nodes can be made only in the case of precise anatomical dissection and identification, which must be obtained independently of the choice of excision “by levels”. This type of excision proposed by the head and neck ENT subcommittee for neck dissection must not hinder either the identification or separate evaluation of the Kuttner and supra-omohyoid lymph nodes, or the recognition of the prelaryngeal node within the surgical specimen removed in the laryngectomy, to ensure a complete analysis of these important lymphatic chains.

ACKNOWLEDGEMENTSThe authors are grateful to Mary V. Pragnell, BA, for language

assistance.

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Marzullo A, Lettini T, Fiorella ML, Di Nicola V, Arborea G, et al. (2017) Sentinel Node Detection Using Rouviere’s Scheme Dissection in Laryngeal Cancer. A Ret-rospective Analysis of 170 Cases. Ann Otolaryngol Rhinol 4(3): 1170.

Cite this article

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