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10.1245/ASO.2004.11.915
Annals of Surgical Oncology 11:267S-270 (2004)
© 2004 Society of Surgical Oncology
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SUPPLEMENT

Value of Sentinel Lymphadenectomy in Head and Neck Cancer

Jochen A. Werner, MD, PhD, Anja A. Dünne, MD, PhD, Benedikt J. Folz, MD, Roland Moll, MD, PhD and Thomas Behr, MD, PhD

From the Department of Otolaryngology, Head and Neck Surgery (JAW, AAD, BJF), Department of Pathology (RM), and Department of Nuclear Medicine (ThB), Philipps University of Marburg, Germany.

Correspondence: Address correspondence and reprint requests to: Jochen A. Werner, MD, Department of Otolaryngology, Head and Neck Surgery, Philipps University, Deutschhausstrasse 3, 35037 Marburg, Germany; Fax: 49-6421-2866367; E-mail: wernerj{at}med.uni-marburg.de

ABSTRACT

The increasing interest in the so-called sentinel node concept, which has recently been adapted to squamous cell carcinomas of the upper aerodigestive tract, can be explained by encouraging results in other tumor entities. Although the publications on this topic do not yet allow a final judgment on the significance of sentinel lymphadenectomy in head and neck squamous cell carcinoma, early results emphasize the importance of this new diagnostic and therapeutic concept. The basic prerequisite is a detailed knowledge of the existing method-specific limitations in this anatomic region. Critical and careful evaluation of the sentinel node concept is mandatory prior to its application to other tumor entities. Sentinel lymphadenectomy for head and neck cancer may prove helpful if the indications for its use are clearly defined.

Key Words: Head and neck • Sentinel lymphadenectomy • Sentinel node • Squamous cell carcinoma

In recent years, the increasing efforts to spare patients unnecessary surgical treatment have been applied to the treatment of squamous cell carcinomas (SCCs) of the upper aerodigestive tract. Reliable diagnostic concepts for identification of possible occult metastases have gained importance. The encouraging results obtained for other tumor entities may explain the increasing interest in the significance of the so-called sentinel node (SN) concept for head and neck squamous cell carcinoma (HNSCC).

The description of the regional lymphatic drainage of a HNSCC by scintigraphic methods is not new. Detailed examinations have been described by Fisch.1,2 However, use of lymphoscintigraphy to reveal metastases in lymph nodes of the head and neck region initially was not very successful.3–5

Introduction of the SN concept renewed interest in scintigraphy. In the past, scintigraphy was performed to localize lymphatic metastases. With the SN concept, scintigraphy is performed to identify the first node (SN) draining the lymph fluid of the tumor region. This objective can be justified in patients who are expected to develop occult metastases in the first lymph node station on the basis of tumor size and location. Dissection and histologic examination of an SN can reveal micrometastasis or limited macrometastasis, the first indication of eventual metastatic spread.

Dynamic Lymphoscintigraphy

Dynamic lymphoscintigraphy in the head and neck region should not be limited to the isolated description of the point of injection and the SN. Adequate evaluation and anatomic classification of the draining lymph node station gain in significance through the additional description of the head and neck silhouette.6 This can be achieved by placing a radioactive phantom behind the head of the patient (Fig. 1). A simultaneous imaging of the bony structures ensures the optimized anatomic orientation and facilitates the topographic assignment of the SNs.7



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  		FIG. 1. The double-detector camera shows right-sided squamous cell carcinoma of the tonsil (I) with lymphatic drainage to both sides (SN1–3).

 
Dynamic lymphoscintigraphy with documentation under the double detector camera can depict the lymphatic drainage in the regional lymph node basin by means of image editing techniques, which allow a differentiation between the SN and the injection point. Transcutaneous differentiation between the point of injection and the SN with a gamma probe, however, seems to be more difficult because radiation from the point of injection and from the SNs shows a summation effect that makes any differentiation between these areas almost impossible.

Although preoperatively performed dynamic lymphoscintigraphy in HNSCC sometimes has only limited importance with regard to consecutive transcutaneous identification of the SNs, this method can show an adequate functional capacity of the lymphatic drainage region. Furthermore, the main direction of the lymphatic drainage from the primary tumor (ipsilateral or contralateral) can be visualized by sufficient intranodal tracer uptake. This procedure could also be indicated for imaging lymphatic drainage to the contralateral side of the neck. It would be helpful in cases of advanced metastatic spread on the ipsilateral side and a probable N0-stage neck on the contralateral side.6,7 However, this procedure is not appropriate for transcutaneous identification of the SN, especially when lymph drains to the deeper jugular lymph nodes (levels II to IV).

Sentinel Lymphadenectomy

Recent studies6–33 do not allow a final judgment on the importance of SN lymphadenectomy in HNSCC. Early results in carcinomas of the anterior oral cavity,12,13,16,17 which can usually be exposed very easily, showed that this new diagnostic and therapeutic concept in fact was of significance. Our group developed a modification of the intraoperative diagnostic procedure, which allowed detection of the sentinel node in the dissected neck. Our findings showed that SN lymphadenectomy could identify clinically occult metastatic spread of limited pharyngeal and laryngeal carcinomas.6,7,14,15,21,24 Serial sections of the SNs at intervals of 1 mm and immunohistochemical staining for keratin with the pancytokeratin antibody MNF 116 (Chemicon, Hofheim, Germany) revealed occult micrometastases (Fig. 2).



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  		FIG. 2. Immunohistochemical staining for keratin with the pancytokeratin antibody MNF 116 (Chemicon, Hofheim, Germany) to verify an occult micrometastasis.

 
In HNSCC, intraoperative injection of blue dye is used in some institutions on the basis of the fact that in less experienced hands a combination of radiotracer and blue dye may facilitate identification of SNs. Most clinical research groups use only radioactive tracers to label the SNs.6,7,11,14–16,18,20,21,24,26 The high sensitivity of the results achieved by this method do not justify additional use of the blue dye, especially because blue dye injections may lead to a variety of different complications.34 For example, accidental damage to the draining lymph collectors would lead to spilling of the dye, resulting in a significant reduction of the intraoperative view.35 This is especially important in the soft tissues of the head and neck, with their dense supply of vessels and nerves. Additionally, anaphylactic reactions after subcutaneous injections of blue dye have been reported to occur in about 2% of the examined patients.36,37 Whether the combination of 99mTc-radiotracers with methylene blue is advantageous for sentinel lymphadenectomy remains to be determined.38

Undoubtedly the validation of the SN concept and sentinel lymphadenectomy requires reliable detection of the SN.14,21 For applications in the head and neck region, this implies familiarity with the method-specific sources of error as well as a detailed knowledge of the basic mechanisms of lymphoscintigraphy. The final discussion concerning the technical feasibility and significance of the method mentioned above should be undertaken only after a critical analysis of the observed limitations.

Pitfalls and Technical Related Problems

Disperse radiation from the primary point of injection can make identification of the SN difficult. This problem may be solved if the primary tumor is resected 15 to 20 minutes after the injection; this interval allows a reduction of disperse radiation and thus improves the procedure.24

The distribution of the lymphatics as well as the direction of the lymphatic drainage may lead to errors in the detection of the first draining lymph nodes. The differences in the density of regional distribution patterns of initial lymphatics in the head and neck region, which have been studied in detail,38–41 have a direct influence on the identification of the SN or SNs. Due to the proximity of different lymphatic regions in the head and neck area, tracer inadvertently may be injected into a neighboring basin. An intraoperative injection technique improves the detection of the SN significantly because of excellent exposure of the primary tumor. In addition, there are no problems with noncompliance (e.g., gagging, motility of the tongue).6,7,14,21

Another possible source of error is that laryngeal or pharyngeal tumors, which extend to very posterior or caudal areas of the upper aerodigestive mucous membranes, may be difficult to expose. In these cases it may be helpful to inject the tracer with a so-called butterfly cannula (e.g., Venofix, 23G, 0.65 x 20 mm; Braun, Melsungen, Germany),24 which allows greater flexibility than a straight cannula. Another reason for inaccurate or incomplete identification of the SN is drainage from a primary tumor to two or even more neighboring lymphatic regions and thus more SNs.14,15 Up to three nodes that show the greatest tracer accumulation should be classified as SNs, resected and examined histologically in order to minimize false-negative results.7,14,21

Advanced intranodal tumor growth with or without extracapsular growth can prevent accurate identification of the SN. Due to this observation, sentinel lymphadenectomy cannot be recommended without reservation in cases of clinically verified ipsilateral lymphogenic metastatic spread.5,15 Possibly this procedure may gain more in importance in cases of contralateral clinical N0-stage necks.7,21,24 However, even small, clinically unsuspicious lymph nodes may show extracapsular spread with misleading radiopharmaceutical absorption.42,43

Finally, prior surgical or radiological treatments may alter the lymphatic system so that drainage of the tracer substance cannot be identified or does not reflect the initial direction of drainage.44 Prior treatments of the neck may also cause drainage to the contralateral side.41 In cases of prior treatments, sentinel lymphadenectomy can thus be recommended only with reservations.

CONCLUSION

Sentinel lymphadenectomy requires a thorough and critical analysis prior to application of this method to oncologic problems in the head and neck region. Although examination descriptions published by different groups6–33 do not allow a final judgment on the significance of the sentinel lymphadenectomy in HNSCC, early results for easily accessible carcinomas of the anterior oral cavity12,13,16,17 confirm the importance of this new diagnostic concept. Indications for SN lymphadenectomy may also be extended to pharyngeal and laryngeal T1 to T2 carcinomas and even T3 glottic carcinomas,24 provided that these tumors can be exposed under general anesthesia.

Future examinations will show whether intraoperative identification of the SNs can reduce the extent of selective neck dissection in the suspected N0 neck. Eventually neck dissection may even be abandoned, if the SN proves to be disease-free on histologic examination. The benefit for patients would be a significant reduction of scar formation, contractures, sensory disturbances, and sometimes persistent lymphedema. For HNSCC, sentinel lymphadenectomy should therefore be studied more intensively to reduce overtreatment in N0 necks.

FOOTNOTES

Critical and careful evaluation of the sentinel node concept is mandatory prior to its application to other tumor entities. Sentinel lymphadenectomy for head and neck cancer may prove helpful if the indications for its use are clearly defined.

Received for publication October 31, 2003. Accepted for publication December 2, 2003.

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