Delhi Journal of Ophthalmology

Sentinel Lymph Node Biopsy: Guarding the Guardian

Mrittika Sen, Santosh G Honavar

Dept of Ophthalmic Plastic Surgery and Ocular Oncology Centre for Sight, Road No 2, Banjara Hills, Hyderabad 500034

Corresponding Author:

Santosh G Honavar (MD, FACS)
Dept of Ophthalmic Plastic Surgery and Ocular Oncology Centre for Sight, Road No 2, Banjara Hills, Hyderabad 500034 
E-mail: santosh.honavar@gmail.com

Published Online: 21-JUN-2020

DOI:http://dx.doi.org/10.7869/djo.536

Abstract

Keywords :

Sentinel, the dictionary defines the word as a soldier or guard whose job is to stand and keep watch. The sentinel lymph node, literally, then becomes the node keeping a lookout for the spread of disease and is the first to be attacked when metastasis starts. While it lights the beacons, it is up to us to pick up the signals and prepare for the battle.
A malignant tumour tends to metastasize preferentially to its regional lymph nodes before hematological dissemination and distant metastasis. Sentinel node is the first of the draining lymph nodes. Lymph node involvement from a malignancy can be identified clinically by palpation or by radiological investigations. The role of sentinel lymph node biopsy (SLNB) comes into play for identifying micrometastasis or subclinical metastasis in tumours with risk factors for lymphatic spread. If the sentinel node is negative, it is safe to conclude that the tumour is confined locally…or so it was thought.
SLN biopsy was introduced in 1960 by Gould for malignant lesions of parotid, but it was nearly 40 years before its role was established in the standard management of neoplasia especially breast cancer and cutaneous melanoma.1 The technique was proposed by Morton et al for intraoperative lymphatic mapping of cutaneous melanoma.2 Prior to this, radical and extensive nodal dissection was done for tumours with high risk of lymphatic spread with significant morbidity. SLN biopsy is a selective, minimally invasive method that allows identification of patients who would definitely benefit from extensive lymphadenectomy and adjuvant radiotherapy, while sparing the others from unnecessary additional trauma.
For periocular and conjunctival tumours, most of our knowledge about SLN biopsy comes from the extensive study done by Esmaeli et al at MD Anderson Cancer Centre.3 Eyelid tumours, apart from locally invasive basal cell carcinoma, have a tendency for lymphatic spread to the regional lymph nodes i.e. the preauricular, parotid, the submandibular and deep cervical nodes. The lymphatic drainage of the ocular adnexa is anatomically well defined but recent studies have shown that the pattern of lymphatic drainage may, in fact, be quite unpredictable and ambiguous, with medially located tumours also draining into the preauricular and parotid nodes.4-6 Thus, localization of the actual drainage basin is important before blind empirical dissection.
A preoperative lymphoscintigraphy is performed to outline the expected draining area and plan the site of biopsy using technetium labelled sulfur colloid (0.3-0.4 mCi of filtered Tc-99m sulfur colloid in 0.2ml normal saline), injected in 3-4 perilesional spots- intradermal or subconjunctival, depending on the site of tumour. Serial scanning is done every 15 minutes till the first SLN is detected or single photon emission computed tomography (SPECT/CT) is performed. SLN biopsy is performed intraoperatively during the time of excision of the lesion or it can be performed at a later stage once the histopathological risk factors for lymphatic spread are also determined. Secondary SLNB is preferred for conjunctival melanoma as it allows the histologic measurement of tumour thickness and also reduces the risk of tumour seeding.6 The same radiolabeled tracer molecule described for lymphoscintigraphy is injected in the preoperative perilesional area. The tracer volume to be injected is much less for ocular adnexa as compared to other anatomical sites. A handheld gamma probe is then used after 1-1.5 hours, intraoperatively, to detect focal uptake. “Hot” nodes are the lymph nodes with radioactivity at least twice the level of background radioactivity. A small incision (1-3cm) made over each SLN, described by Nijhawan et al, is sufficient to excise the nodes.4 The LN basin around the hot nodes are scanned for any more high radioactive uptake till little or no activity is detected.7 Isosulphan or methylene blue dye and indocyanine green dye can also be used for SLN biopsy in places where nuclear medicine facilities are not available.8,9 Combining vital blue dye with Tc-99m does not have additional benefit over using Tc-99m alone.4,6,10
The LN specimen undergo bread-loafing and histopathological evaluation with routine hematoxyline and eosin stains. If they are found to be negative for malignancy, additional sections are reviewed with immunohistochemical and molecular studies. Reverse transcriptase PCR is also utilized in some cases to identify molecular markers. If SLN biopsy is positive, dissection of all the nodes in the drainage basin, including parotidectomy if the parotid basin is involved, is recommended. During dissection if additional nodes are found to be involved, adjuvant treatment like radiotherapy and systemic chemotherapy should be initiated.
Complications are mild and temporary and include facial nerve palsy, lymphedema and inadvertent intraocular injection of the tracer. Radiation toxicity is negligible.11 The main concern are the false negative results when patients with no evidence of micrometastases develop nodal involvement during follow up. Variable lymphatics of head and neck, obstruction to lymphatic drainage of tracer by tumour cells or bulky mass, incorrect injection site, surgical learning curve, error during histopathological evaluation and failure of tracer to identify SLN due to scarring from prior surgery or radiotherapy are some of the causes for this. It is important to counsel the patient preoperatively about the chances of false negative results and the need for close follow up, at least for the initial 5 years.10,11
Table 1 shows the rate of lymph node metastasis, indications for SLN biopsy, specific IHC and molecular markers, rates of SLNB positive and false negative results for common ocular adnexal malignancies. 
Low yield of positive results, increase in surgerical time by 60-90 minutes and false negative results question the potential benefit of SLNB. The Multicentre Selective Lymphadenectomy Trial-1 (MSLT-1) results proved the benefit of SLN biopsy based management with longer disease free survival, rather than observation for LN involvement in patients with cutaneous melanoma.12 MSLT-II concluded that in cases with SLN positive, immediate complete LN dissection improved regional disease control and reduced regional LN recurrence by nearly 70% but did not improve melanoma-specific survival.13 As our experience with SLN biopsy continues to grow, the false negative rates have reduced. It is minimally invasive with very few complications. SLN biopsy is useful for staging eyelid and conjunctival malignancies by the AJCC TNM classification, and thereby, determine prognosis, predict distant metastasis and early adjuvant treatment for patients objectively rather than empirically and reduce unjustified surgical morbidity.14,15 With the availability of immune checkpoint inhibitors and targeted molecular therapy for metastatic melanoma and squamous cell carcinoma, early detection of nodal disease becomes especially important for the initiation of treatment and improving the prognosis for survival. 
Given the safety, feasibility, microscopic involvement of LN in the absence of clinical evidence and survival benefits of early detection and treatment of micrometastasis for cutaneous melanoma, it may be wise to carry out SLN biopsy in specific ocular adnexal malignancies. Further multi-institutional studies are required to determine the importance of SLN status and overall survival for eyelid and conjunctival malignancies.

Table 1: Common ocular adnexal malignancies and their rates of lymph node involvement, indications and outcomes of sentinel lymph node biopsy


References
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S Mrittika, Honavar SGSentinel Lymph Node Biopsy: Guarding the Guardian.DJO [serial online] 2020[cited 2020 Jul 9];30:6-8. Available from: http://www.djo.org.in/articles/30/4/Sentinel-Lymph-Node-Biopsy-Guarding-the-Guardian.html