Sentinel lymph node

The concept of sentinel lymph node (SLN) - the first lymph node(s) draining a given body area - has been introduced in the early 90's from the experience with melanoma patients [1]. The possibility of an early detection of clinically occult node metastasis galvanized surgeons around the world, and currently the sentinel node biopsy (SNB) is widely performed in patients with melanoma [2-5] and breast carcinoma [6], its use being investigated also in other types of cancer [7].

SLN are identified by preoperative lymphoscintigraphy and intraoperative tracing using a vital dye and a hand held gamma-detection probe. The radiotracer (e.g. Tc99 labeled colloid albumin) and the vital dye (e.g. Patent's blue) are injected intradermally around the scar of the previous excisional biopsy of the primary melanoma.

Metastatic deposits are detected in the sentinel nodes in about 16-20% of patients affected with cutaneous melanoma thicker than 1 mm. On one hand, this underlines the ability of this semi-invasive and relatively easy surgical technique to early detect clinically occult metastatic lymph nodes. On the other hand, using the most widely accepted inclusion criterion (tumor thickness >/= 1 mm), about 80% of patients do not harbor metastatic disease in their SLN.

Although several predictors of SLN status have been proposed, no consensus exists on their reliability on a single patient basis [2, 8].

If metastatic disease is found in the SLN at histopathological examination, a formal radical lymph node dissection (RLND) is currently recommended (also called completion lymph node dissection, CLND), as additional metastatic lymph nodes are found in about 20% of cases [4, 5].

Patients with histologically positive SLN have a significantly poorer prognosis as compared to those with negative SLN. At present, the SLN status represents one of the most important prognostic factors in patients with melanoma and clinically negative regional lymph nodes. By contrast, the prognostic significance of molecularly positive SLN (as assessed by polymerase chain reaction, PCR) is not universally accepted [9, 10], although in a recent meta-analysis the SLN positivity at PCR does correlate with worse prognosis of patients [11].

Other active fields of debate and investigation are the significant rate (~ 15-20%) of false negative results (percentage of patients with histologically negative SLN who develop regional lymph node metastasis during the follow-up), and the controversial hypothesis of an increased risk of in-transit metastasis associated with the SNB procedure [12, 13].

Randomized controlled trials (RCT) are testing whether the early detection of lymph node metastasis affects patients' survival, i.e. whether SNB has a therapeutic effect. At the time of writing (June 2008), no level A evidence exists on the therapeutic impact of SNB (at least with current eligibility criteria), as the results of the only available RCT showed no significantly different survival rates between the two study arms (although - at subgroup analysis - among patients with nodal metastases the 5-year survival rate was higher for those undergoing immediate as compared to delayed lymphadenectomy) [14].

The ongoing trials also address the issue of the clinical significance of lymph nodes evaluated by RT-PCR, the value of completion lymph node dissection for patients with tumor-positive sentinel lymph nodes, and the benefits of adjuvant interferon-alpha in patients with clinically occult SLN metastasis.