Melanoma Molecular Maps Projects

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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].



Open issues

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.



References

[1] Morton DL et al. Technical details of intraoperative lymphatic mapping for early stage melanoma. Arch Surg 1992, 127:392-9

[2] Essner R, Sentinel lymph node biopsy and melanoma biology. Clin Cancer Res 2006, 12:2320s-2325s

[3] Thompson JF et al, Lymphatic mapping in management of patients with primary cutaneous melanoma. Lancet Oncol 2005, 6:877-85

[4] Thompson JF et al, Cutaneous melanoma. Lancet 2005, 365:687-701

[5] Tsao H et al, Management of cutaneous melanoma. N Engl J Med 2004, 351:998-1012

[6] Goyal A et al, Recent advances in sentinel lymph node biopsy for breast cancer. Curr Opin Oncol 2008, 20:621-6

[7] Chen SL et al, Lymphatic mapping and sentinel node analysis: current concepts and applications. CA Cancer J Clin 2006, 56:292-309

[8] Sondak VK et al, Mitotic rate and younger age are predictors of sentinel lymph node positivity: lessons learned from the generation of a probabilistic model. Ann Surg Oncol 2004, 11:247-58

[9] Scoggins CR et al, Prospective multi-institutional study of reverse transcriptase polymerase chain reaction for molecular staging of melanoma. J Clin Oncol 2006, 24:2849-57

[10] Takeuchi H et al, Prognostic significance of molecular upstaging of paraffin-embedded sentinel lymph nodes in melanoma patients. J Clin Oncol 2004, 22:2671-80

[11] Mocellin S et al, Sentinel lymph node molecular ultrastaging in patients with melanoma: a systematic review and meta-analysis of prognosis. J Clin Oncol 2007, 25:1588-95

[12]Thomas JM et al, Selective lymphadenectomy in sentinel node-positive patients may increase the risk of local/in-transit recurrence in malignant melanoma. Eur J Surg Oncol 2004, 30:686-91

[13] Kang JC et al, Sentinel lymphadenectomy does not increase the incidence of in-transit metastases in primary melanoma. J Clin Oncol 2005, 23:4764-70

[14] Morton DL et al, Sentinel-node biopsy or nodal observation in melanoma. N Engl J Med 2006, 355: 1307-17


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