1. The Use Of Sentinel Lymph Node Biopsy In MElanoma
Kitty Lo
Queen Elizabeth Hospital

2. 50/M
Presented with a 2 x 1.5 cm irregular pigmented skin lesion over the left side of the trunk

3. Total body skin examination reveals no other suspicious lesions
Palpation of all lymph node basins show no clinically detectable lymphadenopathy

4. Excisional biopsy Malignant melanoma Superficial spreading melanoma
Breslow thickness 1.5mm
Mitotic rate 1/mm2
Ulceration +
Closest margin 1mm

5. Breslow thickness
Depth (in mm) from the granular layer of the epidermis to the deepest part of tumour
T staging in AJCC Melanoma Staging (2010)

6. Breslow Thickness
With increasing tumour thickness, there is a significant decline in the 5 year and 10 year survival rates1
1- Balch CM, Gershenwald JE, Soong SJ, et al: Final Version of 2009 AJCC Melonoma Staging and Classification. J Clin Oncol 2009, 27:

7. Mitotic Rate Powerful predictor of survival, after tumour thickness
>=1/mm2 associated with decreased survival1-4
1- Balch CM, Gershenwald JE, Soong SJ, et al: Final Version of 2009 AJCC Melonoma Staging and Classification. J Clin Oncol 2009, 27:
2- Gimotty PA, Elder DE, Fraker DL, et al: Identification of high risk patients among those diagnosed with thin cutaneous melanomas. J Clin Oncol 2007, 25:
3- Kesmodel SB, Karakousis GC, Botbyl JD, et al: Mitotic rate as a predictor of sentinel lymp node positivity in patients with thin melanomas. Ann Surg Oncol 2005, 12:
4- Fracken AB, Shaw HM, Thompson JF, et al: The prognostic importance of tumor mitotic rate confirmed in 1317 patients with primary cutaneous melanoma and long follo-up. Ann Surg Oncol 2004, 11:

8. Ulceration
Tumour ulceration is significantly associated with decrease in survival 1-3
1- Balch CM, Gershenwald JE, Soong SJ, et al: Final Version of 2009 AJCC Melonoma Staging and Classification. J Clin Oncol 2009, 27:
2- I Koshivuo, Hernberg M, Vihinen P, et al: Sentinel lymph node biopsy and survival in elderly patients with cutaneous melanoma. British Journal of Surgery :
3- Jones EL, Jones TS, Pearlman NW, et al: Long term follow up and survival following a recurrence of melanoma after a negative sentinel lymph node biopsy result. JAMA Surg May; 148(5)

9. Margins

10. USG of left groin and axilla: Clinically cT2N0
No radiologically suspicious lymph nodes
Clinically cT2N0
Proceeded to wide local excision + sentinel lymph node biopsy (SLNB)

11. What is Sentinel LympH Node Biopsy?

12. Sentinel LympH Node Biopsy In Melanoma
The initial route of metastasis in most patients with melanoma is to regional lymph nodes
Historically, clinically LN –ve patients either received elective LN dissection prophylactically, or were observed till clinically LN metastasis was evident and received therapeutic LN dissection
LN dissection associated with significant morbidity

13. Sentinel LympH Node Biopsy
Identify the first lymph node(s) receiving lymphatic drainage from the tumour
SLN no malignancy
unlikely that the tumour involves other nodes in the same LN basin -> no need for LN dissection
SLN +ve for malignancy
possible that the disease has spread into other LN in the same basin -> proceed to LN dissection

14. SLNB –How it’s done
Radioactive tracer (99m Tc labelled colloid) injected around the primary tumour/ excisional biopsy scar subdermally 1 day before or same day of surgery
Lymphoscintigraphy performed to visualize the lymphatic drainage pathways and SLN
If combined with SPECT/ CT, a higher overall SLN detection rate (particularly useful in head & neck melanoma) 1-2
1- Ingo S, Christian B, Thorsten P, etc. Association between sentinel lymph node excision with or without preoperative SPECT/CT and metastatic node detection and disease free survival in melanoma. JAMA 2012; 308 (10) :
2- Bluemel C, Herrmann K, Giammarile F, et al. EANM practice guidelines for lymphoscintigraphy and sentinel lymph node biopsy in melanoma. Eur J Nucl Med Mol Imaging 2015; 42:

15. SLNB – How it’s Done Intraoperatively guided by hand held gamma probe
The most radioactive (hottest) LN removed
Any LN with >=10% of the hottest LN’s radioactive count (measured ex-vivo) are removed
Bluemel C, Herrmann K, Giammarile F, et al. EANM practice guidelines for lymphoscintigraphy and sentinel lymph node biopsy in melanoma. Eur J Nucl Med Mol Imaging 2015; 42:

16. SLNB – How It’s Done
Some surgeons will also inject patent blue/ isosulphan blue intradermally around the tumour/ biopsy site at the beginning of the operation
Dissect the blue draining vessels until it drains into a blue SLN
Bluemel C, Herrmann K, Giammarile F, et al. EANM practice guidelines for lymphoscintigraphy and sentinel lymph node biopsy in melanoma. Eur J Nucl Med Mol Imaging 2015; 42:

17. SLNB – How It’s Done
Any palpable LN (even if non-hot & non-blue) should also be removed
13% SLN are only radioactive (hot), 1% only blue, 86% both hot and blue 1
1- Estourgie SH, Nieweg OE, Valdes Olmos RA, et al. Review and evaluation of sentinel lymph node procedures in 250 melanoma patients with a median follow up of 6 years. Ann Surg Oncol 1998; 5:

18. How IT All STarted
Published in the Archives of Surgery, 1992

19. 223 patients with localized, clinically node –ve melanoma
All patients had WLE + SLNB + immediate lymph node dissection
82% SLN identification rate
SLN +ve in 18%
False omission rate 1%
-see if SLNB was feasible, and whether the SLN status could accurately predict the presence of occult metastasis in the regional LN

20. SLNB can identify with a high degree of accuracy patients with subclinical LN metastases who are likely to benefit from LN dissection

21. Multicentre Selective Lymphadenectomy Trial -1
Final trial report published 2014

22. Multicentre Selective Lymphadenectomy Trial -1
18 centres in Europe, Australia and US
2001 patients with primary cutaneous melanoma ( )
Randomized in a 4:6 ratio to
WLE + observation, with LND for clinically evident nodal relapse
vs WLE + SLNB, with completion LND for +ve SLNB
Stratified by Breslow thickness
Intermediate mm
Thick >3.5mm
Followed up for 10 years
Phase 3 RCT
Main focus was on intermediate thickness group as prelim studies show that SLNB was most likely to benefit those with intermediate thickness
Few patients with thin melanoma so this subgroup was not analyzed
Included patients with breslow thickness >=1mm + clark level III, or clark level IV/ V with any thickness

23. SLN status was the strongest predictor of disease recurrence or death from melanoma

24. Overall 10 year Melanoma Specific Survival
No significant difference between treatment groups for both intermediate and thick melanomas

25. Overall 10 year Disease Free Survival
Significantly higher in the biopsy group for both Intermediate and Thick melanoma

26. Looking at the subgroup with nodal metastasis
SLN +ve with immediate completion LND
versus observation till clinically evident LN metastasis then therapeutic LND
SLNB significantly prolongs melanoma specific survival & distant disease free survival in intermediate thickness melanoma
Similar benefit was not seen for thick melanomas
Still significant effect even after including patients with false –ve SLNB with subsequent LN recurrence into the biopsy group

27. Conclusion SLNB provides important prognostic information
For all patients, biopsy based management prolongs disease free survival
For patients with nodal metastasis from intermediate thickness melanomas, SLNB also prolongs melanoma specific survival and distant disease free survival

28. SLN status incorporated into n staging
Latest AJCC guidelines in 2010
Prognostic significance of SLN validated by many studies

29. Management pathway of Melanoma
Pathology Report:
Breslow thickness
Ulceration status
Mitotic rate
Deep and peripheral margin status
Presence of microsatellitosis
Clark level (for lesions <=1mm)
Excisional biopsy (1-3mm margins) preferred; or full thickness incisional biopsy at clinically thickest portion
Complete skin examination + Locoregional lymph node examination
Suspicious pigmented lesion
1- Wong SL, Balch CM, Hurley P, et al. Sentinel lymph node biopsy for melanoma: American Society of Clinical Oncology and Society of Surgical Oncology Joint Clinical Practice Guideline. J Clin Oncol. 2012;30:
2- NCCN Guidelines Version Melanoma

30. Management pathway of Melanoma
Breslow thickness <=0.75mm
Wide Local Excision
Breslow thickness mm,
no ulceration, mitotic rate 0/mm2
Wide local excision + Consider SLNB
Clinically node negative
SLN
-ve
Observe
SLN +ve
Completion LN dissection
Wide local excision + SLNB
Breslow thickness mm,
with ulceration, or mitotic rate >=1/mm2 OR
Breslow thickness >1mm
1- Wong SL, Balch CM, Hurley P, et al. Sentinel lymph node biopsy for melanoma: American Society of Clinical Oncology and Society of Surgical Oncology Joint Clinical Practice Guideline. J Clin Oncol. 2012;30:
2- NCCN Guidelines Version Melanoma

31. The Future?

32. Can LN dissection be avoided in most patients with +ve SLN?
Only 10-20% of patients with +ve SLN have tumour +ve non SLN identified in completion LN dissection 1
If nodal metastases are limited to one or two sentinel nodes, then SLNB might be therapeutic as well as diagnostic
Can LN dissection be avoided in most patients with +ve SLN?
(12% in MSLT-I trial)
1- Lee JH, Essner R, Torisu-Itakura H, et al. Factors predictive of tumour positive nonsentinel lymph nodes after tumour positive sentinel lymph node dissection for melanoma. J Clin Oncol. 2004; 22:

33. MSLT –II trial Opened in 2005 and ongoing Finished patient recruitment
Patients with +ve SLNB randomized to receive:
Completion LN dissection
Ultrasound observation of the LNs
Primary outcome is melanoma-specific survival
No data published yet
3992 patients
Secondary outcomes include overall survival and disease-free survival, prognostic accuracy of histopathology, molecular and immunologic markers, and quality of life.
Morton DL. Overview and Update of the Phase III Multicenter Selective Lymphadenectomy Trials (MSLT-I and MSLT-II) in Melanoma. Clin Exp Metastasis Oct; 29(7): 699–706.

34. Thank You
Questions are welcome

36. 5840 patients, non-randomized cohort
SLNB significantly improved disease free survival & regional recurrence free survival
Also improved distant metastasis free survival in melanomas >1mm -4mm
No significant difference in melanoma specific survival

37. Current guidelines
American Society of Clinical Oncology & Society of Surgical Oncology1:
Offer SLNB for melanoma >=1mm – 4mm
SLNB recommended for thick melanomas >4mm for staging and to facilitate regional disease control
SLNB recommended for thin melanomas ( mm) when 1 or more adverse prognostic features present (ulceration, mitotic rate >=1/mm2, Clark level IV/V)
1- Wong SL, Balch CM, Hurley P, et al. Sentinel lymph node biopsy for melanoma: American Society of Clinical Oncology and Society of Surgical Oncology Joint Clinical Practice Guideline. J Clin Oncol. 2012;30:

38. For those without nodal metastasis
SLN –ve
versus observation, with no development of clinically evident LN met
No difference in the 10 year melanoma specific survival
In patients with SLN –ve, SLNB provides critical prognostic information but no therapeutic benefit

39. MSLT -1 SLN identification rate 95.3% False omission rate 5.7%
No. of false –ve SLNB/ Total no. of –ve SLNB
Lower complication rate with SLNB vs LND
(10.1% vs 37.2% for local complications)
Local complications such as wound infection,. Separation, seroma/ haematoma
The study did not look into long term morbidity for SLNB vs LND
SN identification rate: 99.3% groin, 95.3% axilla, 84.5% neck
Long term follow up confirmed similar rates of nodal metastasis in the 2 groups, indicating that essentially all metastases detected by SLNB would eventually become clinically evident if not removed