What is the role of sentinel lymph node biopsy in patients with BSTT?

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Lymph node involvement in sarcoma

Lymph node involvement in sarcoma is generally uncommon (1%)[1], though it does occur with increased frequency in certain pathological subtypes. This is particularly true for rhabdomyosarcoma, a tumour that is more common in the paediatric and younger adult population, and several other tumour types, more common in adult patients, as shown in the table below.

Pathological type Lymph node involvement References
Rhabdomyosarcoma 6-32% [2][3][1][4][5]
Epithelioid sarcoma 13-32% [2][3][1][4]
Clear cell sarcoma 11-28% [2][1][4]
Angiosarcoma 8-24% [2][3][1][4]
Leiomyosarcoma 4-8% [5][1][4]
Synovial sarcoma 1-6% [2][1][4]
Osteosarcoma 3% [6]

Other tumour characteristics that increase the likelihood of lymph node involvement include grade of tumour (high grade more likely) and increased tumour size (>5cm more likely).[1][4] Both of these have much smaller effect than the pathological subtype.[1]

Involvement of the lymph nodes significantly reduces prognosis in sarcoma patients. Johannesmeyer et al. report a five-fold increase in mortality in soft tissue sarcoma when lymph nodes are involved[1], and this is mirrored in osteosarcoma[6]. Protocols recommended by the Childrens Oncology Group for the management of rhabdomyosarcoma, and epithelioid sarcoma and clear cell sarcoma[3] in children recommend staging of the regional lymph nodes to direct optimal management. Studies in breast malignancy show that sentinel node biopsy is more sensitive in detecting metastatic disease than unguided lymph node sampling.[7] In these groups, sentinel node biopsy should be considered as the method for lymph node assessment.

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Lymph node assessment in sarcoma

Pathologically enlarged lymph nodes can be identified clinically and on standard radiology (CT), and subsequently can be investigated by biopsy and pathological examination. Standard biopsy is through open surgical biopsy or core biopsy of the enlarged lymph node. Fine needle aspirate of an enlarged lymph node is rarely used in sarcoma management. Fine needle aspiration cytology may be acceptable when the pathology team also has access to the primary specimen for comparison.[8]

When lymph nodes are not pathologically enlarged, clinical and radiological assessment are insufficient to completely assess nodal status in sarcoma. Neville reported that 17% of regional nodal basins that were assessed as uninvolved clinically actually harboured micrometastases.[9] CT and PET are important staging tools for systemic disease, but are also not sensitive enough to detect lymph node micrometastases.[10]

Sentinel lymph node biopsy (SLNB) is a tool used commonly in breast carcinoma and melanoma to target the most likely node within a lymph node basin to be affected by micrometastatic disease. A combination of radio-isotope labelled dye and coloured dye techniques are used to identify the sentinel node and this is assessed histo pathologically. Multiple studies confirm the safety and efficacy of this tool in identifying micrometastatic disease in lymph nodes for sarcoma patients with increased risk of lymph node metastases. [10][11][12][13][14][15][16][17][18][19] Sentinel node biopsy can also identify the relevant nodal basin in areas where drainage patterns can be variable, such as the torso.

The use of SLNB in sarcoma was felt to impact on treatment decision making[14][20], and provide important prognostic information[20].

The table below shows the rate of identification of lymph node involvement:

Paediatric

Tumour type Age group Positive/total SLNB (%) References
RMS
Non-RMS
Paediatric 2/5 (40%)
0/3 (0%)
[10]
RMS
Non-RMS
Paediatric 2/10 (20%)
1/18 (6%)
[12]
RMS
Non-RMS
Paediatric 1/3 (33%)
0/7 (0%)
[13]
RMS
Non-RMS
Paediatric 1/9 (11%)
0/17 (0%)
[14]
RMS
Non-RMS
Paediatric 1/3 (33%)
0/2 (0%)
[16]
RMS
Non-RMS
Paediatric 1/6 (17%)
0/17 (0%)
[17]
Summary
RMS
Non-RMS
Paediatric 8/36 (22%)
1/64 (2%)
[10][12][13][14][16][17]

RMS = Rhabdomyosarcoma

Adult and mixed ages

Tumour type Age group Positive/total SLNB (%) References
Synovial sarcoma
Clear cell sarcoma
Epithelioid sarcoma
Rhabdomyosarcoma
Mixed 2/42 (5%)
6/12 (50%)
0/4 (0%)
0/4 (0%)
[11]
Synovial sarcoma
Clear cell sarcoma
Epithelioid sarcoma
Mixed 2/16 (13%)
0/3 (0%)
1/10 (10%)
[15]
Synovial sarcoma Adult 1/11 (9%) [18]
Clear cell sarcoma Adult 2/5 (40%) [19]
Summary
Synovial sarcoma
Clear cell sarcoma
Epithelioid sarcoma
Rhabdomyosarcoma
Mixed 5/69 (7%)
8/20 (40%)
1/14 (7%)
0/4 (0%)
[11][15][18][19]

SLNB is accepted as a reasonable tool to assist prognosis in melanoma when the rate of positive results is 10% or greater. Applying this general recommendation, the use of SLNB in sarcoma should be considered in rhabdomyosarcoma. This could also be considered in other subtypes with higher rates of lymph node metastasis.

Technical aspects of the SLNB were generally very similar, though there was slight variation in dye injection site. Some studies placed the dye in the soft tissues adjacent the tumour (peritumour)[10][11][16][18], and some studies placed the dye intradermally over the tumour[12][13][14][15][17][19]. The latter approach is accepted in breast carcinoma where the involved organ is subcutaneous, but many sarcomas arise in deeper tissues (e.g. muscle) where different lymph drainage patterns may occur. Both approaches identified positive sentinel nodes and had episodes of nodal involvement after negative sentinel node biopsy. One group adopted an approach to only use the radio-isotope labelled dye (and no coloured dye) with good results, and removal of the recognised risk of anaphylaxis to the commonly used coloured dyes, but had insufficient patients to show a definite benefit.[14]

Several papers described lymph node involvement developing in regional nodes after previously negative SLNB in sarcoma[15][18] A study reviewing sentinel lymph node biopsies in sarcoma, suggested that 7 of 100 cases developed lymph node metastases after negative SLNB.[20] On further review of the original studies[14], and correction of a calculation error by Wright[20], this is actually 5 of 100 or 5%.

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Evidence summary and recommendations

Evidence summary Level References
Sentinel lymph node metastases are identified in 22% of paediatric patients with rhabdomyosarcoma. Sentinel lymph node biopsy in rhabdomyosarcoma can assist management and guide prognosis. IV [10], [12], [13], [14], [15], [16], [17]
Sentinel lymph node metastases are identified in 40% of clear cell sarcoma patients, and 7% of synovial sarcoma and epithelioid sarcoma patients. IV [11], [15], [18], [19]
Sentinel lymph node biopsy is a more accurate technique to stage regional lymph nodes when indicated. IV [7]
Evidence-based recommendationQuestion mark transparent.png Grade
Sentinel lymph node biopsy should be considered as a lymph node staging tool in the management of sarcoma patients with high likelihood of lymph node involvement, particularly rhabdomyosarcoma.
D


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Future questions

  1. Does sentinel lymph node biopsy improve staging in sarcoma, particularly in relevant tumour types (e.g. rhabdomyosarcoma, epithelioid sarcoma, clear cell sarcoma, angiosarcoma)?
  2. In sentinel lymph node biopsy for sarcoma, what is the preferred technique (intradermal/peritumour placement, use of just radio-labelled or both radio-labelled and coloured dyes)?
  3. In sentinel lymph node biopsy for sarcoma, what is the preferred technique of histological assessment of biopsy material?

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References

  1. 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 1.9 Johannesmeyer D, Smith V, Cole DJ, Esnaola NF, Camp ER. The impact of lymph node disease in extremity soft-tissue sarcomas: a population-based analysis. Am J Surg 2013 Sep;206(3):289-95 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/23806824.
  2. 2.0 2.1 2.2 2.3 2.4 Daigeler A, Kuhnen C, Moritz R, Stricker I, Goertz O, Tilkorn D, et al. Lymph node metastases in soft tissue sarcomas: a single center analysis of 1,597 patients. Langenbecks Arch Surg 2009 Mar;394(2):321-9 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/18594854.
  3. 3.0 3.1 3.2 3.3 Fong Y, Coit DG, Woodruff JM, Brennan MF. Lymph node metastasis from soft tissue sarcoma in adults. Analysis of data from a prospective database of 1772 sarcoma patients. Ann Surg 1993 Jan;217(1):72-7 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/8424704.
  4. 4.0 4.1 4.2 4.3 4.4 4.5 4.6 Sherman KL, Kinnier CV, Farina DA, Wayne JD, Laskin WB, Agulnik M, et al. Examination of national lymph node evaluation practices for adult extremity soft tissue sarcoma. J Surg Oncol 2014 Nov;110(6):682-8 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/24910401.
  5. 5.0 5.1 Lamyman MJ, Giele HP, Critchley P, Whitwell D, Gibbons M, Athanasou NA. Local recurrence and assessment of sentinel lymph node biopsy in deep soft tissue leiomyosarcoma of the extremities. Clin Sarcoma Res 2011 Aug 1;1(1):7 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/22612847.
  6. 6.0 6.1 Thampi S, Matthay KK, Goldsby R, DuBois SG. Adverse impact of regional lymph node involvement in osteosarcoma. Eur J Cancer 2013 Nov;49(16):3471-6 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/23867123.
  7. 7.0 7.1 Macaskill EJ, Dewar S, Purdie CA, Brauer K, Baker L, Brown DC. Sentinel node biopsy in breast cancer has a greater node positivity rate than axillary node sample: results from a retrospective analysis. Eur J Surg Oncol 2012 Aug;38(8):662-9 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/22592099.
  8. Khirwadkar N, Dey P, Das A, Gupta SK. Fine-needle aspiration biopsy of metastatic soft-tissue sarcomas to lymph nodes. Diagn Cytopathol 2001 Apr;24(4):229-32 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/11285616.
  9. Neville HL, Andrassy RJ, Lobe TE, Bagwell CE, Anderson JR, Womer RB, et al. Preoperative staging, prognostic factors, and outcome for extremity rhabdomyosarcoma: a preliminary report from the Intergroup Rhabdomyosarcoma Study IV (1991-1997). J Pediatr Surg 2000 Feb;35(2):317-21 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/10693687.
  10. 10.0 10.1 10.2 10.3 10.4 10.5 Alcorn KM, Deans KJ, Congeni A, Sulkowski JP, Bagatell R, Mattei P, et al. Sentinel lymph node biopsy in pediatric soft tissue sarcoma patients: utility and concordance with imaging. J Pediatr Surg 2013 Sep;48(9):1903-6 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/24074665.
  11. 11.0 11.1 11.2 11.3 11.4 Andreou D, Boldt H, Werner M, Hamann C, Pink D, Tunn PU. Sentinel node biopsy in soft tissue sarcoma subtypes with a high propensity for regional lymphatic spread--results of a large prospective trial. Ann Oncol 2013 May;24(5):1400-5 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/23372051.
  12. 12.0 12.1 12.2 12.3 12.4 Dall'Igna P, De Corti F, Alaggio R, Cecchetto G. Sentinel Node Biopsy in Pediatric Patients: The Experience in a Single Institution. Eur J Pediatr Surg 2014 Dec 5 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/25478665.
  13. 13.0 13.1 13.2 13.3 13.4 Gow KW, Rapkin LB, Olson TA, Durham MM, Wyly B, Shehata BM. Sentinel lymph node biopsy in the pediatric population. J Pediatr Surg 2008 Dec;43(12):2193-8 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/19040933.
  14. 14.0 14.1 14.2 14.3 14.4 14.5 14.6 14.7 Kayton ML, Delgado R, Busam K, Cody HS 3rd, Athanasian EA, Coit D, et al. Experience with 31 sentinel lymph node biopsies for sarcomas and carcinomas in pediatric patients. Cancer 2008 May 1;112(9):2052-9 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/18338809.
  15. 15.0 15.1 15.2 15.3 15.4 15.5 15.6 Maduekwe UN, Hornicek FJ, Springfield DS, Raskin KA, Harmon DC, Choy E, et al. Role of sentinel lymph node biopsy in the staging of synovial, epithelioid, and clear cell sarcomas. Ann Surg Oncol 2009 May;16(5):1356-63 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/19259743.
  16. 16.0 16.1 16.2 16.3 16.4 Neville HL, Andrassy RJ, Lally KP, Corpron C, Ross MI. Lymphatic mapping with sentinel node biopsy in pediatric patients. J Pediatr Surg 2000 Jun;35(6):961-4 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/10873044.
  17. 17.0 17.1 17.2 17.3 17.4 Parida L, Morrisson GT, Shammas A, Hossain AK, McCarville MB, Gerstle JT, et al. Role of lymphoscintigraphy and sentinel lymph node biopsy in the management of pediatric melanoma and sarcoma. Pediatr Surg Int 2012 Jun;28(6):571-8 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/22526545.
  18. 18.0 18.1 18.2 18.3 18.4 18.5 Tunn PU, Andreou D, Illing H, Fleige B, Dresel S, Schlag PM. Sentinel node biopsy in synovial sarcoma. Eur J Surg Oncol 2008 Jun;34(6):704-7 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/17870276.
  19. 19.0 19.1 19.2 19.3 19.4 van Akkooi AC, Verhoef C, van Geel AN, Kliffen M, Eggermont AM, de Wilt JH. Sentinel node biopsy for clear cell sarcoma. Eur J Surg Oncol 2006 Nov;32(9):996-9 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/16672185.
  20. 20.0 20.1 20.2 20.3 Wright S, Armeson K, Hill EG, Streck C, Leddy L, Cole D, et al. The role of sentinel lymph node biopsy in select sarcoma patients: a meta-analysis. Am J Surg 2012 Oct;204(4):428-33 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/22578407.

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Appendices


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