The role of sentinel node biopsy in the management of MelTUMPs (melanocytomas)

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Background

Sentinel lymph node biopsy (SLNB) provides the most accurate staging for invasive melanoma and is therefore required for staging tumours greater than 1.0mm Breslow thickness according to the 8th edition of the AJCC system.[1] However, the role of SLNB in MelTUMPs has not been established and therefore a systematic review of the current evidence was undertaken.


Evidence

The systematic review found a total of 19 eligible studies: no randomised controlled trials, two prospective studies, 15 retrospective cohort studies, one case-control study and a systematic review.[2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21]

The duration of follow-up was quite short in most of the studies, with an overall mean of 40 months. Because there were no randomised controlled trials, the reliability of the results is uncertain.

A total of 316 patients underwent sentinel node biopsy, of which 112 were found to have positive nodes, a rate of 35%. However, despite the high rate of sentinel node positivity in the MelTUMP patients, there was only one MelTUMP-related death reported[12] amongst all of the 112 patients with a positive node, a mortality rate of less than 1%. The patient who died had a diagnosis of a borderline deep penetrating naevus. For comparison, the rate of sentinel node positivity in the MSLT-1 study was 16% and the corresponding 5-year mortality rate for this group was 47%.[22]

The quality of the MelTUMP studies included did not permit a formal meta-analysis of the results, however, it is clear that the prognostic significance of a positive sentinel lymph node biopsy is qualitatively very different between melanomas and MelTUMPs. Consequently, there is little prognostic utility in performing sentinel lymph node biopsy for MelTUMPs.


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Evidence summary and recommendations

Evidence summary Level References
Sentinel lymph node biopsy has a highly variable positivity rate in MelTUMPs, but a high mean rate of around 35%. However, positivity does not appear to correlate with melanoma recurrence or death. III-1, III-2, III-3 [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20]
Evidence-based recommendationQuestion mark transparent.png Grade
The routine use of sentinel lymph node biopsy for MelTUMPs is not recommended. In the event of a positive node, its significance should be reviewed by a multidisciplinary melanoma team with expertise in such diagnostic dilemmas.
C


Evidence summary Level References
Most lesions classified as MelTUMPs behave as benign lesions, particularly in young patients. III-2 [21]
Evidence-based recommendationQuestion mark transparent.png Grade
Age should not be used to determine the prognosis of a patient with MelTUMP.
C


Practice pointQuestion mark transparent.png

It is advisable to have pathologists with expertise in the examination of melanocytic lesions review the tumour slides to confirm or reject a suspected diagnosis of MelTUMP.


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Issues requiring more clinical research study

Longer term follow-up of patients with MelTUMPs, particularly those who have had a positive sentinel lymph node biopsy, would be useful to fully determine its clinical significance. Additional studies with molecular characterisation of lesions are necessary to determine whether there are distinct disease entities within the category of MelTUMP and how to distinguish them from bona fide naevi and melanomas.


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References

  1. Gershenwald JE, Scolyer RA, Hess KR et al.. Melanoma of the Skin. In: Amin MB, Edge SB, Greene FL, et al, eds.. AJCC Cancer Staging Manual. 8th ed. New York: Springer; 2017. p. 563-85.
  2. 2.0 2.1 Lohmann CM, Coit DG, Brady MS, Berwick M, Busam KJ. Sentinel lymph node biopsy in patients with diagnostically controversial spitzoid melanocytic tumors. Am J Surg Pathol 2002 Jan;26(1):47-55 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/11756768.
  3. 3.0 3.1 Su LD, Fullen DR, Sondak VK, Johnson TM, Lowe L. Sentinel lymph node biopsy for patients with problematic spitzoid melanocytic lesions: a report on 18 patients. Cancer 2003 Jan 15;97(2):499-507 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/12518375.
  4. 4.0 4.1 Zembowicz A, Carney JA, Mihm MC. Pigmented epithelioid melanocytoma: a low-grade melanocytic tumor with metastatic potential indistinguishable from animal-type melanoma and epithelioid blue nevus. Am J Surg Pathol 2004 Jan;28(1):31-40 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/14707861.
  5. 5.0 5.1 Roaten JB, Partrick DA, Pearlman N, Gonzalez RJ, Gonzalez R, McCarter MD. Sentinel lymph node biopsy for melanoma and other melanocytic tumors in adolescents. J Pediatr Surg 2005 Jan;40(1):232-5 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/15868590.
  6. 6.0 6.1 Gamblin TC, Edington H, Kirkwood JM, Rao UN. Sentinel lymph node biopsy for atypical melanocytic lesions with spitzoid features. Ann Surg Oncol 2006 Dec;13(12):1664-70 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/17024556.
  7. 7.0 7.1 Urso C, Borgognoni L, Saieva C, Ferrara G, Tinacci G, Begliomini B, et al. Sentinel lymph node biopsy in patients with "atypical Spitz tumors." A report on 12 cases. Hum Pathol 2006 Jul;37(7):816-23 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/16784980.
  8. 8.0 8.1 Murali R, Sharma RN, Thompson JF, Stretch JR, Lee CS, McCarthy SW, et al. Sentinel lymph node biopsy in histologically ambiguous melanocytic tumors with spitzoid features (so-called atypical spitzoid tumors). Ann Surg Oncol 2008 Jan;15(1):302-9 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/18000712.
  9. 9.0 9.1 Ludgate MW, Fullen DR, Lee J, Lowe L, Bradford C, Geiger J, et al. The atypical Spitz tumor of uncertain biologic potential: a series of 67 patients from a single institution. Cancer 2009 Feb 1;115(3):631-41 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/19123453.
  10. 10.0 10.1 Berk DR, LaBuz E, Dadras SS, Johnson DL, Swetter SM. Melanoma and melanocytic tumors of uncertain malignant potential in children, adolescents and young adults--the Stanford experience 1995-2008. Pediatr Dermatol 2010 May;27(3):244-54 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20403119.
  11. 11.0 11.1 Ghazi B, Carlson GW, Murray DR, Gow KW, Page A, Durham M, et al. Utility of lymph node assessment for atypical spitzoid melanocytic neoplasms. Ann Surg Oncol 2010 Sep;17(9):2471-5 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20224858.
  12. 12.0 12.1 12.2 Magro CM, Crowson AN, Mihm MC Jr, Gupta K, Walker MJ, Solomon G. The dermal-based borderline melanocytic tumor: a categorical approach. J Am Acad Dermatol 2010 Mar;62(3):469-79 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20159313.
  13. 13.0 13.1 Barnhill RL, Kutzner H, Schmidt B, Ali L, Bagot M, Janin A, et al. Atypical spitzoid melanocytic neoplasms with angiotropism: a potential mechanism of locoregional involvement. Am J Dermatopathol 2011 May;33(3):236-43 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21389834.
  14. 14.0 14.1 Sepehr A, Chao E, Trefrey B, Blackford A, Duncan LM, Flotte TJ, et al. Long-term outcome of Spitz-type melanocytic tumors. Arch Dermatol 2011 Oct;147(10):1173-9 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21680758.
  15. 15.0 15.1 Caracò C, Mozzillo N, Di Monta G, Botti G, Anniciello AM, Marone U, et al. Sentinel lymph node biopsy in atypical Spitz nevi: is it useful? Eur J Surg Oncol 2012 Oct;38(10):932-5 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/22704051.
  16. 16.0 16.1 Hung T, Piris A, Lobo A, Mihm MC Jr, Sober AJ, Tsao H, et al. Sentinel lymph node metastasis is not predictive of poor outcome in patients with problematic spitzoid melanocytic tumors. Hum Pathol 2013 Jan;44(1):87-94 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/22939951.
  17. 17.0 17.1 Shen L, Cooper C, Bajaj S, Liu P, Pestova E, Guitart J, et al. Atypical spitz tumors with 6q23 deletions: a clinical, histological, and molecular study. Am J Dermatopathol 2013 Dec;35(8):804-12 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/23455333.
  18. 18.0 18.1 Busam KJ, Kutzner H, Cerroni L, Wiesner T. Clinical and pathologic findings of Spitz nevi and atypical Spitz tumors with ALK fusions. Am J Surg Pathol 2014 Jul;38(7):925-33 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/24698967.
  19. 19.0 19.1 Lallas A, Kyrgidis A, Ferrara G, Kittler H, Apalla Z, Castagnetti F, et al. Atypical Spitz tumours and sentinel lymph node biopsy: a systematic review. Lancet Oncol 2014 Apr;15(4):e178-83 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/24694641.
  20. 20.0 20.1 Magro CM, Abraham RM, Guo R, Li S, Wang X, Proper S, et al. Deep penetrating nevus-like borderline tumors: A unique subset of ambiguous melanocytic tumors with malignant potential and normal cytogenetics. Eur J Dermatol 2014 Sep;24(5):594-602 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/25118781.
  21. 21.0 21.1 Cerroni L, Barnhill R, Elder D, Gottlieb G, Heenan P, Kutzner H, et al. Melanocytic tumors of uncertain malignant potential: results of a tutorial held at the XXIX Symposium of the International Society of Dermatopathology in Graz, October 2008. Am J Surg Pathol 2010 Mar;34(3):314-26 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20118771.
  22. Morton DL, Thompson JF, Cochran AJ, Mozzillo N, Elashoff R, et al. Sentinel-node biopsy or nodal observation in melanoma. N Engl J Med 2006 Sep 28;355(13):1307-17 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/17005948.


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Appendices