Skip to main content
SpringerLink
Log in
SpringerLink
Log in

Melanoma Prognosis and Staging

  • Living reference work entry
  • First Online:
Cutaneous Melanoma

  • 150 Accesses

Abstract

A standardized, uniformly accepted cancer staging system is an essential and fundamental requirement for meaningful comparisons to be made across patient populations. In the case of melanoma, the identification of increasingly powerful prognostic factors has led to sequential modifications of the cutaneous melanoma staging system. The American Joint Committee on Cancer (AJCC) Melanoma Expert Panel significantly revised the melanoma staging system in 2017 and the current eighth edition AJCC melanoma staging system is the most widely accepted approach to melanoma staging and classification. This chapter reviews the prognostic factors relevant to current melanoma practice with an emphasis on factors that have significance in contemporary statistical analyses, using the eighth edition AJCC melanoma staging system and an international database analysis as a framework.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

References

  • Abdel-Rahman O (2018) Clinical correlates and prognostic value of different metastatic sites in patients with malignant melanoma of the skin: a SEER database analysis. J Dermatolog Treat 29:176–181

    Article  PubMed  Google Scholar 

  • Andtbacka RHI, Gershenwald JE (2009) Role of sentinel lymph node biopsy in patients with thin melanoma. J Natl Compr Cancer Netw 7:308–317

    Article  Google Scholar 

  • Averbook BJ, Lee SJ, Delman KA et al (2013) Pediatric melanoma: analysis of an international registry. Cancer 119:4012–4019

    Article  PubMed  Google Scholar 

  • Azimi F, Scolyer RA, Rumcheva P et al (2012) Tumor-infiltrating lymphocyte grade is an independent predictor of sentinel lymph node status and survival in patients with cutaneous melanoma. J Clin Oncol 30:2678–2683

    Article  PubMed  Google Scholar 

  • Azzola MF, Shaw HM, Thompson JF et al (2003) Tumor mitotic rate is a more powerful prognostic indicator than ulceration in patients with primary cutaneous melanoma: an analysis of 3661 patients from a single center. Cancer 97:1488–1498

    Article  PubMed  Google Scholar 

  • Bae JM, Choi YY, Kim DS et al (2015) Metastatic melanomas of unknown primary show better prognosis than those of known primary: a systematic review and meta-analysis of observational studies. J Am Acad Dermatol 72:59–70

    Article  PubMed  Google Scholar 

  • Balch CM (2002) Melanoma of the the skin. In: Greene F, Page D, Fleming I et al (eds) AJCC cancer staging manual, 6th edn. Springer, New York

    Google Scholar 

  • Balch CM, Murad TM, Soong SJ et al (1978) A multifactorial analysis of melanoma: prognostic histopathological features comparing Clark’s and Breslow’s staging methods. Ann Surg 188:732–742

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Balch CM, Soong SJ, Milton GW et al (1982) A comparison of prognostic factors and surgical results in 1,786 patients with localized (stage I) melanoma treated in Alabama, USA, and New South Wales, Australia. Ann Surg 196:677–684

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Balch CM, Soong S, Ross MI et al (2000) Long-term results of a multi-institutional randomized trial comparing prognostic factors and surgical results for intermediate thickness melanomas (1.0 to 4.0 mm). Intergroup melanoma surgical trial. Ann Surg Oncol 7:87–97

    Article  CAS  PubMed  Google Scholar 

  • Balch CM, Buzaid AC, Soong SJ et al (2001a) Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. J Clin Oncol 19:3635–3648

    Article  CAS  PubMed  Google Scholar 

  • Balch CM, Soong SJ, Gershenwald JE et al (2001b) Prognostic factors analysis of 17,600 melanoma patients: validation of the American Joint Committee on Cancer melanoma staging system. J Clin Oncol 19:3622–3634

    Article  CAS  PubMed  Google Scholar 

  • Balch CM, Gershenwald JE, Soong SJ et al (2009a) Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol 27:6199–6206

    Article  PubMed  PubMed Central  Google Scholar 

  • Balch CM, Soong SJ, Gershenwald JE et al (2009b) Melanoma of the skin. In: Edge S, Byrd D, Compton C et al (eds) AJCC Cancer staging manual, 7th edn. Springer, New York, pp 325–344

    Google Scholar 

  • Balch CM, Gershenwald JE, Soong SJ et al (2010) Multivariate analysis of prognostic factors among 2,313 patients with stage III melanoma: comparison of nodal micrometastases versus macrometastases. J Clin Oncol 28:2452–2459

    Article  PubMed  PubMed Central  Google Scholar 

  • Balch CM, Soong S, Gershenwald JE et al (2013) Age as a prognostic factor in patients with localized melanoma and regional metastases. Ann Surg Oncol 20:3961–3968

    Article  PubMed  PubMed Central  Google Scholar 

  • Balch CM, Thompson JF, Gershenwald JE et al (2014) Age as a predictor of sentinel node metastasis among patients with localized melanoma: an inverse correlation of melanoma mortality and incidence of sentinel node metastasis among young and old patients. Ann Surg Oncol 21:1075–1081

    Article  PubMed  PubMed Central  Google Scholar 

  • Barth A, Wanek LA, Morton DL (1995) Prognostic factors in 1,521 melanoma patients with distant metastases. J Am Coll Surg 181:193–201

    CAS  PubMed  Google Scholar 

  • Bhutiani N, Egger ME, Stromberg AJ et al (2018) A model for predicting low probability of nonsentinel lymph node positivity in melanoma patients with a single positive sentinel lymph node. J Surg Oncol 118:922–927

    Article  PubMed  Google Scholar 

  • Blessing K, McLaren KM, McLean A, Davidson P (1990) Thin malignant melanomas (less than 1.5 mm) with metastasis: a histological study and survival analysis. Histopathology 17:389–395

    Article  CAS  PubMed  Google Scholar 

  • Breslow A (1970) Thickness, cross-sectional areas and depth of invasion in the prognosis of cutaneous melanoma. Ann Surg 172:902–908

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Breslow A (1977) Problems in the measurement of tumor thickness and level of invasion in cutaneous melanoma. Hum Pathol 8:1–2

    Article  CAS  PubMed  Google Scholar 

  • Busam KJ (2004) The prognostic importance of tumor mitotic rate for patients with primary cutaneous melanoma. Ann Surg Oncol 11:360–361

    Article  PubMed  Google Scholar 

  • Buzaid AC, Ross MI, Balch CM et al (1997) Critical analysis of the current American Joint Committee on Cancer staging system for cutaneous melanoma and proposal of a new staging system. J Clin Oncol 15:1039–1051

    Article  CAS  PubMed  Google Scholar 

  • Byrom L, Olsen CM, Knight L et al (2015) Does pregnancy after a diagnosis of melanoma affect prognosis? Systematic review and meta-analysis. Dermatol Surg 41:875–882

    Article  CAS  PubMed  Google Scholar 

  • Caini S, Boniol M, Tosti G et al (2014) Vitamin D and melanoma and non-melanoma skin cancer risk and prognosis: a comprehensive review and meta-analysis. Eur J Cancer 50:2649–2658

    Article  CAS  PubMed  Google Scholar 

  • Cascinelli N, Belli F, Santinami M et al (2000) Sentinel lymph node biopsy in cutaneous melanoma: the WHO melanoma program experience. Ann Surg Oncol 7:469–474

    Article  CAS  PubMed  Google Scholar 

  • Cavanaugh-Hussey MW, Mu EW, Kang S et al (2015) Older age is associated with a higher incidence of melanoma death but a lower incidence of sentinel lymph node metastasis in the SEER databases (2003-2011). Ann Surg Oncol 22:2120–2126

    Article  PubMed  Google Scholar 

  • Clark WH, From L, Bernardino EA, Mihm MC (1969) The histogenesis and biologic behavior of primary human malignant melanomas of the skin. Cancer Res 29:705–727

    PubMed  Google Scholar 

  • Clark WH, Elder DE, Guerry D et al (1989) Model predicting survival in stage I melanoma based on tumor progression. J Natl Cancer Inst 81:1893–1904

    Article  PubMed  Google Scholar 

  • Cochran AJ, Wen D-R, Huang R-R et al (2004) Prediction of metastatic melanoma in nonsentinel nodes and clinical outcome based on the primary melanoma and the sentinel node. Mod Pathol 17:747–755

    Article  PubMed  Google Scholar 

  • Cormier JN, Xing Y, Feng L et al (2006) Metastatic melanoma to lymph nodes in patients with unknown primary sites. Cancer 106:2012–2020

    Article  PubMed  Google Scholar 

  • Crocetti E, Fancelli L, Manneschi G et al (2016) Melanoma survival: sex does matter, but we do not know how. Eur J Cancer Prev 25:404–409

    Article  PubMed  Google Scholar 

  • Crookes TR, Scolyer RA, Lo S et al (2017) Extranodal spread is associated with recurrence and poor survival in stage III cutaneous melanoma patients. Ann Surg Oncol 24:1378–1385

    Article  PubMed  Google Scholar 

  • Davies MA, Liu P, McIntyre S et al (2011) Prognostic factors for survival in melanoma patients with brain metastases. Cancer 117:1687–1696

    Article  PubMed  Google Scholar 

  • de Waal AC, Aben KKH, van Rossum MM, Kiemeney LALM (2013) Melanoma of unknown primary origin: a population-based study in the Netherlands. Eur J Cancer 49:676–683

    Article  PubMed  Google Scholar 

  • Dewar DJ, Newell B, Green MA et al (2004) The microanatomic location of metastatic melanoma in sentinel lymph nodes predicts nonsentinel lymph node involvement. J Clin Oncol 22:3345–3349

    Article  CAS  PubMed  Google Scholar 

  • Diem S, Kasenda B, Spain L et al (2016) Serum lactate dehydrogenase as an early marker for outcome in patients treated with anti-PD-1 therapy in metastatic melanoma. Br J Cancer 114:256–261

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Duprat JP, Brechtbülh ER, Costa de Sá B et al (2016) Absence of tumor-infiltrating lymphocyte is a reproducible predictive factor for sentinel lymph node metastasis: a multicenter database study by the Brazilian melanoma group. PLoS One 11:e0148160

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Egger ME, Bower MR, Czyszczon IA et al (2014) Comparison of sentinel lymph node micrometastatic tumor burden measurements in melanoma. J Am Coll Surg 218:519–528

    Article  PubMed  Google Scholar 

  • Eggermont AMM, Chiarion-Sileni V, Grob J-J et al (2016) Prolonged survival in stage III melanoma with Ipilimumab adjuvant therapy. N Engl J Med 375:1845–1855

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Eldh J, Boeryd B, Peterson LE (1978) Prognostic factors in cutaneous malignant melanoma in stage I. a clinical, morphological and multivariate analysis. Scand J Plast Reconstr Surg 12:243–255

    Article  CAS  PubMed  Google Scholar 

  • Eriksson H, Frohm-Nilsson M, JärÃ¥s J et al (2015) Prognostic factors in localized invasive primary cutaneous malignant melanoma: results of a large population-based study. Br J Dermatol 172:175–186

    Article  CAS  PubMed  Google Scholar 

  • Eton O, Legha SS, Moon TE et al (1998) Prognostic factors for survival of patients treated systemically for disseminated melanoma. J Clin Oncol 16:1103–1111

    Article  CAS  PubMed  Google Scholar 

  • Falchook GS, Long GV, Kurzrock R et al (2012) Dabrafenib in patients with melanoma, untreated brain metastases, and other solid tumours: a phase 1 dose-escalation trial. Lancet 379:1893–1901

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fang S, Sui D, Wang Y et al (2016) Association of vitamin D levels with outcome in patients with melanoma after adjustment for C-reactive protein. J Clin Oncol 34:1741–1747

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Faries MB, Thompson JF, Cochran AJ et al (2017) Completion dissection or observation for sentinel-node metastasis in melanoma. N Engl J Med 376:2211–2222

    Article  PubMed  PubMed Central  Google Scholar 

  • Fink AM, Weihsengruber F, Duschek N et al (2011) Value of micromorphometric criteria of sentinel lymph node metastases in predicting further nonsentinel lymph node metastases in patients with melanoma. Melanoma Res 21:139–143

    Article  PubMed  Google Scholar 

  • Flaherty KT, Infante JR, Daud A et al (2012) Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations. N Engl J Med 367:1694–1703

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Francischetto T, Spector N, Neto Rezende JF et al (2010) Influence of sentinel lymph node tumor burden on survival in melanoma. Ann Surg Oncol 17:1152–1158

    Article  PubMed  Google Scholar 

  • Frankel TL, Griffith KA, Lowe L et al (2008) Do micromorphometric features of metastatic deposits within sentinel nodes predict nonsentinel lymph node involvement in melanoma? Ann Surg Oncol 15:2403–2411

    Article  PubMed  Google Scholar 

  • Frauchiger AL, Mangana J, Rechsteiner M et al (2016) Prognostic relevance of lactate dehydrogenase and serum S100 levels in stage IV melanoma with known BRAF mutation status. Br J Dermatol 174:823–830

    Article  CAS  PubMed  Google Scholar 

  • Garbe C, Eigentler TK, Bauer J et al (2016) Mitotic rate in primary melanoma: interobserver and intraobserver reliability, analyzed using H&E sections and immunohistochemistry. J Dtsch Dermatol Ges 14:910–915

    PubMed  Google Scholar 

  • Gershenwald JE, Colome MI, Lee JE et al (1998) Patterns of recurrence following a negative sentinel lymph node biopsy in 243 patients with stage I or II melanoma. J Clin Oncol 16:2253–2260

    Article  CAS  PubMed  Google Scholar 

  • Gershenwald JE, Thompson W, Mansfield PF et al (1999) Multi-institutional melanoma lymphatic mapping experience: the prognostic value of sentinel lymph node status in 612 stage I or II melanoma patients. J Clin Oncol 17:976–983

    Article  CAS  PubMed  Google Scholar 

  • Gershenwald JE, Andtbacka RHI, Prieto VG et al (2008) Microscopic tumor burden in sentinel lymph nodes predicts synchronous nonsentinel lymph node involvement in patients with melanoma. J Clin Oncol 26:4296–4303

    Article  PubMed  PubMed Central  Google Scholar 

  • Gershenwald J, Balch CM, Soong S, Al E (2009) Prognostic factors and natural history of melanoma. In: Balch CM, Soong S, Sober AJ et al (eds) Cutaneous Melanoma, 5th edn. Quality Medical Publishing, St Louis

    Google Scholar 

  • Gershenwald JE, Scolyer RA, Hess KR et al (2017a) Melanoma staging: evidence-based changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin 67:472–492

    Article  PubMed  PubMed Central  Google Scholar 

  • Gershenwald JE, Scolyer RA, Hess KR et al (2017b) Melanoma of the skin. In: Amin M, Edge SB, Greene FL et al (eds) AJCC cancer staging manual, 8th edn. Springer, New York, pp 563–585

    Google Scholar 

  • Gimotty PA, Elder DE, Fraker DL et al (2007) Identification of high-risk patients among those diagnosed with thin cutaneous melanomas. J Clin Oncol 25:1129–1134

    Article  PubMed  Google Scholar 

  • Goldberg SB, Gettinger SN, Mahajan A et al (2016) Pembrolizumab for patients with melanoma or non-small-cell lung cancer and untreated brain metastases: early analysis of a non-randomised, open-label, phase 2 trial. Lancet Oncol 17:976–983

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Green AC, Baade P, Coory M et al (2012) Population-based 20-year survival among people diagnosed with thin melanomas in Queensland, Australia. J Clin Oncol 30:1462–1467

    Article  PubMed  Google Scholar 

  • Gress DM, Edge SB, Greene FL et al (2017) Principles of Cancer staging. In: Amin M, Edge SB, Greene FL et al (eds) AJCC cancer staging manual, 8th edn. Springer, New York, pp 3–30

    Google Scholar 

  • Gualano MR, Osella-Abate S, Scaioli G et al (2018) Prognostic role of histological regression in primary cutaneous melanoma: a systematic review and meta-analysis. Br J Dermatol 178:357–362

    Article  CAS  PubMed  Google Scholar 

  • Guitart J, Lowe L, Piepkorn M et al (2002) Histological characteristics of metastasizing thin melanomas: a case-control study of 43 cases. Arch Dermatol 138:603–608

    PubMed  Google Scholar 

  • Haddad FF, Stall A, Messina J et al (1999) The progression of melanoma nodal metastasis is dependent on tumor thickness of the primary lesion. Ann Surg Oncol 6:144–149

    Article  CAS  PubMed  Google Scholar 

  • Häffner AC, Garbe C, Burg G et al (1992) The prognosis of primary and metastasising melanoma. An evaluation of the TNM classification in 2,495 patients. Br J Cancer 66:856–861

    Article  PubMed  PubMed Central  Google Scholar 

  • Han D, Zager JS, Shyr Y et al (2013) Clinicopathologic predictors of sentinel lymph node metastasis in thin melanoma. J Clin Oncol 31:4387–4393

    Article  PubMed  Google Scholar 

  • Helsing P, Robsahm TE, Vos L et al (2016) Cutaneous head and neck melanoma (CHNM): a population-based study of the prognostic impact of tumor location. J Am Acad Dermatol 75:975–982.e2

    Article  PubMed  Google Scholar 

  • Hodi FS, O’Day SJ, McDermott DF et al (2010) Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 363:711–723

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huismans AM, Haydu LE, Shannon KF et al (2014) Primary melanoma location on the scalp is an important risk factor for brain metastasis: a study of 1,687 patients with cutaneous head and neck melanomas. Ann Surg Oncol 21:3985–3991

    Article  PubMed  Google Scholar 

  • In ‘t Hout FE, Haydu LE, Murali R et al (2012) Prognostic importance of the extent of ulceration in patients with clinically localized cutaneous melanoma. Ann Surg 255:1165–1170

    Article  PubMed  Google Scholar 

  • Jones MS, Lee J, Stern SL, Faries MB (2017) Is pregnancy-associated melanoma associated with adverse outcomes? J Am Coll Surg 225:149–158

    Article  PubMed  PubMed Central  Google Scholar 

  • Kashani-Sabet M, Sagebiel RW, Ferreira CM et al (2001) Vascular involvement in the prognosis of primary cutaneous melanoma. Arch Dermatol 137:1169–1173

    Article  CAS  PubMed  Google Scholar 

  • Kelderman S, Heemskerk B, Van Tinteren H et al (2014) Lactate dehydrogenase as a selection criterion for ipilimumab treatment in metastatic melanoma. Cancer Immunol Immunother 63:449–458

    CAS  PubMed  Google Scholar 

  • Kelly JW, Sagebiel RW, Blois MS (1985) Regression in malignant melanoma. A histologic feature without independent prognostic significance. Cancer 56:2287–2291

    Article  CAS  PubMed  Google Scholar 

  • Kyrgidis A, Lallas A, Moscarella E et al (2017) Does pregnancy influence melanoma prognosis? A meta-analysis. Melanoma Res 27:289–299

    Article  PubMed  Google Scholar 

  • Lachiewicz AM, Berwick M, Wiggins CL, Thomas NE (2008) Survival differences between patients with scalp or neck melanoma and those with melanoma of other sites in the surveillance, epidemiology, and end results (SEER) program. Arch Dermatol 144:515–521

    Article  PubMed  Google Scholar 

  • Larkin J, Ascierto PA, Dréno B et al (2014) Combined vemurafenib and cobimetinib in BRAF-mutated melanoma. N Engl J Med 371:1867–1876

    Article  CAS  PubMed  Google Scholar 

  • Lee CC, Faries MB, Wanek LA, Morton DL (2008) Improved survival after lymphadenectomy for nodal metastasis from an unknown primary melanoma. J Clin Oncol 26:535–541

    Article  PubMed  Google Scholar 

  • Leiter U, Stadler R, Mauch C et al (2016) Complete lymph node dissection versus no dissection in patients with sentinel lymph node biopsy positive melanoma (DeCOG-SLT): a multicentre, randomised, phase 3 trial. Lancet Oncol 17:757–767

    Article  PubMed  Google Scholar 

  • Leiter UM, Stadler R, Mauch C et al (2018) Final analysis of DECOG-SLT trial: survival outcomes of complete lymph node dissection in melanoma patients with positive sentinel node. J Clin Oncol 36: suppl;abstr 9501

    Google Scholar 

  • Lim A, Shayan R, Varigos G (2018) High serum vitamin D level correlates with better prognostic indicators in primary melanoma: a pilot study. Australas J Dermatol 59(3):182–187. Epub 2017 Mar 23

    Article  PubMed  Google Scholar 

  • Lo SN, Scolyer RA, Thompson JF (2018) Long-term survival of patients with thin (T1) cutaneous melanomas: a Breslow thickness cut point of 0.8 mm separates higher-risk and lower-risk tumors. Ann Surg Oncol 25:894–902

    Article  PubMed  Google Scholar 

  • Long GV, Trefzer U, Davies MA et al (2012) Dabrafenib in patients with Val600Glu or Val600Lys BRAF-mutant melanoma metastatic to the brain (BREAK-MB): a multicentre, open-label, phase 2 trial. Lancet Oncol 13:1087–1095

    Article  CAS  PubMed  Google Scholar 

  • Long GV, Grob J-J, Nathan P et al (2016a) Factors predictive of response, disease progression, and overall survival after dabrafenib and trametinib combination treatment: a pooled analysis of individual patient data from randomised trials. Lancet Oncol 17:1743–1754

    Article  CAS  PubMed  Google Scholar 

  • Long GV, Weber JS, Infante JR et al (2016b) Overall survival and durable responses in patients with BRAF V600-mutant metastatic melanoma receiving Dabrafenib combined with Trametinib. J Clin Oncol 34:871–878

    Article  CAS  PubMed  Google Scholar 

  • Long GV, Hauschild A, Santinami M et al (2017) Adjuvant Dabrafenib plus Trametinib in stage III BRAF-mutated melanoma. N Engl J Med 377:1813–1823

    Article  CAS  PubMed  Google Scholar 

  • Lyth J, Falk M, Maroti M et al (2017) Prognostic risk factors of first recurrence in patients with primary stages I-II cutaneous malignant melanoma – from the population-based Swedish melanoma register. J Eur Acad Dermatol Venereol 31:1468–1474

    Article  CAS  PubMed  Google Scholar 

  • Mandalà M, Galli F, Cattaneo L et al (2017) Mitotic rate correlates with sentinel lymph node status and outcome in cutaneous melanoma greater than 1 millimeter in thickness: a multi-institutional study of 1524 cases. J Am Acad Dermatol 76:264–273

    Article  PubMed  Google Scholar 

  • Manola J, Atkins M, Ibrahim J, Kirkwood J (2000) Prognostic factors in metastatic melanoma: a pooled analysis of eastern cooperative oncology group trials. J Clin Oncol 18:3782–3793

    Article  CAS  PubMed  Google Scholar 

  • Margolin K, Ernstoff MS, Hamid O et al (2012) Ipilimumab in patients with melanoma and brain metastases: an open-label, phase 2 trial. Lancet Oncol 13:459–465

    Article  CAS  PubMed  Google Scholar 

  • Menzies AM, Wilmott JS, Drummond M et al (2015) Clinicopathologic features associated with efficacy and long-term survival in metastatic melanoma patients treated with BRAF or combined BRAF and MEK inhibitors. Cancer 121:3826–3835

    Article  CAS  PubMed  Google Scholar 

  • Moreno-Ramírez D, Ojeda-Vila T, Ríos-Martín JJ et al (2015) Role of age and sex in the diagnosis of early-stage malignant melanoma: a cross-sectional study. Acta Derm Venereol 95:940–942

    Article  PubMed  CAS  Google Scholar 

  • Morton DL, Thompson JF, Cochran AJ et al (2006) Sentinel-node biopsy or nodal observation in melanoma. N Engl J Med 355:1307–1317

    Article  CAS  PubMed  Google Scholar 

  • Morton DL, Thompson JF, Cochran AJ et al (2014) Final trial report of sentinel-node biopsy versus nodal observation in melanoma. N Engl J Med 370:599–609

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Murali R, Hughes MT, Fitzgerald P et al (2009) Interobserver variation in the histopathologic reporting of key prognostic parameters, particularly Clark level, affects pathologic staging of primary cutaneous melanoma. Ann Surg 249:641–647

    Article  PubMed  Google Scholar 

  • Murali R, Desilva C, Thompson JF, Scolyer RA (2010) Non-sentinel node risk score (N-SNORE): a scoring system for accurately stratifying risk of non-sentinel node positivity in patients with cutaneous melanoma with positive sentinel lymph nodes. J Clin Oncol 28:4441–4449

    Article  PubMed  Google Scholar 

  • Nagarajan P, Curry JL, Ning J et al (2017) Tumor thickness and mitotic rate robustly predict melanoma-specific survival in patients with primary vulvar melanoma: a retrospective review of 100 cases. Clin Cancer Res 23:2093–2104

    Article  PubMed  Google Scholar 

  • Nagore E, Oliver V, Botella-Estrada R et al (2005) Prognostic factors in localized invasive cutaneous melanoma: high value of mitotic rate, vascular invasion and microscopic satellitosis. Melanoma Res 15:169–177

    Article  PubMed  Google Scholar 

  • National Comprehensive Cancer Network. Version 1.2019. Date Accessed 16 Feb 2019. Melanoma

    Google Scholar 

  • Paladugu RR, Yonemoto RH (1983) Biologic behavior of thin malignant melanomas with regressive changes. Arch Surg 118:41–44

    Article  CAS  PubMed  Google Scholar 

  • Pawlik TM, Ross MI, Thompson JF et al (2005) The risk of in-transit melanoma metastasis depends on tumor biology and not the surgical approach to regional lymph nodes. J Clin Oncol 23:4588–4590

    Article  PubMed  Google Scholar 

  • Petrelli F, Cabiddu M, Coinu A et al (2015) Prognostic role of lactate dehydrogenase in solid tumors: a systematic review and meta-analysis of 76 studies. Acta Oncol 54:961–970

    Article  CAS  PubMed  Google Scholar 

  • Prade M, Sancho-Garnier H, Cesarini JP, Cochran A (1980) Difficulties encountered in the application of Clark classification and the Breslow thickness measurement in cutaneous malignant melanoma. Int J Cancer 26:159–163

    Article  CAS  PubMed  Google Scholar 

  • Prens SP, van der Ploeg APT, van Akkooi ACJ et al (2011) Outcome after therapeutic lymph node dissection in patients with unknown primary melanoma site. Ann Surg Oncol 18:3586–3592

    Article  PubMed  PubMed Central  Google Scholar 

  • Quaglino P, Marenco F, Osella-Abate S et al (2010) Vitiligo is an independent favourable prognostic factor in stage III and IV metastatic melanoma patients: results from a single-institution hospital-based observational cohort study. Ann Oncol 21:409–414

    Article  CAS  PubMed  Google Scholar 

  • Ranieri JM, Wagner JD, Azuaje R et al (2002) Prognostic importance of lymph node tumor burden in melanoma patients staged by sentinel node biopsy. Ann Surg Oncol 9:975–981

    Article  PubMed  Google Scholar 

  • Rao UNM, Ibrahim J, Flaherty LE et al (2002) Implications of microscopic satellites of the primary and extracapsular lymph node spread in patients with high-risk melanoma: pathologic corollary of eastern cooperative oncology group trial E1690. J Clin Oncol 20:2053–2057

    Article  CAS  PubMed  Google Scholar 

  • Read RL, Haydu L, Saw RPM et al (2015) In-transit melanoma metastases: incidence, prognosis, and the role of lymphadenectomy. Ann Surg Oncol 22:475–481

    Article  PubMed  Google Scholar 

  • Rees MJ, Liao H, Spillane J et al (2016) Localized melanoma in older patients, the impact of increasing age and comorbid medical conditions. Eur J Surg Oncol 42:1359–1366

    Article  CAS  PubMed  Google Scholar 

  • Ribero S, Osella-Abate S, Sanlorenzo M et al (2013) Favourable prognostic role of regression of primary melanoma in AJCC stage I-II patients. Br J Dermatol 169:1240–1245

    Article  CAS  PubMed  Google Scholar 

  • Ribero S, Gualano MR, Osella-Abate S et al (2015) Association of histologic regression in primary melanoma with sentinel lymph node status: a systematic review and meta-analysis. JAMA Dermatol 151:1301–1307

    Article  PubMed  Google Scholar 

  • Ribero S, Moscarella E, Ferrara G et al (2016) Regression in cutaneous melanoma: a comprehensive review from diagnosis to prognosis. J Eur Acad Dermatol Venereol 30:2030–2037

    Article  CAS  PubMed  Google Scholar 

  • Ribero S, Stucci LS, Marra E et al (2018) Effect of age on melanoma risk, prognosis and treatment response. Acta Derm Venereol 98:624–629

    Article  CAS  PubMed  Google Scholar 

  • Robert C, Thomas L, Bondarenko I et al (2011) Ipilimumab plus Dacarbazine for previously untreated metastatic melanoma. N Engl J Med 364:2517–2526

    Article  CAS  PubMed  Google Scholar 

  • Robert C, Long GV, Brady B et al (2015a) Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med 372:320–330

    Article  CAS  PubMed  Google Scholar 

  • Robert C, Schachter J, Long GV et al (2015b) Pembrolizumab versus Ipilimumab in Advanced Melanoma. N Engl J Med 372:2521–2532

    Article  CAS  PubMed  Google Scholar 

  • Ronan SG, Eng AM, Briele HA et al (1987) Thin malignant melanomas with regression and metastases. Arch Dermatol 123:1326–1330

    Article  CAS  PubMed  Google Scholar 

  • Rousseau DL, Ross MI, Johnson MM et al (2003) Revised American Joint Committee on Cancer staging criteria accurately predict sentinel lymph node positivity in clinically node-negative melanoma patients. Ann Surg Oncol 10:569–574

    Article  PubMed  Google Scholar 

  • Rutkowski P, Nowecki ZI, Dziewirski W et al (2010) Melanoma without a detectable primary site with metastases to lymph nodes. Dermatol Surg 36:868–876

    Article  CAS  PubMed  Google Scholar 

  • Schatton T, Scolyer RA, Thompson JF, Mihm MC (2014) Tumor-infiltrating lymphocytes and their significance in melanoma prognosis. Methods Mol Biol 1102:287–324

    Article  CAS  PubMed  Google Scholar 

  • Schmoeckel C, Bockelbrink A, Bockelbrink H, Braun-Falco O (1983) Low- and high-risk malignant melanoma--II. Multivariate analyses for a prognostic classification. Eur J Cancer Clin Oncol 19:237–243

    Article  CAS  PubMed  Google Scholar 

  • Schultz S, Kane M, Roush R et al (1990) Time to recurrence varies inversely with thickness in clinical stage 1 cutaneous melanoma. Surg Gynecol Obstet 171:393–397

    CAS  PubMed  Google Scholar 

  • Scolyer RA, Li L-XL, McCarthy SW et al (2004) Micromorphometric features of positive sentinel lymph nodes predict involvement of nonsentinel nodes in patients with melanoma. Am J Clin Pathol 122:532–539

    Article  PubMed  Google Scholar 

  • Sinnamon AJ, Sharon CE, Song Y et al (2018) The prognostic significance of tumor-infiltrating lymphocytes for primary melanoma varies by sex. J Am Acad Dermatol 79:245–251

    Article  PubMed  Google Scholar 

  • Spatz A, Cook MG, Elder DE et al (2003) Interobserver reproducibility of ulceration assessment in primary cutaneous melanomas. Eur J Cancer 39:1861–1865

    Article  CAS  PubMed  Google Scholar 

  • Speijers MJ, Bastiaannet E, Sloot S et al (2015) Tumor mitotic rate added to the equation: melanoma prognostic factors changed? : a single-institution database study on the prognostic value of tumor mitotic rate for sentinel lymph node status and survival of cutaneous melanoma patients. Ann Surg Oncol 22:2978–2987

    Article  CAS  PubMed  Google Scholar 

  • Starz H, Balda BR, Krämer KU et al (2001) A micromorphometry-based concept for routine classification of sentinel lymph node metastases and its clinical relevance for patients with melanoma. Cancer 91:2110–2121

    Article  CAS  PubMed  Google Scholar 

  • Staudt M, Lasithiotakis K, Leiter U et al (2010) Determinants of survival in patients with brain metastases from cutaneous melanoma. Br J Cancer 102:1213–1218

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Storr SJ, Safuan S, Mitra A et al (2012) Objective assessment of blood and lymphatic vessel invasion and association with macrophage infiltration in cutaneous melanoma. Mod Pathol 25:493–504

    Article  PubMed  Google Scholar 

  • Sullivan RJ (2016) Serum lactate dehydrogenase is a more useful biomarker of prognosis than serum S100B in patients with BRAF-mutant melanoma. Br J Dermatol 174:716–717

    Article  CAS  PubMed  Google Scholar 

  • Tas F, Erturk K (2017) Scalp melanoma is associated with high mitotic rate and is a poor prognostic factor for recurrence and outcome. Melanoma Res 27:387–390

    Article  PubMed  Google Scholar 

  • Taylor RC, Patel A, Panageas KS et al (2007) Tumor-infiltrating lymphocytes predict sentinel lymph node positivity in patients with cutaneous melanoma. J Clin Oncol 25:869–875

    Article  PubMed  Google Scholar 

  • Thomas NE, Busam KJ, From L et al (2013) Tumor-infiltrating lymphocyte grade in primary melanomas is independently associated with melanoma-specific survival in the population-based genes, environment and melanoma study. J Clin Oncol 31:4252–4259

    Article  PubMed  PubMed Central  Google Scholar 

  • Thompson JF, Soong SJ, Balch CM et al (2011) Prognostic significance of mitotic rate in localized primary cutaneous melanoma: an analysis of patients in the multi-institutional American Joint Committee on Cancer melanoma staging database. J Clin Oncol 29:2199–2205

    Article  PubMed  PubMed Central  Google Scholar 

  • Thörn M, Pontén F, Bergström R et al (1994) Clinical and histopathologic predictors of survival in patients with malignant melanoma: a population-based study in Sweden. J Natl Cancer Inst 86:761–769

    Article  PubMed  Google Scholar 

  • Timerman D, McEnery-Stonelake M, Joyce CJ et al (2017) Vitamin D deficiency is associated with a worse prognosis in metastatic melanoma. Oncotarget 8:6873–6882

    Article  PubMed  Google Scholar 

  • Tio M, Wang X, Carlino MS et al (2018) Survival and prognostic factors for patients with melanoma brain metastases in the era of modern systemic therapy. Pigment Cell Melanoma Res 31(4):509–515. Epub 2018 Jan 10

    Article  Google Scholar 

  • Unger JM, Flaherty LE, Liu PY et al (2001) Gender and other survival predictors in patients with metastatic melanoma on Southwest Oncology Group trials. Cancer 91:1148–1155

    Article  CAS  PubMed  Google Scholar 

  • van Akkooi ACJ, Nowecki ZI, Voit C et al (2008) Sentinel node tumor burden according to the Rotterdam criteria is the most important prognostic factor for survival in melanoma patients: a multicenter study in 388 patients with positive sentinel nodes. Ann Surg 248:949–955

    Article  PubMed  Google Scholar 

  • van der Ploeg APT, van Akkooi ACJ, Rutkowski P et al (2011) Prognosis in patients with sentinel node-positive melanoma is accurately defined by the combined Rotterdam tumor load and Dewar topography criteria. J Clin Oncol 29:2206–2214

    Article  PubMed  Google Scholar 

  • Van Der Ploeg APT, Van Akkooi ACJ, Haydu LE et al (2014a) The prognostic significance of sentinel node tumour burden in melanoma patients: an international, multicenter study of 1539 sentinel node-positive melanoma patients. Eur J Cancer 50:111–120

    Article  PubMed  Google Scholar 

  • van Der Ploeg APT, Haydu LE, Spillane AJ et al (2014b) Melanoma patients with an unknown primary tumor site have a better outcome than those with a known primary following therapeutic lymph node dissection for macroscopic (clinically palpable) nodal disease. Ann Surg Oncol 21:3108–3116

    Article  PubMed  Google Scholar 

  • Van Es SL, Colman M, Thompson JF et al (2008) Angiotropism is an independent predictor of local recurrence and in-transit metastasis in primary cutaneous melanoma. Am J Surg Pathol 32:1396–1403

    Article  PubMed  Google Scholar 

  • Varey AHR, Goumas C, Hong AM et al (2017) Neurotropic melanoma: an analysis of the clinicopathological features, management strategies and survival outcomes for 671 patients treated at a tertiary referral center. Mod Pathol 30:1538–1550

    Article  PubMed  Google Scholar 

  • Vosoughi E, Lee JM, Miller JR et al (2018) Survival and clinical outcomes of patients with melanoma brain metastasis in the era of checkpoint inhibitors and targeted therapies. BMC Cancer 18:490

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wargo JA, Amaria RN, Ross MI et al (2015) Neoadjuvant BRAF (dabrafenib) and MEK (trametinib) inhibition for high-risk resectable stage III and IV melanoma. J Clin Oncol 33(Suppl):TPS9091

    Article  Google Scholar 

  • Wat H, Senthilselvan A, Salopek TG (2016) A retrospective, multicenter analysis of the predictive value of mitotic rate for sentinel lymph node (SLN) positivity in thin melanomas. J Am Acad Dermatol 74:94–101

    Article  PubMed  Google Scholar 

  • Weide B, Faller C, Elsässer M et al (2013) Melanoma patients with unknown primary site or nodal recurrence after initial diagnosis have a favourable survival compared to those with synchronous lymph node metastasis and primary tumour. PLoS One 8:e66953

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wilmott J, Haydu L, Bagot M et al (2012) Angiotropism is an independent predictor of microscopic satellites in primary cutaneous melanoma. Histopathology 61:889–898

    Article  PubMed  Google Scholar 

  • Wong SL, Faries MB, Kennedy EB et al (2018) Sentinel lymph node biopsy and management of regional lymph nodes in melanoma: American Society of Clinical Oncology and Society of Surgical Oncology clinical practice guideline update. J Clin Oncol 36:399–413

    Article  PubMed  Google Scholar 

  • Wyatt C, Lucas RM, Hurst C, Kimlin MG (2015) Vitamin D deficiency at melanoma diagnosis is associated with higher Breslow thickness. PLoS One 10:e0126394

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Xie C, Pan Y, McLean C et al (2017) Impact of scalp location on survival in head and neck melanoma: a retrospective cohort study. J Am Acad Dermatol 76:494–498.e2

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors gratefully acknowledge the members of the eighth Edition AJCC Melanoma Expert Panel and collaborating institutions that contributed clinicopathological data to the International Melanoma Database and Discovery Platform (IMDDP), developed at The University of Texas MD Anderson Cancer Center, that was used to inform revisions to the AJCC melanoma staging system.

Author information

Authors and Affiliations

  1. Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Emily Z. Keung, Charles M. Balch & Jeffrey E. Gershenwald

  2. Melanoma and Skin Center, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Jeffrey E. Gershenwald

  3. Department of Medicine, University of Pittsburgh, Pittsburg, PA, USA

    John M. Kirkwood

  4. Central Clinical School, The University of Sydney and Melanoma Institute Australia, The University of Sydney, Sydney, Australia

    John F. Thompson & Richard A. Scolyer

  5. Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL, USA

    Vernon K. Sondak

Authors
  1. Emily Z. Keung
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Charles M. Balch
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. John F. Thompson
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. John M. Kirkwood
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Richard A. Scolyer
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Vernon K. Sondak
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jeffrey E. Gershenwald
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jeffrey E. Gershenwald .

Editor information

Editors and Affiliations

  1. Division of Surgical Oncology, University of Texas Southwestern, Dallas, TX, USA

    Charles Balch

  2. Division of Surgery, UT MD Anderson Cancer Center, Houston, TX, USA

    Jeffrey Gershenwald

  3. Melanoma Institute of Australia, Wollstonecraft, Australia

    John Thompson

  4. Georgetown Medical Center, Washington, DC, USA

    Michael Atkins

  5. Melanoma and Skin Cancer Program, University of Pittsburgh, Pittsburgh, PA, USA

    John Kirkwood

  6. University of Sydney, Sydney, NSW, Australia

    Richard Kefford

  7. Department of Dermatology, Harvard Medical Center, Boston, MA, USA

    Arthur Sober

  8. Department of Dermatology, Memorial Sloan Kettering, New York, NY, USA

    Allan Halpern

  9. Department of Dermatology, University Hospital, Tübingen, Tübingen, Germany

    Claus Garbe

  10. Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown NSW, Australia

    Richard Scolyer

Rights and permissions

Reprints and permissions

Copyright information

© 2019 This is a U.S. Government work and not under copyright protection in the U.S.; foreign copyright protection may apply

About this entry

Check for updates. Verify currency and authenticity via CrossMark

Cite this entry

Keung, E.Z. et al. (2019). Melanoma Prognosis and Staging. In: Balch, C., et al. Cutaneous Melanoma. Springer, Cham. https://doi.org/10.1007/978-3-319-46029-1_4-1

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-46029-1_4-1

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-46029-1

  • Online ISBN: 978-3-319-46029-1

  • eBook Packages: Springer Reference MedicineReference Module Medicine

Publish with us

Policies and ethics

Search

Navigation