Claus Garbe
Center for DermatooncologyDepartment of Dermatology
University of Tübingen, Germany
AJCC classification - TNM, 2009, preview of the new 2015
classification
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AJCC Melanoma Staging System
Stages I/II Stage III
Primary tumor Regional Metastasis
5-year-survival97% - 53%
5-year-survival70% - 39%
Stage IV5-year-survival25% - 9%
Distant Metastasis
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E. Hölzle et al. 1993
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Breslow‘sTumor Thickness
Measured from stratum corneum to deepest tumor formation at the microscop in millimeter
Clark‘s Level of Invasion
Level I: intraepidermal (in situ)Level II: few cells in stratum papillareLevel III: fills stratum papillareLevel IV: invades stratum reticulareLevel V: invades subcutaneous fat
Breslow ´s tumor thickness and Clark ´slevel of invasion
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TNM Classification 1987/1997 vs. 2002
pT classif. 1987/1997pTis Melanoma in situ
pT1 TT ≤ 0.75 mm and level II
pT2 TT 0.76 - 1.5 mm and/or level III
pT3a TT 1.51 - 3.0 mm and/or level IV
pT3b TT 3.01 - 4.0 mm and/or level IV
pT4a TT > 4.0 mm and/or level V
pT – classification 2002pT1 TT ≤ 1.00 mm
a: Ø ulzeration and level II/IIIb: with ulzeration or level IV/V
pT2 TT 1.01-2.0mma: Ø ulzerationb: with ulzeration
pT3 TT 2.01-4.0mma: Ø ulzerationb: with ulzeration
pT4 TT > 4.0mma: Ø ulzerationb: with ulzeration
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T Classification
Clinical Stage T Tumor thickness Ulc./Level IA T1a < 1 mm no ulc. IB T1b < 1 mm Ulc./Lev IV/V T2a 1-2 mm no ulc. IIA T2b 1-2 mm ulc. T3a 2-4 mm no ulc. IIB T3b 2-4 mm ulc. T4a > 4 mm no ulc. IIC T4b > 4 mm ulc.
AJCC Classification 2002
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AJCC Classification 2009
T-classification – main changes compared to 2002
Main parameters remain Breslow ´s tumorthickness and ulceration
Newly introduced will be mitosis rate/mm² in T1
Clark ´s level of invasion is no longer a T para-meter
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Tumor thickness und case fatality
J. Gershenwald 2009
AJCC Classification 2009
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Tumor thickness and case fatality
J. Gershenwald 2009
AJCC Classification 2009
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Mitoses/mm² and case fatality
J. Gershenwald 2009
AJCC Classification 2009
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Mitoses/mm² und tumor thickness
J. Gershenwald 2009
AJCC Classification 2009
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Cox regression analysis for 10,233 melanoma patient s with localized melanoma including mitotic rate
VariableChi-square
values(1 d.f.)
P HR95%CI
Tumor thickness 84.6 <0.0001 1.25 1.91 – 1.31
Ulceration 47.2 <0.0001 1.56 1.38 – 1.78
Clark’s Level 8.2 0.0041 1.15 1.04 – 1.26
Mitotic Rate 79.1 <0.0001 1.26 1.20 – 1.32
Site 29.1 <0.0001 1.38 1.23 – 1.54
Gender 32.4 <0.0001 0.70 0.62 – 0.79
Age 40.8 <0.0001 1.16 1.11 – 1.22
Melanoma of the Skin, 7th Edition AJCC Manual for Staging of Cancer –In Press, 2009.
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T Classification
Clinical stage T Tumor thickness Ulc./Level IA T1a < 1 mm no ulc./< 1m. IB T1b < 1 mm ulc./≥ 1m./mm² T2a 1-2 mm no ulc. IIA T2b 1-2 mm ulc. T3a 2-4 mm no ulc. IIB T3b 2-4 mm ulc. T4a > 4 mm no ulc. IIC T4b > 4 mm ulc.
AJCC Classification 2009
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N-Classification – main changes in comparison to 2002
Micrometastasis can be detected with HE staining or with immunohistochemistry
There is no lower threshold for the diagnosis of micrometastasis, one metastatic cell is enough
Soft tissue metastases of unknown primary melanoma are classified as stage III disease
AJCC Classification 2009
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N Number of metastatic lymp nodes. Kind of metastas es
N1 1 lymph node a: Micrometastasesb: Macrometastases
N2 2-3 lymph nodes a: Micrometastasesb: Macrometastasesc: intransit/satellitemetastases without met. lymph nodes
N3 4 or more lymph nodes or in-transit/satellite metastases with met. lymph nodes
N-Classification
AJCC Classification 2009
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Number of metastatic lymph nodes and case fatality
J. Gershenwald 2009
AJCC Classification 2009
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Stage III and TNM classification
IIIA T1-4a N1a M0T1-4a N2a M0
IIIB T1-4b N1a M0T1-4b N2a M0T1-4a N1b M0T1-4a N2b M0T1-4a/b N2c M0
IIIC T1-4b N1b M0T1-4b N2b M0Each T N3 M0
AJCC Classification 2009
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Melanoma of unknown primary tumor
J. Gershenwald 2009
AJCC Classification 2009
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MUP – clinical implications
Cutaneous and subcutaneous metastases and lymph node metastases of MUP are classified as stage III
Radical surgical therapy is indicated as in regiona l metastases
Patients should be offered an adjuvant treatment
AJCC Classification 2009
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M-Classification
Localisation Serum LDHM1a Distant skin
metastases, subcutaneous or lymph node metastases
Normal
M1b Lung metastases NormalM1c Other visceral
metastases Each distant metastasis
Normal
Elevated
AJCC Classification 2009
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Kind of distant metastasis and case fatality
J. Gershenwald 2009
AJCC Classification 2009
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AJCC Classification 2015
Methods and Findings: We analyzed 1,834 sentinel nodes from 1,027 patients with ultrasound node-negative melanoma who underwent sentinel node biopsy between February 8, 2000, and June 19, 2008, by histopathology including immunohistochemistry and quantitative immunocytology. For immunocytology we recorded the number of disseminated cancer cells (DCCs) per million lymph node cells (DCC density [DCCD]) after disaggregation and immunostaining for the melanocytic marker gp100.
Ulmer A, et al. PLOS Medicine 2014
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Ulmer A, et al. PLOS Medicine 2014
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Ulmer A, et al. PLOS Medicine 2014
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Ulmer A, et al. PLOS Medicine 2014
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AJCC Melanoma Staging System
Stages I/II Stage III
Primary tumor Regional Metastasis
5-year-survival97% - 53%
5-year-survival70% - 39%
Stage IV5-year-survival25% - 9%
Distant Metastasis
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