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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