Melanoma Molecular Maps Projects

Padova

TNM staging


The American Joint Committee on Cancer (AJCC) TNM classification is the most widely accepted staging system for cutaneous melanoma [1, 2].

It is based on the combination of three factors: 1) tumor depth (T), as described by Breslow's thickness (expressed in millimeters), 2) lymph node status (N), including in-transit metastasis, and 3) distant metastasis (M), including plasma levels of lactate dehydrogenase (LDH). Their combination defines four stages and nine substages (Figure 1).

The TNM staging system has been recently updated according to the survival data obtained from over 17,000 patients [1, 2].

For a quick TNM stage/prognosis definition, go to the dedicated MMMP section (TNM calculator) just by clicking on the following link: TNM CALCULATOR

THE DETAILS OF THE LATEST AJCC TNM STAGING SYSTEM (7th EDITION, 2010) ARE AT THE BOTTOM OF THIS PAGE.





TNM definitions

Tx

unknown primary tumor


Tis

in situ melanoma


T1

< 1 mm



T1a

without ulceration and Clark level II-III



T1b

with ulceration or Clark level IV-V


T2

1-2 mm



T2a

without ulceration



T2b

with ulceration


T3

2-4 mm



T3a

without ulceration



T3b

with ulceration


T4

> 4 mm



T4a

without ulceration



T4b

with ulceration





Nx

lymph node status unknown


N0

no regional lymph node metastasis


N1

1 metastatic lymph node



N1a

micrometastasis *



N1b

macrometastasis **


N2

2-3 metastatic lymph nodes



N2a

micrometastasis *



N2b

macrometastasis **



N2c

in-transit metastasis without lymph node involvement


N3

4 or more metastatic lymph nodes or in-transit metastasis with lymph node involvement


*

micrometastasis: clinically occult microscopic metastatic disease detected by pathological examination

**

macrometastasis: clinically evident metastatic disease, or extracapsular lymph node metastasis at pathological examination




Mx

unknown


M0

no distant metastasis


M1

distant metastatic disease



M1a

skin, subcutis and extra-regional lymph nodes with normal LDH



M1b

lungs with normal LDH



M1c

any other visceral metastasis or any distant metastasis with elevated LDH





TNM stages and survival

The TNM staging system (Figure 1) identifies four stages (Figure 2) and nine substages (Table 1) associated with different clinical outcomes [1, 2].

Stage I is characterized by very high overall survival (OS) rates (5-year OS ≥90%), which underscores the importance of early diagnosis (see Prevention section).

Stage II is associated with a very variable outcome, the 5-year OS ranging from 45% (stage IIC) to 78% (stage IIA). The prognostic value of ulceration is of particular relevance in this stage: the presence of this adverse prognostic factor shifts patients with the same tumor thickness from stage IB to IIA (T2), from IIA to IIB (T3), and from IIB to IIC (T4). The impact on survival is evident: for instance, T4 melanoma (thickness >4 mm) is associated with a 67% 5-year OS rate when ulceration is absent (T4a, stage IIB), the survival rate drops to 45% when ulceration is present (T4b, stage IIC).

Given the wide range of survival rates observed in stage II patients, it is not surprising that stage III survival rates are in part overlapping (5-year OS rates range from 24% to 69%). With stage III disease, only 49% of all patients with nodal metastases survive 5 years (37% at 10 years), but the range of melanoma-specific survival is large, ranging from 13% at 5 years for patients with the combination of the worst risk factors (ulceration of the primary tumor, high regional lymph node burden) to 69% at 5 years for the most favorable combination of prognostic factors.

Stage IV is characterized by a dismal prognosis, although some variability is found according to the site of metastasis and the LDH plasma levels (5-year OS rates range from 9% to 18%).

Of note, there is a significant variability in overall survival rates within each single TNM stage and substage (see Table 1).

Although the TNM classification is the best prognostic tool currently available, the above considerations highlight the limited ability of this staging system to accurately predict the clinical outcome on a single patient basis.


References

[1] Balch CM et al, Prognostic factors analysis of 17,600 melanoma patients: validation of the American Joint Committee on Cancer melanoma staging system. J Clin Oncol 2001, 19: 3622-34

[2] Balch CM et al, An evidence-based staging system for cutaneous melanoma. CA Cancer J Clin 2004, 54(3): 131-49



Figure 1: A synopsis of the AJCC TNM staging system for cutaneous melanoma.


T1a

T2a

T1b

T2b

T3a

T4a

T3b

T4b


N0

IA

IB

IIA

IIB

IIC

Stage I-II

N1a

IIIA

IIIB

IIIA

IIIB

Stage III

N2a

N1b

IIIB

IIIC

IIIB

IIIC

N2b

N2c

IIIB

N3

IIIC

M1a

IV

Stage IV

M1b

M1c




Figure 2: AJCC TNM stages and overall survival of patients with cutaneous melanoma.




Table 1: Disease-specific 5-year and 10-year overall survival (OS) rates (and their standard error, SE) of patients with cutaneous melanoma according to the TNM staging system.

Stage

5y OS (%)

SE

10y OS (%)

SE

IA

95.3

0.4

87.9

1.0

IB

90.9

1.0

83.1

1.5

IIA

78.7

1.2

63.8

1.7

IIB

67.4

2.4

53.9

3.3

IIC

45.1

1.9

32.3

2.1

IIIA

69.5

3.7

63.0

4.4

IIIB

52.8

4.1

37.8

4.8

IIIC

26.7

2.5

18.4

2.5

IV

9.5

1.1

6.0

0.9





AJCC TNM STAGING SYSTEM 7th EDITION (2010)

The latest version of the AJCC TNM staging system for cutaneous melanoma has been released (based on 30,946 cases). Main changes: 1) mitotic rate (added); 2) Clark level (removed). Main limit: no molecular biomarker has been implemented.

REFERENCE: Balch CM et al, Final Version of 2009 AJCC Melanoma Staging and Classification. J Clin Oncol 2009, Epub ahead of print



Figure 3: AJCC TNM staging system 7th edition (2010): TNM categories.




Figure 4: AJCC TNM staging system 7th edition (2010): TNM stages.




Figure 5: AJCC TNM staging system 7th edition (2010): Survival curves based on the TNM classification.




Table 2: Differences between the previous (6th edition, 2001) and the current (7th edition, 2010) AJCC TNM staging systems.


Search the site


Risk Assessment Tools

TNM Staging System | Total Dermoscopy Score | Thin Melanoma Prognosis |


Melanoma News


NCBI's Disclaimer and Copyright notice