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Melanoma Treatment (PDQ®)

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Stage Information for Melanoma

Clark Classification (Level of Invasion)
American Joint Committee on Cancer (AJCC) Stage Groupings and TNM Definitions

Clinical staging is based on whether the tumor has spread to regional lymph nodes or distant sites. For melanoma that is clinically confined to the primary site, the chance of lymph node or systemic metastases increases as the thickness and depth of local invasion increases, which worsens the prognosis. Melanoma can spread by local extension (through lymphatics) and/or by hematogenous routes to distant sites. Any organ may be involved by metastases, but lungs and liver are common sites.

The microstage of malignant melanoma is determined on histologic examination by the vertical thickness of the lesion in millimeters (Breslow classification) and/or the anatomic level of local invasion (Clark classification). The Breslow thickness is more reproducible and more accurately predicts subsequent behavior of malignant melanoma in lesions thicker than 1.5 mm and should always be reported.

Accurate microstaging of the primary tumor requires careful histologic evaluation of the entire specimen by an experienced pathologist.

Clark Classification (Level of Invasion)

Table 1. Clark Classification (Level of Invasion)
Level of Invasion  Description 
Level ILesions involving only the epidermis (in situ melanoma); not an invasive lesion.
Level IIInvasion of the papillary dermis; does not reach the papillary-reticular dermal interface.
Level IIIInvasion fills and expands the papillary dermis but does not penetrate the reticular dermis.
Level IVInvasion into the reticular dermis but not into the subcutaneous tissue.
Level VInvasion through the reticular dermis into the subcutaneous tissue.

American Joint Committee on Cancer (AJCC) Stage Groupings and TNM Definitions

Melanoma staging is defined by the AJCC's TNM classification system.[1]

Table 2. TNM Definitions for Stage 0 Melanoma
Stage TNM Description Image 
Clinicala Pathologicalb
Enlarge
Stage 0 melanoma in situ; drawing shows skin anatomy with an abnormal area on the surface of the skin. Both normal and abnormal melanocytes and melanin are shown in the epidermis (outer layer of the skin). Also shown are the dermis (inner layer of the skin) and the subcutaneous tissue below the dermis.
Stage 0 melanoma in situ.
00TisMelanoma in situ
N0No regional metastases
M0No detectable evidence of distant metastases
T = primary tumor; N = regional lymph nodes; M = distant metastasis.
Adapted with permission from AJCC: Melanoma of the skin. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 325-44.
The explanations for superscripts a and b are at the end of Table 7.

Table 3. TNM Definitions for Stage I Melanoma
Stage TNM Description Image 
ClinicalaPathologicalb
Enlarge
Two-panel drawing of stage I melanoma. The first panel shows a stage IA tumor that is not more than 1 millimeter thick, with no ulceration (break in the skin). The second panel shows two stage IB tumors. One tumor is not more than 1 millimeter thick, with ulceration, and the other tumor is more than 1 but not more than 2 millimeters thick, with no ulceration. Also shown are the epidermis (outer layer of the skin), the dermis (inner layer of the skin), and the subcutaneous tissue below the dermis.
Stage I melanoma.
IAIAT1aMelanomas ≤1.0 mm in thickness without ulceration; mitosis <1/mm2
N0No regional metastases detected
M0No detectable evidence of distant metastases
IBIBT1bMelanomas ≤1.0 mm in thickness with ulceration or mitoses ≥1/mm2
T2aMelanomas 1.01–2.0 mm in thickness without ulceration
N0No regional metastases detected
M0No detectable evidence of distant metastases

T = primary tumor; N = regional lymph nodes; M = distant metastasis.
Adapted with permission from AJCC: Melanoma of the skin. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 325-44.
The explanations for superscripts a and b are at the end of Table 7.

Table 4. TNM Definitions for Stage II Melanoma
Stage TNM Description Image 
Clinicala Pathologicalb
Enlarge
Three-panel drawing of stage II melanoma. The left panel shows two stage IIA tumors. One tumor is more than 1 but not more than 2 millimeters thick, with ulceration (break in the skin); the other tumor is more than 2 but not more than 4 millimeters thick, with no ulceration. The right panel shows two stage IIB tumors. One tumor is more than 2 but not more than 4 millimeters thick, with ulceration; the other tumor is more than 4 millimeters thick, with no ulceration. The bottom panel shows a stage IIC tumor that is more than 4 millimeters thick, with ulceration. Also shown are the epidermis (outer layer of the skin), the dermis (inner layer of the skin), and the subcutaneous tissue below the dermis.
Stage II melanoma.
IIAIIAT2bMelanomas 1.01–2.0 mm in thickness with ulceration
T3aMelanomas 2.01–4.0 mm in thickness without ulceration
N0No regional metastases detected
M0No detectable evidence of distant metastases
IIBIIBT3bMelanomas 2.01–4.0 mm in thickness with ulceration
T4aMelanomas >4.0 mm in thickness without ulceration
N0No regional metastases detected
M0No detectable evidence of distant metastases
IICIICT4bMelanomas >4.0 mm in thickness with ulceration
N0No regional metastases detected
M0No detectable evidence of distant metastases
T = primary tumor; N = regional lymph nodes; M = distant metastasis.
Adapted with permission from AJCC: Melanoma of the skin. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 325-44.
The explanations for superscripts a and b are at the end of Table 7.

Table 5. TNM Definitions for Stage III Melanoma: Clinical Staginga
Stage TNM Description Image 
IIIAny TTX = Primary tumor cannot be assessed (e.g., curettaged or severely regressed melanoma)
Enlarge
Stage III melanoma; drawing shows a primary tumor on the lower arm. In the top inset, cancer is shown (a) in lymph nodes near a blood vessel. In the bottom inset, cancer is shown (b) in lymph nodes that are joined together (matted), (c) in a lymph vessel, and (d) not more than 2 centimeters away from the primary tumor.
Stage III melanoma.
T0 = No evidence of primary tumor
Tis = Melanoma in situ
T1a = Melanomas ≤1.0 mm in thickness without ulceration; mitosis <1/mm2
T1b = Melanomas ≤1.0 mm in thickness with ulceration or mitoses ≥1/mm2
T2a = Melanomas 1.01–2.0 mm in thickness without ulceration
T2b = Melanomas 1.01–2.0 mm in thickness with ulceration
T3a = Melanomas 2.01–4.0 mm in thickness without ulceration
T3b = Melanomas 2.01–4.0 mm in thickness with ulceration
T4a = Melanomas >4.0 mm in thickness without ulceration
T4b = Melanomas >4.0 mm in thickness with ulceration
≥N1N1 = 1 regional lymph node metastasis
N2 = 2–3 regional lymph node metastases
N3 = ≥4 regional lymph node metastases; or matted nodes; or in transit met(s)/satellite(s) with metastatic lymph node(s)
M0No detectable evidence of distant metastases
T = primary tumor; N = regional lymph nodes; M = distant metastasis.
Adapted with permission from AJCC: Melanoma of the skin. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 325-44.
The explanation for superscript a is at the end of Table 7.

Table 6. TNM Definitions for Stage III Melanoma: Pathologic Stagingb
Stage TNM Description 
IIIAT1–4aT1a = Melanomas ≤1.0 mm in thickness without ulceration; mitosis <1/mm2
T1b = Melanomas ≤1.0 mm in thickness with ulceration or mitoses ≥1/mm2
T2a = Melanomas 1.01–2.0 mm in thickness without ulceration
T2b = Melanomas 1.01–2.0 mm in thickness with ulceration
T3a = Melanomas 2.01–4.0 mm in thickness without ulceration
T3b = Melanomas 2.01–4.0 mm in thickness with ulceration
T4a = Melanomas >4.0 mm in thickness without ulceration
N1a1 regional lymph node metastasis with micrometastasisc
N2a2–3 regional lymph node metastases with micrometastasisc
M0No detectable evidence of distant metastases
IIIBT1–4bT1a = Melanomas ≤1.0 mm in thickness without ulceration; mitosis <1/mm2
T1b = Melanomas ≤1.0 mm in thickness with ulceration or mitoses ≥1/mm2
T2a = Melanomas 1.01–2.0 mm in thickness without ulceration
T2b = Melanomas 1.01–2.0 mm in thickness with ulceration
T3a = Melanomas 2.01–4.0 mm in thickness without ulceration
T3b = Melanomas 2.01–4.0 mm in thickness with ulceration
T4a = Melanomas >4.0 mm in thickness without ulceration
T4b = Melanomas >4.0 mm in thickness with ulceration
N1a1 regional lymph node metastasis with micrometastasisc
N2a2–3 regional lymph node metastases with micrometastasisc
M0No detectable evidence of distant metastases
IIIBT1–4aT1a = Melanomas ≤1.0 mm in thickness without ulceration; mitosis <1/mm2
T1b = Melanomas ≤1.0 mm in thickness with ulceration or mitoses ≥1/mm2
T2a = Melanomas 1.01–2.0 mm in thickness without ulceration
T2b = Melanomas 1.01–2.0 mm in thickness with ulceration
T3a = Melanomas 2.01–4.0 mm in thickness without ulceration
T3b = Melanomas 2.01–4.0 mm in thickness with ulceration
T4a = Melanomas >4.0 mm in thickness without ulceration
N1bN1b = 1 regional lymph node metastasis with macrometastasisd
N2bN2b = 2–3 regional lymph node metastases with macrometastasisd
N2cN2c = In transit met(s)/satellite(s) without metastatic lymph nodes
M0No detectable evidence of distant metastases
IIICT1–4bT1a = Melanomas ≤1.0 mm in thickness without ulceration; mitosis <1/mm2
T1b = Melanomas ≤1.0 mm in thickness with ulceration or mitoses ≥1/mm2
T2a = Melanomas 1.01–2.0 mm in thickness without ulceration
T2b = Melanomas 1.01–2.0 mm in thickness with ulceration
T3a = Melanomas 2.01–4.0 mm in thickness without ulceration
T3b = Melanomas 2.01–4.0 mm in thickness with ulceration
T4a = Melanomas >4.0 mm in thickness without ulceration
T4b = Melanomas >4.0 mm in thickness with ulceration
N1bN1b = 1 regional lymph node metastasis with macrometastasisd
N2bN2b = 2–3 regional lymph node metastases with macrometastasisd
N2cN2c = In transit met(s)/satellite(s) without metastatic lymph nodes
M0No detectable evidence of distant metastases
IIICAny TTX = Primary tumor cannot be assessed (e.g., curettaged or severely regressed melanoma)
T0 = No evidence of primary tumor
Tis = Melanoma in situ
T1a = Melanomas ≤1.0 mm in thickness without ulceration; mitosis <1/mm2
T1b = Melanomas ≤1.0 mm in thickness with ulceration or mitoses ≥1/mm2
T2a = Melanomas 1.01–2.0 mm in thickness without ulceration.
T2b = Melanomas 1.01–2.0 mm in thickness with ulceration
T3a = Melanomas 2.01–4.0 mm in thickness without ulceration
T3b = Melanomas 2.01–4.0 mm in thickness with ulceration
T4a = Melanomas >4.0 mm in thickness without ulceration
T4b = Melanomas >4.0 mm in thickness with ulceration
N3≥4 regional lymph node metastases; or matted nodes; or in transit met(s)/satellite(s) with metastatic lymph node(s)
M0No detectable evidence of distant metastases
T = primary tumor; N = regional lymph nodes; M = distant metastasis.
Adapted with permission from AJCC: Melanoma of the skin. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 325-44.
The explanations for superscripts b–d are at the end of Table 7.

Table 7. TNM Definitions for Stage IV Melanoma
Stage TNM Description Image 
Clinicala Pathologicalb
Enlarge
Stage IV melanoma; drawing shows that the primary tumor has spread to other parts of the body, such as the brain, lung, liver, lymph nodes, small intestine, or bone. The pullout shows cancer in the lymph nodes, lymph vessels, and blood vessel.
Stage IV melanoma.
IVIVAny TTX = Primary tumor cannot be assessed (e.g., curettaged or severely regressed melanoma)
T0 = No evidence of primary tumor
Tis = Melanoma in situ
T1a = Melanomas ≤1.0 mm in thickness without ulceration; mitosis <1/mm2
T1b = Melanomas ≤1.0 mm in thickness with ulceration or mitoses ≥1/mm2
T2a = Melanomas 1.01–2.0 mm in thickness without ulceration
T2b = Melanomas 1.01–2.0 mm in thickness with ulceration
T3a = Melanomas 2.01–4.0 mm in thickness without ulceration
T3b = Melanomas 2.01–4.0 mm in thickness with ulceration
T4a = Melanomas >4.0 mm in thickness without ulceration
T4b = Melanomas >4.0 mm in thickness with ulceration
Any NNX = Regional lymph nodes cannot be assessed (e.g., previously removed for another reason)
N1a = 1 regional lymph node metastasis with micrometastasisc
N1b = 1 regional lymph node metastasis with macrometastasisd
N2a = 2–3 regional lymph node metastases with micrometastasisc
N2b = 2–3 regional lymph node metastases with macrometastasisd
N2c = In transit met(s)/satellite(s) without metastatic lymph nodes
N3 = ≥4 regional lymph node metastases; or matted nodes; or in transit met(s)/satellite(s) with metastatic lymph node(s)
M1M1a = Metastases to skin, subcutaneous, or distant lymph nodes and normal serum LDH
M1b = Metastases to lung and normal serum LDH
M1c = Metastases to all other visceral sites and normal serum LDH; or distant metastases to any site and elevated serum LDH
LDH = Lactate dehydrogenase; T = primary tumor; N = regional lymph nodes; M = distant metastasis.
Adapted with permission from AJCC: Melanoma of the skin. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 325-44.
aClinical staging includes microstaging of the primary melanoma and clinical and/or radiologic evaluation for metastases. By convention, it should be used after complete excision of the primary melanoma with clinical assessment for regional and distant metastases.
bPathologic staging includes microstaging of the primary melanoma and pathologic information about the regional lymph nodes after partial or complete lymphadenectomy. Pathologic stage 0 or stage IA patients are the exception; they do not require pathologic evaluation of their lymph nodes.
cMicrometastases are diagnosed after sentinel lymph node biopsy and complete lymphadenectomy (if performed).
dMacrometastases are defined as clinically detectable nodal metastases confirmed by therapeutic lymphadenectomy or when nodal metastasis exhibits gross extracapsular extension.

References
  1. Melanoma of the skin. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 325-44.