Radiation Oncology/Melanoma/Staging

Melanoma Staging

Clark Levels

• Level I - Confined to epidermis (in situ); not an invasive lesion
• Level II - Invasion of papillary dermis; invasion past basement membrane
• Level III - Papillary dermis filled by tumor and reticular dermis compressed, but not invaded
• Level IV - Invasion of reticular dermis; subcutaneous tissue not involved
• Level V - Invasion of subcutaneous tissue

• Univ Pennsylvania; 1989 PMID 2593166 -- "Model predicting survival in stage I melanoma based on tumor progression." (Clark WH Jr, J Natl Cancer Inst. 1989 Dec 20;81(24):1893-904.)
  • Prognostic model for primary, clinical Stage I cutaneous melanoma. Clark levels defined

Current staging

AJCC 7th Edition (2009)
Primary Tumor:
(Based on thickness, not level of invasion)

• Tis - melanoma in situ (epidermis only)
• T1 - <= 1.0 mm in thickness
  • T1a - no ulceration; mitotic rate < 1/mm2
  • T1b - with ulceration or mitotic rate >= 1/mm2
• T2 - 1.01 - 2 mm in thickness
  • T2a - no ulceration
  • T2b - with ulceration
• T3 - 2.01 - 4 mm in thickness
  • T3a - no ulceration
  • T3b - with ulceration
• T4 - > 4 mm in thickness
  • T4a - no ulceration
  • T4b - with ulceration

Regional Lymph Nodes:

• N0 - no nodes
• N1 - 1 positive lymph node
  • N1a - micrometastasis
  • N1b - macrometastasis
• N2 - 2-3 nodes or intralymphatic regional metastasis without nodal metastasis
  • N2a - micrometastasis
  • N2b - macrometastasis
  • N2c - satellite or in-transit metastasis without nodal metastasis
• N3 - 4 or more nodes, or matted metastatic nodes, or satellite/in-transit metastases with nodal mets

Satellite metastases: defined as grossly visible cutaneous or subcutaneous intralymphatic metastases occurring within 2 cm of primary melanoma
Microsatellites: any discontinuous nest of intralymphatic metastatic cells >0.05 mm in diameter that are clearly separated from the main invasive lesion by a distance of at least 0.3 mm
In-transit metastases: grossly visible cutaneous or subcutaneous intralymphatic metastases more than 2 cm from primary melanoma but before the first echelon of regional lymph nodes

Distant Metastases:

• M1a - metastasis to skin, subcutaneous tissues, or distant lymph nodes
• M1b - metastasis to lung
• M1c - all other visceral sites, or mets to any site with elevated LDH

Clinical Stage Grouping:

Clinical staging is based on information from excision of the melanoma and clinical evaluation for distant metastatic disease but does not include lymphadenectomy

• 0 - Tis
• IA - T1a N0
• IB - T2a or T1b N0
• IIA - T3a or T2b N0
• IIB - T4a or T3b N0
• IIC - T4b N0
• III - Any N+
• IV - Any M1

Note: ulceration (b) upstages by one grouping

Pathologic Stage Grouping:

Includes information obtained from lymphadenectomy

Same as clinical staging except for Stage III

• IIIA - N1a or N2a (micrometastasis), no ulceration (T1-4a)
• IIIB - N1b or N2b or N2c (micromets or satellite), no ulceration (T1-4a); N1a or N2a (micromets), with ulceration (T1-4b)
• IIIC - N1b or N2b or N2c (micromets or satellite), with ulceration (T1-4b); or any N3

Changes from 6th Edition:

• T-stage: T1a vs T1b now includes mitotic rate in addition to ulceration; eliminated use of Clark level. T2-T4 unchanged.
• No changes in N-stage or M-stage
• No changes in Stages I or II.
• No changes in Clinical Stage III
• For Pathologic Stage III, N2c with ulceration reclassified from IIIB to IIIC

Older staging systems

AJCC 6th Edition (2002)

T-stage: (Based on thickness, not level of invasion, except for T1 melanomas)

• Tis - melanoma in situ (epidermis only)
• T1 - <= 1.0 mm in thickness
  • T1a - Clark level II or III, no ulceration
  • T1b - Clark level IV or IV or with ulceration
• T2 - 1.01 - 2 mm in thickness
  • T2a - no ulceration
  • T2b - with ulceration
• T3 - 2.01 - 4 mm in thickness
  • T3a - no ulceration
  • T3b - with ulceration
• T4 - > 4 mm in thickness
  • T4a - no ulceration
  • T4b - with ulceration

N-stage:

• N0 - no nodes
• N1 - 1 positive lymph node
  • N1a - clinically occult (microscopic)
  • N1b - clinically apparent (macroscopic)
• N2 - 2-3 nodes or intralymphatic regional metastasis without nodal metastasis
  • N2a - microscopic
  • N2b - macroscopic
  • N2c - satellite or in-transit metastasis without nodal metastasis
• N3 - 4 or more nodes, or matted metastatic nodes, or satellite/in-transit metastases with nodal mets

M-stage:

• M1a - metastasis to skin, subcutaneous tissues, or distant lymph nodes
• M1b - metastasis to lung
• M1c - all other visceral sites, or mets to any site with elevated LDH

Clinical stage grouping:

Clinical staging is based on information from excision of the melanoma and clinical evaluation for distant metastatic disease but does not include lymphadenectomy

• 0 - Tis
• IA - T1a N0
• IB - T2a or T1b N0
• IIA - T3a or T2b N0
• IIB - T4a or T3b N0
• IIC - T4b N0
• III - Any N+
• IV - Any M1

Note: ulceration (b) upstages by one grouping

Pathologic stage grouping:

Includes information obtained from lymphadenectomy

Same as clinical staging except for Stage III

• IIIA - N1a or N2a, no ulceration (T1-4a)
• IIIB - N1b or N2b, no ulceration (T1-4a); N1a or N2a, with ulceration (T1-4b); or any N2c
• IIIC - N1b or N2b, with ulceration (T1-4b); or any N3

Satellite metastases: defined as intralymphatic metastases occurring within 2 cm of primary melanoma
In-transit metastases: more than 2 cm from primary melanoma but before the first echelon of regional lymph nodes

AJCC 5th edition (1997)
T stage was based primary on Clark level of invasion. Used Breslow thickness as a secondary prognostic factor: with different thresholds of 0.75, 1.5, and 4 mm. Did not include ulceration. Satellite mets were in the T-stage. Thick (>4mm) melanomas were Stage III, not IIC. For N-stage used size not number of mets. Did not use microscopic vs macroscopic. Did not have separate M stage for lung mets. Did not use LDH.

Survival

10-year OS: (estimated from graph, AJCC staging manual)

• Stage IA: 90%, IB: 80%
• Stage IIA: 65%, IIB: 50%, IIC: 35%
• Stage III: 35%
• Stage IV: < 10%