Melanoma of the Skin, Vulva, Penis and Scrotum Staging

Clinical staging is rarely utilized for melanoma due to inaccuracy of the estimation of lesion thickness as well as regional nodal involvement. However, clinical staging may be utilized to stage metastatic melanomas, or when adequate tissue is unavailable for pathologic assessment. Biopsy and pathologic assessment of the entire tumor (not a shave, punch or wedge biopsy) are crucial for accurate staging.

Tumor thickness as defined by the Breslow’s Depth of Invasion is the most important determinant of prognosis for melanomas. Increased tumor thickness is correlated with metastasis and poorer prognosis. Recent findings have shown that the presence of ulceration microscopically is the second most important determinant of prognosis. Clark’s Level of Invasion measures the level of tumor invasion through the layers of the skin, but has recently been shown to affect prognosis only in melanomas that are <1 mm depth.

Breslow’s Depth of Invasion (Thickness)

Breslow’s depth of invasion is an actual measurement of the depth of the lesion, measured vertically in millimeters from the top of the granular layer (or base of superficial ulceration) to the deepest point of tumor involvement. Tumors are classified into four categories based on the depth:

Less than or equal to 0.75 mm (equivalent to Clark’s Level II)

0.76-1.5 mm (equivalent to Clark’s Level III)

1.51-4 mm (equivalent to Clark’s Level IV)

Greater than or equal to 4 mm (equivalent to Clark’s Level V)

Clark’s Level of Invasion

Clark’s level of invasion is based on the level of tumor invasion relative to the layers of the skin. Tumors are classified into five levels:

Level I - All tumor cells are confined to the epidermis, above the basement membrane (in situ)

Level II - Tumor invades into the papillary dermis, past basement membrane

Level III - Tumor fills the papillary dermis and extends to the interface between the papillary and reticular dermis

Level IV - Tumor invades the reticular dermis

Level V - Tumor invasion of subcutaneous tissue

SEER Summary Stage 2000, Breslow’s Depth and Clark’s Level

SEER Summary Stage 2000	Breslow’s Thickness/Depth	Clark’s Level
In Situ	In Situ	Level I
Localized	Less than or equal to 0.75 mm	Level II
	0.76-1.5 mm	Level III
	> 1.5 mm	Level IV
Regional by Direct Extension	Through entire dermis	Level V
Regional by Direct Extension	Satellite nodules < 2cm from primary
Regional Lymph Nodes	See SSS2000 manual for lymph nodes by primary site
Distant	Underlying cartilage, bone, muscle, or metastatic skin lesions

AJCC Staging 5th Edition

Criteria for TNM Clinical Staging: Because thickness is the primary determinant of prognosis, clinical “T” classification is rarely utilized. Excisional biopsy and histopathologic assessment of primary lesion are necessary for proper staging.

Criteria for TNM Pathologic Staging: Pathologic staging is based on Breslow’s thickness and Clark’s level of invasion. Evaluation of entire tumor and adjacent normal skin are required for pathologic staging; wedge, punch and shave biopsies are inadequate. Regional nodes should be evaluated, and size of lymph node metastasis should be recorded.

Stage	TNM Classification	Histological/Clinical Features
0	pTis N0 M0	Intraepithelial/in situ melanoma
I	pT1 N0 M0 pT2 N0 M0	Melanoma < = 0.75 mm in thickness, Clark’s level II Melanoma > 0.75 –1.5 in thickness, Clark’s level III
II	pT3 N0 M0	Melanoma > 1.5-4 mm in thickness, Clark’s level IV
III	pT4 N0 M0 Any pT N1 M0 Any pT N2 M0	Melanoma >4 mm in thickness, Clark’s level V Metastasis 3cm or less in greatest dimension in any regional lymph node Metastasis more than 3cm in greatest dimension in any regional lymph node and/or in-transit metastasis
IV	Any pT Any N M1	Distant metastasis

AJCC 6th Staging Edition (Revised Melanoma Staging, 2002)

The AJCC 6th edition includes a heavily revised staging system for melanoma of the skin. Modifications include incorporation of information regarding the presence of ulceration and number of lymph nodes involved rather than size, so that prognosis may be more accurately assessed. Clark’s level is included only for primary tumors <1 mm in thickness (stages IA and IB), because it has been shown to be of low prognostic value for thicker melanoma. Micrometastasis to regional lymph nodes is differentiated from macroscopic nodal metastasis.

Summary of Revisions to AJCC Staging from 5th to 6th Edition

Factor	AJCC 5th Edition	AJCC 6th Edition
Thickness	Secondary prognostic factor; thresholds of 0.75, 1.5 and 4.0 mm	Primary determinant of T staging; thresholds of 1.0, 2.0 and 4.0 mm
Level of invasion	Primary determinant of T staging	Used only for defining T1 melanomas
Ulceration	Not included	Included as a second determinant of T and N staging
Satellite metastases	In T category	In N category
Thicker melanomas (>4.0 mm)	Stage III	Stage IIC
Size of nodal metastases	Dominant determinant of N staging	Not used
Number of nodal metastases	Not included	Primary determinant of N staging
Metastatic tumor burden	Not included	Included as a second determinant of N staging
Lung metastases	Merged with all other visceral metastases	Separate category as M1b
Elevated serum LDH	Not included	Included as a second determinant of M staging
Clinical vs. pathologic staging	Did not account for sentinel node technology	Sentinel node results incorporated into definition of pathologic staging

(From AJCC 6th Edition staging manual)

Criteria for TNM Clinical Staging: Complete excision of the melanoma, including microstaging, and clinical, radiologic, and laboratory assessment of regional or distant metastasis are required for staging. Microstaging occurs after excisional biopsy with pathologic assessment of Breslow’s thickness, Clark’s level and ulceration.

Criteria for TNM Pathologic Staging: Pathologic staging is based on the same criteria as Clinical Staging, with additional information obtained from pathologic evaluation of regional lymph nodes after sentinel or complete lymphadenectomy, and pathologic confirmation of metastases. Number of lymph node metastases should be recorded, and serum LDH levels should be obtained.

Stage	TNM Classification	Histological/Clinical Features
0	Tis N0 M0	Intraepithelial/in situ melanoma
IA	T1a N0 M0	Melanoma <=1 mm in thickness, Clark’s level II or III, without ulceration
IB	T1b N0 M0 T2a N0 M0	Melanoma <=1 mm in thickness, Clark’s level IV or V, with ulceration Melanoma 1.01-2 mm in thickness without ulceration
IIA	T2b N0 M0 T3a N0 M0	Melanoma 1.01-2 mm in thickness with ulceration Melanoma 2.01-4 mm in thickness without ulceration
IIB	T3b N0 M0 T4a N0 M0	Melanoma 2.01-4 mm in thickness with ulceration Melanoma >4 mm in thickness without ulceration
IIC	T4b N0 M0	Melanoma >4 mm in thickness with ulceration
IIIA	T1-4a N1a M0 T1-4a N2a M0	Single regional nodal microscopic metastasis without ulceration of primary lesion 2-3 microscopic positive regional nodes without ulceration of primary lesion
IIIB	T1-4bN1a M0 T1-4bN2a M0 T1-4a N1b M0 T1-4a N2b M0 T1-4a/b N2c M0	Single regional nodal micrometastasis, with ulceration of primary lesion 2-3 microscopic regional nodes, with ulceration of primary lesion Single regional nodal macrometastasis, without ulceration of primary lesion 2-3 macroscopic regional nodes, without ulceration of primary lesion Satellite or in-transit metastasis without metastatic lymph nodes or ulceration of primary lesion
IIIC	T1-4b N2a M0 T1-4b N2b M0 Any T N3 M0	Single macroscopic regional node, with ulceration of primary lesion 2-3 macroscopic metastatic regional nodes, with ulceration of primary lesion 4 or more metastatic nodes, matted nodes/gross extracapsular extension, or satellite or in-transit metastasis with metastatic lymph nodes
IV	Any T any N M1a Any T any N M1b Any T any N M1c	Metastasis to skin, subcutaneous tissues, or distant lymph nodes Metastasis to lung Metastasis to all other visceral sites or distant metastasis at any site associated with an elevated serum LDH

Collaborative Stage Elements

Fore more details on Collaborative Stage, see the CS module.