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Melanoma Treatment (PDQ®)

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Stage Information for Melanoma

Clark Classification (Level of Invasion)
Definitions of TNM

Agreement between pathologists in the histologic diagnosis of melanomas and benign pigmented lesions has been studied and found to be considerably variable. One such study found that there was discordance on the diagnosis of melanoma versus benign lesions in 37 of 140 cases examined by a panel of experienced dermatopathologists.[1] For the histologic classification of cutaneous melanoma, the highest concordance was attained for Breslow thickness and presence of ulceration, while the agreement was poor for other histologic features such as Clark level of invasion, presence of regression, and lymphocytic infiltration. In another study, 38% of cases examined by a panel of expert pathologists had two or more discordant interpretations. These studies convincingly show that distinguishing between benign pigmented lesions and early melanoma can be difficult, and even experienced dermatopathologists can have differing opinions. To reduce the possibility of misdiagnosis for an individual patient, a second review by an independent qualified pathologist should be considered.[2]

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 larger than 1.5 mm in thickness and should always be reported. Accurate microstaging of the primary tumor requires careful histologic evaluation of the entire specimen by an experienced pathologist. Estimates of prognosis should be modified by sex and anatomic site as well as by clinical and histologic evaluation.

Clark Classification (Level of Invasion)
  • Level I: Lesions involving only the epidermis (in situ melanoma); not an invasive lesion.
  • Level II: Invasion of the papillary dermis but does not reach the papillary-reticular dermal interface.
  • Level III: Invasion fills and expands the papillary dermis but does not penetrate the reticular dermis.
  • Level IV: Invasion into the reticular dermis but not into the subcutaneous tissue.
  • Level V: Invasion through the reticular dermis into the subcutaneous tissue.
Definitions of TNM

The American Joint Committee on Cancer (AJCC) has designated staging by TNM classification to define melanoma.[3]

Table 1. Primary Tumor (T)a
aReprinted 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.
TXPrimary tumor cannot be assessed (e.g., curettaged or severely regressed melanoma).
T0No evidence of primary tumor.
TisMelanoma in situ.
T1Melanomas ≤1.0 mm in thickness.
T2Melanomas 1.01–2.0 mm.
T3Melanomas 2.01–4.0 mm.
T4Melanomas >4.0 mm.
Note: a and b subcategories of T are assigned based on ulceration and number of mitoses per mm2 as shown below:
T classification Thickness (mm) Ulceration Status/Mitoses
T1≤1.0a: w/o ulceration and mitosis <1/mm2.
b: with ulceration or mitoses ≥1/mm2.
T21.01–2.0a: w/o ulceration.
b: with ulceration.
T32.01–4.0a: w/o ulceration.
b: with ulceration.
T4>4.0a: w/o ulceration.
b: with ulceration.

Table 2. Regional Lymph Nodes (N)a
NXPatients in whom the regional nodes cannot be assessed (e.g., previously removed for another reason).
N0No regional metastases detected.
N1–3Regional metastases based upon the number of metastatic nodes and presence or absence of intralymphatic metastases (in transit or satellite metastases).
Note: N1–3 and a–c subcategories assigned as shown below:
N Classification No. of Metastatic Nodes Nodal Metastatic Mass
N11a: micrometastasis.b
b: macrometastasis.c
N22–3a: micrometastasis.b
b: macrometastasis.c
c: in transit met(s)/satellites(s) without metastatic nodes.
N3≥4 metastatic nodes, or matted nodes, or in transit met(s)/satellite(s) with metastatic node(s).

No = number.
aReprinted 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.
bMicrometastases are diagnosed after sentinel lymph node biopsy and completion lymphadenectomy (if performed).
cMacrometastases are defined as clinically detectable nodal metastases confirmed by therapeutic lymphadenectomy or when nodal metastasis exhibits gross extracapsular extension.

Table 3. Distant Metastasis (M)a
M0No detectable evidence of distant metastases.
M1aMetastases to skin, subcutaneous, or distant lymph nodes.
M1bMetastases to lung.
M1cMetastases to all other visceral sites or distant metastases to any site combined with an elevated serum LDH.
Note: Serum LDH is incorporated into the M category as shown below:
M Classification Site Serum LDH
M1aDistant skin, subcutaneous, or nodal mets.Normal.
M1bLung metastases.Normal.
M1cAll other visceral metastases.Normal.
Any distant metastasis.Elevated.

LDH = lactate dehydrogenase.
aReprinted 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.

Table 4. Anatomic Stage/Prognostic Groupsa
Stage T N M Stage T N M 
Clinical Stagingb Pathologic Stagingc 
0TisN0M00TisN0M0
IAT1aN0M0IAT1aN0M0
IBT1bN0M0IBT1bN0M0
T2aN0M0T2aN0M0
IIAT2bN0M0IIAT2bN0M0
T3aN0M0T3aN0M0
IIBT3bN0M0IIBT3bN0M0
T4aN0M0T4aN0M0
IICT4bN0M0IICT4bN0M0
IIIAny T≥N1M0IIIAT1–4aN1aM0
T1–4aN2aM0
IIIBT1–4bN1aM0
T1–4bN2aM0
T1–4aN1bM0
T1–4aN2bM0
T1–4aN2cM0
IIICT1–4bN1bM0
T1–4bN2bM0
T1–4bN2cM0
Any TN3M0
IVAny TAny NM1IVAny TAny NM1

aReprinted 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.
bClinical 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.
cPathologic 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.

References
  1. Corona R, Mele A, Amini M, et al.: Interobserver variability on the histopathologic diagnosis of cutaneous melanoma and other pigmented skin lesions. J Clin Oncol 14 (4): 1218-23, 1996.  [PUBMED Abstract]

  2. Farmer ER, Gonin R, Hanna MP: Discordance in the histopathologic diagnosis of melanoma and melanocytic nevi between expert pathologists. Hum Pathol 27 (6): 528-31, 1996.  [PUBMED Abstract]

  3. 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.