Clark Classification (Level of Invasion)
TNM Definitions
Clinical Staging
        AJCC stage groupings
Pathologic Staging
        AJCC stage groupings

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.

• 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.

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

Primary tumor (T)

• TX: Primary tumor cannot be assessed (e.g., shave biopsy or regressed melanoma)
• T0: No evidence of primary tumor
• Tis: Melanoma in situ
• T1: Tumor 1.0 mm or less in thickness with or without ulceration
  • T1a: Tumor 1.0 mm or less in thickness and Clark level II or III with no ulceration
  • T1b: Tumor 1.0 mm or less in thickness and Clark level IV or V or with ulceration
• T2: Tumor more than 1.0 mm but 2.0 mm or less in thickness with or without ulceration
  • T2a: Tumor more than 1.0 mm but 2.0 mm or less in thickness with no ulceration
  • T2b: Tumor more than 1.0 mm but 2.0 mm or less in thickness with ulceration
• T3: Tumor more than 2.0 mm but 4.0 mm or less in thickness with or without ulceration
  • T3a: Tumor more than 2.0 mm but 4.0 mm or less in thickness without ulceration
  • T3b: Tumor more than 2.0 mm but 4.0 mm or less in thickness with ulceration
• T4: Tumor more than 4.0 mm in thickness with or without ulceration
  • T4a: Tumor more than 4.0 mm in thickness without ulceration
  • T4b: Tumor more than 4.0 mm in thickness with ulceration

Regional lymph nodes (N)

• NX: Regional lymph nodes cannot be assessed
• N0: No regional lymph node metastasis
• N1: Metastasis to one lymph node
  • N1a: Clinically occult (microscopic) metastasis
  • N1b: Clinically apparent (macroscopic) metastasis
• N2: Metastasis to two or three regional nodes or intralymphatic regional metastasis without nodal metastases
  • N2a: Clinically occult (microscopic) metastasis
  • N2b: Clinically apparent (macroscopic) metastasis
  • N2c: Satellite or in-transit metastasis without nodal metastasis
• N3: Metastasis in more than four regional nodes, or matted lymph nodes, or in-transit metastasis or satellite(s) with metastatic regional node(s)

   [Note: Micrometastases are diagnosed after elective or sentinel lymphadenectomy; macrometastases are defined as clinically detectable lymph nodes metastases confirmed by therapeutic lymphadenectomy, or when any lymph node metastasis exhibits gross extracapsular extension.]

Distant Metastasis (M)

• MX: Distant metastasis cannot be assessed
• M0: No distant metastasis
• M1: Distant metastasis
  • M1a: Metastasis to skin, subcutaneous tissues, or distant lymph nodes
  • M1b: Metastasis to lung
  • M1c: Metastasis to all other visceral sites or distant metastasis at any site associated with an elevated serum lactic dehydrogenase

Clinical staging includes microstaging of the primary melanoma and clinical and/or radiologic evaluation for metastases. By convention, it should be assigned after complete excision of the primary melanoma with clinical assessment for regional and distant metastases.[3]

Stage 0

• Tis, N0, M0

Stage IA

• T1a, N0, M0

Stage IB

• T1b, N0, M0
• T2a, N0, M0

Stage IIA

• T2b, N0, M0
• T3a, N0, M0

Stage IIB

• T3b, N0, M0
• T4a, N0, M0

Stage IIC

• T4b, N0, M0

Stage III

• Any T, N1, M0
• Any T, N2, M0
• Any T, N3, M0

Stage IV

• Any T, any N, M1

With the exception of clinical stage 0 or stage IA patients (who have a low risk of lymphatic involvement and do not require pathologic evaluation of their lymph nodes), pathologic staging includes microstaging of the primary melanoma and pathologic information about the regional lymph nodes after sentinel node biopsy and, if indicated, complete lymphadenectomy.[3]

Stage 0

• Tis, N0, M0

Stage IA

• T1a, N0, M0

Stage IB

• T1b, N0, M0
• T2a, N0, M0

Stage IIA

• T2b, N0, M0
• T3a, N0, M0

Stage IIB

• T3b, N0, M0
• T4a, N0, M0

Stage IIC

• T4b, N0, M0

Stage IIIA

• T1–4a, N1a, M0
• T1–4a, N2a, M0

Stage IIIB

• T1–4b, N1a, M0
• T1–4b, N2a, M0
• T1–4a, N1b, M0
• T1–4a, N2b, M0
• T1–4a/b, N2c, M0

Stage IIIC

• T1–4b, N1b, M0
• T1–4b, N2b, M0
• T1–4b, N2c, M0
• Any T, N3, M0

Stage IV

• Any T, any N, M1

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: American Joint Committee on Cancer.: AJCC Cancer Staging Manual. 6th ed. New York, NY: Springer, 2002, pp 209-220. 
   
   

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