- Breslow's depth
Depth of invasion was first reported as a prognostic factor in melanoma by the pathologist Alexander Breslow, M.D. at George Washington University in 1970. In recognition of his contribution, the depth of invasion of melanoma is referred to by the eponym Breslow's depth.
Subsequent studies confirmed and refined the role of depth of invasion in the prognosis of malignant melanoma. Currently, Breslow's depth is included in the AJCC staging guidelines for melanoma as a major prognostic factor.
Breslow's depth is most accurately measured by evaluating the entire tumor via an excisional biopsy. Determination from specimens obtained using other biopsy techniques, such as a wedge or punch biopsy, are less accurate. Breslow's depth cannot be calculated from a shave biopsy that only contains a portion of the tumor because it leads to an underestimation of its thickness.
Breslow's depth is determined by using an ocular micrometer at a right angle to the skin to directly measure the depth to which tumor cells have invaded the skin. Breslow's depth is measured from the granular layer of the epidermis down to the deepest point of invasion (sometimes involving detached nests of cells).
Breslow's depth is one of the cornerstones of the current AJCC TNM staging of malignant melanoma. A large study validated the importance of Breslow's depth as one of the three most important prognostic factors in melanoma (the others being T stage and ulceration). Breslow's depth also accurately predicted the risk for lymph node metastasis, with deeper tumors being more likely to involve the nodes.
The above studies showed that depth was a continuous variable correlating with prognosis. However, for staging purposes, the most recent AJCC guidelines use cutoffs of 1 mm, 2 mm, and 4 mm to divide patients into stages.
Breslow Thickness Approximate 5 year survival <1 mm 95-100% 1 - 2 mm 80-96% 2.1 - 4 mm 60-75% >4 mm 50%
Survival figures from British Association of Dermatologist Guidelines 2002
Breslow thickness in the presence of ulceration also gives useful prognostic information.
Clark's level is a related staging system, used in conjunction with Breslow's depth, which describes the level of anatomical invasion of the melanoma in the skin. Clark's level was the primary factor in earlier AJCC staging schemae for melanoma. However, with further study, it has been shown that Clark's level has a lower predictive value, is less reproducible, and is more operator-dependent as compared with Breslow's depth. Thus, in the current (2010) AJCC staging system, Clark's level has prognostic significance only in patients with very thin (Breslow depth <1 mm) melanomas.
Five anatomical levels are recognized, and higher levels have worsening prognostic implications. These levels are:
- Melanoma confined to the epidermis (melanoma in situ)
- Invasion into the papillary dermis
- Invasion to the junction of the papillary and reticular dermis
- Invasion into the reticular dermis
- Invasion into the subcutaneous fat 
- ^ Thickness, cross-sectional areas and depth of invasion in the prognosis of cutaneous melanoma. Breslow A. Ann Surg 1970; 172:902.
- ^ Primary cutaneous melanoma. Optimized cutoff points of tumor thickness and importance of Clark's level for prognostic classification. Buttner P; Garbe C; Bertz J; Burg G; d'Hoedt B; Drepper H; Guggenmoos-Holzmann I; Lechner W; Lippold A; Orfanos CE; et al. Cancer 1995 May 15;75(10):2499-2506.
- ^ Critical analysis of the current American Joint Committee on Cancer staging system for cutaneous melanoma and proposal of a new staging system. Buzaid AC; Ross MI; Balch CM; Soong S; McCarthy WH; Tinoco L; Mansfield P; Lee JE; Bedikian A; Eton O; Plager C; Papadopoulos N; Legha SS; Benjamin RS. J Clin Oncol 1997 Mar;15(3):1039-51.
- ^ Prognostic factors analysis of 17,600 melanoma patients: validation of the American Joint Committee on Cancer melanoma staging system. Balch CM; Soong SJ; Gershenwald JE; Thompson JF; Reintgen DS; Cascinelli N; Urist M; McMasters KM; Ross MI; Kirkwood JM; Atkins MB; Thompson JA; Coit DG; Byrd D; Desmond R; Zhang Y; Liu PY; Lyman GH; Morabito A. J Clin Oncol 2001 Aug 15;19(16):3622-34.
- ^ Revised American Joint Committee on Cancer staging criteria accurately predict sentinel lymph node positivity in clinically node-negative melanoma patients. Rousseau DL Jr; Ross MI; Johnson MM; Prieto VG; Lee JE; Mansfield PF; Gershenwald JE. Ann Surg Oncol 2003 Jun;10(5):569-74.
- ^ a b Weedon, D. Skin pathology. 2nd Edition. 2002. Sydney: Churchill-Livingstone. ISBN 0-443-07069-5
- Melanoma Staging Systems. National Cancer Institute. A resource on Clark's levels and Breslow's depth.
- Breslow Thickness and Ulceration Predict Survival. Malignant-Melanoma.org. Article demonstrating how Breslow Thickness relates to prognosis and survival time in melanoma.
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