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The Revised AJCC Melanoma Staging CriteriaMary M. Feldman, M.D.


THE REVISED AJCC MELANOMA STAGING CRITERIA by Mary M. Feldman, M.D.

The American Joint Committee on Cancer (AJCC) recently published an updated Cancer Staging Manual (7th edition). (1) Multivariate analysis was performed on nearly 40,000 melanoma patients from multiple treatment centers (the Melanoma Task Force).(2) This resulted in modifications to the prior melanoma staging guidelines, which had been in use since 2002. (3) The new system was implemented in January 2010.

The current guidelines are similar to the previous, and many components remain unchanged. Primary tumor thickness continues to be the factor most closely correlated with prognosis. Tumor thickness, divided by even integers, is thus utilized to stratify tumors into risk categories. Within each category, the presence of ulceration upgrades the tumor classification (from a to b). Ulceration is associated with poor prognosis, and an ulcerated tumor has equivalent prognosis to a non-ulcerated tumor in the next higher (increased depth) category. (1)

Thin melanomas (<1.00 mm)
Perhaps the most clinically relevant modifications relate to the stratification of thin melanomas. Nearly 5,000 patients with thin melanomas were included in the Melanoma Task Force. Based on emerging data, mitotic rate was introduced into analyses as an independent variable and was determined to be an important predictor of outcome, second only to the primary tumor thickness. (2, 4, 5) For nonulcerated, thin melanomas, 10 year survival was 95% if there were fewer than 1 mitosis per mm2, compared with 88% 10 year survival if at least one mitosis per mm2 was present. At the same time, level of invasion, as defined by Wallace Clark (6), was found to no longer have statistical significant in staging. Accordingly, for the first time in over 40 years, Clark level has been excluded from the staging system. The mitotic rate (in conjunction with ulceration) has replaced Clark level IV as a determinant of T1a vs. T1b disease. (1, 2)

In the recommended “hot spot” technique, the dermatopathologist begins the mitotic count with the most active tumor focus. Adjacent fields are inspected until a total of 1 mm2 has been examined. The mitotic rate should be reported as “mitoses/mm2.” Stage T1b is defined as tumor thickness ≤1 mm and the presence of either ulceration or increased mitotic rate (≥ 1/mm2). In the event mitotic rate cannot be accurately determined, however, the Clark level is considered; Clark level IV increases a thin melanoma to stage T1b. (1)

KEY FACTS
• New guidelines were implemented in January 2010.
• Tumor thickness and ulceration remain
• Mitotic rate has replaced Clark level for stratification of thin melanomas.
• Sentinel node biopsy (SLNB) is recommended for: T1b, T2, T3 and T4.
• SLNB is a recommended requirement for inclusion in clinical trials.
 
Sentinel lymph node biopsy
Sentinel lymph node biopsy (SLNB) is useful in detecting microscopic nodal disease in patients without clinical adenopathy. Despite considerable controversy regarding its therapeutic utility and cost effectiveness, performance of the sentinel node procedure has become increasingly prevalent over the past several years. This has resulted in a couple of notable changes. First, because microscopic nodal disease has been recognized and grouped with other metastatic disease, the overall survival rate for Stage III has improved. In addition, as SNLB allows for more refined staging, information from clinical trials can be more accurately interpreted. The AJCC now recommends SLNB (or at least discussion of) for patients with T1b, T2, T3 and T4 melanoma. Further, SLNB is a recommended requirement for participation in clinical trials. (1, 2)

Ajcc_staging_080910_table1
Note: cTNM is the clinical classification, TNM is the pathologic classification.

* Macrometastases are diagnosed after sentinel lymph node biopsy and completion lymphadenectomy (if performed).

* Macrometastases are defined as clinically detectable lymph node metastases confirmed by therapeutic lymphadenectomy or when any lymph node metastasis exhibits gross extracapsular extension.

Used with permission of the American Joint Committee on Cancer (AJCC), Chicago, Illinois. The original source for this material is the AJCC Cancer Staging Manual, Seventh Edition (2010) published by Springer New York, Inc.

 
Ajcc_staging_080910_table2

*Clinical staging includes microstaging of the primary melanoma and clinical/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.
. Pathologic staging includes microstaging of the primary melanoma and pathologic information about the regional lymph nodes after the partial or complete lymphadenedtomy. Pathologic Stage 0 or Stage I A patients are the exception; they do not require pathologic evaluation of their lymph nodes.

Used with permission of the American Joint Committee on Cancer (AJCC), Chicago, Illinois. The original source for this material is the AJCC Cancer Staging Manual, Seventh Edition (2010) published by Springer New York, Inc.


Metastatic disease

The histologic examination of the sentinel node has become integral to the staging of early melanomas. Until recently, only tumor identified on routine H&E staining was considered significant. Immunohistochemical markers for melanoma, including Mart-1 and MelanA, increase the sensitivity of tumor detection in the sentinel node. (7) Because this testing is commonly used and widely available, the current guidelines allow the use of melanoma markers in the identification of tumor. (1)

Elevated serum lactate dehydrogenase (LDH) at the time of diagnosis portends a particularly dismal outcome. (8) Multivariate analysis of >7,000 patients with advanced melanoma confirmed elevated LDH as a significant, independent prognostic indicator. (2) In the current Manual, elevated LDH at the time of diagnosis (regardless of site or number of metastases) automatically places a patient into the worst prognostic category, stage M1c.(1)

Melanoma is the seventh most common malignancy in the United States, and the incidence has risen dramatically over the past three decades.(9) As more information becomes available, staging guidelines are periodically modified to better reflect current understanding. The refined classification results in improved prognostic and therapeutic information. Accurate staging is thus critical to the appropriate management of melanoma patients.

 
References:

1. Edge SE, Byrd DR, Compton CC, et al (eds.): AJCC Cancer Staging Manual. New York, NY, Springer, 2009.
2. Balch CM, Gershenwald JE, Soong SJ, et al. Final Version of 2009 AJCC Melanoma Staging and Classification. J Clin Oncol 27:6199-206, 2009.
3. Balch CM, Buziad AC, Soong SJ, et al: Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. J Clin Oncol 19:363548, 2001.
4. Gimotty PA, Elder DE, Fraker DL, et al: Identification of high-risk patients among those diagnosed with thin cutaneous melanomas. J Clin Oncol 25:1129-34, 2007.
5. Kesmodel SB, Karakousis GC, Botbyl JD, et al: Mitotic rate as a predictor of sentinel lymph node positivity in patients with thin melanomas. Ann Surg Oncol 12:449-58, 2005.
6. Clark WH Jr, From L, Bernardino EA, et al. The histogenesis and biologic behavior of primary human malignant melanomas of the skin. Cancer Res 29:705-27, 1969.
7. Spanknebel K, Coit DG, Bieligk SC, et al. Characterization of micrometastatic disease in melanoma sentinel lymph nodes by enhanced pathology: recommendations for standardizing pathologic analysis. Am J Surg Pathol 29:305-17, 2005.
8. Bedikian AY, Johnson MM, Warneke CL, et al. Prognostic factors that determine the long-term survival of patients with unresectable metastatic melanoma. Cancer Invest
26:624-33, 2008.
9. American Cancer Society. Cancer facts & figures, 2008. Atlanta: American Cancer Society. 2008.