F i n a l V e r s i o n o f t h e A m e r i c a n J o i n t C o m m i t t e e o n C a n c e r S t a g i n g S y s t e m f o r C u t a n e o u s M e l a n o m aByMaterials and Methods: The prognostic factors analysis described in the companion publication (this issue), as well as evidence from the published literature, was used to assemble the tumor-node-metastasis criteria and stage grouping for the melanoma staging system.Results: Major changes include (1) melanoma thickness and ulceration but not level of invasion to be used in the T category (except for T1 melanomas); (2) the number of metastatic lymph nodes rather than their gross dimensions and the delineation of clinically occult (ie, microscopic) versus clinically apparent (ie, macroscopic) nodal metastases to be used in the N category; (3) the site of distant metastases and the presence of elevated serum lactic dehydrogenase to be used in the M category; (4) an upstaging of all patients with stage I, II, and III disease when a primary melanoma is ulcerated; (5) a merging of satellite metastases around a primary melanoma and in-transit metastases into a single staging entity that is grouped into stage III disease; and (6) a new convention for defining clinical and pathologic staging so as to take into account the staging information gained from intraoperative lymphatic mapping and sentinel node biopsy. T HE AMERICAN JOINT Committee on Cancer (AJCC)has now formally approved the final version of a revised melanoma staging system, which is described herein, along with operational definitions. The final version is similar to the initial recommendations from the AJCC Melanoma Staging Committee published last year.1 Subsequent to the published recommendations, a number of clinicians made comments and recommendations to members of the AJCC Melanoma Staging Committee. In addition, a major database analysis of prognostic factors involving 17,600 patients from 13 cancer centers and organizations was performed to validate the original proposal.2 Results from the prognostics factors analyses, as well as input from melanoma clinicians, were used by the AJCC Melanoma Staging Committee to make final adjustments to the melanoma staging system, changes that largely impacted the stage grouping criteria. The AJCC Executive Committee has approved the final version of the melanoma staging system. It will become official with publication of the sixth edition of the AJCC Cancer Staging Manual in the year 2002.The AJCC Melanoma Staging Committee used the following guidelines to determine which criteria should be used in the tumor-node-metastasis (TNM) classification and the stage groupings. First, the staging system must be practical, reproducible, and applicable to the diverse needs of all medical disciplines. Second, the criteria must accurately reflect the biology of melanoma based on consistent outcome results of patients treated at multiple institutions from multiple countries. Third, the criteria used must be evidence-based and reflect the dominant prognostic factors cons...

Concomitant tumor immunity describes immune responses in a host with a progressive tumor that rejects the same tumor at a remote site. In this work, concomitant tumor immunity was investigated in mice bearing poorly immunogenic B16 melanoma. Progression of B16 tumors did not spontaneously elicit concomitant immunity. However, depletion of CD4 ϩ T cells in tumor-bearing mice resulted in CD8 ϩ T cell-mediated rejection of challenge tumors given on day 6. Concomitant immunity was also elicited by treatment with cyclophosphamide or DTA-1 monoclonal antibody against the glucocorticoid-induced tumor necrosis factor receptor. Immunity elicited by B16 melanoma cross-reacted with a distinct syngeneic melanoma, but not with nonmelanoma tumors. Furthermore, CD8 ϩ T cells from mice with concomitant immunity specifically responded to major histocompatibility complex class I-restricted epitopes of two melanocyte differentiation antigens. RAG1 ϪրϪ mice adoptively transferred with CD8 ϩ and CD4 ϩ T cells lacking the CD4 ϩ CD25 ϩ compartment mounted robust concomitant immunity, which was suppressed by readdition of CD4 ϩ CD25 ϩ cells. Naturally occurring CD4 ϩ CD25 ϩ T cells efficiently suppressed concomitant immunity mediated by previously activated CD8 ϩ T cells, demonstrating that precursor regulatory T cells in naive hosts give rise to effective suppressors. These results show that regulatory T cells are the major regulators of concomitant tumor immunity against this weakly immunogenic tumor.