Purpose To revise the staging system for cutaneous melanoma on the basis of data from an expanded American Joint Committee on Cancer (AJCC) Melanoma Staging Database. Methods The melanoma staging recommendations were made on the basis of a multivariate analysis of 30,946 patients with stages I, II, and III melanoma and 7,972 patients with stage IV melanoma to revise and clarify TNM classifications and stage grouping criteria. Results Findings and new definitions include the following: (1) in patients with localized melanoma, tumor thickness, mitotic rate (histologically defined as mitoses/mm 2 ), and ulceration were the most dominant prognostic factors. (2) Mitotic rate replaces level of invasion as a primary criterion for defining T1b melanomas. (3) Among the 3,307 patients with regional metastases, components that defined the N category were the number of metastatic nodes, tumor burden, and ulceration of the primary melanoma. (4) For staging purposes, all patients with microscopic nodal metastases, regardless of extent of tumor burden, are classified as stage III. Micrometastases detected by immunohistochemistry are specifically included. (5) On the basis of a multivariate analysis of patients with distant metastases, the two dominant components in defining the M category continue to be the site of distant metastases (nonvisceral v lung v all other visceral metastatic sites) and an elevated serum lactate dehydrogenase level.

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Final Version of 2009 AJCC Melanoma Staging and Classification

• The initial route of metastases in most patients with melanoma is via the lymphatics to the regional nodes. However, routine lymphadenectomy for patients with clinical stage I melanoma remains controversial because most of these patients do not have nodal metastases, are unlikely to benefit from the operation, and may suffer troublesome postoperative edema of the limbs. A new procedure was developed using vital dyes that permits intraoperative identification of the sentinel lymph node, the lymph node nearest the site of the primary melanoma, on the direct drainage pathway. The most likely site of early metastases, the sentinel node can be removed for immediate intraoperative study to identify clinically occult melanoma cells. We successfully identified the sentinel node(s) in 194 of 237 lymphatic basins and detected metastases in 40 specimens (21%) on examination of routine hematoxylin-eosin—stained slides (12%) or exclusively in immunohistochemically stained preparations (9%). Metastases were present in 47 (18%) of 259 sentinel nodes, while nonsentinel nodes were the sole site of metastasis in only two of 3079 nodes from 194 lymphadenectomy specimens that had an identifiable sentinel node, a false-negative rate of less than 1%. Thus, this technique identifies, with a high degree of accuracy, patients with early stage melanoma who have nodal metastases and are likely to benefit from radical lymphadenectomy. (Arch Surg.1992;127:392-399)

Technical details of intraoperative lymphatic mapping for early stage melanoma.

Tumours grow within an intricate network of epithelial cells, vascular and lymphatic vessels, cytokines and chemokines, and infiltrating immune cells. Different types of infiltrating immune cells have different effects on tumour progression, which can vary according to cancer type. In this Opinion article we discuss how the context-specific nature of infiltrating immune cells can affect the prognosis of patients.

The immune contexture in human tumours: impact on clinical outcome

Pathology and genetics of tumours of the urinary system and male genital organs

PURPOSE: To revise the staging system for cutaneous melanoma under the auspices of the American Joint Committee on Cancer (AJCC). MATERIALS 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 sa...

/pdf/final-version-of-the-american-joint-committee-on-cancer-4h72571lv0.pdf

Final Version of the American Joint Committee on Cancer Staging System for Cutaneous Melanoma

ContextThe incidence of cutaneous melanoma has increased over the past several
decades, making its early diagnosis a continuing public health priority. The
ABCD (Asymmetry, Border irregularity, Color variegation, Diameter >6 mm) acronym
for the appraisal of cutaneous pigmented lesions was devised in 1985 and has
been widely adopted but requires reexamination in light of recent data regarding
the existence of small-diameter (≤6 mm) melanomas.Evidence AcquisitionCochrane Library and PubMed searches for the period 1980-2004 were conducted
using search terms ABCD and melanoma and small-diameter melanoma. Bibliographies of retrieved articles were
also used to identify additional relevant information.Evidence SynthesisAvailable data do not support the utility of lowering the diameter criterion
of ABCD from the current greater than 6 mm guideline. However, the data support
expansion to ABCDE to emphasize the significance of evolving pigmented lesions
in the natural history of melanoma. Physicians and patients with nevi should
be attentive to changes (evolving) of size, shape, symptoms (itching, tenderness),
surface (especially bleeding), and shades of color.ConclusionsThe ABCD criteria for the gross inspection of pigmented skin lesions
and early diagnosis of cutaneous melanoma should be expanded to ABCDE (to
include “evolving”). No change to the existing diameter criterion
is required at this time.

https://jamanetwork.com/journals/jama/articlepdf/199929/jcr40044.pdf

Early Diagnosis of Cutaneous Melanoma: Revisiting the ABCD Criteria

The value of elective lymph node dissection (ELND) for melanoma patients with clinically uninvolved regional nodes remains controversial. However, it has been proposed that selective 'sentinel' lymph node biopsy reliably identifies individuals with micrometastases, who are most likely to benefit from full ELND. The aim of this study was to confirm that metastatic melanoma cells travelling in lymphatics do not bypass the sentinel node. After preoperative lymphoscintigraphy and intraoperative injection of blue dye around the primary melanoma site, sentinel node biopsy was performed in 118 melanoma patients for whom full ELND was planned as part of their definitive surgical treatment. A confidently identified sentinel node was tumour positive in 22 out of 105 regional lymph node fields (21%). In 18 cases the sentinel node was the only node found to be involved and in four cases, additional nodes were positive. In two other patients a positive node was found when the sentinel lymph node had been negative. However, in each case an avoidable error of technique had occurred and definite blue staining indicated that the positive node was in fact another sentinel node. This study thus confirms that sentinel lymph node status reliably indicates whether metastatic melanoma is present in regional lymph nodes.

Sentinel lymph node status as an indicator of the presence of metastatic melanoma in regional lymph nodes.

Purpose To analyze prognostic factors, effects of treatment, and survival for patients with cerebral metastases from melanoma. Patients and Methods All melanoma patients with cerebral metastases treated at the Sydney Melanoma Unit between 1952 and 2000 were identified. From 1985 to 2000, patients were diagnosed and treated using consistent modern techniques and this cohort was analyzed in detail. Multivariate analysis of prognostic factors for survival was performed. Results A total of 1,137 patients with cerebral metastases were identified; 686 were treated between 1985 and 2000. For these 686 patients, the median time from primary diagnosis to cerebral metastasis was 3.1 years (range, 0 to 41 years). A total of 646 patients (94%) have died as a result of melanoma. The median survival from the time of diagnosis of cerebral metastasis was 4.1 months (range, 0 to 17.2 years). Treatment was as follows: surgery and postoperative radiotherapy, 158 patients; surgery alone, 47 patients; radiotherapy alone, 236 ...

Determinants of outcome in melanoma patients with cerebral metastases

Objectives: To create a simple diagnostic method for invasive melanoma with in vivo cutaneous surface microscopy (epiluminescence microscopy, dermoscopy, dermatoscopy) and to analyze the incidence and characteristics of those invasive melanomas that had no diagnostic features by means of hand-held surface microscopes. Design: Pigmented skin lesions were photographed in vivo with the use of immersion oil. All were excised and reviewed for histological diagnosis. A training set of 62 invasive melanomas and 159 atypical nonmelanomas and a test set of 45 invasive melanomas and 119 atypical nonmelanomas were used. Images from the training set were scored for 72 surface microscopic features. Those features with a low sensitivity (0%) and high specificity (>85%) were used to create a simple diagnostic model for invasive melanoma. Setting: All patients were recruited from the Sydney (Australia) Melanoma Unit (a primary case and referral center). Patients: A random sample of patients whose lesions were excised, selected from a larger database. Main Outcome Measures: Sensitivity and specificity of the model for diagnosis of invasive melanona. Results: The model gave a sensitivity of 92% (98/107) and specificity of 71%. Of the 9 "featureless" melanomas the model failed to detect, 6 were pigmented and thin and had a pigment network. The other 3 were thicker, hypomelanotic lesions lacking a pigment network, some with prominent telangiectases, and all with only small areas of pigment. All featureless melanomas noted by the patients had a history of change in color, shape, or size. Conclusions: Surface microscopy does not allow 100% sensitivity in diagnosing invasive melanoma and therefore cannot be used as the sole indicator for excision. Clinical history is an important consideration when featureless lesions are diagnosed. Arch Dermatol. 1996;132:1178-1182

Frequency and Morphologic Characteristics of Invasive Melanomas Lacking Specific Surface Microscopic Features

Twelve clinical and pathologic parameters were compared in two series of Stage I melanoma patients treated at the University of Alabama in Birmingham, USA (676 patients) and at the University of Sydney in New South Wales, Australia (1,110 patients). Actuarial survival rates were virtually the same at the two institutions over a 25-year follow-up period. The incidence of thin melanomas (less than 0.76 mm) was also similar at both geographic locations (25% vs. 26%). Other similarities of these two patient populations included the following: 1) tumor thickness (Breslow Microstaging). 2) level of invasion (Clark Microstaging), 3) surgical results, 4) sex distribution, and 5) age distribution. The greatest differences between the two patient populations were their 1) anatomic distribution, 2) growth pattern, and 3) incidence of ulceration. The trunk was the most common site of melanoma, and occurred more frequently among Australian patients (37% vs. 28%). A multifactorial analysis (Cox's regression model) was then performed that included a comparison of the two institutions as a variable (Alabama vs. Australia). The dominant prognostic factors (p less than 0.0001) were 1) ulceration, 2) tumor thickness, 3) initial surgical management (wide excision +/- node dissection), 4) anatomic location, 5) pathologic stage (I vs. II), and 6) level of invasion. The benefit of elective lymph node dissection was demonstrated in both series for patients with intermediate thickness melanoma (0.76 to 3.99 mm.) For melanomas ranging from 0.76 to 1.5 mm in thickness, the benefit of node dissection was primarily in male patients. Survival rates for melanoma at the two institutions were not significantly different in the multifactorial analysis, even after adjusting for all other variable. Thus, the biologic behavior of melanoma in these two different parts of the world was virtually the same, with only minor differences that did not significantly influence survival rates. Long-term follow-up exceeding eight to ten years after surgery is critical in the interpretation of these prognostic factors and the surgical results.

A comparison of prognostic factors and surgical results in 1,786 patients with localized (stage I) melanoma treated in Alabama, USA, and New South Wales, Australia.

William H. McCarthy

Papers

Early Diagnosis of Cutaneous Melanoma: Revisiting the ABCD Criteria

Sentinel lymph node status as an indicator of the presence of metastatic melanoma in regional lymph nodes.

Determinants of outcome in melanoma patients with cerebral metastases

Frequency and Morphologic Characteristics of Invasive Melanomas Lacking Specific Surface Microscopic Features

A comparison of prognostic factors and surgical results in 1,786 patients with localized (stage I) melanoma treated in Alabama, USA, and New South Wales, Australia.