Thickness, cross-sectional areas and depth of invasion in the prognosis of cutaneous melanoma.
TL;DR: The depth of invasion was studied using the criteria for staging of Clark et al.2 to see if maximal cross-sectional area, thickness, stage of invasion, or a combination of these can be of value in assessing the prognosis of cutaneous melanoma.
Abstract: CuTANEous melanoma is a most unpredictable lesion. The marked variation in prognosis is probably a function of many variables, one of which is the size of the tumor. Though there is a roughly inverse relationship between the diameter of the lesion and survival,5 very small lesions have recurred or metastasized. One possible reason for the lack of reliability of tumor size in estimating prognosis may be that studies to date have considered size in only two diamensions and have neglected tumor volume. Two melanomas can have the same diameter but differ greatly in thickness because of variation in either depth of invasion or degree of protrusion from the surface of the skin or both. A recent study 2 has shown that prognosis correlates well with staging of the depth of invasion, but there have been no studies relating survival to tumor volume. To measure tumor volume it is necessary to know the surface area of the tumor, but in this retrospective study we only know the maximal diameters of the lesions. By measuring the maximal thickness of the lesions we can calculate the maximal crosssectional area, which should be roughly proportional to the volume of the tumor. The depth of invasion was also studied using the criteria for staging of Clark et al.2 to see if maximal cross-sectional area, thickness, stage of invasion, or a combination of these can be of value in assessing the prognosis of cutaneous melanoma. A total of 98 lesions were so studied.
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TL;DR: This new capillary growth is even more vigorous and continuous than a similar outgrowth of capillary sprouts observed in 2016 and is likely to be accompanied by neovascularization.
Abstract: THE growth of solid neoplasms is always accompanied by neovascularization. This new capillary growth is even more vigorous and continuous than a similar outgrowth of capillary sprouts observed in f...
9,874 citations
TL;DR: Patients with early stage melanoma who have nodal metastases and are likely to benefit from radical lymphadenectomy are identified, with a high degree of accuracy, by a new procedure developed using vital dyes.
Abstract: • 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)
4,169 citations
TL;DR: This revision of the staging system for cutaneous melanoma will become official with publication of the sixth edition of the AJCC Cancer Staging Manual in the year 2002.
Abstract: 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...
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...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....
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TL;DR: The melanoma staging system of the American Joint Committee on Cancer (AJCC) was updated in 2017 as discussed by the authors, with several important changes to the tumor, nodes, metastasis (TNM) classification and stage grouping criteria.
Abstract: Answer questions and earn CME/CNE To update the melanoma staging system of the American Joint Committee on Cancer (AJCC) a large database was assembled comprising >46,000 patients from 10 centers worldwide with stages I, II, and III melanoma diagnosed since 1998. Based on analyses of this new database, the existing seventh edition AJCC stage IV database, and contemporary clinical trial data, the AJCC Melanoma Expert Panel introduced several important changes to the Tumor, Nodes, Metastasis (TNM) classification and stage grouping criteria. Key changes in the eighth edition AJCC Cancer Staging Manual include: 1) tumor thickness measurements to be recorded to the nearest 0.1 mm, not 0.01 mm; 2) definitions of T1a and T1b are revised (T1a, <0.8 mm without ulceration; T1b, 0.8-1.0 mm with or without ulceration or <0.8 mm with ulceration), with mitotic rate no longer a T category criterion; 3) pathological (but not clinical) stage IA is revised to include T1b N0 M0 (formerly pathologic stage IB); 4) the N category descriptors "microscopic" and "macroscopic" for regional node metastasis are redefined as "clinically occult" and "clinically apparent"; 5) prognostic stage III groupings are based on N category criteria and T category criteria (ie, primary tumor thickness and ulceration) and increased from 3 to 4 subgroups (stages IIIA-IIID); 6) definitions of N subcategories are revised, with the presence of microsatellites, satellites, or in-transit metastases now categorized as N1c, N2c, or N3c based on the number of tumor-involved regional lymph nodes, if any; 7) descriptors are added to each M1 subcategory designation for lactate dehydrogenase (LDH) level (LDH elevation no longer upstages to M1c); and 8) a new M1d designation is added for central nervous system metastases. This evidence-based revision of the AJCC melanoma staging system will guide patient treatment, provide better prognostic estimates, and refine stratification of patients entering clinical trials. CA Cancer J Clin 2017;67:472-492. © 2017 American Cancer Society.
1,530 citations
TL;DR: A prognostic model for primary, clinical stage I cutaneous melanoma was developed using the lesional steps in tumor progression and multivariable logistic regression to develop a model that is 89% accurate in predicting survival.
Abstract: We used the lesional steps in tumor progression and multivariable logistic regression to develop a prognostic model for primary, clinical stage I cutaneous melanoma. This model is 89% accurate in predicting survival. Using histologic criteria, we assigned melanomas to tumor progression steps by ascertaining their particular growth phase. These phases were the in situ and invasive radial growth phase and the vertical growth phase (the focal formation of a dermal tumor nodule or dermal tumor plaque within the radial growth phase or such dermal growth without an evident radial growth phase). After a minimum follow-up of 100.6 months and a median follow-up of 150.2 months, 122 invasive radial-growth-phase tumors were found to be without metastases. Eight-year survival among the 264 patients whose tumors had entered the vertical growth phase was 71.2%. Survival prediction in these patients was enhanced by the use of a multivariable logistic regression model. Twenty-three attributes were tested for entry into this model. Six had independently predictive prognostic information: (a) mitotic rate per square millimeter, (b) tumor-infiltrating lymphocytes, (c) tumor thickness, (d) anatomic site of primary melanoma, (e) sex of the patient, and (f) histologic regression. When mitotic rate per square millimeter, tumor-infiltrating lymphocytes, primary site, sex, and histologic regression are added to a logistic regression model containing tumor thickness alone, they are independent predictors of 8-year survival (P less than .0005).
1,160 citations
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TL;DR: In this article, the authors discuss two kinds of failure to make the best use of x2 tests which I have observed from time to time in reading reports of biological research, and propose a number of methods for strengthening or supplementing the most common uses of the ordinary x2 test.
Abstract: Since the x2 tests of goodness of fit and of association in contingency tables are presented in many courses on statistical methods for beginners in the subject, it is not surprising that x2 has become one of the most commonly-used techniques, even by scientists who profess only a smattering of knowledge of statistics. It is also not surprising that the technique is sometimes misused, e.g. by calculating x2 from data that are not frequencies or by errors in counting the number of degrees of freedom. A good catalogue of mistakes of this kind has been given by Lewis and Burke (1). In this paper I want to discuss two kinds of failure to make the best use of x2 tests which I have observed from time to time in reading reports of biological research. The first arises because x2 tests, as has often been pointed out, are not directed against any specific alternative to the null hypothesis. In the computation of x2, the deviations (fi mi) between observed and expected frequencies are squared, divided by mi in order to equalize the variances (approximately), and added. No attempt is made to detect any particular pattern of deviations (fi mi) that may hold if the null hypothesis is false. One consequence is that the usual x2 tests are often insensitive, and do not indicate significant results when the null hypothesis is actually false. Some forethought about the kind of alternative hypothesis that is likely to hold may lead to alternative tests that are more powerful and appropriate. Further, when the ordinary x2 test does give a significant result, it does not direct attention to the way in which the null hypothesis disagrees with the data, although the pattern of deviations may be informative and suggestive for future research. The remedy here is to supplement the ordinary test by additional tests that help to reveal the significant type of deviation. In this paper a number of methods for strengthening or supplementing the most common uses of the ordinary x2 test will be presented and illustrated by numerical examples. The principal devices are as follows:
3,351 citations
Journal Article•
TL;DR: Evidence is presented suggesting that superficial spreading melanoma and lentigo maligna melanoma (Hutchinson9s melanotic freckle) show a long period of superficial growth, followed by the relatively rapid appearance of nodules or deeper invasion within the primary lesion.
Abstract: Summary This paper describes the histogenesis of 3 forms of human malignant melanoma: superficial spreading melanoma, nodular melanoma, and lentigo maligna melanoma. A comparative analysis by computer of the biologic behavior and clinical characteristics of the different neoplasms has been done. An additional 60 tumors have been studied by serial block sectioning. Evidence is presented suggesting that superficial spreading melanoma and lentigo maligna melanoma (Hutchinson9s melanotic freckle), though evolving at different rates, show a long period of superficial growth, followed by the relatively rapid appearance of nodules or deeper invasion within the primary lesion. This change in the nature of the primary lesion may be due to the appearance of one or more strains of cells of aggressive biologic potential. Thus the primary melanoma may exist for a relatively long period of time during which host selectional forces act to permit the growth of quite malignant strains of cells. It is these cells that seem to be capable of deeper growth. The subdivision of each of the forms of melanoma into 5 anatomic levels of invasion permits the accurate assignment of prognosis to each case. It is suggested that melanomas are tumors of the epidermal melanocytes and are not necessarily derived from melanocytic nevi. Each melanoma has a distinctive clinical appearance, even in its superficial and curable phases, and this appearance is the same whether or not the process arose in association with a melanocytic nevus.
2,058 citations
TL;DR: In this article, a criterion for testing null hypotheses of conditional independence of two dichotomous random variables is derived for testing whether the association of the two random variables in the conditional distribution is, in a certain sense, constant.
Abstract: SUMMARY A criterion is derived for testing null hypotheses of conditional independence of two dichotomous random variables. This test has optimum properties when the alternative hypothesis is that the association of the two random variables in the conditional distribution is, in a certain sense, constant.
156 citations
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