The descriptive epidemiology and trends in incidence of nonocular malignant melanoma in Bombay and India

Nonocular malignant melanoma is a rare but lethal disease increasing in incidence and mortality in western countries with improved survival if diagnosed and treated early. This study reports its epidemiology from cancer registry data in six different parts of India; its anatomic distribution and trends in Bombay from 1964 to 1984. Age-adjusted incidence in Bombay patients shows no increase from 1964 to 1984 unlike in white caucasians. Males exceed females in patients 45 years or older unlike whites, but are equalled or exceeded by females in those less than 45 years. The sole of foot and internal mucous membranes are its major anatomic sites in Indians as in negroid blacks. This cancer in Indians resembles that in blacks and nonwhites in affecting less pigmented epithelia and skin. Susceptible melanosomes and ultraviolet light exposure may both be involved in its aetiopathogenesis.     

Prognosis in malignant melanoma

A uniform and practical classification and staging system for melanoma must exist and be widely adopted if useful comparisons between different treatment centers and databases are to be made. This article reviews the 1992 American Joint Committee on Cancer pTNM staging system. In this classification, localized disease without regional nodal involvement is defined as stage I or II, depending on the tumor thickness of the primary melanoma. Regional lymph node involvement and/or in-transit metastasis is defined as stage III, and systemic metastatic disease is defined as stage IV.     

Choroidal malignant melanoma

Choroidal nevi are found on routine fundus evaluations in 1% to 2% of patients. It is felt that these usually benign lesions are the precursors of choroidal malignant melanomas. The incidence of choroidal malignant melanoma in the United States is approximately 6 cases per 1 million persons per year. Diagnosis is multifactorial, based on the tumor's funduscopic, angiographic, and ultrasonographic appearance. Once a melanoma is diagnosed in a patient, a complete metastatic workup is performed. A small tumor is observed for change. Medium-sized tumors are treated with radioactive plaque therapy, external beam radiation, or enucleation. Large tumors are treated with enucleation with or without external beam radiation. Studies are underway to establish the optimum form of treatment.     

Amelanotic malignant melanoma

The purpose of this study was to investigate whether extracellular matrix proteins which influence human keratinocyte behaviour are capable of altering intracellular signalling systems in these cells. The effects of extracellular matrix proteins on two major signal transduction pathways, intracellular calcium and cyclic adenosine monophosphate (cyclic AMP), were investigated. The extracellular matrix proteins examined were the basement membrane preparation matrigel, collagens type I and IV, vitronectin and its active tripeptide component Arg-Gly-Asp (RGD). Acute additions of matrigel, vitronectin and RGD caused rapid transient increases in intracellular calcium and, together with collagen type I, also caused sustained elevations in basal calcium when cells were grown on these substrates. Cyclic AMP production was unaffected by acute exposure to these extracellular matrix proteins. Culture of cells on matrigel, collagen type I or IV, however, significantly reduced basal cyclic AMP accumulation and increased the response of the cells to the receptor-independent agonist forskolin. It is concluded that in vitro some extracellular matrix proteins can initiate both acute and sustained changes in intracellular signalling in human keratinocytes.     

Conjunctival malignant melanoma in children

The first case concerns a 14-year-old girl with a brown conjunctival mass temporally in her right eye which was excised and diagnosed as active conjunctival melanotic lesion. Five years later, a malignant melanoma of the right lacrimal sac and orbit led to general metastatic spread. The second case demonstrates a conjunctival brown mass temporally in the left eye of a 3-year-old boy which enlarged over 4 years. The excision revealed a melanotic lesion which was of uncertain histological dignity. The third case occurred in a 4-year-old boy with a conjunctival glassy tumor temporally in his right eye which after excision led to controversial discussions concerning benign nevus or malignant melanoma.     

Extremity perfusion in malignant melanoma

The Drosophila giant lens (gil) gene encodes a secreted molecule which if absent leads to the recruitment of additional ommatidial cells normally eliminated by apoptosis. Heat induced ectopic gil expression leads to a reduction of ommatidial cells suggesting that gil is secreted by differentiating cells to prevent the development of an excess of cells of a given ommatidial cell type. A second important defect is the misrouting of photoreceptor axons in gil mutants. However, gil function is not required in photoreceptor axons for the establishment of proper connections. We propose that gil acts on the development of lamina cells preventing the correct differentiation of the target region of photoreceptor axons and therefore leading to an axon guidance phenotype.     

Tamoxifen in metastatic malignant melanoma

Eight patients with advanced metastatic malignant melanoma were treated with tamoxifen at a dose of 10 mg orally twice a day for a minimum of 4 weeks. There was one complete response of skin disease occurring over a period of 40 weeks. This patient has remained disease-free for 8+ weeks. Two other patients demonstrated a partial but brief (4 weeks) shrinkage of gross subcutaneous disease. Three patients exhibited no response to the drug, but two patients had rapid acceleration of disease between the second and fourth weeks of treatment. Further exploration of the basis for these favorable and adverse responses is being pursued.     

Prognostic factors in malignant melanoma

The clinical spectrum and biologic behavior of melanoma are heterogeneous. Several clinical factors may include sex, location, and age. Histologic prognostic factors may include tumor type, tumor thickness, and mitotic index in relationship to the primary tumor. With respect to metastatic melanoma, the prognostic factors may include lymph node status, number of lymph nodes, and extracapsular extension. Cytogenetic and molecular determinants of progression of melanoma may aid the current prognostic factors when they are established more firmly. Current surgical treatment is determined by the clinical and histologic factors.     

Prevention of malignant melanoma

Dermatologists and physicians of other specialties, as well as other health professionals have made tremendous efforts to improve the public education (primary prevention) and early detection (secondary prevention) of cutaneous malignant melanoma (CMM) especially during the last decade. In Australia, the country with the highest incidence of CMM in the world, the first public and effective campaigns were already carried out in the sixties. Through the public campaigns, the knowledge increased about skin cancer, and the attitude and behavior toward sun exposure changed in the population. In the USA and Great Britain too, effective public campaigns were carried out in great numbers and extensive experience was acquired. In Germany, prevention campaigns were first run in regional areas. In 1989, the Commission of Early Detection and Prevention of Melanoma of the German Dermatological Society launched nation-wide campaigns. These activities were complemented by regional campaigns in the 1990s. The analysis of previous campaigns demonstrates that single activities are less effective and repeated campaigns are necessary to increase knowledge about skin and to change attitudes and behavior towards UV-exposure. In addition, the development of sun protective clothing and structural changes, e.g. creation of shady places around open-air swimming pools, should be aimed for. Physicians of other specialties and other health professionals should also be included in prevention campaigns.     

Chemotherapy of malignant melanoma

Previous studies have shown the kidney to be an important site for the catabolism of secretin. We have investigated possible sites within the kidney for secretin uptake in four intact anesthetized dogs. The disappearance half-time of an intravenous infusion of secretin, measured by a sensitive and specific ratioimmunoassay in four intact anesthetized dogs was 2.84 minutes. After ureteral ligation (to arrest glomerular filtration), the half-time of a similar intravenous dose of secretin was 2.78 minutes. Finally, the renal vascular pedicles were ligated to totally exclude the kidneys from the circulation and the half-time was found to be 5.43 minutes. These findings demonstrate that the efficient renal mechanisms for secretin degradation are not dependent upon glomerular filtration but upon some other mechanism, presumably located in renal tubular cells.     

Immunology of malignant melanoma

Traditionally a homograft valve is used as a pulmonary replacement device for the Ross operation. Right ventricular outflow tract reconstruction during aortic valve replacement with an autograft was performed with stentless xenograft valves in nine patients. Hemodynamic performance is satisfying, but, long term evaluation is needed.     

Biochemistry of malignant melanoma

The biochemistry of malignant melanoma is reviewed. The biosynthesis of melanin from tyrosine is described and the role of tyrosinase and other enzymes in melanoma considered. Detailed methods for the assay of free catechols, their metabolites and urinary indole melanogens are included. Normal values for these constituents and their significance in the evaluation of melanoma patients are discussed.     

Changing trends in melanoma incidence and mortality

OBJECTIVES: This article analyzes trends in melanoma incidence and mortality rates. Information on sun exposure supplements these statistics. DATA SOURCES: Melanoma incidence data were obtained from the National Cancer Incidence Reporting System and from the Canadian Cancer Registry. Cancer mortality data were extracted from the Canadian Vital Statistics Data Base. Information on sun exposure is from the 1996 Sun Exposure Survey. ANALYTICAL TECHNIQUES: Incidence and mortality rates were age-standardized to the 1991 Canadian population to account for changes in the age structure of the population over time. The average annual percentage changes in age-specific rates were calculated for selected time periods. MAIN RESULTS: After years of steady increases, melanoma incidence and mortality rates have levelled off as a result of declining rates in younger age groups, and for melanoma of the trunk among men and of the leg among women. Incidence rates for men are now higher than those for women; mortality rates for men are twice as high as for women.     

Therapeutic node dissections in malignant melanoma

BACKGROUND: Therapeutic lymphadenectomies involve the dissection and removal of clinically enlarged, histologically positive nodes at the regional nodal basin, in the absence of detectable distant disease. METHODS: The literature dealing with therapeutic lymphadenectomies in malignant melanoma was reviewed. RESULTS: The rate of wound complications varies with the particular nodal basin. The 5-year survival varies from 19% to 38%, with an average of 26%. Survival is affected primarily by the number of histologically positive nodes and extracapsular spread, and secondarily by the extent of disease at the various levels of the nodal basin, fixation of the nodes, and, probably, the preceding disease-free interval. Prognostic parameters of the primary lesion, e.g., thickness, ulceration, and location, also may have an effect on survival. The rate of local recurrence at the nodal basin after lymphadenectomy has varied from 0.8% to 52%. Adjuvant therapy with interferon alfa-2b has improved the 5-year disease-free survival from 26% to 37%. CONCLUSIONS: Therapeutic node dissections in melanoma provide an appreciable 5-year survival rate, which is further augmented by adjuvant therapy. Many series report a significant rate of local recurrence at the nodal basin following therapeutic dissection. Complete lymphadenectomy reduces the rate of local failure with its attendant morbidity.     

Markers of melanogenesis in malignant melanoma

Biochemical specifity of malignant melanoma is represented in part by the formation of specific cytoplasmatic particles of the pigment cell--melanosomes--in which the synthesis of pigment eumelanin and pheomelanin takes place and in part by the presence of a specific enzyme--tyrosinase--which catalyzes the formation of pigment eumelanin and pheomelanin and even the formation of specific metabolites (so called melanogens) which are excreted in increased amounts in the course of the disease. Tyrosinase and melanogens are specific for pigment cell and therefore can be used for monitoring of melanogenesis in malignant melanoma. When comparing our results and the results of other authors we can conclude that following of specific markers of melanogenesis in malignant melanoma should serve for the evaluation of prognosis of the disease. The study of melanoma markers is by far not finished. We do hope that nearly future will be able to give a sufficient answer to the question, whether melanogenuria is actually an expression of expected different biochemical or metabolic types of malignant melanoma on the one hand and/or biochemically or immunologically conditioned responses of the host organism on the other.