Immediate effects of a public education campaign on prognostic features of melanoma.
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Biomedical subjects
Publications and source records attributed to H Pehamberger.
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The majority of pigmented skin lesions can be diagnosed correctly on the basis of clinical criteria; however, there remain a surprisingly high number of small pigmented lesions in which the distinction between melanocytic and non-melanocytic and benign and malignant lesions, and thus between melanoma and non-melanoma, is difficult or impossible to make with the naked eye. Epiluminescence microscopy is a non-invasive technique that, by use of oil immersion, makes sub-surface structures of skin accessible for in vivo microscopic examination and thus provides additional criteria for the diagnosis of pigmented lesions. The technique of epiluminescence microscopy is reviewed, and the significant improvement in the clinical diagnosis of pigmented skin lesions and, in particular, melanoma by this technique is documented.
Malignant melanoma can be cured if the tumour is recognized at an early phase. Therefore, early recognition is of critical importance and cannot be overemphasized. Epiluminescence microscopy is a non-invasive technique that makes sub-surface structures of skin accessible for in vivo microscopic examination and thus provides additional criteria for the diagnosis of pigmented skin lesions. Thereby preoperative clinical diagnosis can be improved. In order to assess the prognosis of a melanoma patient and to predict the outcome of the disease a number of morphological and immunological parameters these will be reviewed, are helpful.
BACKGROUND: Pigmented Spitz nevi have distinct clinical features but often may be difficult to differentiate from malignant melanoma by clinical criteria. OBJECTIVE: The purpose of this study was to use a new noninvasive diagnostic approach to improve the clinical diagnosis of Spitz nevi. METHODS: Epiluminescence microscopy (ELM) is a new, noninvasive technique for which criteria for the diagnosis of melanocytic tumors, benign and malignant, recently have been established. These criteria were tested in an investigation of 54 pigmented Spitz nevi. RESULTS: With ELM the accuracy of clinical diagnosis of pigmented Spitz nevi improved from 56% (clinical) to 93% (ELM). CONCLUSION: Our findings suggest that ELM criteria are useful to improve the accuracy of clinical diagnosis of Spitz nevi.
19 patients with advanced malignant melanoma were treated with fotemustine and dacarbazine. Data recorded and available for evaluation in all patients included clinical and histopathological parameters of the primary melanoma, blood chemistry, blood cell count, chest X-ray, ultrasound and bone scan for initial staging of the site of metastases and follow-up during treatment. Dosage was fotemustine 100 mg/m2 and dacarbazine 200 mg/m2 intravenously twice monthly on days 1 and 8, repeated for a maximum of six courses. There were two complete and three partial responses in 5/19 patients (26%), and 8 patients (42%) had stable disease. 6 (32%) patients had no response. Median length of complete and partial responses was 3.9 months, and that of stable disease 4.2 months. The main side-effects were thrombocytopenia in 10 patients (53%) and nausea in 6 (32%); the nausea was easily suppressed by ondasetron. Thus, fotemustine-dacarbazine may be new treatment in advanced melanoma.
At present, tumor invasion represents the most reliable prognostic factor for primary malignant melanoma. The 10-year survival rate of "thin" melanomas (Breslow less than 0.76 mm) is more than 95%, but approximately 5% of these low-risk tumors do metastasize. In an attempt to determine prognostic markers for "thin" melanomas we investigated the volume-weighted mean nuclear volume (Vv) of primary melanomas with tumor invasions below 0.76 mm in 32 patients. Ten of these patients had developed melanoma metastases within a mean follow-up period of 49 months; 22 patients who had not developed metastases and who were comparable with regard to clinical and histologic criteria as well as to follow-up period were selected as a comparison group. Vv was determined by computer-assisted image analysis (IBAS 20, Kontron, Germany) on hematoxylin-eosin-stained sections employing stereologic estimation of the volume-weighted mean nuclear volume. In addition, two-dimensional morphometric parameters (nuclear area and shape factors) as well as clinical (sex, age, location) and histologic characteristics (Breslow's thickness, Clark's level, and growth patterns) were recorded. The mean Vv (+/- SD) of primary melanomas with subsequent metastatic course was 273 microns 3 (+/- 81.3), whereas primary melanoma lesions without subsequent metastases exhibited a significantly lower Vv of 154 microns 3 (+/- 25.3) (p = 0.0008). On the other hand, two-dimensional morphometric and clinical and histologic parameters did not correlate with prognosis. Vv thus seems to represent a powerful and independent prognostic marker for "thin" primary melanomas. Assessment of Vv may provide a valuable tool in selecting patients with high-risk stage I, Breslow less than 0.76 mm, melanoma for adjuvant therapy.
The skin of a patient with diffuse melanosis as a result of malignant melanoma was examined by light microscopy, immunohistochemistry, and electron microscopy. Our findings indicate that the slate-blue discoloration in this patient was due to pigment deposition in dermal macrophages and endothelial cells. Multiple attempts to identify disseminated metastatic melanoma cells were unsuccessful.
The present retrospective study includes 12 patients with melanoma of the vulva who underwent vulvectomy between 1977 and 1987. Six patients were less than 55 and 6 other patients more than 69 years old. Three women of the younger age group survived (31, 44 and 116 months, respectively), whereas three of them died of the tumour. In the patient group of over 69 years of age 4 patients died of the tumour, one patient did not appear for follow-up and one further patient died in the meantime. Nine patients suffered from deeply infiltrating tumours (Clark levels IV and V), 2 patients had a Clark level II tumour, and in one case the Clark level was unknown. Depth of infiltration correlated with the prognosis of disease, i.e. only one patient with deep tumour infiltration, but both patients with Clark level II tumours survived. Therefore, the importance of early diagnosis of melanoma of the vulva should be emphasized, and accurate inspection of the vulva should be indispensable in the course of routine gynaecological examination also in younger women.
High-resolution real-time sonography was done in 217 patients with malignant melanoma to compare its value in detecting regional lymph-node metastases with that of palpation. Lymph-node metastases were found in 29 patients by ultrasound whereas, by palpation, metastases were detected in 15 patients only. The presence of metastases was proven by histopathology after surgical lymphadenectomy in these ultrasound positive cases. Thus sonography was superior to palpation, and in addition permitted distinction between metastatic changes and inflammatory lymph-node enlargement. Ultrasound is recommended for preoperative staging as well as in postoperative monitoring of patients with malignant melanoma.
In patients with malignant melanoma elective regional lymph node dissection (ELND) is controversial. This retrospective study evaluated differences in prognosis in patients who were treated with or without ELND. 168 patients were included who initially presented with stage I melanoma (without palpable regional lymph nodes), and who had a minimum observation period of at least 5 years, or had died of malignant melanoma within 5 years of diagnosis. In 66 patients a wide local excision (WLE) followed by ELND was done. In 102 cases only a WLE was done. Assignment of patients to the two groups was non-random but there was no significant difference in age, sex, type and location of primary tumour and depth of invasion. No significant difference was found in survival of the two groups. The 5 year survival of the WLE group was 85.7% and that of the WLE plus ELND group was 89.1%. The 10 year survival rate was 77.9% and 73.1%, respectively. Neither in the whole series nor after sub-division of the patients into three classes according to Breslow depth of invasion (up to 1.5, 1.51-2.5, and greater than 2.5 mm) was a significant influence of ELND on the survival of patients apparent. Cox's regression model did not show ELND as a prognostic factor. ELND cannot be recommended as a routine treatment in patients with stage I melanoma.
Although severe mercury-associated side effects, such as poisoning and high irritant and allergic potential, as well as the weak potency of mercury as an antiseptic or antipsoriatic agent, are well-known, topical mercury preparations are still listed in several pharmacopoeias, including that of the United States, UK and several other European countries. Thus, topical mercurials are still in use, even though more effective and less toxic drugs are now available. We report 2 cases of severe allergic reaction to ammoniated mercury and hope, in agreement with the pertinent literature, to contribute to its removal, and that of most other mercurials, from the therapeutic armamentarium.
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Unstimulated and interferon (IFN)-stimulated natural killer cell (NK) activity was investigated in patients with malignant melanoma prior to the removal of the primary melanoma (stage I disease) or in patients with melanoma metastases. Unstimulated as well as IFN-stimulated NK activities, directed against the primarily NK-sensitive K562 cell line, were found not to differ significantly from the NK activity of healthy control subjects. In contrast, IFN-stimulated NK activity directed against the primarily NK-insensitive Chang hepatoma and JY cell lines was significantly lower in patients with metastatic melanoma than in patients with non-metastatic disease (Chang hepatoma cell line: P less than 0.02; JY cell line: P less than 0.0017) and - in experiments using the JY cell line - than in healthy controls (P less than 0.01). Stage I melanoma patients did not differ in their IFN-induced NK activity from healthy control subjects using Chang hepatoma and JY cell lines. Finally, the IFN-induced increase in NK activity directed against primarily NK-insensitive target cell lines was significant in stage I melanoma patients and in healthy controls (P less than 0.01, respectively), but not in patients with metastatic melanoma (P greater than 0.5). We thus conclude that patients with metastatic malignant melanoma exhibited a defect in IFN-augmented NK activity directed against primarily NK-insensitive targets.
A 40-year-old woman had monthly episodes of angioedema, eruption of pruritic papules and plaques and fever. During acute episodes white blood cell counts increased to 31,000/mm3 with 75% eosinophils, body weight increased to 10% of baseline weight, and urine excretion decreased to 40 ml/24 hours. No evidence was found for cardiac or other visceral organ involvement. Extensive diagnostic evaluations revealed no evidence for parasitic infestation, connective tissue disease, or neoplastic disorders. Results of immunologic studies revealed increased serum IgM and IgE levels and showed elevated levels of circulating activated T-helper cells. Biopsy specimens of lesional skin showed dermal infiltration of lymphocytes and eosinophils with deposition of eosinophil granule major basic protein in the extracellular matrix within the dermis. Immunophenotyping of the dermal infiltrate with monoclonal antibodies revealed the predominance of T-helper cells, many of them expressing the human leukocyte antigen (HLA)-DR, suggesting that angioedema with eosinophilia may be a T-helper cell-mediated disease.
To detect regional lymph node metastases 217 patients with melanoma were examined both sonographically and clinically. Metastases were found in 15 patients by means of palpation, and in 26 patients via ultrasound. Sonography was evidently superior and enabled differentiation between metastatic changes and inflammatory enlargements of lymph nodes. Because of its excellent accuracy ultrasound examination should be performed both in preoperative tumour staging and in posttherapeutic monitoring.
Five cases of verrucous malignant melanoma--a rare variant of melanoma that was described in 1967, but is rarely mentioned today--are presented and the clinical and histopathologic criteria defining this variant are discussed. The importance of this rare entity in the differential diagnosis of verrucous pigmented skin lesions is emphasized.
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