Evaluation of new putative tumor markers for melanoma

Background: The early diagnosis of recurrent melanoma can contribute to better outcome if the disease can be surgically resected or if the metastases are responsive to systemic therapies. Lipid-associated sialic acid (LASA-P) and the S-100 protein (S-100) were evaluated as tumor markers for melanoma with the goal of early detection of recurrence. Methods: Sixty-seven patients were identified who had levels of S-100 and LASA-P drawn during their clinical course. A multivariate regression analysis was performed to determine the significance of the serum markers in relation to other prognostic factors for melanoma. Results: After a median follow-up of 30 months, 58 patients had recurrences, and 49 patients died of disease. LASA-P elevation was not associated with the time to recurrence (p=0.2176) or survival (p=0.2507). S-100 positivity was a significant predictor of recurrence (p<0.0001) and survival (p=0.0059). The median time to recurrence for S-100-positive and S-100-negative patients was 7.6 and 33.8 months, respectively. The median survival time was 59.2 months for S-100-negative patients and 29.6 months for patients positive for S-100. Conclusions: Serum S-100 shows significant correlations to both time to recurrence and survival and could be useful in the clinical detection of malignant melanoma.Presented at the 47th Annual Cancer Symposium of The Society of Surgical Oncology, Houston, Texas, March 17–20, 1994.     

Immunotherapy for malignant melanoma with a tumor cell vaccine.

Specific active immunotherapy for melanoma has been administered to several thousand patients since 1972, using an irradiated whole-cell preparation. A humoral response to vaccination can be demonstrated in a large percentage of patients. This response increases while immunizations are continued and decreases after cessation of therapy. The vaccinations are well tolerated; however, the therapeutic impact of this whole-cell vaccine awaits a randomized trial for definitive evaluation.     

Desmoplastic malignant melanoma: An aggressive tumor

Summary The clinical features and histological appearance of desmoplastic malignant melanoma are presented. Aggressive surgical management and close follow-up are mandatory if this highly aggressive tumor is to be controlled. Despite this, the prognosis is poor.     

Prognostic evaluation of intracranial metastasis in malignant melanoma

Background: Malignant melanoma (MM) is often reported as the third most common cause of intracranial metastasis (IM) after carcinoma of the breast and lung. Most patients with advanced MM will have widespread extracranial disease, but the majority will die from intracerebral spread. Methods: A retrospective review of 117 patients with documented IM from MM over the past 25 years was undertaken. Various factors (including age, race, sex distribution, primary lesions with Clark's level, Breslow's thickness, primary sites and staging at initial presentation, diagnosis of IM and its various treatment methods, survival data, and autopsy findings) were analyzed. Prognostic indicators were clarified from this analysis as a predictor of central nervous system (CNS) metastasis. An ideal treatment plan was also analyzed in order to predict a better survival. Results: Fifty-eight percent of patients were male; 42% were female. Seventy-one percent of the primary lesions were of Clark's level IV and V, with mean Breslow's thickness of 3.5 mm. Median time interval between the initial diagnosis and development of IM was 3.5 years. Complete surgical resection of the intracranial lesion in the brain resulted in the longest mean survival of 10.3 months, whereas mean survival for the group with no treatment was only 3 weeks. Patients with primary lesions of the head and neck had the lowest mean survival of 3.3 months, whereas those whose primary sites were unknown had the longest mean survival of 7.5 months. One- and 2-year survival were 9% and 3%, respectively. All but one of the 30 patients at autopsy were found to have visceral metastasis, namely of the lung, liver, and bone. Conclusion: An aggressive search for metastasis should be undertaken in patients at high risk of developing CNS metastasis, e.g., male, head and neck primary, Clark's level IV and V, Breslow's thickness of >3 mm, and presence of visceral metastases, mainly lung. A complete surgical resection should be attempted whenever possible, with adjunctive use of whole-brain irradiation, along with systemic chemotherapy for further control of recurrence and to prolong survival.Presented at the 46th Annual Cancer Symposium of the Society of Surgical Oncology, Los Angeles, March 18–21, 1993.     

Molecular oncogene markers and their significance in cutaneous malignant melanoma

Background: Oncogenes and other molecular tumor markers that predict tumor aggressiveness may allow individualization and optimization of surgical therapy of intermediate-thickness malignant melanoma. We examined the expression of selected markers, including the HLA-DR antigen, the heat shock protein-70 (HSP-70), and the c-myc oncogene in primary melanoma and regional nodes and related these findings to metastatic potential and survival. Methods: Forty patients with primary melanoma (1.5–4.0 mm) were studied, all of whom had prophylactic lymph node dissection and were followed for 18 months to 7 years. The primary tissue and nodes were examined using immunohistochemical techniques for the presence of HLA-DR antigen and HSP-70 protein and the expression of the c-myc oncogene. Results: Of 40 patients, there were 23 with lesions 1 to 2.9 mm thick and 17 with lesions 3 to 4 mm thick. Nodal metastases were present in 25 of the 40 patients who had elective node dissection. HLA-DR antibody stained the primary tumor in 10 patients (25%), but there was no correlation with survival in this group. HLA-DR antibody stained the stroma and cellular infiltrates surrounding the primary tumor in 28 of 40 patients; in this group there was a correlation of HLA-DR staining of the peritumoral stroma with improved survival overall. HLA-DR staining of the peritumoral stroma also influenced survival when patients were stratified by tumor thickness groups 1 to 2.9 mm and 3 to 4 mm and presence of nodal metastases. HSP-70 was demonstrated in the primary tumor in 25% of patients, who were also shown to have significantly improved survival when compared with those whose primary tumor did not stain with HSP-70. C-myc was expressed in the primary tumor in 25%, but showed no correlation with survival. None of these proteins correlated with or predicted the presence of nodal metastases. Conclusion: We conclude that the use of specific molecular-oncogene markers in intermediate-thickness primary melanoma may identify patients at high risk for conventional treatment failure and reduced survival who may profit from more aggressive surgery, adjuvant therapy, or both.Presented at the 48th Annual Cancer Symposium of The Society of Surgical Oncology, Boston, Massachusetts, March 23–26, 1995.     

The learning curve for sentinel node biopsy in malignant melanoma.

Sentinel node biopsy (SNB) has emerged as an accurate means of identifying nodal micrometastasis in cutaneous melanoma. In order to assess our learning curve, we compared our first 30 cases with our subsequent 30 cases. A total of 60 patients underwent SNB for cutaneous melanoma, using preoperative lymphoscintigraphy together with the intraoperative use of a Neoprobe and Patent Blue V dye. At least one sentinel node was identified in 93% of patients (90% in our first 30 cases; 97% in our subsequent 30 cases). Sentinel nodes contained tumour in 21% of cases. Of the sentinel nodes that contained tumour in the first 30 cases, 87% were identified by Neoprobe examination and 60% using blue dye. In the second 30 cases, the tumour-containing sentinel nodes were identified in all cases by both the Neoprobe and the blue dye. The sentinel node appeared to be the only involved node in 71% of patients. In the first 30 patients, one patient with a negative sentinel node developed nodal recurrence. These data confirm the feasibility of the sentinel-node technique in cutaneous melanoma. However, there is a learning curve, and the technique should be performed only by limited numbers of people with suitable training.     

Hypercalcemia and malignant melanoma.

Malignant melanoma occurs in approximately 1.7 per cent of all patients admitted to the Clinical Center, National Institutes of Health, and approximately 1.8 per cent of patients admitted with hypercalcemia and malignant disease. The incidence of hypercalcemia and malignant melanoma is 1.1 per cent. Bone metastases are diagnosed before death in approximately 5.2 per cent of patients with malignant melanoma. The cause of hypercalcemia in our patients appears to be bone metastases in 83.3 per cent and primary hyperparathyroidism in 16.9 per cent.     

3项肿瘤标志物联合检测在肺癌诊断中的价值

目的:探讨联合检测血清癌胚抗原(CEA)、细胞角蛋白19片段(CYFRA21-1)、神经元特异性烯醇化酶(NSE)水平对肺癌的诊断价值.方法:用电化学发光法检测113例肺癌确诊患者、60例肺良性病变患者血清中CEA、CYFRA21-1、NSE水平.结果:肺癌组CEA、CYFRA21-1、NSE检测阳性率均明显高于肺良性...     

Surgical prophylaxis of malignant melanoma.

A review of a 14-year experience with prophylactic pigmented skin lesion removal is presented. Data obtained during a 4-year interval of this 14-year experience is analyzed specifically. During this 4-year interval, 250 patients with melanoma were seen. Of these patients, 75 with a history of stage I (localized) melanoma and three patients with stage II (history of controlled regionally metastatic melanoma) underwent removal of multiple skin lesions on a prophylactic basis. Of the removed lesions, 28% showed hyperplasia, atypia, dysplasia, or melanoma. Nine unsuspected in situ, or level I melanomas, and three unsuspected invasive melanomas were removed from these 75 melanoma patients while excising lesions prophylactically during the 4-year interval. It is estimated that four to six additional melanomas were prevented by excision of precursor lesions. During the same 4-year interval, an additional 112 of approximately 1000 patients without a previous history of melanoma underwent prophylactic lesion removals. In 31% of the 112 patients, there was a history of melanoma in a first-degree relative. In 22% of the removed lesions there was hyperplasia, atypia, or dysplasia. Three cases of melanoma in situ were detected and it is estimated that an additional three to five cases of melanoma were prevented. Atypical findings occurred in 71, or 63%, of the patients biopsied, which represented 7% of the approximately 1000 patients screened. During the 4-year interval, an average of 17.7 lesions were removed from each of the 190 melanoma and nonmelanoma patients undergoing prophylactic skin lesion excision. This was accomplished in one to four sessions per patient. This average reflects only those patients who underwent one excision or more and does not include those patients treated without operation. When including the nonoperated patients screened during this interval, the average number of lesions removed was 2.7 per patient. Death from new melanomas was prevented during the 14-year period of this study as evidenced by the fact that no patient died or developed metastatic disease from a cutaneous melanoma that was not apparent or known about at the time of first examination.     

Metastatic malignant melanoma resembling malignant peripheral nerve sheath tumor: report of 16 cases

We report 16 cases of metastatic malignant melanoma presenting clinically as lymphadenopathy or a soft-tissue mass and histologically resembling malignant peripheral nerve sheath tumor (MPNST). In two cases, the metastatic malignant melanoma was preceded by a primary cutaneous malignant melanoma; in four cases, it presented synchronously with such a tumor; and in 10 cases, there was no evidence of a previous or concomitant malignant skin lesion. Histologically, the tumors were characterized by a malignant-appearing spindle cell proliferation arranged in fascicles, often accompanied by a peritheliomatous growth pattern, alternating hypercellular and hypocellular areas, numerous mitoses, and foci of necrosis. In nine cases, there was residual lymph node tissue. In none of the cases was there evidence of an anatomic connection with a nerve, a coexistent neurofibroma, or the stigmata of neurofibromatosis. Fourteen of the cases showed strong and generally diffuse immunoreactivity for S-100 protein, and five cases showed positivity for HMB-45. Four of eight patients with follow-up information died of the disease. Tumors with a microscopic appearance compatible with MPNST but showing strong diffuse S-100 protein staining and featuring remnants of lymph node may represent metastatic malignant melanomas and should elicit a search for a previous or concomitant tumor in the skin and other sites. The similarities these tumors share with MPNST are probably related to their common neuroectodermal histogenesis.     

Thoracotomy for metastatic malignant melanoma of the lung.

The outcome of 29 patients who underwent lung resection for treatment of metastatic malignant melanoma from January 1976 to November 1988 was studied. Twenty-two patients underwent total resection for cure of all apparent metastatic disease, whereas seven patients did not undergo total resection. Of the 22 patients who underwent curative resection, the median survival was 11 months, with a 2-year survival of 13.6% and a 5-year survival of 4.5%. Four patients who underwent curative resection are currently alive and free of disease, with one patient surviving more than 10 years. The patients who underwent palliative resection had a median survival of 5 months, only one patient living longer than 10 months. The difference in survival of the patients who underwent curative resection compared with palliative resection was statistically significant. The thickness of the primary cutaneous malignant melanoma, the presence of regional lymph node metastases, the disease-free interval from primary diagnosis to metastatic pulmonary disease, and whether one or two metastatic nodules were removed during curative lung resection were not statistically significant in altering survival. These results demonstrate that although prolonged survival for metastatic melanoma is rare, lung resection in selected patients may be associated with long-term survival.