Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Development of multiple primary melanomas is a rare but well recognized disease, with an estimated incidence ranging from 1.75% to 8.5% in several series. The clinical, histological and epidemiological characteristics of 49 patients, identified from 2470 with histologically confirmed melanoma, are described in this study. Thirty-five of these patients had two primary melanomas, 11 had three melanomas and three had four, five and six melanomas, respectively. Diagnosis was concurrent in 22 patients (45%); in the remaining cases the median time interval between the first and second melanoma was 22.6 months and the longest interval was 21.5 years. The mean Breslow's thickness decreased significantly (P < 0.001) from the first melanoma to the second and third lesion. The multiple melanoma patients had a higher percentage of subjects over 70 years of age or with lentigo maligna melanoma than single melanoma patients. The mean follow-up time was 12 years (range 4 23 years). The 5-year survival rate from first melanoma excision (83%) does not differ from that of patients with a single melanoma. In conclusion, the presence of multiple primary melanomas does not appear to be a negative prognostic factor; our data show the importance of close follow-up in melanoma patients in order to detect not only metastases, but also subsequent primaries in their earliest phases.
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PMID:Multiple primary melanomas: analysis of 49 cases. 976 12

We have examined the expression of the cellular apoptosis susceptibility protein, a nuclear transport factor that plays a role in apoptosis and cell proliferation, in benign and malignant melanocytic lesions. Tissue samples of 55 formalin-fixed, paraffin-embedded melanoma (primary n=32, metastatic n=23) and of 27 control cases (junctional dermal, compound, Spitz, Reed, blue nevi, balloon-cell nevus, lentigo maligna) were analyzed by immunohistochemistry with anti-cellular apoptosis susceptibility antibodies. The percentage of cellular apoptosis susceptibility-positive cells as well as the intensity on a four-point scale was evaluated. In normal skin, expression of cellular apoptosis susceptibility was primarily found in the basal cell layer of the epidermis. Benign melanocytic lesions that stained positive for cellular apoptosis susceptibility (13 of 27) showed a homogeneously distributed staining pattern with a mean of 5+/-12% cellular apoptosis susceptibility positive cells. Five out of 7 lentigo maligna melanoma, 11 out of 12 superficial spreading melanoma and all acrolentiginous (n=7) and nodular (n=6) melanoma showed immunoreactivity of medium (++) to high ( ) intensity. Vertical growth phases of primary cutaneous melanoma stained stronger than horizontally growing cell clusters. All metastases (n= 23) stained strongly positive, the staining pattern being inhomogeneous. Cellular apoptosis susceptibility detection in clinical stages according to UICC showed an increase from 43+/-34% cellular apoptosis susceptibility positive cells in stage I, to 53+/-26% in stage II, 68+/-24% in stage III and 72+/-24% in stage IV, respectively. Because the expression of cellular apoptosis susceptibility correlates predominantly with advanced stages of melanoma, staining with anti-cellular apoptosis susceptibility antibodies may be useful for diagnosis of melanoma and possibly as an immunohistochemical prognostic factor in cutaneous melanocytic lesions.
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PMID:Expression of the proliferation and apoptosis-associated CAS protein in benign and malignant cutaneous melanocytic lesions. 1021 71

The 20-year radiotherapy (RT) experience in patients with locally advanced, recurrent or metastatic malignant melanoma (MM) is analyzed with respect to different endpoints and prognostic factors. From 1977 to 1995, 2917 consecutive patients were entered in our MM registry. RT was indicated in 121 patients (56 females, 65 males) for palliation in advanced MM stages. The histology of the primary lesion was nodular in 51, superficial spreading in 35, acral-lentiginous in 8 and lentigo maligna in 4 patients); 22 were missing or could not be reclassified. Eleven patients had primary or recurrent lesions which were ineligible for surgery or had residual disease (R2) after resection of a primary or recurrent lesion (UICC IIB); 57 patients had lymph node (33) or in-transit metastases (24) (UICC III), 53 had distant organ metastases (7 M1a; 46 M1b) (UICC IV). Time from first diagnosis to on-study RT averaged 19 (median: 18; range: 3-186) months. In most cases conventional RT was applied (2-6 Gy single fractions) up to a mean total RT dose of 45 (median: 48; range: 20-66) Gy. At 3 months follow-up (FU), complete response (CR) was achieved in 7 (64%) and overall response (CR+PR) in all (100%) UICC IIB patients, in 25 (44%)/44 (77%) of 57 UICC III patients, and in 9 (17%)/26 (49%) of 53 UICC IV patients. Progression during RT occurred in 25 (21%) patients. Patients with CR survived longer (median: 40 months) than those without CR (median: 10 months) (p<0. 01). At last FU, 26 patients were alive: 6 (55%) UICC IIB, 17 (30%) UICC III, and 3 (6%) UICC IV patients (p<0.01). In univariate analysis following favorable prognostic factors for CR and long-term survival were identified: low UICC stage (p<0.001), primary site head and neck and total dose >40 Gy (all p<0).
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PMID:[Long term results following radiation therapy of locally recurrent and metastatic malignant melanoma]. 1046 Mar 1

Between 1987 and 1998, 64 patients with lentigo maligna (LM) (n = 42) or lentigo maligna melanoma (LMM) (n = 22) were treated by fractionated radiotherapy. In all 22 patients with LMM, excision of the nodular part of the LMM was performed before radiation of the residual lentiginous tumor. During the follow-up period of 1 to 96 months (mean, 23 months; median, 15 months), none of the 42 patients with LM displayed any signs of recurrence of LM after radiation therapy alone. Of the 22 patients with LMM, only 2 patients showed local recurrence of the tumor, salvaged by excision in both cases. One patient with LMM suffered from metastatic disease without local recurrence of the melanoma 44 months after radiation therapy. The cosmetic results of radiotherapy were good or excellent in the vast majority of patients, with only a few experiencing hypopigmentation or hyperpigmentation in the irradiated area. Fractionated radiation therapy with superficial x-rays is an effective method of treatment of LM associated with low morbidity and leading to clinical results comparable to those of surgical excision.
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PMID:Fractionated radiotherapy of lentigo maligna and lentigo maligna melanoma in 64 patients. 1095 59

Ku70 and Ku80 heterodimers function as regulatory subunits of the DNA-dependent protein kinase and play a very important role in the repairing of DNA double-strand breaks. Although Ku70 is proposed as a candidate for a tumor suppressor gene, not many data are available on Ku70 and Ku80 expression in human tumors. The main aim of this study was to investigate the expression of Ku70 and Ku80 in the ultraviolet-induced lesions-nevus cell nevi, lentigos maligna, and malignant melanomas. Nineteen nevus cell nevi, 23 lentigos maligna, 76 primary melanomas, and 31 melanoma metastases were stained immunohistochemically for the presence of Ku70 and Ku80 proteins. Ku70 and Ku80 expression was preserved in about 80% of nevi, 26% of lentigo maligna, 45% of primary melanomas, and 67% of melanoma metastases. Highly significant differences in Ku70 and Ku80 expression were found between nevi, lentigo maligna, and melanomas. In Cox regression, Ku70 and Ku80 were shown to be highly significant influences on patients' prognosis. Significant correlations between Ku70 and Ku80 expressions were found in nevi, lentigo maligna, and primary melanomas. These correlations were not more present in melanoma metastases. To summarize, earlier phases of melanoma progression seem to be connected with the loss of expression of Ku proteins. Metastatic spread is related to dysregulation of the Ku70 and Ku80 axis.
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PMID:Differential expression of DNA nonhomologous end-joining proteins Ku70 and Ku80 in melanoma progression. 1195 Sep 17

Melanoma is a significant health problem. Despite public education and free cancer screenings, the incidence and mortality of melanoma continues to rise; however, many currently diagnosed melanomas are thin lesions, suggesting that education and awareness is having an impact. In addition, there are still subsets of patients who need increased surveillance in order to increase their survival. Although large congenital nevi may be precursors of melanoma, small and medium congenital nevi have an insignificant risk for melanoma development. Large congenital nevi, which are axial in location, appear to be more likely to develop melanoma and are associated with melanocytosis and melanoma of the CNS, both of which portend a poor prognosis. Recently, the recommended margins of excision have become more conservative so that many of the surgical defects can be closed primarily. Lymphoscintigraphy and sentinel node biopsy have replaced elective node dissections, thus decreasing the morbidity associated with the surgical management of melanoma. Although controversy still exists as to whether or not sentinel lymph node biopsy alters a patient's prognosis, it has been shown to be a powerful prognostic indicator. Although most melanomas are managed by routine surgical excision, other modalities are sometimes employed. For example, cryosurgery or radiation therapy may be indicated in the frail, elderly individual with a large facial lentigo maligna. Mohs surgery is the treatment of choice for head and neck melanomas and those located in areas where maximum preservation of tissue is required and for desmoplastic and acral lentiginous melanomas. Much more work remains in the area of adjuvant therapy, chemotherapy, and immunotherapy. Dacarbazine remains the drug of choice in disseminated melanoma, but remissions are usually short lived. Interleukin and biochemotherapy has yielded good results but the percentage benefiting is small. Although high dose interferon increases disease-free and overall survival in some patients, it remains a controversial drug which is not easily tolerated. In the new staging system for melanoma, ulceration is second only to Breslow's thickness. In transit (satellite) lesions have also been included in this new system. The new system also recognizes that patients with only microscopic metastatic nodal disease fare better than patients with clinically enlarged metastatic nodes and that it is the number of nodes involved with metastases, not their size, that determines the patient's prognosis. Except for lesions <1mm thick, the Clark's level of invasion has been de-emphasized.
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PMID:Current concepts in the management of patients with melanoma. 1211 49

The gastrointestinal tract (GIT) is a common site of metastases for malignant melanoma. These metastatic tumors are often asymptomatic. We describe a case of a 58-year-old male who presented with a sudden onset of generalized abdominal pain. The patient's past medical history was significant for lentigo melanoma of the right cheek. Laparotomy was performed and two segments of small bowel, one with a perforated tumor, the other with a non-perforated tumor, were removed. Histology and immunohistochemical staining revealed the perforated tumor to be a metastatic malignant melanoma and the non-perforated tumor was found to be a gastrointestinal stromal tumor (GIST). The patient was discharged 7 d postoperatively. To the best of our knowledge, this is the first reported case in the literature of a simultaneous metastatic malignant melanoma and a GIST. Surgical intervention is warranted in patients with symptomatic GIT metastases to improve the quality of life or in those patients with surgical emergencies.
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PMID:Perforation of metastatic melanoma to the small bowel with simultaneous gastrointestinal stromal tumor. 1584 37

Melanoma is one of the most serious skin cancers. It arises from neural crest-derived melanocytes located in the epidermis or dermis of the skin. Melanoma also can arise from melanocytes located in other regions of the body such as the eye, meninges, digestive tract, mucosal surfaces, or lymph nodes. There are no proven causes of melanoma but the most commonly associated factor is episodic exposure to the sun. Melanoma is a common cancer that has been increasing in incidence for the last 35 years. The median age at the time of diagnosis is 53 years. It is much more common in whites than in people of color. Five-year survival rates for melanoma of the skin have been increasing since 1976. There are four types of melanoma: superficial spreading melanoma, nodular melanoma, lentigo maligna melanoma, and acral lintiginous melanoma. Clinical signs indicating possible melanoma are asymmetry, border irregularity, color variation, increase in diameter, elevation, ulceration, and bleeding of pigmented lesions. Histopathologic findings (tumor thickness, tumor invasion), surface ulceration, spread to lymph nodes, and distant metastases are used to project patient prognosis. Treatment consists of surgical excision, lymph node dissection, limb perfusion, regional chemotherapy infusion, radiation, intralesional immunotherapy, systemic chemotherapy, and/or interferon-alpha, depending on the staging of the melanoma. Oral melanomas are rare; however, approximately 20% of all melanomas are found in the head and neck region. The role of the dentist is to be alert for changes in pigmented lesions of the oral mucosa and skin of the head and neck. Lesions suspected of melanoma must be biopsied, which usually involves referral of the patient.
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PMID:Melanoma: etiology, treatment, and dental implications. 1649 25

The first step of the two-step algorithm of dermoscopy aims at differentiating melanocytic from nonmelanocytic pigmented lesions, using a stepwise evaluation for the presence of specific dermoscopic criteria. The purpose of this article is to heighten awareness of clinicians to nonmelanocytic lesions that defy the two-step algorithm, thus simulating melanocytic lesions dermoscopically. Seborrheic keratosis, solar lentigo, dermatofibroma, and supernumerary accessory nipple may present with network-like structures. Seborrheic keratosis, dermatofibroma, subcorneal hemorrhage, basal cell carcinoma (BCC), and cutaneous metastases of breast and other cancers may contain pigmented globules. Peripheral streaks can also be seen in seborrheic keratosis and BCC. Homogenous bluish pigmentation, simulating a blue nevus, can also be seen in benign vascular lesions, Kaposi sarcoma, radiation tattoo, and BCC. This overlap of features between melanocytic and nonmelanocytic lesions suggests that integration of all dermoscopic features in the lesion, rather than a stepwise evaluation, may facilitate reaching the correct diagnosis in select cases as outlined in this article.
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PMID:Nonmelanocytic lesions defying the two-step dermoscopy algorithm. 1708 95

Earlier studies have shown frequent mutations in the BRAF and NRAS genes in cutaneous melanoma, but these alterations have not been examined in the rare category of melanoma from black Africans. Moreover, the frequency of epidermal growth factor receptor (EGFR) mutations in melanocytic tumors is not known. We therefore examined 165 benign and malignant melanocytic lesions (including 118 invasive melanomas and 18 metastases collected as consecutive cases from various time periods and from two different pathology departments; the 51 nodular melanomas were randomly selected from a larger, consecutive, population-based series of nodular melanomas) with respect to alterations in the EGFR, BRAF and NRAS genes. Mutations in EGFR (exons 18-21) were not detected. EGFR protein expression was observed in a subgroup of melanomas, but without associations with clinicopathologic phenotype or prognosis. Cytoplasmic EGFR expression was, however, significantly increased from benign nevi to melanomas. Mutations in BRAF and NRAS were detected in superficial melanoma (25 and 29%, respectively), nodular melanoma (29 and 28%, respectively) and lentigo maligna melanoma (15 and 16%, respectively). In a series of melanomas from black Africans (n=26), only two BRAF mutations (8%) were found, both being different from the common T1799A substitution. Moreover, melanomas from black Africans exhibited mutations in NRAS exon 1 only (12%), whereas NRAS exon 2 mutations were predominant in melanomas from Caucasians. Thus, the frequencies of BRAF and NRAS mutations were particularly low in melanomas from black Africans, supporting a different pathogenesis of these tumors.
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PMID:Mutation analysis of the EGFR-NRAS-BRAF pathway in melanomas from black Africans and other subgroups of cutaneous melanoma. 1822 5


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