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Metastatic Melanoma (metastatic + melanoma)

Distribution by Scientific Domains

Medical Sciences	89%
Life Sciences	10%

Distribution within Medical Sciences

Dermatology	50%
Oncology & Radiotherapy	33%
6 Other Subdomains	17%

Selected Abstracts

Detection of Micrometastasis in the Sentinel Lymph Node via Lymphoscintigraphy for a Patient With In-Transit Metastatic Melanoma

DERMATOLOGIC SURGERY, Issue 9 2003
Chih-Hsun Yang MD
Background. Lymphoscintigraphy and sentinel lymph node (SLN) biopsy are highly accurate methods of detecting regional lymph node status for melanoma. Previously, these procedures were mainly performed in patients with primary melanoma before wide local excision. Objective. To present a case with in-transit recurrence melanoma using lymphoscintigraphy and SLN biopsy for detection of nodal basin status. Methods. The patient discussed here had a subungual melanoma that developed as an in-transit metastatic melanoma on the pretibia area 2 years after right big toe amputation. By using lymphoscintigraphy and SLN biopsy technique with injection of technetium-99m colloid around the in-transit metastatic site, the first node (SLN) draining the in-transit metastatic tumor was identified and harvested on the right inguinal area. Immediate right inguinal node dissection was subsequently performed. Results. Under thorough histologic examination, the first node (SLN) draining the in-transit metastatic tumor was the only node that contained micrometastatic tumor cells in the surgical specimens. Conclusion. Lymphoscintigraphy and SLN biopsy techniques are sensitive procedures for detecting the regional nodal basin micrometastasis in in-transit recurrence melanoma patients. [source]

Management of Metastatic Melanoma to the Breast with High-Dose Interleukin-2 and Surgical Resection

THE BREAST JOURNAL, Issue 2 2005
Ian K. Komenaka MD
No abstract is available for this article. [source]

pH-dependent antitumor activity of proton pump inhibitors against human melanoma is mediated by inhibition of tumor acidity

INTERNATIONAL JOURNAL OF CANCER, Issue 1 2010
Angelo De Milito
Abstract Metastatic melanoma is associated with poor prognosis and still limited therapeutic options. An innovative treatment approach for this disease is represented by targeting acidosis, a feature characterizing tumor microenvironment and playing an important role in cancer malignancy. Proton pump inhibitors (PPI), such as esomeprazole (ESOM) are prodrugs functionally activated by acidic environment, fostering pH neutralization by inhibiting proton extrusion. We used human melanoma cell lines and xeno-transplated SCID mice to provide preclinical evidence of ESOM antineoplastic activity. Human melanoma cell lines, characterized by different mutation and signaling profiles, were treated with ESOM in different pH conditions and evaluated for proliferation, viability and cell death. SCID mice engrafted with human melanoma were used to study ESOM administration effects on tumor growth and tumor pH by magnetic resonance spectroscopy (MRS). ESOM inhibited proliferation of melanoma cells in vitro and induced a cytotoxicity strongly boosted by low pH culture conditions. ESOM-induced tumor cell death occurred via rapid intracellular acidification and activation of several caspases. Inhibition of caspases activity by pan-caspase inhibitor z-vad-fmk completely abrogated the ESOM-induced cell death. ESOM administration (2.5 mg kg,1) to SCID mice engrafted with human melanoma reduced tumor growth, consistent with decrease of proliferating cells and clear reduction of pH gradients in tumor tissue. Moreover, systemic ESOM administration dramatically increased survival of human melanoma-bearing animals, in absence of any relevant toxicity. These data show preclinical evidence supporting the use of PPI as novel therapeutic strategy for melanoma, providing the proof of concept that PPI target human melanoma modifying tumor pH gradients. [source]

Metastatic melanoma to lymph nodes in patients with unknown primary sites

CANCER, Issue 9 2006
Janice N. Cormier M.D., M.P.H.
Abstract BACKGROUND The natural history of metastatic melanoma in lymph nodes in the absence of a known primary site (MUP) has been defined poorly; thus, treatment guidelines for patients with MUP are not clear-cut. METHODS The authors conducted a retrospective analysis of consecutive patients with melanoma (from 1990 to 2001) who underwent surgical resection for melanoma metastatic to regional lymph nodes. Among those patients, 71 patients with MUP and 466 control patients who had regional lymph node metastases of similar stage with a known primary site were identified. Associations between clinicopathologic factors and survival were estimated by using the Cox proportional hazards model. RESULTS After they underwent lymph node dissection, patients with MUP were classified with N1b disease (47%), N2b disease (14%), or N3 disease (39%). With a median follow-up of 7.7 years, the 5-year and 10-year overall survival rates were 55% and 44%, respectively, for patients with MUP, compared with 42% and 32%, respectively, for the control group (P = .04). In multivariate analyses, age 50 years or older, male gender, and N2b or N3 disease status were identified as adverse prognostic factors, and MUP was identified as a favorable prognostic factor (hazard ratio, 0.61; 95% confidence interval, 0.42,0.86; P = .006) for overall survival. CONCLUSIONS The relatively favorable long-term survival of patients with MUP in the current study suggested that patients with MUP have a natural history that is similar to (if not better than) the survival of many patients with Stage III disease. Therefore, patients with MUP should be treated with an aggressive surgical approach with curative intent and should be considered for Stage III adjuvant therapy protocols. Cancer 2006. © 2006 American Cancer Society. [source]

EVER Lecture: Can uveal melanoma be conquered?

ACTA OPHTHALMOLOGICA, Issue 2007
T KIVELÄ
The deadly natural history of uveal melanoma was fully described, unknowingly, in a well known English artist in 1792 and soon thereafter in an unknown Scottish woman around 1808. It became a well recognised entity much later, by 1868. Today, with the exception of being able to save the eye of their patient, ocular oncologists managing patients with uveal melanoma find themselves in essentially the same situation than their forebears: mortality rates have not noticeably decreased and metastatic melanoma continues to be the "hideous picture of disease" that it was 150 years ago. Metastatic melanoma is the single overwhelming cause of death in patients with uveal melanoma, and no consistently effective treatment is known for disseminated disease. One reason for this unhappy state of affairs is that patients formerly were dismissed after enucleation until they presented with advanced metastasis to an oncologist who did not recognise uveal melanoma as a disease very different from cutaneous melanoma. The advent of ocular oncology has led to rational early detection programs for subclinical metastasis, validated staging of metastatic disease, and first controlled clinical trials of managing metastases with therapies specifically aimed against this cancer. Basic research highlights uveal melanoma as a typically slowly growing, early metastasising cancer, and staging, grading and typing of primary tumours is leading to rational assignment of patients to follow-up and adjuvant treatment trials, which hopefully will improve their survival rate. The current understanding is that, by the time the eye becomes symptomatic, uveal melanomas prone to metastasis already have seeded micrometastases, which need to be kept under control if we are to eventually conquer this disease. [source]

Expression of cyclooxygenase-2 and peroxisome proliferator-activated receptor gamma during malignant melanoma progression

JOURNAL OF CUTANEOUS PATHOLOGY, Issue 11 2008
Carolyn Lee
Background:, Cancer chemoprevention using nonsteroidal anti-inflammatory drugs is frequently attributed to cyclooxygenase-2 (COX-2) inhibition, although recent studies suggest that peroxisome proliferator-activated receptor gamma (PPAR,) may also be involved. While surgical excision remains the treatment mainstay for localized malignant melanoma, certain high-risk patients may benefit from adjunctive chemotherapy. In this study, we compared COX-2 and PPAR, immunohistological staining in benign nevi, primary melanomas and metastatic melanomas to help predict the effectiveness of compounds targeting these markers. Methods:, COX-2 and PPAR, immunohistological staining was performed and reviewed in 99 melanocytic lesions, including 38 benign nevi, 32 primary melanomas and 29 metastatic melanomas. Results:, There was a significant increase in both COX-2 and PPAR, immunostaining in melanomas compared with benign nevi. Metastatic melanomas were more likely to have a higher number of PPAR,-immunopositive cells. They were also more likely to express COX-2 than primary melanomas. Neither COX-2 nor PPAR, expression was associated with a specific pathologic subtype. Conclusions:, COX-2 and PPAR, may help modulate the progression of melanocytic precursor lesions to disseminated malignant melanoma. As such, they may serve as candidate substrates for targeted cancer therapies and may be particularly useful as adjuncts to surgery. [source]

Detection of Micrometastasis in the Sentinel Lymph Node via Lymphoscintigraphy for a Patient With In-Transit Metastatic Melanoma

Effect of Perilesional Injections of PEG-Interleukin-2 on Basal Cell Carcinoma

DERMATOLOGIC SURGERY, Issue 11 2000
Baruch Kaplan MD
Background: Multiple modalities are available for the treatment of basal cell carcinoma (BCC). The most commonly used modalities include simple excision, Mohs micrographic surgery, curettage and electrodessication, cryosurgery, and irradiation therapy. Interleukin-2 (IL-2) is a cytokine produced chiefly by activated T lymphocytes and has effects on various components of the immune system. Until now the primary clinical use of IL-2 has been in advanced stages of metastatic melanoma and renal cell carcinoma. Systemic administration of IL-2 is known to cause significant toxicity. Objective: The objective of this study was to evaluate the therapeutic efficacy and safety of perilesional PEG-IL-2 injections in patients with BCC in an open label, uncontrolled pilot study. Methods: Patients with histologically confirmed primary BCC over 18 years of age were included in the study. Lesions were treated by injecting a total volume of 0.5 cc of IL-2 in a radial fashion in the subcutaneous tissue. Injection dosages ranged from 3000 to 1,200,000 IU in one to four weekly dosages. A total of 12 tumors were treated in eight patients. Results: Overall response rates were as follows: complete response in 8 of 12 treated tumors (66.6% cure rate), partial response in 3 of 12 injected tumors (25% partial response rate), stable disease with no improvement in 1 treatment site (8.4%). Side effects included local pain, swelling, and erythema, and in one patient flulike symptoms. There were no significant changes of blood tests as compared to baseline levels. Conclusions: The therapeutic response induced by perilesional PEG-IL-2 injections was found to be an encouraging, safe, and well-tolerated treatment of BCC. Further studies including a larger patient population and long-term follow-up are necessary in order to substantiate these findings. [source]

Cutaneous melanoma: available therapy for metastatic disease

DERMATOLOGIC THERAPY, Issue 1 2006
Ahmad A. Tarhini
ABSTRACT:, Survival of melanoma varies widely by stage, from a potentially highly curable disease when detected in early stages, to a disease with dismal prognosis when it reaches advanced inoperable stages. Stage IV melanoma defines distant metastasis and continues to comprise an ominous prognosis, with a median survival of 6,9 months. Currently, there is no therapeutic agent known to prolong survival in patients with metastatic melanoma. Therapeutic approaches studied in metastatic melanoma include chemotherapy, biochemotherapy, nonspecific immune adjuvants, cancer-specific vaccines, cytokines, monoclonal antibodies, and specific immunostimulants. Chemotherapy with single-agent dacarbazine is the only United States Food and Drug Administration (US-FDA)-approved chemotherapy agent for metastatic melanoma. Immunological approaches have yielded the only newly US-FDA-approved agent for metastatic disease in 30 years, high-dose bolus IL-2, based on durable responses in some patients with metastatic melanoma, but with associated high toxicity rate and cost. A number of novel therapeutic agents are undergoing active clinical investigation. [source]

Depletion of tumor-induced Treg prior to reconstitution rescues enhanced priming of tumor-specific, therapeutic effector T cells in lymphopenic hosts

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 11 2009
Christian H. Poehlein
Abstract We reported previously that vaccination of reconstituted, lymphopenic mice resulted in a higher frequency of tumor-specific effector T cells with therapeutic activity than vaccination of normal mice. Here, we show that lymphopenic mice reconstituted with spleen cells from tumor-bearing mice (TBM), a situation that resembles the clinical condition, failed to generate tumor-specific T cells with therapeutic efficacy. However, depletion of CD25+ Treg from the spleen cells of TBM restored tumor-specific priming and therapeutic efficacy. Adding back TBM CD25+ Treg to CD25, naïve and TBM donor T cells prior to reconstitution confirmed their suppressive role. CD25+ Treg from TBM prevented priming of tumor-specific T cells since subsequent depletion of CD4+ T cells did not restore therapeutic efficacy. This effect may not be antigen-specific as three histologically distinct tumors generated CD25+ Treg that could suppress the T-cell immune response to a melanoma vaccine. Importantly, since ex vivo depletion of CD25+ Treg from TBM spleen cells prior to reconstitution and vaccination fully restored the generation of therapeutic effector T cells, even in animals with established tumor burden, we have initiated a translational clinical trial of this strategy in patients with metastatic melanoma. [source]

Selective expression of inhibitory Fc, receptor by metastatic melanoma impairs tumor susceptibility to IgG-dependent cellular response

INTERNATIONAL JOURNAL OF CANCER, Issue 12 2008
Lydie Cassard
Abstract During melanoma progression, patients develop anti-tumor immunity including the production of anti-tumor antibodies. Although the strategies developed by malignant cells to escape anti-tumor cellular immunity have been extensively investigated, little is known about tumor resistance to humoral immunity. The main effect of IgG antibodies is to activate the immune response by binding to host Fc gamma receptors (Fc,R) expressed by immune cells. We previously reported in a limited study that some human metastatic melanoma cells ectopically express the Fc,RIIB1, an inhibitory isoform of Fc,R. By analyzing a large panel of different types of human primary and metastatic solid tumors, we report herein that expression of Fc,RIIB is restricted to melanoma and is acquired during tumor progression. We show that Fc,RIIB expression prevents the lysis of human metastatic melanoma cells by NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC) in vitro, independently of the intracytoplasmic region of Fc,RIIB. Using experimental mouse models, we demonstrate that expression of Fc,RIIB protects B16F0 melanoma tumors from the ADCC induced by monoclonal and polyclonal anti-tumor IgG in vivo. Thus, our results identify Fc,RIIB as a marker of human metastatic melanoma that impairs the tumor susceptibility to Fc,R-dependent innate effector responses. © 2008 Wiley-Liss, Inc. [source]

New research advances for treating metastatic melanoma

INTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 6 2010
Ettore Minutilli MD
No abstract is available for this article. [source]

Chemokine receptor expression in non-melanoma skin cancer

JOURNAL OF CUTANEOUS PATHOLOGY, Issue 7 2008
Jeff Basile
Background:, Previous studies suggest that chemokines and chemokine receptors have a role in the metastatic process. A correlation exists between the specific expression of these chemoattractive, pro-inflammatory cytokines and the ability of cancer to disseminate. Prior studies have shown that in metastatic melanoma and squamous cell carcinoma of the head and neck upregulation of CXC (,) chemokine receptor (CXCR)4 and CC (,) chemokine receptor (CCR)7 expression is accompanied by downregulation of the chemokine receptor CCR6. However, the expression patterns of CCR6, CCR7 and CXCR4 in non-melanoma skin cancer have yet to be elucidated. Methods:, The expression patterns of CCR6, CCR7 and CXCR4 were determined using an immunohistochemical approach on formalin-fixed, paraffin-embedded normal, pre-cancerous actinic (solar) keratosis, squamous cell carcinoma and basal cell carcinoma tissues. Results:, Analysis of chemokine receptor expression showed downregulation of CCR6 and upregulation of CCR7 and CXCR4 in potentially metastatic non-melanoma skin cancer, invasive squamous cell carcinoma, but this pattern did not exist in non-melanoma skin cancer with no metastatic potential, basal cell carcinoma; or actinic keratosis, when compared with normal skin. Conclusions:, Chemokine receptor expression may influence the biological behavior of non-melanoma skin cancer. The exact mechanism by which this occurs requires further study. [source]

Expression of polycomb group protein EZH2 in nevi and melanoma

JOURNAL OF CUTANEOUS PATHOLOGY, Issue 8 2007
Jonathan B. McHugh
Background:, Enhancer of zeste homolog 2 (EZH2), a polycomb group protein that regulates the cell cycle, has recently been implicated in the progression of several human cancers. We sought to determine the pattern of EZH2 expression in benign and malignant melanocytic tumors to see if EZH2 might play a role in melanoma pathogenesis and progression. Methods:, We identified and reviewed 11 compound nevi, 13 dysplastic nevi, 13 Spitz nevi, 9 in situ melanomas, 10 non-metastatic invasive melanomas and 19 melanomas metastatic to lymph nodes from the University of Michigan pathology archives. Sections immunostained with anti-EZH2 antibody were scored independently and blindly for staining intensity on a scale of 1,4 by three dermatopathologists. Results were analyzed and compared statistically. Results:, We observed an incremental increase in EZH2 expression from benign nevi to melanoma: scores of 1.18 and 1.08 for ordinary and dysplastic nevi, 1.7 and 1.78 for Spitz nevi and in situ melanoma, and 1.9 and 3.0 for invasive and metastatic melanoma, respectively. EZH2 expression for metastatic melanoma was significantly higher compared with invasive and in situ melanoma and benign nevi (p , 0.01). Conclusions:, EZH2 protein levels increase incrementally from benign nevi to melanoma, which suggests that EZH2 may play a role in the pathogenesis and progression of melanoma. [source]

Chromogenic in situ hybridization analysis of melastatin mRNA expression in melanomas from American Joint Committee on Cancer stage I and II patients with recurrent melanoma

JOURNAL OF CUTANEOUS PATHOLOGY, Issue 9 2006
L. Hammock
Objective:, To determine whether loss of melastatin (MLSN) is a universal phenomenon in American Joint Committee on Cancer (AJCC) stage I and II melanoma patients who experienced recurrence. Material and methods:, Paraffin blocks of primary melanomas (PMs) were retrieved from 30 patients who had a negative sentinel lymph node biopsy and developed recurrent melanoma (AJCC stage I and II). Chromogenic in situ hybridization (CISH) methods were utilized to evaluate the expression of MLSN mRNA. These results were correlated with clinicopathologic data. Results:, Variable, heterogeneous expression of MLSN mRNA was identified in normal, in situ and invasive melanocytes within and between cases. For the invasive PM component, 24 (80%) had focal, regional or complete loss of MLSN mRNA. The remaining 20% had either regional or total partial downregulation of MLSN mRNA. Intact MLSN mRNA expression was present regionally in 14/30 (47%), with mean relative tumor area of 38%, range 5,85%. Increasing loss of MLSN mRNA significantly correlated with increasing tumor depth and microsatellites (r = 0.1/0.4, p = 0.04). However, thin, AJCC T stage 1a PM had higher relative mean loss than intermediate AJCC T stage 2a/2b/3a thickness PM (65% vs. 34%/48%/25%). Increasing loss of MLSN mRNA significantly impacted on disease free survival (DFS) by multivariate analysis (58 vs. 0% 2 years DFS, , 75 vs. >75% mRNA loss, p = 0.02). Decreased overall survival significantly correlated with increasing age and vascular invasion on multivariate analysis. Conclusion:, Extensive loss of MLSN in PM correlated with aggressive metastatic melanoma. Ancillary testing for MLSN mRNA expression by CISH could offer a means to more accurately identify AJCC stage I and II patients at risk for metastatic disease, who could benefit from adjuvant therapy. [source]

Skp2 and p27kip1 expression in melanocytic nevi and melanoma: an inverse relationship,

JOURNAL OF CUTANEOUS PATHOLOGY, Issue 10 2004
Qing Li
Background:, S-phase kinase associated protein-2 (Skp2) ubiquitin ligase p45SKP2 is important in the degradation of p27kip1 (a cyclin dependent kinase inhibitor) and progression through the G1-S cell-cycle checkpoint. Low levels of p27 and high levels of Skp2 are related to poor prognosis in some cancers. Methods:, Clinicopathologic features and immunohistochemical expression of Skp2 and p27kip1 were investigated in 198 melanocytic proliferations: 21 melanocytic nevi, 23 melanoma in situ, 119 primary melanoma, and 35 metastatic melanoma samples. Comparative and survival analyses were performed. Results:, Progressive and significant increases and decreases in the nuclear expression of Skp2 and p27kip1, respectively, was identified moving from melanocytic nevi (0.05 ± 0.2/85 ± 15) to melanoma in situ (3 ± 2/45 ± 20) to primary cutaneous melanoma (12 ± 9/30 ± 25) to metastatic melanoma (25 ± 15/15 ± 20) (p , 0.006). Expression of these proteins also significantly correlated with increasing American Joint Committee on Cancer (AJCC) T (tumor) classification and AJCC stage (p , 0.01). Moreover, the level of these two proteins exhibited a significant inverse relationship (r = ,0.4, p = 0.0001). Skp2 cytoplasmic labeling index of >20% predicted worse 10-year overall survival (38% vs. 86%, p = 0.04) in primary melanoma. Neither p27 nor Skp2 nuclear expression impacted significantly on prognosis. Conclusions:, Gain of Skp2 and loss of p27kip1 protein expression are implicated in melanoma progression where the level of p27kip1 may be regulated by targeted proteolysis via Skp2. Cytoplasmic expression of Skp2 defines a subset of aggressive melanomas and could represent another pathway of deregulation of the cell cycle. [source]

Cutaneous metastasis: a clinical, pathological, and immunohistochemical appraisal

JOURNAL OF CUTANEOUS PATHOLOGY, Issue 6 2004
Sadia Saeed
Background:, Cutaneous tumor metastasis may be the first manifestation of cancer, but more often is a harbinger of advanced disease that portends an ominous prognosis. All skin accessions over the past 10 years from a large Veterans Administration (VA) hospital were reviewed. Methods:, Archived histories, glass slides, and the immunohistochemical battery (IHC), were assessed to determine diagnostic accuracy. Results:, Of the 100,453 cases reviewed, there were a total of 77 cases (75 males and 2 females) of cutaneous metastasis from the lungs (28.6%), metastatic melanoma (18.2%), gastrointestinal tract (14.2%), genitourinary tract (10.4%), head and neck (9.1%), hematologic (5.2%), breast (5.2%), and miscellaneous (<2%). Metastasis represented the first indication of an internal malignancy in 7.8% of cases. The cutaneous sites of involvement included the head and neck (28%), the trunk (40%), the extremities (18%), and multiple sites (14%). The age range was 38,83 years, with a mean of 62 years. The average time interval between diagnosis of internal malignancy and cutaneous presentation was 33 months (range: <1 month,22 years), and the average survival following diagnosis was 7.5 months (range: <1 month,8 years). In a cohort of subjects, a truncated immunohistochemical battery consisting of CK-7, CK-20, and S-100 was consistent with the expected staining pattern of the primary source of cutaneous metastasis in 83.33% of the patients. Conclusions:, Excluding the potential for age and gender bias in this study conducted in a VA setting, cutaneous metastases represent an uncommon, deadly, and late-developing occurrence in many patients. Compared with previous studies, lung carcinoma remains the most common of the cutaneous metastases, with a relative rise in the incidence of metastatic melanoma. The immunohistochemical battery of CK-7, CK-20, and S-100 is a helpful adjunct in narrowing the differential diagnosis of the primary site of a large proportion of cutaneous metastases, particularly tumors with an epithelioid appearance such as carcinomas and melanomas. [source]

Late solitary metastasis of cutaneous malignant melanoma presenting as abnormal uterine bleeding

JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 4pt2 2008
Massimiliano Fambrini
Abstract We present the case of a 52-year-old woman with a history of excised cutaneous malignant melanoma complaining of abnormal uterine bleeding 11 years after initial diagnosis. Hysteroscopic examination showed an endometrial lesion with polypoid shape and endometrial biopsy was suggestive for melanoma. After a complete clinical work-up ruling out other metastatic sites, the patient underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy and pelvic lymphadenectomy. Final histopathological and immunohistochemical analysis confirmed the diagnosis of endometrial melanoma with initial myometrial invasion. After a 6-month follow-up period, the patient was disease free. Even after many years of negative follow up, gynecologists should be aware of the possibility that abnormal uterine bleeding could represent the clinical expression of metastatic melanoma in order to offer a prompt diagnosis and a personalized strategy of treatment. [source]

Possible role of dermoscopy in the detection of a primary cutaneous melanoma of unknown origin

JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 3 2006
M Stante
Abstract For 2,8% of patients with metastatic melanoma, cutaneous and mucosal clinical examination does not lead to diagnosis of the primary tumour, which remains unknown. We report the case of a 41-year-old male patient who had received a diagnosis of metastatic melanoma after histological examination of an enlarged axillary lymph node, without previous detection of the primary lesion at his first dermatological examination. No pigmented skin lesions located in the anatomical area potentially drained by the affected axillary basin showed clinical features suggestive of a melanoma. Neither did the so-called ,ugly duckling' sign help us to identify the melanoma, because of the presence of a large number of clinically similar, common or slightly atypical melanocytic lesions located in that area. After dermoscopic examination we were able to narrow the field of possible candidates for excision to four lesions, selected on the basis of their dermoscopic features. Histological examination revealed the primary melanoma (superficial spreading melanoma (SSM), level III, thickness 0.5 mm) , located on the back , and three naevi with atypia. Preoperative distinction of the melanoma from the other three lesions was not possible because of the lack of well-established features of malignancy, even at dermoscopic analysis (,featureless' melanoma). Dermoscopy may thus play a role in the detection of a clinically unknown primary melanoma by narrowing the field of lesions to be removed for histological examination, saving many unnecessary excisions that would otherwise be inevitable. [source]

Metaplastic breast carcinoma with melanocytic differentiation

PATHOLOGY INTERNATIONAL, Issue 9 2009
Antonia Bendic
Metaplastic carcinoma of the breast is a rare heterogeneous malignancy, accounting for <1% of all invasive breast carcinomas, in which adenocarcinoma is found to coexist with an admixture of spindle, squamous, chondroid or bone-forming neoplastic cells. Metaplastic breast carcinoma composed of both epithelial and melanocytic elements is rare, and only seven cases have been reported so far. Reported herein is the case of a 38-year-old woman with a nodular mass in her left breast suspicious of malignancy, discovered during routine ultrasound examination. After histological and immunohistochemical examination of the resected tumor mass, initial diagnosis was collision tumor: ductal invasive carcinoma and metastatic melanoma. The patient underwent quadrantectomy, chemotherapy and radiotherapy. At 6 years follow up the patient was alive and healthy, without local recurrence or metastases. After revising slides and the literature, in addition to patient follow up, it was concluded that this case represents metaplastic carcinoma with melanocytic differentiation. [source]

Alpha 1 antichymotrypsin is aberrantly expressed during melanoma progression and predicts poor survival for patients with metastatic melanoma

PIGMENT CELL & MELANOMA RESEARCH, Issue 4 2010
Yang Wang
First page of article [source]

REVIEW ARTICLE: Cancer stem cells and human malignant melanoma

PIGMENT CELL & MELANOMA RESEARCH, Issue 1 2008
Tobias Schatton
Summary Cancer stem cells (CSC) have been identified in hematological malignancies and several solid cancers. Similar to physiological stem cells, CSC are capable of self-renewal and differentiation and have the potential for indefinite proliferation, a function through which they may cause tumor growth. Although conventional anti-cancer treatments might eradicate most malignant cells in a tumor, they are potentially ineffective against chemoresistant CSC, which may ultimately be responsible for recurrence and progression. Human malignant melanoma is a highly aggressive and drug-resistant cancer. Detection of tumor heterogeneity, undifferentiated molecular signatures, and increased tumorigenicity of melanoma subsets with embryonic-like differentiation plasticity strongly suggest the presence and involvement of malignant melanoma stem cells (MMSC) in the initiation and propagation of this malignancy. Here, we review these findings in the context of functional properties ascribed to melanocyte stem cells and CSC in other cancers. We discuss the association of deregulated signaling pathways, genomic instability, and vasculogenic mimicry phenomena observed in melanoma subpopulations in light of the CSC concept. We propose that a subset of MMSC may be responsible for melanoma therapy-resistance, tumor invasiveness, and neoplastic progression and that targeted abrogation of a MMSC compartment could therefore ultimately lead to stable remissions and perhaps cures of metastatic melanoma. [source]

Effect of Boron Neutron Capture Therapy for Melanotic and Amelanotic Melanoma Transplanted into Mouse Brain

PIGMENT CELL & MELANOMA RESEARCH, Issue 1 2002
Masaki Iwakura
In order to develop a protocol to treat brain metastatic melanoma using our 10B- p -boronophenylalanine (BPA) boron neutron capture therapy (BNCT), we initiated the following studies (i), Comparative analyses of boron biodistribution between melanoma proliferating in the brain and skin among melanotic and amelanotic types, and (ii) Therapeutic evaluation of BPA,BNCT for brain melanoma models of both types, using survival times. Our present data have revealed that boron concentration in melanoma proliferating in the brain, the major prerequisite for successful BNCT, showed a positive correlation to melanin synthesizing activity in the same way as melanoma proliferating in skin. Further, the boron concentration ratio of melanoma to normal surrounding tissue for brain melanoma models was considerably higher than that for subcutaneous (s.c.) ones because of the existence of the blood,brain barrier (BBB). Additionally, from analyses of median and mean survival times following BNCT using low, middle, and high neutron doses, the therapeutic effect of BNCT for the amelanotic A1059 melanoma appeared at first glance to be higher than that for the highly BPA attracting and highly relative biological effect equivalent dose obtaining B15b melanoma. As the survival time was dependent on both regression and regrowth curves, and because the brain melanoma model in small animals made it difficult to evaluate these curves separately, we further examined the in vivo growth curve of both types of melanomas following implantation in s.c. tissue. The melanotic B15b melanoma was indeed found to possess much higher growth rate as compared with that of the amelanotic A1059 melanoma. The significance of boron biodistribution studies and BNCT survival curve analyses in forming an effective clinical protocol for individual human cases of melanoma brain metastasis is discussed. [source]

Cutaneous melanoma in New Zealand: 2000,2004

ANZ JOURNAL OF SURGERY, Issue 5 2010
Jennifer J. C. Liang
Abstract Background:, In 2004, we published data on the trends in New Zealand (NZ) cutaneous melanoma (CM) for the period 1995,1999. The present report documents the trends in the next period from 2000 to 2004. Method:, Data were obtained from the New Zealand Cancer Registry by way of a computerized search of CM ICD-10 (172) codes from 2000 to 2004. Only one registration per person was made to avoid including patients with metastatic melanoma. The exclusion criteria were: incorrect or absent data; benign naevi; and melanoma in situ. Incidence rates were age standardised to the Segi world population. Results:, The total study population was 8262 patients. There was no increase found in the overall incidence rate over the time period, but men had a statistically higher overall incidence rate (P= 0.0002) and thicker CMs (P= 0.003) compared with women. This gender difference was particularly marked in those patients aged greater than 59 years. Breslow thickness increased from 0.7 to 0.8 mm. The incidence rates varied quite significantly among District Health Boards, with Taranaki having the highest rate (70.3/100 000/year) and Southland had the lowest rate (20.1/100 000). Overall, NZ had a CM incidence rate of 41.2/100 000/year). Conclusion:, The current study confirmed that NZ has the highest overall CM incidence rate in the world. Elderly men (>59 years old) have the highest risk of developing melanoma. The increase in melanoma thickness with its associated higher mortality risk is of grave concern. [source]

The role of debulking surgery in metastatic melanoma

ANZ JOURNAL OF SURGERY, Issue 7-8 2009
Ali Cadili MD
No abstract is available for this article. [source]

Topical diphencyprone immunotherapy for cutaneous metastatic melanoma

AUSTRALASIAN JOURNAL OF DERMATOLOGY, Issue 4 2009
Diona L Damian
ABSTRACT Topical immunotherapy with contact sensitizers for metastatic melanoma was first reported more than 30 years ago. Diphencyprone (DPCP) immunotherapy is frequently used to treat cutaneous warts and alopecia areata, and we have previously reported the use of DPCP as a single agent to successfully treat extensive, radiotherapy-resistant melanoma metastases on the scalp. We now report DPCP treatment of a further six patients with cutaneous metastatic melanoma. Of seven patients treated with DPCP thus far, four have demonstrated complete responses of their cutaneous lesions and three have had partial responses. The treatment was well-tolerated by all patients. Topical immunotherapy with DPCP is inexpensive and relatively non-invasive and should be considered in patients with locally advanced skin metastases that are unsuitable for other therapies. [source]

Trichilemmal cyst with homogeneous blue pigmentation on dermoscopy

AUSTRALASIAN JOURNAL OF DERMATOLOGY, Issue 4 2009
Gulsum Gencoglan
ABSTRACT A 61-year-old woman was referred to our dermoscopy unit for a pigmented lesion that had been present on her left arm for 8 years. The patient did not notice any enlargement or change in colour. On dermoscopy, homogeneous blue pigmentation was seen. The lesion was excised with the pre-operative diagnosis of melanoma, blue naevus and dermatofibroma. Histopathological examination showed a trichilemmal cyst in the mid-dermis. Although homogeneous blue pigmentation on dermoscopy is the hallmark of blue naevus, it may be seen in metastatic melanoma and exceptionally in hemosiderotic and cellular types of dermatofibroma. Trichilemmal cyst should be borne in mind also in the dermoscopic differential diagnosis. [source]

Effect of millimeter wave irradiation on tumor metastasis

BIOELECTROMAGNETICS, Issue 4 2006
Mahendra K. Logani
Abstract One of the major side effects of chemotherapy in cancer treatment is that it can enhance tumor metastasis due to suppression of natural killer (NK) cell activity. The present study was undertaken to examine whether millimeter electromagnetic waves (MMWs) irradiation (42.2 GHz) can inhibit tumor metastasis enhanced by cyclophosphamide (CPA), an anticancer drug. MMWs were produced with a Russian-made YAV-1 generator. Peak SAR and incident power density were measured as 730,±,100 W/kg and 36.5,±,5 mW/cm2, respectively. Tumor metastasis was evaluated in C57BL/6 mice, an experimental murine model commonly used for metastatic melanoma. The animals were divided into 5 groups, 10 animals per group. The first group was not given any treatment. The second group was irradiated on the nasal area with MMWs for 30 min. The third group served as a sham control for group 2. The fourth group was given CPA (150 mg/kg body weight, ip) before irradiation. The fifth group served as a sham control for group 4. On day 2, all animals were injected, through a tail vein, with B16F10 melanoma cells, a tumor cell line syngeneic to C57BL/6 mice. Tumor colonies in lungs were counted 2 weeks following inoculation. CPA caused a marked enhancement in tumor metastases (fivefold), which was significantly reduced when CPA-treated animals were irradiated with MMWs. Millimeter waves also increased NK cell activity suppressed by CPA, suggesting that a reduction in tumor metastasis by MMWs is mediated through activation of NK cells. Bioelectromagnetics 27:258,264, 2006. © 2006 Wiley-Liss, Inc. [source]

Production and Molecular Characterization of Clinical Phase I Anti-Melanoma Mouse IgG3 Monoclonal Antibody R24

BIOTECHNOLOGY PROGRESS, Issue 5 2001
Sven E. Kemminer
R24 is a mouse IgG3 monoclonal antibody (mab) that reacts with the ganglioside GD3 expressed by cells of neuroectodermal origin. The anti-tumor activity of R24 has been demonstrated in initial phase I and pilot trials in patients suffering from metastatic melanoma. The purpose of this study was to investigate the biotechnological production and particularly the glycosylation of this clinically important antibody. Growth, metabolism, and IgG production of R24 secreting hybridoma cells were analyzed on 1 L bioreactor bench scale using repeated-batch mode. The amount of 57 mg of pure mab was obtained from 1.6 L crude supernatant by protein A chromatography. Western blot binding assays with sugar-specific lectins revealed glycosylation of the heavy chains, whereas no carbohydrates were detectable on the light chains. Because glycosylation is essential for antibody effector functions in vivo (such as complement fixation or binding to macrophage Fc receptors), mab R24 was subjected to both enzymatic deglycosylation using PNGase F and chemical deglycosylation by hydrazinolysis. Released glycans were structurally characterized by high pH anion exchange chromatography with pulsed amperometric detection (HPAEC-PAD), matrix assisted laser desorption ionization time-of-flight (MALDI-TOF), and electrospray ionization quadrupole time-of-flight (ESI-QTOF) mass spectrometry. Six major biantennary chains of the complex glycosylation phenotype were found with variations in galactosylation and core fucosylation. The predominant N-linked structure, indicating the high degree of agalactosyl glycoforms, was the agalacto biantennary chain with a relative percentage of 57% (51% core-fucosylated, 6% nonfucosylated). The second most abundant oligosaccharide was the monogalacto biantennary chain amounting to 30% (26% core- and 4% nonfucosylated). The antibody contained 0.46 ,g sialic acid per mg protein, which splits into 0.243 ,g Neu5Gc and 0.217 ,g Neu5Ac, corresponding to a Neu5Ac:Neu5Gc ratio of 1:1.06. Furthermore, the antigen specificity of R24 was determined by immunodetection of GD3 on thin-layer chromatograms, and real time GD3-antibody binding interactions were measured with an optical biosensor (BIAcore). From the structural data obtained in this study it is concluded that glycosylation of the antibody may be important in the clinical outcome of targeted anti-cancer immunotherapy. [source]

A phase 2 pilot trial of low-dose, continuous infusion, or "metronomic" paclitaxel and oral celecoxib in patients with metastatic melanoma

CANCER, Issue 7 2010
Rupal S. Bhatt MD
Abstract BACKGROUND: Tumor angiogenesis has been associated with a poor prognosis in patients with metastatic melanoma (MM). Microtubule stabilizers and cyclooxygenase 2 (COX-2) inhibitors, alone and in combination, have produced inhibitory effects on endothelial cells and tumor angiogenesis. Angiogenesis, which is the growth of new blood vessels, is necessary for tumor growth and progression. Thus, the authors tested the safety and efficacy of a low dose of paclitaxel and celecoxib in patients with MM. METHODS: Patients received paclitaxel 10 mg/m2 for 96 hours weekly as a continuous intravenous infusion and oral celecoxib 400 mg twice daily. Systemic tumor response was assessed at 6-week intervals. Tumor measurements at the end of Cycle 1 were used as the baseline for assessment of tumor progression. Patients with unacceptable toxicity or disease progression after Cycle 2 relative to the end of Cycle 1 were taken off study. RESULTS: Twenty patients were enrolled. Twelve of 20 patients (60%) had received ,2 previous systemic therapies. Three patients did not receive treatment because of rapid disease progression. Treatment-related grade 3/4 toxicities were limited to catheter-related complications. One patient achieved a partial response, and 3 of 20 patients (15%) had stable disease for >6 months. The median time to progression was 57 days (95% confidence interval, 43-151 days), and the median overall survival was 212 days (95% confidence interval, 147-811 days). CONCLUSIONS: Low-dose, continuous intravenous infusion paclitaxel and oral celecoxib produced disease stabilization in a significant proportion of heavily pretreated patients with MM. These findings support a role for metronomic therapy in patients with this disease. Cancer 2010. © 2010 American Cancer Society. [source]