Special Issue "Current Concepts in the Diagnosis and Treatment of Cutaneous Melanoma"
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A special issue of Cancers (ISSN 2072-6694).
Deadline for manuscript submissions: closed (13 April 2010)
Special Issue Editor
Guest Editor
Dr. Chyi-Chia Richard Lee
Laboratory of Pathology, National Cancer Institute, Building 10, Room 2B50, 10 Center Drive, Bethesda, MD 20892, USA
Website: http://ccr.cancer.gov/staff/staff.asp?profileid=12822
E-Mail: leechy@mail.nih.gov
Phone: +1 301 594 7365
Fax: +1 301 480 9488
Interests: melanoma; skin cancers; dermatopathology; skin pathology; melanocytic skin lesions
Special Issue Information
Dear Colleagues,
In regard to the diagnosis of melanoma, possible topics of interest may include: histopathology and diagnostic reporting of cutaneous melanoma, diagnostic markers (immunohistochemistry and molecular methods such as PCR, FISH, array CGH), dermatoscopy as a clinical diagnostic tool (including digital dermatoscopy), whole body skin examination with digital photography, imaging studies, etc. In regard to the treatment of melanoma, possible topics of interest may include: surgery, therapeutic and progonostic value of lymph node dissection, chemotheraphy (interferon), radiotherapy, tumor vaccines, cellular therapy (tumor infiltrating lymphocytes), and gene therapy (educated T-cells targeting tumor cells), etc.
Chyi-Chia Richard Lee, MD Ph. D.
Guest Editor
Submission Information
All manuscripts should be submitted to cancers@mdpi.com with a copy to the Guest Editor. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.
Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed Open Access monthly journal published by MDPI.
For the first two issues, to be published in 2009 and 2010, the Article Processing Charges (APC) will be waived for well-prepared manuscripts. English correction and/or formatting fees of 250 CHF (Swiss Francs) will be charged in certain cases for those articles accepted for publication that require extensive additional formatting and/or English corrections.
Published Papers (19 papers)
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Received: 14 January 2010; in revised form: 9 February 2010 / Accepted: 9 February 2010 / Published: 10 February 2010
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Abstract: Melanoma patients with recurrent disease confined to an extremity can be offered one of two regional therapies that both give high complete response rates. Isolated limb infusion (ILI) is a newer technique performed with catheters and tourniquets that has a reduced potential morbidity, decreased efficacy and does not treat the regional nodal basin. Hyperthermic Isolated Limb Perfusion (HILP) is an open surgical technique that includes removal of the regional nodal basin as part of the surgical procedure. An analysis was performed of the rates of regional nodal disease in this patient population to determine the percentage of patients with stage III metastatic disease to the lymph nodes that would be under treated with the ILI technique. A total of 229 patients underwent a HILP for melanoma with regional lymph node dissection as is our standard between July 1987 and December 2009. Ninty-two of the 229 patients (40%) had metastatic regional nodal disease documented at the time of the HILP procedure. HILP is the only technique that addresses all micrometastatic disease on the extremity.
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Received: 11 January 2010; in revised form: 10 February 2010 / Accepted: 24 February 2010 / Published: 25 February 2010
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Abstract: Angiogenesis occurs in pathological conditions, such as tumors, where a specific critical point in tumor progression is the transition from the avascular to the vascular phase. Tumor angiogenesis depends mainly on the release by neoplastic cells of growth factors specific for endothelial cells, which are able to stimulate the growth of the host’s blood vessels. This article summarizes the literature concerning the relationship between angiogenesis and human melanoma progression. The recent applications of antiangiogenic agents which interfere with melanoma progression are also described.
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Received: 28 January 2010; in revised form: 4 March 2010 / Accepted: 9 March 2010 / Published: 12 March 2010
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Abstract: A review of the natural behavior of cutaneous melanoma, clinical and pathological factors, prognostic indicators, some basic research and the present and possible futuristic strategies in the management of this disease are presented. While surgery remains to be the most effective therapeutic approach in the management of early primary lesions, there is no standard adjuvant therapy after surgical resection, or for metastatic disease.
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Received: 23 February 2010; in revised form: 15 March 2010 / Accepted: 25 March 2010 / Published: 26 March 2010
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Abstract: Dermoscopy (dermatoscopy, epiluminescence microscopy) is a non-invasive diagnostic technique for the in vivo observation of pigmented skin lesions (PSLs), allowing a better visualization of surface and subsurface structures (from the epidermis to the papillary dermis). This diagnostic tool permits the recognition of morphologic structures not visible by the naked eye, thus opening a new dimension in the analysis of the clinical morphologic features of PSLs. In order to reduce the learning-curve of non-expert clinicians and to mitigate problems inherent in the reliability and reproducibility of the diagnostic criteria used in pattern analysis, several indicative methods based on diagnostic algorithms have been introduced in the last few years. Recently, numerous systems designed to provide computer-aided analysis of digital images obtained by dermoscopy have been reported in the literature. The goal of this article is to review these systems, focusing on the most recent approaches based on content-based image retrieval systems (CBIR).
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Received: 11 March 2010; in revised form: 25 March 2010 / Accepted: 1 April 2010 / Published: 6 April 2010
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Abstract: Of all primary cancers in humans, melanoma has the highest propensity to metastasize to the brain. The prognosis of patients with this disease is extremely poor. Due to its radioresistance and poor response to existing chemotherapeutic regimes, no treatment options other than surgical extirpation, when feasible, have been shown to be effective. An understanding of the underlying tumor biology therefore remains the cornerstone of offering new hope in the treatment. In this review, we comment on the current treatment strategies for melanoma brain metastases and summarize some recent experimental findings from our laboratory with potential for the development of target specific antitumor therapies.
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Received: 25 February 2010; in revised form: 25 March 2010 / Accepted: 6 April 2010 / Published: 9 April 2010
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Abstract: Cutaneous malignant melanoma is the most lethal form of skin cancer and an increasingly common disease worldwide. It remains one of the most treatment-refractory malignancies. The current treatment options for patients with metastatic melanoma are limited and in most cases non-curative. This review focuses on conventional chemotherapeutic drugs for melanoma treatment, by a single or combinational agent approach, but also summarizes some potential novel phytoagents discovered from dietary vegetables or traditional herbal medicines as alternative options or future medicine for melanoma prevention. We explore the mode of actions of these natural phytoagents against metastatic melanoma.
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Received: 11 February 2010; in revised form: 12 April 2010 / Accepted: 14 April 2010 / Published: 16 April 2010
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Abstract: In this review we have aimed to focus on the clinical management of familial melanoma patients and their relatives. Along this line three major topics will be discussed: (1) management/screening of familial melanoma families: what is advised and what is the evidence thereof; (2) variability of families worldwide with regard to clinical phenotype, including cancer spectrum and likelihood of finding germline mutations and (3) background information for clinicians on the molecular biology of familial melanoma and recent developments in this field.
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Received: 17 March 2010; in revised form: 14 April 2010 / Accepted: 19 April 2010 / Published: 20 April 2010
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Abstract: It has been recently demonstrated that substance P (SP) and neurokinin-1 (NK-1) receptor antagonists induce cell proliferation and cell inhibition in human melanoma cells, respectively. However, the antitumor action of the NK-1 receptor antagonist L-732,138 on such cells is unknown. The aim of this study was to demonstrate an antitumor action of L-732,138 against three human melanoma cell lines (COLO 858, MEL HO, COLO 679). We found that L-732,138 elicits cell growth inhibition in a concentration dependent manner in the melanoma cells studied. Moreover, L-732,138 blocks SP mitogen stimulation. The specific antitumor action of L-732,138 occurred through the NK-1 receptor and melanoma cell death was by apoptosis. These findings indicate that the NK-1 receptor antagonist L-732,138 could be a new antitumor agent in the treatment of human melanoma.
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Received: 4 March 2010; in revised form: 8 April 2010 / Accepted: 19 April 2010 / Published: 20 April 2010
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Abstract: Early stage recognition of acral lentiginous melanoma (ALM) is important for a better prognosis, but in-depth understanding and proper management of ALM in situ is complicated, because there are only a few reports, probably due to its rarity and diagnostic difficulty. We have reviewed our experience with seven patients who were diagnosed as having ALM in situ and discuss how to accurately diagnose and properly manage these rare lesions. Clinically the lesions showed black to brown discoloration of the nail with Hutchinson’s sign and hyperpigmented macules on the heel with color variegation. All the lesions showed a diffuse lentiginous pattern of melanocytic proliferation with variable level of atypism along the dermoepidermal junction. Dermoscopic findings were available in three and revealed parallel ridge patterns. Confrontation of clinical and histopathologic findings was observed in three, and the lesions were not recognized or diagnosed as ALM in situ in the first place. Excision of the primary lesion with variable operative margin was done as an initial treatment. Recurrence was observed in three patients and one developed invasive ALM and lymph node metastasis. Integration of all available information concerning the clinical presentation, histopathology, and dermoscopic findings is very important and can lead to the best classification for correct diagnosis. Lack of knowledge upon clinical course and optimal margin to control ALM in situ provokes the need for further studies with longer follow up and larger number of cases.
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Received: 2 March 2010; in revised form: 14 April 2010 / Accepted: 30 April 2010 / Published: 4 May 2010
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Abstract: Autologous melanoma associated antigens (MAA) on murine melanoma cells can elicit a protective anti-tumor immune response following a variety of vaccine strategies. Most require effective uptake by antigen presenting cells (APC). APC transport and process internalized MAA for activation of anti-tumor T cells. One potential problem with clinical melanoma vaccines against autologous tumors may be that often tumor cells do not express surface markers that label them for uptake by APC. Effective uptake of melanoma cells by APC might be achieved by exploiting the natural anti-Gal antibody which constitutes ~1% of immunoglobulins in humans. This approach has been developed in a syngeneic mouse model using mice capable of producing anti-Gal. Anti-Gal binds specifically to α-gal epitopes (Galα1-3Galα1-4GlcNAc-R). Injection of glycolipids carrying α-gal epitopes (α-gal glycolipids) into melanoma lesions results in glycolipid insertion into melanoma cell membranes, expression of α-gal epitopes on the tumor cells and binding of anti-Gal to these epitopes. Interaction between the Fc portions of bound anti-Gal and Fcγ receptors on APC induces effective uptake of tumor cells by APC. The resulting anti-MAA immune response can be potent enough to destroy distant micrometastases. A clinical trial is now open testing effects of intratumoral α-gal glycolipid injections in melanoma patients.
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Received: 14 April 2010; in revised form: 4 May 2010 / Accepted: 5 May 2010 / Published: 7 May 2010
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Abstract: Cytokines and growth factors have biologic effects that could stimulate tumor growth, invasion and angiogenesis. The incidence of 24 factors was investigated in 25 cultured human melanoma cell lines and in 62 fixed tissues at different stages of the disease. Over 80% of the human melanoma cell lines expressed TGF-β, IL-8, IL-6, VEGF, PDGF-AA and OPN. Significantly higher TGF-β, IGF-1 and IL-15 were determined in primary lesions compared to distant metastases by immunohistochemistry. Illustrating the complexity of the milieu of the tumor microenvironment, some of these factors may have to be considered in targeted therapy.
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Received: 29 March 2010; in revised form: 2 May 2010 / Accepted: 5 May 2010 / Published: 11 May 2010
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Abstract: Surgery remains the mainstay of melanoma therapy, regardless of the tumor site. Only the early diagnosis combined with proper surgical therapy currently gives patients affected by this malignancy the chance for a full cure. The main goal of surgical therapy is to provide the local control of the disease and to secure long-term survival of the patient without reasonable functional and esthetic impairment. The recommended method of biopsy—excisional biopsy, as an initial diagnostic and, to some extent, therapeutic procedure—is performed under local anesthesia as an elliptical incision with visual clear margins of 1–3 mm and with some mm of subcutaneous tissue. The extent of radical excision of the primary tumor (or scar after excisional biopsy) is based on the histopathologic characteristics of the primary tumor and usually consists of 1–2 cm margins with primary closure. The philosophy behind conducted randomized clinical trials has been to find the most conservative surgical approach that is able to guarantee the same results as more demolitive treatment. This has been the background of the trials designed to define the correct margins of excision around a primary cutaneous melanoma. Much less definition can be dedicated to the surgical management of patients with non-cutaneous melanomas.
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Received: 8 March 2010; in revised form: 11 May 2010 / Accepted: 12 May 2010 / Published: 26 May 2010
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Abstract: In advanced metastatic melanoma (non-resectable stage III/IV), the prognosis still remains poor, with median survival times between six and twelve months. Systemic therapeutic approaches for metastatic melanoma include chemotherapy, immunotherapy, immunochemotherapy, small molecules and targeted therapy. In this review, we will focus on the various treatment modalities as well as new agents used for targeted therapy.
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Received: 2 March 2010; in revised form: 13 April 2010 / Accepted: 18 May 2010 / Published: 26 May 2010
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Abstract: Cutaneous malignant melanomas share a number of molecular attributes such as limitless replicative potential that define capabilities acquired by most malignancies. Accordingly, much effort has been focused on evaluating and validating protein markers related to these capabilities to function as melanoma prognostic markers. However, a few studies have also highlighted the prognostic value of markers that define melanocytic differentiation and the plasticity of melanoma cells to trans-differentiate along several other cellular pathways. Here, we provide a comprehensive review and evaluation of the prognostic significance of melanocyte-lineage markers such as MITF and melanogenic proteins, as well as markers of vascular epithelial and neuronal differentiation.
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Received: 27 April 2010; in revised form: 21 May 2010 / Accepted: 24 May 2010 / Published: 26 May 2010
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Abstract: Given the pivotal roles of morphogen pathways including Wnt, Notch, Hedgehog, and BMP pathways in the development of the neural crest lineage, it is not surprising that these signaling networks have also been implicated in the biology of malignant melanoma. Understanding the mechanisms by which these pathways can alter cell fate and other biological properties in tumor cells will be essential for determining whether the therapeutic targeting of these pathways has a potential role in melanoma treatment. This review highlights some of the recent findings with regards to how morphogen signaling may regulate melanoma cell biology.
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Received: 5 May 2010; in revised form: 3 June 2010 / Accepted: 4 June 2010 / Published: 4 June 2010
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Abstract: An accurate diagnosis of melanomas at an early stage correlates directly with a better prognosis. However the incidence of melanoma is still increasing along with the number of related deaths. Melanoma cells grow extremely fast, with the result that many patients present after metastasis has occurred, too late for effective treatment. This paper describes the changes in the fibre diffraction patterns of skin that indicate the presence of a melanoma. Identification of these changes would provide an alternative early low-cost, reliable diagnostic test which could be conducted on a regular basis in local radiology facilities using rotating anode X-ray generators or as a mass screening test using suitable small angle x-ray beam-lines at synchrotrons.
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Received: 7 April 2010; in revised form: 21 May 2010 / Accepted: 28 May 2010 / Published: 7 June 2010
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Abstract: The neuromediator serotonin (5-hydroxytryptamine; 5-HT) has been proposed to play a role in tumor progression. Thus, the aim of the present investigation was to determine whether alterations in the serotonergic system occur in nevomelanocytic tumors. For this purpose, paraffin-embedded biopsies of superficial spreading malignant melanoma (SSM), dysplastic compound nevi (DN) and benign compound nevi (BCN) were characterized with regard to their expression of 5-HT, the 5-HT1A and 5-HT2A receptors, and the serotonin transporter protein (SERT), by immunohistochemical analysis. Melanocytes in the region surrounding the tumor were found to express both the 5-HT1A and 5-HT2A receptors. Tumor cells that immunostained positively for the different serotonergic markers were observed in the suprabasal epidermis of DN tissue and, to an even greater extent, in the case of SSM. Furthermore, some of these latter cells expressed both 5-HT1AR and 5-HT2AR. The level of expression of 5-HT1AR at the junctional area was lower for SSM than for DN or BCN. As the degree of atypia increased, the intensity of tumor cell staining in the dermis for 5-HT1AR and SERT declined. Vessel immunoreactivity for 5-HT2A was more intense in SSM than in BCN tissue. Round-to-dendritic cells that expressed both SERT and 5-HT1AR were seen to infiltrate into the dermal region of the tumor, this infiltration being more evident in the case of DN and SSM. These latter cells were also tryptase-positive, indicating that they are mast cells. Thus, alterations in serotonergic system may be involved in nevomelanocytic tumors and mast cells may play an important role in this connection.
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Received: 23 April 2010; in revised form: 2 June 2010 / Accepted: 3 June 2010 / Published: 7 June 2010
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Abstract: Health care providers and their patients jointly participate in melanoma prevention, surveillance, diagnosis, and treatment. This paper reviews screening and follow-up strategies for patients who have been diagnosed with melanoma, based on current available evidence, and focuses on methods to assess disease recurrence and second primary occurrence. Secondary prevention, including the roles of behavioral modification and chemoprevention are also reviewed. The role of follow-up dermatologist consultation, with focused physical examinations complemented by dermatoscopy, reflectance confocal microscopy, and/or full-body mapping is discussed. Furthermore, we address the inclusion of routine imaging and laboratory assessment as components of follow-up and monitoring of advanced stage melanoma. The role of physicians in addressing the psychosocial stresses associated with a diagnosis of melanoma is reviewed.
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Received: 27 August 2010; in revised form: 14 September 2010 / Accepted: 15 September 2010 / Published: 27 September 2010
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Abstract: Two new cancer therapies apply bioelectric principles. These methods target tumor structures locally and function by applying millisecond electric fields to deliver plasmid DNA encoding cytokines using electrogene transfer (EGT) or by applying rapid rise-time nanosecond pulsed electric fields (nsPEFs). EGT has been used to locally deliver cytokines such as IL-12 to activate an immune response, resulting in bystander effects. NsPEFs locally induce apoptosis-like effects and affect vascular networks, both promoting tumor demise and restoration of normal vascular homeostasis. EGT with IL-12 is in melanoma clinical trials and nsPEFs are used in models with B16F10 melanoma in vitro and in mice. Applications of bioelectrics, using conventional electroporation and extensions of it, provide effective alternative therapies for melanoma.
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Last update: 25 September 2012
