Special Issue "Current Concepts in the Diagnosis and Treatment of Cutaneous Melanoma"

Guest Editor
Dr. Chyi-Chia Richard Lee
Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 10, Room 2B50, 9000 Rockville Pike, Bethesda, MD 20892-0001, USA
Website: http://ccr.cancer.gov/staff/staff.asp?profileid=12822
E-Mail:
Interests: melanoma; skin cancers; dermatopathology; skin pathology; melanocytic skin lesions

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.org 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.

Type of Paper: Article
Title: Clinically Malignant but Histologically Indiscernible Irregularly Pigmented Lesions on Acral Areas in a Spectrum of Acral Lentiginous Melanoma
Author: Hyun Sun Park
Affiliation: Department of Dermatology, Seoul National University College of Medicine, Seoul, Korea; E-Mail: snudm@paran.com
Abstract: Malignant melanoma most frequently occurs on acral areas in Asians. Many authors observed clinically malignant lesions which showed histopathologically subtle changes such as proliferation of melanocyte with slight atypism. After they observed these cases did not progress to invasive melanoma for the follow up period, they entitled these cases not to malignant melanoma but to atypical melanosis of foot or atypical melanocytic hyperplasia and suggested that they can be treated with conservative resection. However, they could not totally exclude the possibility that those lesions belong to early acral lentiginous malignant melanoma in situ and progress to invasive melanoma if they follow up for the longer period. It has been controversial whether they are truly benign or not, which makes clinicians confusing in setting up treatment plans. In the present study, we investigated irregularly pigmented lesions on acral areas which are seemingly malignant but histopatholgocially indiscernible and analyzed clinical and histopathologic findings to help to elucidate their true identity.

Type of Paper: Review
Title: Automated Dermoscopy Image Analysis of Pigmented Skin Lesions
Author: Alfonso Baldi
Affiliation: Department of Biochemistry, Section of Pathology, Second University of Naples, Naples, Italy; E-Mail: alfonsobaldi@tiscali.it
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 (epidermis until 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 literature. Goal of this article is to review all these systems, including the most recent approaches based on content-based image retrieval systems.

Title: The NK-1 Receptor Antagonist L-732, 138 Induces Apoptosis and Counteracts Substance P-Related Mitogenesis in Human Melanoma Cell Lines
Authors: Miguel Muñoz¹, Marisa Rosso¹, Ana Gonzalez-Ortega¹ and Rafael Coveñas²
Affiliations: ¹ Research Laboratory on Neuropeptides, Virgen del Rocío University Hospital, Sevilla, Spain; E-Mail: mmunoz@cica.es
² Laboratory of Neuroanatomy of the Peptidergic Systems, Institute of Neurosciences of Castilla y León (INCYL, Lab. 14), Salamanca, Spain
This work was supported by the Consejería de Innovacion, Ciencia y Empresa of the Junta de Andalucía,CTS-2247, Spain.
Abstract: Melanoma represents 1% of cancers and it accounts for approximately 65% of skin cancer deaths. At the present effective treatment does not exist. The last two decades have seen no significant progress in extending the survival of patients with metastases, thus an urgent need to improve therapy interventions in melanoma is required. It has previously reported that substance P (SP) and neurokinin 1 (NK-1) receptor antagonists respectively induce cell proliferation and cell inhibition in human melanoma cell lines. Moreover, SP is expressed in invasive malignant melanomas. Moreover, the antitumor action of NK-1 receptor antagonist L-732,138 has been reported. However, the antitumor action of such antagonist on melanoma cells is unknown. In this sense, the main aim of the present study is to demonstrate the antitumor action of the NK-1 receptor antagonist L-732,138 against human melanoma cells. We carried out an study of the citotoxicity of the L-732,138 against COLO 858, MEL HO and COLO 679 human melanoma cell lines. Coulter counter was used to determine viable cell numbers followed by application of the tetrazolium compound MTS and the DAPI method was applied to demonstrate apoptosis in the human melanoma cells. We have demonstrated that L-732,138 at 10-100 μM elicits growth cell inhibition in a concentration dependent manner in all the melanoma cell line studied. The IC50 values for the first doubling time were respectively 44.3, 76.3 and 64.2 µM for COLO 858, MEL HO and COLO 679. Nanomolar concentrations of SP increased the growth rate of the cell lines and micromolar concentrations of L-732,138 inhibited the growth of the melanoma cells, with and without previous administration of SP. The specific antitumor action of L-732,138 occurs through the NK-1 receptor and melanoma cells death was by apoptosis. These findings reported here, for the first time, indicate that the NK-1 receptor antagonist L-732,138 could be a new antitumor agent in the treatment of human melanoma.
Keywords: melanoma; NK-1 receptor antagonist; L-732,138; antitumor; apoptosis

Type of Paper: Review
Title: Cerebral Metastases from Malignant Melanoma: Current Concepts in the Biology and Therapy and Future Directions
Authors: Timothy Siu and Suyun Huang
Affiliation: Department of Neurosurgery-1004, The University of Texas M D Anderson Cancer, Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA; E-Mail: suhuang@mdanderson.org
Abstract: Of all primary cancers in humans, melanoma has the highest propensity to metastasize to the brain. The prognosis of patients with such 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 of such disease. In this review, we comment on the current treatment strategy for melanoma brain metastases and summarize some recent experimental findings from our laboratory of potential for the development of target specific antitumor therapies.

Type of Paper: Review
Title: How to Follow Melanoma Patients in the Dermatology Clinic?
Author: Ryan Gamble
Affiliation: School of Medicine, University of Colorado Denver, CO, USA; E-Mail: Ryan.Gamble@ucdenver.edu
Abstract: Health care providers and their patients jointly participate in melanoma prevention, surveillance, diagnosis, and treatment. This paper reviews screening and follow up strategies based on current available evidence and focuses on methods to assess disease extent, disease recurrence and second primary occurrence. Routine imaging and laboratory assessment are components of the workup and monitoring of advanced stage melanoma. Evidence supports baseline and follow up imaging for early stage cutaneous melanoma mainly as directed by history and physical examination. The role of serum markers and lymph node evaluation methods will also be discussed.

Type of Paper: Review
Title: Surgery of Primary Melanomas
Authors: Piotr Rutkowski, Marcin Zdzienicki and Zbigniew I. Nowecki
Affiliation: M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland; E-Mail: rutkowskip@coi.waw.pl
Abstract: Surgery remains the mainstay of melanoma therapy of all sites and only early diagnosis combined with proper surgical therapy give currently the chance for cure the patients affected by this malignant tumor. The main goal of surgical therapy is to provide the local control of the disease and to secure long-term survival of patient without reasonable functional and esthetic impairment. The recommended method of biopsy - excisional biopsy as initial diagnostic and, to some extent, therapeutic procedure is performed under local anesthesia as elliptical incision with visual clear margins of 1-3 mm and with some millimeters of subcutaneous tissue. The extent of radical excision of primary tumor (or scar after excisional biopsy) is based on the histopathologic characteristics of 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, which has been 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.

Type of Paper: Review
Title: Systemic Therapy of Non-resectable Metastatic Melanoma
Authors: Azadeh Orouji, Sergij Goerdt and Jochen Utikal
Affiliation: Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Germany; E-Mail: jochen.utikal@umm.de
Abstract: In advanced metastatic melanoma (non-resectable stage III/IV), the prognosis remains still poor with median survival times between 7 and 9 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.
Keywords: melanoma; metastatic; chemotherapy; targeted therapy; small molecules

Type of Paper: Review
Title: Bioelectric Applications for Treatment of Melanoma
Authors: Stephen J. Beebe, Karl H. Schoenbach and Richard Heller
Affiliation: Frank Reidy Research Center for Bioelectrics, Old Dominion University, VA, USA; E-Mail: SBeebe@odu.edu
Abstract: Applications of bioelectrics, using conventional electroporation and nanoporation, provide effective alternative therapies for melanoma. The electroporation based method locally target tumors by applying micro- or millisecond electric fields to deliver immune stimulating cytokines using electro-gene transfer (EGT). The nanoporation based method utilizes rapid rise-time nanosecond pulsed electric fields (nsPEF) to directly eradicate melanoma. EGT is designed to activate tumor specific immune responses. NsPEFs locally induce apoptosis and affect vascular networks, both promoting tumor demise and restoration of normal vascular homeostasis. EGT with IL-12 is in clinical trials for melanoma and nsPEFs are studied in a model with B16F10 melanoma.

Type of Paper: Review
Title: Epigenetic Modulation of Tumor-Associated Antigens: A New Weapon for Melanoma Immunotherapy
Authors: Hugues J.M. Nicolay ^1,2, Luca Sigalotti ², Alessia Covre ², Elisabetta Fratta ², Giulia Parisi ², Ester Fonsatti ¹, Sandra Coral ² and Michele Maio ^1,2
Affiliations: ¹ Division of Medical Oncology and Immunotherapy, Department of Oncology, University Hospital of Siena, Istituto Toscano Tumori, Siena, Italy
² Cancer Bioimmunotherapy Unit, Department of Medical Oncology, Centro di Riferimento Oncologico, Istituto di Ricovero e Cura a Carattere Scientifico, Aviano, Italy; E-Mail: mmaio@cro.it
Abstract: Epigenetic modifications have emerged as playing a central role in development and progression of human cutaneous melanoma, by affecting different pathways involved in disease progression. Along this line, DNA hypermethylation is also involved in favoring tumor escape from host’s immune recognition, by affecting the expression of selected antigens (i.e., HLA antigens, tumor-associated antigens (TAA), accessory/co-stimulatory molecules) required for an efficient immunologic recognition of melanoma cells.This review will focus on the epigenetic regulation of TAA constitutively expressed by melanoma cells, and on their modulation by epigenetic drugs. Particular emphasis will be given to TAA utilized as therapeutic targets in ongoing immunotherapy trials for cutaneous melanoma patients (i.e., High Molecular Weight-Melanoma-Associated Antigen, Cancer Testis Antigens).

Type of Paper: Article
Title: In Situ Conversion of Melanoma Lesions Into Autologous Vaccine by Intratumoral Injection of -Gal Glycolipids
Authors: Uri Galili
Affiliations: Department of Surgery, University of Massachusetts Medical School, Worcester, MA, USA; E-Mail: Uri.Galili@umassmed.edu
Abstract: Autologous melanoma associated antigens (MAA) on melanoma cells in the individual patient can elicit a protective anti-tumor immune response following effective internalization by antigen presenting cells (APC). APC transport and process internalized MAA for activation of anti-tumor T cells. Internalization of melanoma cells by APC is achieved by exploiting the abundant natural anti-Gal antibody. Anti-Gal binds to -gal epitopes. Injection of -gal glycolipids carrying -gal epitopes into melanoma lesions results in glycolipids insertion into melanoma cell membranes and binding of anti-Gal to these cells. Interaction between the Fc portion of the bound anti-Gal and Fcγ receptors on APC induces effective internalization of tumor cells by APC and induction of an anti-tumor immune response that destroys distant micrometastases.

Type of Paper: Review
Title: Circulating Tumour Cells in Cutaneous Malignant Melanoma: Are they prognostic?
Author: Mel Ziman
Affiliation: School of Exercise, Biomedical and Health Science, Edith Cowan University, 100 Joondalup Drive, Joondalup, Perth, Western Australia 6027; E-Mail: m.ziman@ecu.edu.au
Abstract: An important clinical aspect of the long term survival of patients with melanoma is the assessment and prevention of systemic metastasis. One measure of disease spread that may be useful as a prognostic tool is the quantification of circulating melanoma cells. A number of studies have now shown that circulating melanoma cells are a prognostic indicator in Cutaneous Malignant Melanoma (CMM). Several important issues remain to be clarified. One issue is whether the quantity of circulating cells or their phenotype is the most accurate prediction of patient outcome. In addition, obtaining accurate and reliable results for the measurement of very small quantities of circulating cells in a background of normal blood cells presents logistical problems. We review here accurate and reliable methods of isolating, quantifying and characterising circulating cells, and suggest informative markers for analysis of circulating melanoma cells.

Type of Paper: Article
Titles: Cytokines & Growth Factors Expressed by Human Cutaneous Melanoma
Authors: Elias G. Elias, Joanne H. Hasskamp and Bhuvnesh K. Sharma
Affiliation: Maryland Melanoma Center at Weinberg Cancer Institute, Franklin Square Hospital Center, Baltimore, Maryland 21237, USA; E-Mail: george.elias@medstar.net
Abstract: Several cytokines, growth factors including adhesion molecules and anti-apoptotic proteins (factors) have been reported in cultured melanoma cell lines. These have several 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. The results expressed the natural history of melanoma, and points out the heterogeneity of this disease. Some of these factors may have to be considered in targeted therapy.