Melanoma from bench to bedside: meeting report from the 6th international melanoma congress (2009)

The 2009 International Melanoma Congress sponsored by the Society for Melanoma Research brought together a large collection of laboratory researchers, students, and clinicians. Presentations were made in numerous areas spanning biological analyses to clinical management of the disease. The meeting was characterized by numerous presentations of provocative, unpublished data, including multiple aspects which impact greatly on our understanding and management of melanoma. This meeting summary has been compiled by the authors in an effort to convey some of the newly presented data despite the fact that a comprehensive treatment of the meeting contents is not feasible. Therefore, the authors apologize to the many speakers and poster presenters whose interesting and important discoveries could not be included here. The Second Melanoma Pathology Symposium was organized by Raymond Barnhill (Hospital Saint-Louis and University of Paris VII, Paris, France) and convened as a satellite session just prior to the beginning of the Congress. It covered a diverse spectrum of topics pertinent to the biology and histopathology of melanoma during this 1-day program. These subjects in the Symposium included: Regression in melanoma: what significance does it have in 2009 – C. Shea, Melanocytic lesions of the scalp region – A. Spatz, Sentinel lymph node biopsy and minimal tumor burden – M. Cook, Histological evaluation of melanonchia S. Binder, Spitzoid lesions and sentinel lymph node biopsy – K. Busam, Angiotropic melanoma and extravascular migratory metastasis: An update – R. Barnhill, Reproducibility of histologic diagnosis of atypical nevi and melanoma with a 20-yr interval- L. Duncan, Blue nevi and pigmented epitheliod melanocytomas – A. Zembowicz, A study of acral melanoma in Brazil – G. Landman, The pigmented macular lesions in chronically sun-exposed skin – S. McCarthy, Melanoma and the pre-metastatic niche – M. Mihm, Melanocytic lesions: discordance in diagnosis – M. Piepkorn, Immunohistochemistry and melanocytic lesions – V. Prieto, A critique of ancillary diagnostic techniques in melanoma – D. Elder, The reporting of melanoma and melanoma prognostic factors in 2009 – R. Scolyer, and A multi-observer study in to validate genotype–phenotype correlations to improve melanoma classification – B. Bastian. As a biological phenomenon in melanoma, regression is of considerable importance but nonetheless continues to be very poorly understood. A major problem in the pathology of regression is the ongoing failure to apply standardized and reproducible criteria for its histopathological assessment. Thus, to a significant degree the conflicting data associated with regression and outcome in melanoma can be ascribed to the difficulty and lack of consensus in how regression is evaluated histologically. From this review, it was also concluded that at present there are no objective data that the presence of regression in a primary melanoma is a definite indication for sentinel lymph node biopsy. The scalp constitutes an important site for particular melanocytic lesions such as small cell melanoma in children, both arising de novo and in congenital nevi, blue nevus-like melanomas (malignant blue nevi), and atypical melanocytic nevi that are frequently misclassified as melanoma. There is ongoing debate about whether a minimal tumor burden may exist in metastatic melanoma, as for example, micrometastases measuring <0.1 or 0.2 mm, and in particular, in sentinel lymph nodes (SLN), which has predictive value for patient management and outcome. On the other hand, there is also evidence that documented metastases of any size may potentially correlate with melanoma progression. A review of the application of SLN biopsy for spitzoid melanocytic lesions has demonstrated SLN deposits in about 50% of patients undergoing this procedure. Interestingly, although tentative, virtually all of the latter patients have failed to show any evidence of disease progression with follow-up. There has been controversy surrounding the nomenclature of pigmented epithelioid melanocytic neoplasms described as epithelioid blue nevi in the context of Carney complex and the subsequent entity pigmented epithelioid melanocytoma (PEM). However, recent documentation of the mutations in the protein kinase A regulatory subunit 1alpha gene and loss of protein R1alpha expression in the latter lesions provides support for PEM as a distinct entity and a close relationship with epithelioid blue nevi. Angiotropic melanoma and extravascular migratory metastasis (EVMM) has been the subject of serious research for more than a decade. Accumulating evidence indicates that angiotropism in melanoma is a prognostic factor, and that extravascular migratory metastasis (EVMM) is an important mechanism of melanoma spread. Recent molecular analysis and gene-expression profiling are beginning to yield new information about the molecular basis of EVMM. Although not studied to any significant degree in melanoma thus far, the potential creation of a ‘premetastatic niche’ by the primary tumor has relevance to melanoma. Pigmented macular lesions involving chronically sun-exposed skin constitute a challenging spectrum of entities ranging from pigmented actinic keratosis to in situ or thin invasive melanoma. Because of the striking heterogeneity of many lesions, great attention to adequate sampling and careful assessment of margins are needed. The rates of discordance in the pathological diagnosis of atypical melanocytic lesions are well-established in the However, the basis for this lack of has not been to for the striking in of melanoma has been that of or in more a for the diagnosis of melanoma by A recent study rates of for a of atypical melanocytic lesions and thin melanomas with a 20-yr has a to for melanoma This outcome was also by rates of melanoma diagnosis the study Immunohistochemistry continues to be an important for melanocytic and to in the of lesions from melanoma. particular, which and such as are the example, nevi show expression of the in but with melanomas the A review of the of in melanoma has that is the very that have been to There is evidence that the of may potentially important prognostic information for clinical management of the prognostic for patients with primary melanoma, has been as a major prognostic in the new melanoma clinical of the on with the of or melanoma patient a recent study has the for particular to correlate with particular such as the latter are with to for many the to are not for a significant of melanomas the of genotype–phenotype to improve The with by a in the of the and of It that of the major to is the that of this of the of which in the of of could also for of The which that have the to the which that all have the potential to from laboratory the that any cell can be to The session from to melanoma and melanoma with the melanomas from in which melanomas were with cell associated the many a and a of melanoma distinct a which and rates of tumor but to a which and rates of tumor that were to and and a that to with a of and and These concluded that more than distinct of melanoma could be from the tumor and that tumor heterogeneity does not have to be for a to of melanoma the in which melanomas are of melanoma in the importance of the for the potential of melanoma were brought in the and has as a of melanoma that and the cell that and have that are to disease progression. that the tumor and with tumor progression. on that of of a of in of melanoma provides an to which may not factors but that on for tumor the was brought that the of which are by many to the of provides an to melanoma that be by the of that a of melanoma were to in the than the failed to the potential of melanoma despite of potential melanoma cell no or of including could from in to at the cell that all melanoma have the potential to the and that some including the of the cell some melanoma the example, to this The Congress with a by of for the of a review of to a of melanoma. described of of cell and of laboratory have on the described the and of a cell which in a melanoma by of also described of cell that tumor associated to be in with the cell A clinical in is with clinical at and significant were described to have in all patients to A striking was made with to the of in many metastatic lesions were to in a despite the The cell in the is from the laboratory of and is the melanocytic of the that this metastasis was of loss of expression may thus a significant to the of this the for loss of expression to a striking the mechanism of and in The recent understanding of the regulatory of the provides great for significant clinical the important for study of was to be for expression of the protein in Interestingly, the tumor is and to disease progression The of by and the of in with tumor of The of a in of This has for melanoma, as expression is with progression of the in primary were to in by in This of as a to for melanoma the with of on clinical involving with to and in the presence of and The included of to with of in in the presence of This the of the significance of in the at the of disease. of of disease with of both and were also present the tumor there was also with the presence of These evidence for of in the to for melanoma and the of A clinical expression in is associated with in cell and of clinical with an that clinical in a of including melanoma. particular is the of treatment with the of cell involving the of of for As of a primary Research described the of as a for by of for to was as as clinical including in a also clinical that also to and The and the of University of presented data that a in of melanoma. of to melanoma in and in a small of melanoma cell and were characterized as As to the cell not a melanoma that on the data, it was that melanoma is a and that the is for tumor of the cell on the of metastatic of melanoma. a and its melanoma is to of by or metastatic melanoma a more invasive also that of expression in melanoma. data that the and melanoma cell S. presented a in which melanoma metastases the of primary This was melanoma and the of melanoma cell which can to and metastases were with was but metastases from metastases can to the in tumor This has the of which can be small to of metastatic of whether melanoma a or a cell including some cell and some are organized and small of can disease in a melanoma in in can in a more with potential is a of melanoma of cell metastatic melanoma with of cell a a of the of as a gene that is in metastatic melanoma during with is in cell during and is in and its in cell thus an important in cell to the session by about the of in have been on of melanoma in the have of melanoma by but no significant for in in the this to by the of in pigmented that of on a with melanoma at the in pigmented and However, was to melanoma in pigmented that were in both pigmented and with in pigmented on of melanoma, that both and can melanoma but by the on this by to in by which melanoma. described a that the and of from the this to the in molecular of to and both and with in that a to was that a gene was from associated with a of This was in associated with a of melanocytic characterized by and the that this was by also presented in data that can in melanoma by that to could be in by the of which could also potentially with a of on of the that of the skin to both cell and to of the regulatory which a in expression of described the of in melanoma, as as in the skin associated with and that to in the of in but that can be by application of a a clinical for small of also expression by of which can be to for that is and which as a for can also to which may to of to melanoma associated with skin and described the of to assessment of the melanoma and the As a in described the of melanoma from to be associated with to the of The at including the protein melanoma have been to melanocytic nevi This is striking this is the melanoma Melanoma are to correlate to and of about discoveries the of in and that is to of and the of that the is for of for of at the of the on as the for Interestingly, was by and by data that can by and a as to the of in melanoma that in the in a it is not an as an for the and of melanoma of be have that of by melanoma to the of a for of in the a The with that of and to of in by the of the Interestingly, a in but not or that the of a may cell on the that to of to potential of and that the by the of of the melanoma of the for and the its for and The University of to melanoma and from the of from which are in melanoma has metastatic and with and are to Thus, understanding the and biology of the – from with and – may be for new to melanoma. The the which the of in as as progression to melanoma. have a of nevi in that can to melanoma in a on that in can also melanoma in a with the or in a with the tumor and molecular pathology of the melanomas is and to be by the or and unpublished The in with of have a small that aspects of biology in and may as molecular to the that during as as the is during and from to and and may from the that may be to treatment and unpublished and may the mechanism of for S. Research of in melanoma. It is that metastatic melanoma is to and Therefore, the of cell is a in this disease. is an as it the potential of cell by of However, can also tumor a of including of or of is in melanoma is and the multiple that to the of or melanoma cell However, were also to by an cell These were by the Interestingly, the of was on the to the the was to tumor also Thus, no on cell were in also that have the as a of to to the the protein These a for new of and that could be Research presented data on in melanoma. melanoma mutations in can that may to the diagnosis and treatment of melanoma, a more on gene of are that of and have been associated with and small of were as potential However, clinical no tumor that some can have an by a comprehensive analysis of the gene in melanoma. The analysis of the gene mutations in of mutations in of the of but not in melanoma on in and tumor in that has the to melanoma progression. gene the a analysis of the gene in metastatic melanoma. This study mutations in the kinase of The region of was evaluated for mutations in a of melanoma This analysis mutations in in of melanoma the of the mutations that and are in close to mutations described in other tumor and kinase mutations were to kinase and in as as melanoma cell Melanoma of or treatment with the that melanoma are and that melanoma patients mutations may from at The Melanoma session with of the review of the comprehensive of a melanoma cell from a metastatic prior to described the from the as as for the of mutations in this tumor were and of mutations were the than with and were as as The that the are mutations than mutations were in on to data the presence of A of to mutations was with a a significant of to A mutations was which could be to or a a region on with loss of and This region that to mutations were present in all an to A mutations were in of the in and thus to and more to also presented evidence that was than with and expression mutations were in than of at a review of the that the gene is in a significant of This protein is to a of on to the of a as in an of a made in with of The and mutations are and together of melanoma described data that the of is with primary and and of was to be and to which is in of blue nevi, is in of blue nevi. may that may a more clinical analyses on patient outcome are The in which is the as in described a clinical to for patients with metastatic melanoma. in about the of for melanoma metastatic and to expression of metastatic These data were to in primary metastatic melanomas to metastasis associated analysis a for in From analyses were and by for in of were thus and of was for described that also that is a in and the gene is to described a for melanoma. a of melanomas together with it was to mutations as as a of the were including which potentially a of the were also including which the gene also described which to mutations that to treatment in melanoma. A of was in of was in tumor from a tumor from a patient during a clinical the with the been from the biopsy. Research described a of which on skin cell and as as a at for This is analyses of multiple which are to described of which is in cell as an in actinic also described the gene in melanoma, whose expression to to on to the of clinical for as for to described of a clinical at multiple which on multiple and multiple analyses with the of for the importance to for diagnosis and in melanoma. the clinical and histopathological of melanoma, the for a distinct clinical management of this melanoma from the presented the of the metastatic niche as an important of metastasis in of and the of presented new data to support the of in melanoma Melanoma in in that were with melanoma tumor was of that may in melanoma a of including which are by in and The and melanoma is a of a and was from laboratory which the of in the of expression and the the of in the of As is important in the of and this newly the for an in by of melanoma in a by was by of and of by melanoma for University of the for in melanoma. that of to a to a with expression was by that a distinct of melanoma than with of a cell from the was to show that invasive were pigmented and The presented data a by which the major melanoma metastasis is by and that of melanoma of the of the protein in the and potential treatment of melanoma. was by this in a as of factors for an to in of in primary to and of which an to The of both of which and of These a in which expression is by and an to evidence that in melanomas an may be which to be a in melanoma of by of in melanoma cell and of primary in a of metastatic melanoma, this that of of metastatic disease and of the of cell that in to melanoma, in other in particular cell in cell that an in or and that are to of of an or in of presented evidence that the is in melanoma and progression. a of is in primary and metastatic melanoma of present in the tumor or by the melanoma The demonstrated that is for and for melanoma in the to this to that a in that in the region of in melanoma These are associated with of the of the also data on how as a and of by protein and These of and and other factors associated with the of understanding of of has for clinical of described the of melanoma gene profiling in analysis of This major areas can be a that is for and to some lack that are to to the of tumor many that as as As a cell and are all of an on of described the clinical to the a in of in patients with a of patients in with in patients both prior This provides for of this for clinical the importance of of that in the of of expression of that This that can the and be an to its the a of the cell and is on and with on and and which is on and and are in and of and to of These also with of has an important in and at than with but than and and is This the of in the of the session on with a summary and update of of a melanoma in the of an for the in has a to large of associated with in melanoma for on progression. a of that melanomas as a of the expression of the in of melanoma, and The is on a a that of a also expression of in of and potentially in melanoma. of the gene as to presented data that is the major for in melanoma and that was for cell the described the new melanoma has in with of This was to of the by of expression of cell that to the of melanocytic However, that lesions have an to to melanoma with of or the constitutes a for of that or in has demonstrated that the of for and can melanoma and to its This has clinical of also but with a of of metastatic melanoma, in with of the of Research in the of and in melanocytic described the of in which mutations for described the of on and in described recent to a metastatic melanoma that could be to study the of at the of for The predictive of including can be in by failure to the clinical particular, the to the creation of to that more the of patients with metastatic on melanoma and cell described a that a that of and the to metastatic progression and was for a for that was as tumor any in was and were in a to and metastasis are to this of for melanoma. of on the of in melanoma the fact that despite significant in the and of the of new it clinical to this is the of to from to the of the which on the and of and of and the to to the of the to analysis of with and described at in melanoma and in and at whose is and with associated with This session the of and on melanoma and progression. As melanoma of both thin and lesions is in recent with a by and on the and in from in to in melanomas show in the the the in at a from to with no particular in of rates are in than with an that the in may be to of and of of and and of and melanoma the of in a study at was as a from the International for Research on for its are As University the for lack of and of of primary in skin for of melanoma. clinical skin was associated with a of and other skin in is in although with of a Although the of 2009 has concluded that evidence is to for skin the melanoma is to impact on clinical of debate is whether has a on melanoma progression. of presented data that subjects with of melanoma lesions progression to metastasis and was associated with melanoma lesions, of or of D. evidence of a of melanoma or progression is lack of adequate study about of of and by and and of of for the to of in melanoma from the Melanoma and from a which the with melanoma of and associated with nevi to and disease and there was no evidence of the Interestingly, on a region including and of it that was for the as in and were no significant for the This the importance of prior of melanoma factors in an as and the of in understanding the of factors with and nevi This session presented new clinical that demonstrated how many of the during the meeting were presented recent on were including of tumor and with tumor of the patient with or to and of the subsequent of and by patients can to tumor and can be the has to rates with great of of patients have demonstrated objective with very the great of patients were to other of tumor from is not feasible. patients and for with other have the of the from a cell with The gene has been in the the were on the of by and to of small of patients have objective This the to the for many patients and this for other presented an of with of the some and the potential of all the large of characterized are the can regression progression in its some patients this but or tumor and can be the at in some of patients were with the have progression and and with or by progression at that can be to have a outcome to show a presented is to that may to improve the of patients for These may be of or may be a for may be and to be associated with clinical data were on the of or of at a on the of kinase in patients with mutations or it been demonstrated that mutations and were in patients with or acral melanoma and in melanomas from and chronically areas of the by this of patients with acral or melanoma the of mutations in was and in of patients of which were the These in of patients were a of The included and patients and with of the and patients have disease a On the other hand, of of the patients demonstrated objective by with a and and a kinase both to have in These are very are a to the of and acral melanoma and a of mutations of A as to how melanoma from skin with in or of demonstrated It is that many to to patients to study this disease this presented from the of a kinase in melanoma The presented at demonstrated of patients with a of there have been an patients all with mutations and very have objective in of the It was also that both by clinical and the were significant were also cell of the have in to of with close evaluation have lesions has been and is the of which to in This may of understanding of what treatment to patients and what of including could be to and described a of multiple melanoma the with to the of by including the understanding of mechanism of to the as as in the poster The Melanoma Congress thus presented new from the to the in management of melanoma patients are in the from multiple it is that very major it is also that have to in the surrounding melanoma. A of to on this The International Melanoma Congress by the Society for Melanoma Research be in in