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Initial misdiagnosis of melanoma located on the foot is associated with poorer prognosis.

ABSTRACT: Acral melanoma has been reported to be associated with poorer outcomes than melanoma occurring on other cutaneous sites. It has been suggested that part of this disparity in outcomes may be related to delay in diagnosis. Therefore, we have analyzed the rate of misdiagnoses in patients with melanoma located on the foot and have characterized the influence on the clinical course and survival of the patients. A prospective, computerized melanoma database at the Skin Cancer Center of the University Hospital Essen, Germany was used to identify patients with histologically confirmed melanoma located on the foot between 2002 and July 2013 for subsequent analysis. A cohort of 151 patients diagnosed with primary melanoma located on the foot was identified. One hundred seven patients qualified for subsequent analysis. Forty-two patients were male (39.3%) and 65 (60.7%) were female; the mean age at first diagnosis was 61.6 years (median 66 years). The youngest patient was 19 years, the oldest 88 years old.Of the 107 patients analyzed, 32 (30%) were initially misdiagnosed. Misdiagnoses included chronic wounds, nevi, hematoma, fungal infections, warts, and paronychia. Misdiagnosis caused a median delay in diagnosis of 9 months. The 5-year disease-free survival rate (47.8% vs 72.7%) and the 5-year overall survival rate (63.5% vs 88.4%) were statistically significant lower in the misdiagnosis cohort.The awareness of potentially overlooked melanoma located on the foot has to increase among physicians.To improve early detection and, thus, the prognosis of patients with melanoma located on the foot, taking a biopsy from any suspicious lesion should be taken into consideration as soon as possible.

SUBMITTER: Sondermann W

PROVIDER: S-EPMC5265802 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Initial misdiagnosis of melanoma located on the foot is associated with poorer prognosis.

Sondermann Wiebke W Zimmer Lisa L Schadendorf Dirk D Roesch Alexander A Klode Joachim J Dissemond Joachim J

Medicine 20160701 29

Acral melanoma has been reported to be associated with poorer outcomes than melanoma occurring on other cutaneous sites. It has been suggested that part of this disparity in outcomes may be related to delay in diagnosis. Therefore, we have analyzed the rate of misdiagnoses in patients with melanoma located on the foot and have characterized the influence on the clinical course and survival of the patients. A prospective, computerized melanoma database at the Skin Cancer Center of the University ...[more]

PMID: 27442685

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Project description:BACKGROUND: Our understanding of the molecular pathways that underlie melanoma remains incomplete. Although several published microarray studies of clinical melanomas have provided valuable information, we found only limited concordance between these studies. Therefore, we took an in vitro functional genomics approach to understand melanoma molecular pathways. METHODOLOGY/PRINCIPAL FINDINGS: Affymetrix microarray data were generated from A375 melanoma cells treated in vitro with siRNAs against 45 transcription factors and signaling molecules. Analysis of this data using unsupervised hierarchical clustering and Bayesian gene networks identified proliferation-association RNA clusters, which were co-ordinately expressed across the A375 cells and also across melanomas from patients. The abundance in metastatic melanomas of these cellular proliferation clusters and their putative upstream regulators was significantly associated with patient prognosis. An 8-gene classifier derived from gene network hub genes correctly classified the prognosis of 23/26 metastatic melanoma patients in a cross-validation study. Unlike the RNA clusters associated with cellular proliferation described above, co-ordinately expressed RNA clusters associated with immune response were clearly identified across melanoma tumours from patients but not across the siRNA-treated A375 cells, in which immune responses are not active. Three uncharacterised genes, which the gene networks predicted to be upstream of apoptosis- or cellular proliferation-associated RNAs, were found to significantly alter apoptosis and cell number when over-expressed in vitro. CONCLUSIONS/SIGNIFICANCE: This analysis identified co-expression of RNAs that encode functionally-related proteins, in particular, proliferation-associated RNA clusters that are linked to melanoma patient prognosis. Our analysis suggests that A375 cells in vitro may be valid models in which to study the gene expression modules that underlie some melanoma biological processes (e.g., proliferation) but not others (e.g., immune response). The gene expression modules identified here, and the RNAs predicted by Bayesian network inference to be upstream of these modules, are potential prognostic biomarkers and drug targets.

Project description:BACKGROUND:Approximately one third of women who develop melanoma at childbearing age are diagnosed during gestation or the postpartum period, facing pregnancy-associated melanoma (PAM). However, only some retrospective studies with heterogeneous data have analyzed the impact of pregnancy on melanoma development, and no evidence exists about the behavior and the management of BRAF-mutated disease. SUBJECTS, MATERIALS, AND METHODS:In order to better describe the evolution of BRAF V600E-mutated PAM, we present here all consecutive cases diagnosed in our site during the last 7?years, recording oncological, obstetrical, and perinatal parameters, as well as the therapeutic decisions for both melanoma and gestation. Based on our institutional experience, we weigh the current published evidence and discuss upcoming clinical considerations about the prognosis of PAM, the role of BRAF status, and the possible treatment options during pregnancy in localized or advanced/metastatic disease. Five women were diagnosed with newly metastatic or relapsed BRAF V600E-mutated PAM (four during gestation and one in the 1st year postpartum) between 2012 and 2019. All of them developed extensive metastatic disease with multiple organ involvement, and four developed brain metastases. All cases experienced melanoma progression in less than 6 months under targeted therapy and died soon independently of the followed sequence of treatments. All the neonates were delivered alive and healthy, but one developed melanoma earlier than the second year of life. RESULTS:Reviewing the literature to confirm our unfavorable outcomes, no specific data on BRAF-mutated PAM were retrieved and current evidence still supports that the prognosis of PAM should be guided by the established risk factors, whereas the management of advanced/metastatic PAM should be evaluated on a case-by-case basis. CONCLUSION:More data are required to ascertain whether BRAF-mutated profile adversely affects PAM outcome, although the clinicians should be aware to detect any potential melanoma lesion during pregnancy as soon as possible, treating it locally, regardless of its BRAF status. IMPLICATIONS FOR PRACTICE:The prognosis and management of pregnancy-associated melanoma whether BRAF-mutated or wild type, is currently guided by the same parameters as in the nonpregnant condition. In this special nontrial subpopulation, BRAF-mutated status seems to have a detrimental effect on disease outcome, independently of the following treatments. In early stage melanoma, wide local excision with or without sentinel lymph node dissection may be curative at any trimester of gestation, while in advanced/metastatic setting, therapeutic strategy including immune-checkpoint or BRAF/MEK inhibitors, is more challenging, regardless of BRAF status, and should be based on an individualized decision in each case at a multidisciplinary level.

Dataset Information

Initial misdiagnosis of melanoma located on the foot is associated with poorer prognosis.

Publications

Initial misdiagnosis of melanoma located on the foot is associated with poorer prognosis.

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