Although the clinical and pathologic diagnosis of some melanomas is clear-cut, there are many histopathologic simulators of melanoma that pose problems. Over-diagnosis of melanoma can lead to inappropriate therapy and psychologic burdens, whereas under-diagnosis can lead to inadequate treatment of a deadly cancer. We used existing data on DNA copy number alterations in melanoma to assemble panels of fluorescence in situ hybridization (FISH) probes suitable for the analysis of paraffin-embedded tissue. Using FISH data from a training set of 301 tumors, we established a discriminatory algorithm and validated it on an independent set of 169 unequivocal nevi and melanomas as well as 27 cases with ambiguous pathology, for which we had long-term follow-up data. An algorithm-using signal counts from a combination of 4 probes targeting chromosome 6p25, 6 centromere, 6q23, and 11q13 provided the highest diagnostic discrimination. This algorithm correctly classified melanoma with 86.7% sensitivity and 95.4% specificity in the validation cohort. The test also correctly identified as melanoma all 6 of 6 cases with ambiguous pathology that later metastasized. There was a significant difference in the metastasis free survival between test-positive and negative cases with ambiguous pathology (P=0.003). Sufficient chromosomal alterations are present in melanoma that a limited panel of FISH probes can distinguish most melanomas from most nevi, providing useful diagnostic information in cases that cannot be classified reliably by current methods. As a diagnostic aid to traditional histologic evaluation, this assay can have significant clinical impact and improve classification of melanocytic neoplasms with conflicting morphologic criteria.
Biologic agents targeting the epidermal growth factor receptor (EGFR) have emerged as a robust treatment option for various solid tumors. Despite lower systemic side effects than conventional chemotherapy, the majority of patients treated with these agents experience cutaneous toxicities, including papulopustular rashes, hair and nail changes, xerosis and pruritus, which have a significant impact on health and quality of life. Currently no consensus or management guidelines exist for these untoward events. Therefore, a retrospective survey was carried out across 110 oncology practioners in the US that were administering EGFR inhibitors. Providers were queried on the impact and management of these untoward events in their practices. Responses suggest that combination therapies (topical and oral) were more effective than either therapy alone, and also lead to a more rapid resolution of the papulopustular rash. Providers also reported that patients frequently complained of physical symptoms associated with the rash (itching and pain), and that they had a positive perception when being treated for their cutaneous side effects. The survey results support that attentive cutaneous care is important in patients treated with EGFR inhibitors, and that proactive/combined interventions may enhance quality of life and optimize consistent drug administration.
To study the clinical features, therapeutic responses, and outcomes in patients with folliculotropic mycosis fungoides (FMF) and to compare our single-center experience of 43 patients with the findings from the Dutch Cutaneous Lymphoma Group.Setting: A single-center experience from the Northwestern University Multidisciplinary Cutaneous Lymphoma Group.Patients: Forty-three patients with FMF were included in the study and compared with 43 age-and stagematched patients with classic epidermotropic mycosis fungoides (MF) with similar follow-up time.Results: Folliculotropic mycosis fungoides showed distinct clinical features, with 37 patients having facial involvement (86%) and only 6 having lesions limited to the torso (14%). The morphologic spectrum of lesions is broad and includes erythematous papules and plaques with follicular prominence with or without alopecia; comedonal, acneiform, and cystic lesions; alopecic patches with or without scarring; and nodular and prurigolike lesions. Sixty-five percent of patients had alopecia, which in 71% of cases involved the face. Severe pruritus was seen in 68% of patients. In general, patients responded poorly to skin-directed therapy and in almost all cases required systemic agents to induce even a partial remission, including patients with early-stage disease. Overall survival was poor. Patients with early-stage disease (ՅIIA) had a 10-year survival of 82%, which took a steep drop off to 41% by 15 years. Patients with late-stage disease (ՆIIB) had an outcome similar to those patients in the control group with conventional epidermotropic MF of a similar stage. Conclusions:The morphologic spectrum of clinical presentation for FMF is broad and distinct from those in conventional MF. This is at least partially attributed to the ability of FMF to simulate a variety of inflammatory conditions afflicting the follicular unit. The disease course is aggressive, and many patients, including those with early disease, show a poor outcome particularly between 10 and 15 years after the initial onset of disease. Response to skindirected therapy is poor even in early-stage disease, and our best results were seen with psoralen plus UV-A (PUVA) therapy with oral bexarotene or PUVA with interferon alfa. These findings corroborate those of the Dutch Cutaneous Lymphoma Group and further validate the classification of FMF as a distinct entity.
The aim of this study was to determine the thoroughness of deliberate skin examination by people with a history of melanoma. Patients were randomized into one of two conditions: either to receive the brief educational and skills training intervention alone or as a couple with their spouse or cohabiting partner. Subjects recorded concerning lesions on body maps. At the 4-month visit, a total body skin examination was performed by a dermatologist blinded to the subjects’ condition and to their recorded responses. The skin surface was divided according to the region’s visibility during skin self-examination and sexual connotations: visible/not sexually sensitive, non-visible/not sexually sensitive and sexually sensitive. The primary point of comparison was missed lesions, defined as the difference between lesions recorded by the subjects and their partners and those recorded by the dermatologist. Among 130 participants, 56 subjects reported partner assistance while performing SSE. Participants missed more lesions in sexually sensitive areas than in the other regions. With the increasing age of the patient, the number of missed lesions in non-visible/not sexually sensitive and sexually sensitive areas decreased. Male patients assisted by female partners missed fewer lesions in all three regions than female patients assisted by male partners. In easily visible areas, male patients missed significantly fewer lesions than female patients (P = 0.01). Older couples performed more thorough partner-assisted skin examinations in non-visible and sexually sensitive areas than younger couples. Male patients who were assisted by female partners performed more thorough partner-assisted skin examinations than female patients assisted by male partners.
Lee had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
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