Susan L. Boone

Fluorescence In Situ Hybridization (FISH) as an Ancillary Diagnostic Tool in the Diagnosis of Melanoma

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.

Folliculotropic Mycosis Fungoides: An Aggressive Variant of Cutaneous T-Cell Lymphoma

OBJECTIVES 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 stage-matched 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 (< or =IIA) had a 10-year survival of 82%, which took a steep drop off to 41% by 15 years. Patients with late-stage disease (> or =IIB) 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 skin-directed 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.

Impact and Management of Skin Toxicity Associated with Anti-Epidermal Growth Factor Receptor Therapy: Survey Results

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.

Two cases of multiple Spitz nevi: Correlating clinical, histologic, and fluorescence in situ hybridization findings

BACKGROUND The occurrence of multiple Spitz nevi is rare, especially the disseminated variant. Multiple Spitz nevi may be confused with, and must be differentiated from, primary spitzoid melanoma and cutaneous melanoma metastases. Over the past decade, fluorescence in situ hybridization (FISH) has emerged as a tool for studying melanocytic neoplasms, helping to differentiate between melanoma and benign melanocytic nevi. We describe 2 cases of patients with multiple Spitz nevi and their FISH results. OBSERVATIONS One case of disseminated Spitz nevi, in a 17-year-old female, showed balanced tetraploidy using FISH, while the other case, in a 51-year-old female with multiple Spitz nevi, showed normal diploid cells without significant gains or losses in chromosomes 6 or 11. CONCLUSIONS Patients may present with multiple, even disseminated, Spitz nevi. This phenotype should not be confused with melanoma and/or cutaneous metastasis. The use of FISH studies in context with careful correlation of clinical features and dermoscopic and histologic findings can assist in the diagnostic workup.

Blackberry-induced hand-foot skin reaction to sunitinib

SummarySunitinib is an orally administered small molecule that was approved by the US Food and Drug Administration in January 2006 as monotherapy for the treatment of patients with advanced renal cell carcinoma (RCC) and patients with gastrointestinal stromal tumor after disease progression on or intolerance to imatinib mesylate. Data pooled from multiple sunitinib dose-escalation trials showed that sunitinib is associated with various adverse events, with HFSR occurring in up to 20% of patients. We describe a 48-year-old woman with a history of metastatic colorectal cancer treated with single-agent sunitinib who developed pain and tenderness in areas of friction secondary to Blackberry use, and was diagnosed with trauma-induced hand-foot skin reaction (HFSR) secondary to sunitinib therapy.

Comparison of Electrodesiccation and Potassium‐Titanyl‐Phosphate Laser for Treatment of Dermatosis Papulosa Nigra

BACKGROUND There is a lack of randomized split‐face studies investigating treatments for dermatosis papulosa nigra (DPN) in dark skin. OBJECTIVE To compare the efficacy, safety, and tolerability of potassium‐titanyl‐phosphate (KTP) laser with efficacy, safety, and tolerability of electrodesiccation in the treatment of DPN in subjects with Fitzpatrick skin phototypes IV to VI. METHODS Fourteen subjects with Fitzpatrick skin phototypes IV to VI were randomized to receive two KTP laser treatments 4 weeks apart to half of the face. The contralateral half received two electrodesiccation treatments 4 weeks apart. Response was evaluated by photography reviewed by blinded dermatologists at 4 weeks after the second treatment. A treatment quality questionnaire about side effects and cosmetic outcome was also administered. RESULTS Difference in improvement of DPN between the KTP side and the electrodesiccation side per each rater (p=.99, p=.54) and per raters combined (p=.50) did not reach statistical significance. There was no treatment difference for subjective effectiveness (p=.06) or subjective confidence improvement (p=.99), although there was a significant treatment difference for subjective discomfort (p=.002) in favor of KTP. Both treatments were well tolerated without significant adverse effects. CONCLUSIONS Although treatment of DPN with KTP laser and electrodesiccation are comparable in efficacy, KTP laser is preferable for patient comfort. The authors have indicated no significant interest with commercial supporters.

Perception of Skin Cancer Risk by Those With Ethnic Skin

tology, Kyungpook National University Hospital, 50 Samdeok 2-ga, Chung-Gu, Daegu, South Korea, 700-721 (shinam73@hotmail.com). Author Contributions: Dr W. J. 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. Study concept and design: Park, S.-J. Lee, D. W. Kim, B. S. Kim, H. Y. Kim, Choi, and W. J. Lee. Acquisition of data: Park, S.-J. Lee, D. W. Kim, B. S. Kim, H. Y. Kim, Choi, and W. J. Lee. Analysis and interpretation of data: Park, S.-J. Lee, D. W. Kim, B. S. Kim, H. Y. Kim, Choi, E.-S. Lee, and W. J. Lee. Drafting of the manuscript: Park, S.-J. Lee, D. W. Kim, B. S. Kim, H. Y. Kim, Choi, and W. J. Lee. Critical revision of the manuscript for important intellectual content: Park, S.-J. Lee, D. W. Kim, B. S. Kim, H. Y. Kim, Choi, E.-S. Lee, and W. J. Lee. Administrative, technical, and material support: Park, S.-J. Lee, D. W. Kim, B. S. Kim, H. Y. Kim, Choi, and W. J. Lee. Study supervision: Park, S.-J. Lee, D. W. Kim, B. S. Kim, H. Y. Kim, Choi, and W. J. Lee. Financial Disclosure: None reported.

Efficacy of an Educational Intervention With Kidney Transplant Recipients to Promote Skin Self-examination for Squamous Cell Carcinoma Detection

OBJECTIVES To develop easily disseminated educational materials that enable early detection of skin cancer, and to examine the effectiveness of the materials to promote skin self-examination (SSE) among kidney transplant recipients (KTRs). DESIGN Randomized controlled trial of an educational intervention in comparison with a group that received only the assessment, education, and treatment as part of usual care with a nephrologist. SETTING Academic ambulatory nephrology practice. PATIENTS Seventy-five KTRs returning for routine care to their nephrologists 1 to 1.2 years or 3 to 7 years after transplantation. INTERVENTION Educational workbook. MAIN OUTCOME MEASURES Skin self-examination performance and new appointments with a dermatologist if a concerning skin lesion was found. RESULTS Twenty-two percent of those in the control group checked their skin after the visit compared with 89% of the treatment condition; thus, KTRs receiving the intervention were significantly more likely to have checked their skin (χ(2); P < .001). Among the 8 control KTRs who checked their skin, none found areas of concern. Of the 34 intervention KTRs who checked their skin, 12 participants (35%) found areas of concern. All 12 of these individuals made appointments with a dermatologist for follow-up. CONCLUSIONS The KTRs were receptive to performing SSE and acted on the recommendation made in the workbook to make an appointment with a dermatologist when a concerning lesion was discovered. Printed educational materials can be initiated in the tertiary care center 1 year after transplantation and used across a continuum of time during which KTRs may be transferred from the tertiary care center to community nephrologists. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01127737.

Squamous cell carcinoma in solid organ transplant recipients: influences on perception of risk and optimal time to provide education.

Squamous cell carcinoma (SCC) has a mortality rate of up to 8% in solid organ transplant recipients (OTRs), and the risk of OTRs developing SCC is up to 250-fold greater than that of the general population.1-3 Despite these risks, patients commonly do not seek health care for skin checks, nor do they routinely perform skin self-examinations (SSEs). Moreover, although patients in 1 study recalled being told to use sunscreen, few were aware that their immunosuppressive medication increased skin cancer risk.4 The present study assesses (1) the optimal time after transplantation to deliver SSE educational intervention; (2) the relationship between lifetime sun exposure and OTRs’ perception of SSE importance; and (3) the impact of SCC discussion with a health care worker on the likelihood of SSE performance.

Comparison of Treatment of Cherry Angiomata With Pulsed-Dye Laser, Potassium Titanyl Phosphate Laser, and Electrodesiccation A Randomized Controlled Trial

OBJECTIVE To assess the comparative efficacy of energy treatments in resolving cherry angiomata. DESIGN Rater-blinded randomized controlled trial. SETTING Outpatient dermatology clinic in an urban referral academic medical center. PARTICIPANTS Fifteen healthy adults aged 21 to 65 years were enrolled. Two eligible individuals who were approached declined to participate, and no one enrolled was withdrawn for adverse effects. INTERVENTIONS For each participant, 3 areas on the torso were demarcated such that each area contained 4 cherry angiomata. Each area was then randomly assigned to receive 1 of the 3 treatments: pulsed-dye laser (PDL) (595 nm), potassium titanyl phosphate (KTP) laser (532 nm), or electrodesiccation. Two treatments spaced 2 weeks apart were delivered to each area. MAIN OUTCOME MEASURES Standardized photographs from before treatment and 3 months after the last treatment were evaluated for color and texture on visual analog scales. RESULTS Mean change in color was a significant improvement of 7.77 (P<.001), but there was no significant difference across treatment arms (P=.19). Mean change in texture was a significant improvement of 6.23 (P<.001), and the degree of textural change also differed across treatments (P<.001). In pairwise comparisons, cherry angiomata treated with electrodesiccation were significantly less improved than were those receiving KTP laser (P=.003) and those treated with PDL (P=.001). The effects of KTP laser and PDL on texture were not different (P=.50). CONCLUSIONS Cherry angiomata can be effectively treated with electrodesiccation and with laser. Laser, especially PDL, may minimize the likelihood of treatment-associated textural change. Trial Registration clinicaltrials.gov Identifier: NCT00509977.