Stephen W. Dusza

Randomized Double-Blind Trial of Prophylactic Oral Minocycline and Topical Tazarotene for Cetuximab-Associated Acne-Like Eruption

PURPOSE To evaluate the ability of either oral minocycline, topical tazarotene or both, to reduce or prevent cetuximab-related acneiform rash when administered starting on day 1 of cetuximab therapy. PATIENTS AND METHODS Metastatic colorectal cancer patients preparing to initiate cetuximab were randomly assigned to receive daily oral minocycline or placebo, and to receive topical tazarotene application to either left or right side of the face. Both therapies were administered for 8 weeks. RESULTS Forty-eight eligible patients were randomly assigned to minocycline (n = 24) or placebo (n = 24). Total facial lesion counts were significantly lower in patients receiving minocycline at weeks 1 through 4. At week 4, a lower proportion of patients in the minocycline arm reported moderate to severe itch than in the placebo arm (20% v 50%, P = .05). Facial photographs, obtained at week 4, were reviewed for rash global severity. Patients in the minocycline arm trended toward lower frequency of moderate to severe rash than patients receiving placebo (20% v 42%, P = .13). The differences in total facial lesion counts and subjectively assessed itch were diminished by week 8. Cetuximab treatment was interrupted because of grade 3 skin rash in four patients in the placebo arm, and none in the minocycline arm. There was no observed clinical benefit to tazarotene application. Tazarotene treatment was associated with significant irritation, causing its discontinuation in one third of patients. CONCLUSION Prophylaxis with oral minocycline may be useful in decreasing the severity of the acneiform rash during the first month of cetuximab treatment. Topical tazarotene is not recommended for management of cetuximab-related rash.

Site and Timing of First Relapse in Stage III Melanoma Patients: Implications for Follow-Up Guidelines

PURPOSE Stage III melanoma is associated with a high risk of relapse and mortality. Nevertheless, follow-up guidelines have largely been empirical rather than evidence-based. PATIENTS AND METHODS Clinical records of stage III patients with no evidence of disease seen at Memorial Sloan-Kettering Cancer Center (MSKCC) between 1992 and 2004, who ultimately relapsed, were reviewed retrospectively to evaluate date of first relapse, time to first relapse, method of first relapse detection, and survival. We also determined overall 5-year relapse-free survival (RFS) of all stage III patients seen at MSKCC during this period. RESULTS The overall 5-year RFS for stage IIIA, IIIB, and IIIIC patients was 63%, 32%, and 11%, respectively. Among relapsing patients, 340 had adequate follow-up to be evaluable for all parameters. Site of first relapse was local/in-transit (28%), regional nodal (21%), or systemic (51%). First relapses were detected by the patient or family, physician, or by screening radiologic tests in 47%, 21%, and 32% of patients, respectively. Multivariate analysis revealed that better overall survival was associated with younger age and first relapse being local/in-transit or nodal, asymptomatic, or resectable. For each substage, we estimated site-specific risk of first relapse. CONCLUSION Patients detected almost half of first relapses. Our data suggest that routine physical examinations beyond 3 years for stage IIIA, 2 years for stage IIIB, and 1 year for stage IIIC patients and radiologic imaging beyond 3 years for stages IIIA and IIIB and 2 years for stage IIIC patients would be expected to detect few first systemic relapses.

Melanomas detected with the aid of total cutaneous photography

Background  Early detection of melanoma results in excision of thinner melanomas, which are associated with better prognosis. Total cutaneous photography provides a temporal comparison of lesions, which allows clinicians and patients to recognize new and subtly changing lesions.

Atypical Spitzoid Melanocytic Tumors With Positive Sentinel Lymph Nodes in Children and Teenagers, and Comparison With Histologically Unambiguous and Lethal Melanomas

Children and teenagers with a positive sentinel lymph node (SLN) after a prior diagnosis of an atypical spitzoid melanocytic tumor (ASMT) are usually cared for clinically in the same way as patients with melanoma. Little is known about long-term follow-up of these individuals to determine whether this practice is appropriate. To learn more about the biology of these tumors we retrospectively reviewed the clinical and pathologic findings of children and teenagers (<18 y of age at the time of diagnosis) with an ASMT, positive SLN and follow-up of at least 3 years. Their findings were compared with histologically unambiguous melanomas of children or teenagers, who had a positive SLN or died of metastatic melanoma. Eleven individuals, 6 girls and 5 boys, with primary ASMT and positive SLN were identified. The primary tumors ranged in thickness from 2.1 to 12 mm (median, 4.6 mm; mean, 5 mm). The tumor mitotic rate ranged from 1 to 10 mitoses/mm2 (median, 3/mm2, median, 3/mm2). The positive SLNs included 6 nodes with intranodal melanocytic aggregates measuring <1 mm in greatest dimension, and 5 nodes, in which the size of the melanocyte deposits was ≥1 mm. All the patients with ASMT and positive SLN remained free of disease with a median follow-up of 47 months (mean, 61 mo, range: 36 to 132 mo). In contrast, 2 of 5 patients <18 years of age with a histologically unambiguous melanoma and a positive SLN died of metastatic melanoma. The overall disease-specific mortality rate for all patients <18 years of age diagnosed with melanoma was 12%. Our findings confirm that children and teenagers with ASMTs and positive SLNs have a less aggressive clinical course than those with histologically unambiguous melanoma.

New recommendations for the categorization of cutaneous features of congenital melanocytic nevi

BACKGROUND The diameter of congenital melanocytic nevi (CMN) has served as the lone criterion for determining risks of adverse outcomes such as melanoma. A standardized description of additional morphologic features is needed. OBJECTIVE We sought to develop a consensus-based standardized categorization of cutaneous features of CMN and to test agreement among experts on the proposed scheme. METHODS An interdisciplinary group of experts in the field of CMN was surveyed using a detailed questionnaire. Applicability of the expert consensus-based scheme was tested for interobserver agreement. RESULTS The principal variable of the consensus-based categorization is CMN size, based on maximal diameter the CMN is projected to attain by adulthood. CMN size categories include: small (<1.5 cm); medium (M1: 1.5-10 cm, M2: >10-20 cm); large (L1: >20-30 cm, L2: >30-40 cm); and giant (G1: >40-60 cm, G2: >60 cm). In addition, number of satellite nevi in the first year of life is categorized into none, 1 to 20, more than 20 to 50, and more than 50 satellites. Additional descriptors of CMN include anatomic localization, color heterogeneity, surface rugousity and presence of hypertrichosis (described as none, moderate, marked), and presence of dermal or subcutaneous nodules (none, scattered, extensive). Assessment of consistency among 3 experts showed moderate to excellent interobserver agreement for categorization of the clinical descriptors (kappa values 0.54-0.93). LIMITATIONS Applicability of the proposed scheme was tested in a virtual setting and only among experts. CONCLUSION The proposed categorization scheme for CMN was agreed upon by experts and showed good interobserver agreement. Such standardized reporting of patients with CMN facilitates the development of an international clinical database for the study of large and giant CMN.

Sensitivity and specificity for detecting basal cell carcinomas in Mohs excisions with confocal fluorescence mosaicing microscopy

Recent studies have demonstrated the ability of confocal fluorescence mosaicing microscopy to rapidly detect basal cell carcinomas (BCCs) directly in thick and fresh Mohs surgical excisions. Mosaics of confocal images display large areas of tissue with high resolution and magnification equivalent to 2x, which is the standard magnification when examining pathology. Comparison of mosaics to Mohs frozen histopathology was shown to be excellent for all types of BCCs. However, comparisons in the previous studies were visual and qualitative. In this work, we report the results of a semiquantitative preclinical study in which 45 confocal mosaics are blindly evaluated for the presence (or absence) of BCC tumor. The evaluations are made by two clinicians: a senior Mohs surgeon with prior expertise in interpreting confocal images, and a novice Mohs fellow with limited experience. The blinded evaluation is compared to the gold standard of frozen histopathology. BCCs are detected with an overall sensitivity of 96.6%, specificity of 89.2%, positive predictive value of 93.0%, and negative predictive value of 94.7%. The results demonstrate the potential clinical utility of confocal mosaicing microscopy toward rapid surgical pathology at the bedside to expedite and guide surgery.

The association between large congenital melanocytic naevi and cutaneous melanoma: preliminary findings from an Internet-based registry of 379 patients.

There is ample evidence in the literature to support the fact that there is an increased risk of the development of melanoma in individuals with a large congenital melanocytic naevus (LCMN). The published melanoma risk estimates, by and large, do not distinguish between cutaneous and extracutaneous melanomas. It is currently not known to what extent each contributes to the overall cited melanoma risk estimates. In order to obtain a better understanding of the association between LCMN and cutaneous melanoma arising within an LCMN, we report the preliminary findings of a cross-sectional study of 379 patients, with a median age of 3 years, from the first self-referred, Internet-based registry of patients with LCMN. To date, no cutaneous melanoma has been reported; possible reasons for this finding are discussed. Further research is required to clarify the risk of the development of cutaneous melanoma separate from non-cutaneous melanoma and to identify subgroups of patients with LCMN at highest risk for the development of melanoma. This information will help to formulate appropriate decisions concerning the management of patients with LCMN.

The significance of crystalline/chrysalis structures in the diagnosis of melanocytic and nonmelanocytic lesions

BACKGROUND Crystalline/chrysalis structures (CS) are white shiny streaks that can only be seen with polarized dermatoscopy. OBJECTIVES We sought to estimate the prevalence and assess the clinical significance of CS in melanocytic and nonmelanocytic lesions. METHODS This was a prospective observational study in which dermatoscopic assessment of lesions was recorded in consecutive patients examined during a 6-month period. In addition, a data set of biopsy-proven melanomas was retrospectively analyzed. RESULTS In all, 11,225 lesions in 881 patients were prospectively examined. Retrospectively, 229 melanomas imaged with polarized dermatoscopy were analyzed. In the prospective data set, a median of 12.7 lesions (range, 1-54) were evaluated per patient. None of clinically diagnosed Clark nevi (n = 9750, 86.8%) demonstrated CS. Overall, CS were observed in 206 (1.8%) lesions, most commonly dermatofibromas and scars among nonbiopsied lesions. A total of 265 (2.4%) lesions were biopsied, including 20 melanomas and 36 nevi. Among biopsied malignant lesions, CS were most commonly observed in basal cell carcinoma (47.6%) and invasive melanomas (84.6%). Melanomas were more likely to have CS than biopsied nevi (odds ratio = 9.7, 95% confidence interval 2.7-34.1). In the retrospective data set, CS were more commonly observed among invasive melanomas (41%) compared with in situ melanomas (17%) (odds ratio = 3.4, 95% confidence interval 1.9-6.3, P < .001). The prevalence of CS correlated with increased melanoma thickness (P = .001). LIMITATIONS Biopsied lesions represent a small percentage of the total number of lesions evaluated. CONCLUSION Among biopsied malignant lesions, CS are most commonly observed in basal cell carcinoma and invasive melanomas and rarely seen in nevi. In melanoma, CS may reflect increased tumor thickness and progression.

Differences in Dermoscopic Images from Nonpolarized Dermoscope and Polarized Dermoscope Influence the Diagnostic Accuracy and Confidence Level: A Pilot Study

BACKGROUND Studies have demonstrated differences in colors and dermoscopic structures observed with polarized dermoscopes (PDs) and nonpolarized dermoscopes (NPDs). OBJECTIVE The objective was to evaluate whether diagnosis and diagnostic confidence changes when viewing dermoscopic images from NPDs and PDs. METHODS A total of 100 dermatologists participated in the study. Twenty-five pigmented lesions were shown in the study, consisting of 7 seborrheic keratoses (SK), 3 basal cell carcinomas, 2 atypical nevi, 5 malignant melanomas (MM), 3 dermatofibromas, 3 blue nevi, and 2 hemangiomas. Two images of each lesion (one NPD and one PD) were included. The McNemar test and paired t-test were used for the statistical analysis. RESULTS Ninety-one participants completed the study. Significant differences in the diagnoses were observed for the SK, atypical nevus, and MM images. Seventy-five percent and 59% of the final participants correctly diagnosed SK when presented with the NPD and PD images, respectively. For MM, 23 and 34% made the correct diagnoses with the NPD and PD images, respectively. CONCLUSIONS Viewing lesions with NPD versus PD can affect the diagnosis and diagnostic confidence of physicians that are novices with dermoscopy. Further studies including physicians at different expertise levels and a larger sample of lesions are needed to further explore the differences.

Clinical and Dermoscopic Stability and Volatility of Melanocytic Nevi in a Population-Based Cohort of Children in Framingham School System

Nevi are important risk markers of melanoma. The study aim was to describe changes in nevi of children using longitudinal data from a population-based cohort. Overview back photography and dermoscopic imaging of up to 4 index back nevi was performed at age 11 (baseline) and repeated at age 14 (follow-up). Of 443 children (39% females) imaged at baseline, 366 children (39% females) had repeated imaging three year later. At age 14, median back nevus counts increased by 2; 75% of students (n=274) had at least one new back nevus and 28% (n=103) had at least one nevus that disappeared. Of 936 index nevi imaged dermoscopically at baseline and follow-up, 69% (645 nevi) had retained the same dermoscopic classification from baseline evaluation. Only 4% (n=13) of nevi assessed as globular at baseline were classified as reticular at follow-up, and just 3% (n=3) of baseline reticular nevi were classified as globular at follow-up. Of 9 (1%) index nevi that disappeared at follow-up, none showed halo or regression at baseline. In conclusion, the relative stability of dermoscopic pattern of individual nevi in the face of the overall volatility of nevi during adolescence suggests that specific dermoscopic patterns may represent distinct biologic nevus subsets.