Livedo reticularis.

Livedo reticularis (LR) is a net-like, violaceous, hyperpigmented pattern on the skin that reflects an underlying change in cutaneous blood flow. The causes of LR are many and most commonly include connective tissue diseases, vasculitis, hypercoagulability, and embolic events. We describe a 49-year-old man who presented with painful LR and ulcers on the lower extremities as a manifestation of chronic natural killer cell leukemia (CNKL). There have been only a few cases previously reported in the literature. We report an additional case of a patient with both LR and CNKL and suggest a possible mechanism that explains this association.

Lichen sclerosus et atrophicus.

Morphea and lichen sclerosus et atrophicus (LSA) have similar clinical presentations. Reports of patients with overlapping clinical and histopathologic features of both conditions have led some to speculate that they may represent different presentations along the same disease spectrum. It has been postulated that there is a common etiologic agent, which may involve autoimmunity, response to trauma, or infection. The link between Borrelia infection and both morphea and LSA has been widely studied but remains controversial. We present a case of a patient with lesions characterized by overlapping features of morphea and LSA with rapid decrease in joint mobility.

Syringocystadenoma.

We present a case of a 35-year-old woman with a yellow, verrucous, and itchy plaque on her scalp. Within this plaque, there was an erythematous, bleeding papule. Histopathologic findings were compatible with a diagnosis of syringocystadenoma papilliferum within a nevus sebaceous. We present a brief review of the natural history of nevus sebaceus, its pathogenesis, and management.

Successful treatment of facial telangiectasias using a micropulse 1,064-nm neodymium-doped yttrium aluminum garnet laser.

OBJECTIVES: To evaluate the safety and efficacy of a microsecond 1,064-nm neodymium-doped yttrium aluminum garnet (Nd:YAG) laser for the treatment of facial telangiectasias. METHODS: Subjects ages 35-70 with Fitzpatrick skin types I to III and facial telangiectasias underwent two treatments with a micropulse (0.65 ms) 1,064-nm Nd:YAG laser. Treatments were spaced 30 days apart, with a final evaluation 60 days after the second treatment. Evaluation included digital photography and an assessment of the degree of improvement on a scale from 1 to 5 by the subject and a nontreating investigator. RESULTS: Twenty subjects (18 women, two men) with Fitzpatrick skin type II and III completed the study. The nontreating investigator rated the objective clinical response as total clearance (100% clear) in 10% (n = 2) of subjects, significant clearance (≥50% clear) in 75% (n = 15), and some clearance (0-49% clear) in 15% (n = 3). None of the subjects was rated as having no clearance or worsening. In terms of subjective clearance reported by subjects, 80% (n = 16) reported significant clearance, with the remainder reporting some clearance. No adverse events were reported. CONCLUSION: The micropulse 1,064-nm Nd:YAG successfully treated facial telangiectasias with a high degree of patient satisfaction, minimal discomfort, and no adverse events.

Safety and efficacy of intradermal injection of botulinum toxin for the treatment of oily skin.

OBJECTIVE: To evaluate the safety and efficacy of intradermal injection of abobotulinumtoxinA for the treatment of oily skin. METHODS AND MATERIALS: Twenty-five patients with oily skin were treated in the forehead region with intradermal injections of botulinum toxin. Baseline and post-treatment sebum production was measured using a sebometer. Photographs were taken. Patients were also asked to rate their satisfaction with the treatment in terms of improvement in their oily skin. RESULTS: Treatment with botulinum toxin resulted in significantly lower sebum production at 1 week and 1, 2, and 3 months after injection (p < .001, t-test). Twenty-one patients (91%) reported that they were satisfied (50-75% improvement) with intradermal botulinum toxin as a treatment for oily skin. [Correction added after online publication 7-Jan-2013: the number of satisfied patients has been updated] CONCLUSION: Intradermal injection of botulinum toxin significantly reduced sebum production in the forehead region, with a high degree of patient satisfaction. Intradermal botulinum toxin may be an effective treatment to reduce sebum production in patients with oily skin. Larger, randomized, blinded, placebo-controlled studies are warranted.

Esthetic rejuvenation of the temple.

Loss of volume in the temples is an early sign of aging that is often overlooked by both the physician and the patient. Augmentation of the temple using soft tissue fillers improves the contours of the upper face with the secondary effect of lengthening and lifting the lateral brow. After replacement of volume, treatment of the overlying skin with skin-tightening devices or laser resurfacing help to complete a comprehensive rejuvenation of the temple and upper one-third of the face.

Impact of race on survival in patients with clinically nonmetastatic prostate cancer who deferred primary treatment.

BACKGROUND: Prostate cancer (PCa) racial disparity studies typically focus on survival differences after curative treatment. The authors of this report hypothesized that comparing mortality rates between African American (AA) and Caucasian American (CA) patients who deferred primary treatment for clinically nonmetastatic PCa may provide a better assessment of the impact of race on the natural course of PCa. METHODS: The pathology database of the New York Veterans Administration Medical Center (VAMC), an equal access-of-care facility, was searched for patients with biopsy-proven PCa. Inclusion criteria included 1) no evidence of metastatic disease or death within 3 years after diagnosis, 2) no primary treatment, and 3) a minimum of 5 years of follow-up for survivors. RESULTS: In total, 518 patients met inclusion criteria between 1990 and 2005. AA patients were younger (P = .02) and had higher median prostate-specific antigen (PSA) levels (P = .001) at the time of diagnosis compared with CA patients. In a multivariate model, higher Gleason score and PSA level were associated with increased mortality (P = .001 and P = .03, respectively), but race was not a predictor of death from PCa. CONCLUSIONS: The current data suggested that race did not have a major impact on survival in patients with PCa who deferred primary treatment for clinically nonmetastatic disease.

Cheilitis granulomatosa.

Melkersson-Rosenthal Syndrome (MRS) is a rare syndrome that is characterized by a triad of facial paralysis, chronic edema of the lip, and a fissured tongue. Most commonly, one element of the triad precedes the development of the other symptoms. We present a case of cheilitis granulomatosa (CG) as a manifestation of incomplete MRS. As the etiology remains unknown, treatment of CG is challenging. Intralesional glucocorticoids remain the first-line treatment, but recurrences are common. We discuss alternative treatment strategies that include combination therapy with other anti-inflammatory agents and biologics, such as infliximab.

Erythrodermic lichen planus.

Lichen planus (LP) is a relatively common papulosquamous disorder that is characterized by pruritic, polygonal papules in a characteristic distribution. We present a case of a 71-year-old man with erythroderma, who was ultimately diagnosed with severe, generalized LP. Treatment of severe LP is challenging, and there are few, robust, clinical trials in the literature to guide the selection of appropriate treatment. We discuss the treatment options for generalized LP and the evidence in support of these agents.

Clinical relevance of detection of lymphovascular invasion in primary melanoma using endothelial markers D2-40 and CD34.

Immunohistochemistry (IHC) using endothelial markers may facilitate the detection of lymphovascular invasion (LVI) in primary melanoma; however, the clinical implications of enhanced detection are unknown. We evaluated whether the use of lymphatic endothelial marker D2-40 and panvascular marker CD34 increases LVI positivity relative to routine histology alone and then evaluated the prognostic relevance of LVI detected using these markers in terms of disease-free (DFS) and overall survival (OS). A total of 246 primary melanomas were assessed for LVI using D2-40, CD34, and routine histology. Associations between LVI positivity and clinicopathologic variables, DFS, and OS were compared using univariate and multivariate analyses. The use of endothelial markers increased the rate of LVI positivity (18% using D2-40 and/or CD34 vs. 3% by routine histology, P<0.0001). On univariate analysis, IHC-detected LVI was significantly associated with more adverse clinicopathologic variables (thickness, ulceration, mitoses, and nodular subtype) compared with LVI detected by routine histology (thickness and ulceration only). In a multivariate model controlling for stage, LVI detected using IHC markers remained a significant marker of both reduced DFS [hazard ratio (HR), 2.01; 95% confidence interval (CI): 1.27-3.18; P=0.003] and OS (HR, 2.08; 95% CI: 1.25-3.46; P=0.005). Results show that D2-40 and CD34 increase the detection of LVI in primary melanoma and that cases missed by routine histology have prognostic relevance.

A high proliferative index of recurrent melanoma is associated with worse survival.

OBJECTIVE: Previous melanoma studies evaluating prognostic factors of survival at recurrence have focused on primary tumor characteristics and clinical variables at first recurrence. We examined the prognostic relevance of recurrent tumor proliferation. METHODS: 114 melanoma patients with available recurrent tissues who were prospectively enrolled at New York University Medical Center were studied. Standard of care prognostic variables (e.g. stage at initial diagnosis and lactate dehydrogenase level) and recurrent tissue expression of proliferative marker Ki-67 were evaluated for their association with overall survival. RESULTS: High Ki-67 expression was observed in 57 (50%) of the 114 recurrent melanomas. On univariate analysis, the median overall survival of patients whose recurrent tumors overexpressed Ki-67 was significantly shorter than that of patients whose recurrent tumors had low Ki-67 expression (3.6 vs. 9.5 years, p = 0.03). On multivariate analysis, a high proliferative index of the recurrent melanoma remained an independent predictor of worse overall survival, controlling for stage at initial diagnosis, disease-free survival, and stage at first recurrence [HR = 2.09 (95% CI 1.24-3.54), p = 0.006]. CONCLUSIONS: Our results demonstrate the prognostic relevance of tumor proliferation in recurrent melanoma patients. Data also support restratification of risk assessment upon recurrence that considers tumor biology in addition to clinical variables evaluated as part of the standard of care.

Clinical variables and primary tumor characteristics predictive of the development of melanoma brain metastases and post-brain metastases survival.

BACKGROUND: Melanoma patients who develop brain metastases (B-Met) have limited survival and are excluded from most clinical trials. In the current study, the authors attempted to identify primary tumor characteristics and clinical features predictive of B-Met development and post-B-Met survival. METHODS: A prospectively accrued cohort of 900 melanoma patients was studied to identify clinicopathologic features of primary melanoma (eg, thickness, ulceration, mitotic index, and lymphovascular invasion) that are predictive of B-Met development and survival after a diagnosis of B-Met. Associations between clinical variables present at the time of B-Met diagnosis (eg, extracranial metastases, B-Met location, and the presence of neurological symptoms) and post-B-Met survival were also assessed. Univariate associations were analyzed using Kaplan-Meier survival analysis, and the effect of independent predictors was assessed using multivariate Cox proportional hazards regression analysis. RESULTS: Of the 900 melanoma patients studied, 89 (10%) developed B-Met. Ulceration and site of the primary tumor on the head and neck were found to be independent predictors of B-Met development on multivariate analysis (P = .001 and P = .003, respectively). Clinical variables found to be predictive of post-B-Met survival on multivariate analysis included the presence of neurological symptoms (P = .008) and extracranial metastases (P = .04). Ulceration was the only primary tumor characteristic that remained a significant predictor of post-B-Met survival on multivariate analysis (P = .04). CONCLUSIONS: Primary tumor ulceration was found to be the strongest predictor of B-Met development and remained an independent predictor of decreased post-B-Met survival in a multivariate analysis inclusive of primary tumor characteristics and clinical variables. The results of the current study suggest that patients with ulcerated primary tumors should be prospectively studied to determine whether heightened surveillance for B-Met can improve clinical outcome.

Integrative genomics identifies molecular alterations that challenge the linear model of melanoma progression.

Superficial spreading melanoma (SSM) and nodular melanoma (NM) are believed to represent sequential phases of linear progression from radial to vertical growth. Several lines of clinical, pathologic, and epidemiologic evidence suggest, however, that SSM and NM might be the result of independent pathways of tumor development. We utilized an integrative genomic approach that combines single nucleotide polymorphism array (6.0; Affymetrix) with gene expression array (U133A 2.0; Affymetrix) to examine molecular differences between SSM and NM. Pathway analysis of the most differentially expressed genes between SSM and NM (N = 114) revealed significant differences related to metabolic processes. We identified 8 genes (DIS3, FGFR1OP, G3BP2, GALNT7, MTAP, SEC23IP, USO1, and ZNF668) in which NM/SSM-specific copy number alterations correlated with differential gene expression (P < 0.05; Spearman's rank). SSM-specific genomic deletions in G3BP2, MTAP, and SEC23IP were independently verified in two external data sets. Forced overexpression of metabolism-related gene MTAP (methylthioadenosine phosphorylase) in SSM resulted in reduced cell growth. The differential expression of another metabolic-related gene, aldehyde dehydrogenase 7A1 (ALDH7A1), was validated at the protein level by using tissue microarrays of human melanoma. In addition, we show that the decreased ALDH7A1 expression in SSM may be the result of epigenetic modifications. Our data reveal recurrent genomic deletions in SSM not present in NM, which challenge the linear model of melanoma progression. Furthermore, our data suggest a role for altered regulation of metabolism-related genes as a possible cause of the different clinical behavior of SSM and NM.

Clinical relevance of SKP2 alterations in metastatic melanoma.

In this study, we investigated the mechanism(s) of altered expression of protooncogene SKP2 in metastatic melanoma and its clinical relevance in patients with metastatic melanoma. The genomic status of SKP2 was assessed in cell lines by sequencing, single nucleotide polymorphism array, and genomic PCR. Copy number status was then evaluated for concordance with SKP2 mRNA and protein expression. SKP2 protein was further evaluated by immunohistochemistry in 93 human metastatic tissues. No mutations were identified in SKP2. Increased copy number at the SKP2 locus was observed in 6/14 (43%) metastatic cell lines and in 9/22 (41%) human metastatic tissues which was associated with overexpression of SKP2 protein. Overexpression of SKP2 protein in human tissues was associated with worse survival in a multivariate model controlling for the site of metastasis. Copy number gain is a major contributing mechanism of SKP2 overexpression in metastatic melanoma. Results may have implications for the development of therapeutics that target SKP2.

Copy number and gene expression differences between African American and Caucasian American prostate cancer.

BACKGROUND: The goal of our study was to investigate the molecular underpinnings associated with the relatively aggressive clinical behavior of prostate cancer (PCa) in African American (AA) compared to Caucasian American (CA) patients using a genome-wide approach. METHODS: AA and CA patients treated with radical prostatectomy (RP) were frequency matched for age at RP, Gleason grade, and tumor stage. Array-CGH (BAC SpectralChip2600) was used to identify genomic regions with significantly different DNA copy number between the groups. Gene expression profiling of the same set of tumors was also evaluated using Affymetrix HG-U133 Plus 2.0 arrays. Concordance between copy number alteration and gene expression was examined. A second aCGH analysis was performed in a larger validation cohort using an oligo-based platform (Agilent 244K). RESULTS: BAC-based array identified 27 chromosomal regions with significantly different copy number changes between the AA and CA tumors in the first cohort (Fisher's exact test, P < 0.05). Copy number alterations in these 27 regions were also significantly associated with gene expression changes. aCGH performed in a larger, independent cohort of AA and CA tumors validated 4 of the 27 (15%) most significantly altered regions from the initial analysis (3q26, 5p15-p14, 14q32, and 16p11). Functional annotation of overlapping genes within the 4 validated regions of AA/CA DNA copy number changes revealed significant enrichment of genes related to immune response. CONCLUSIONS: Our data reveal molecular alterations at the level of gene expression and DNA copy number that are specific to African American and Caucasian prostate cancer and may be related to underlying differences in immune response.

Outcomes of patients lost to followup after mid urethral synthetic slings--successes or failures?

PURPOSE: We classified patients lost to followup after mid urethral synthetic sling placement as examples of treatment success or failure based on the Patient Global Impression of Improvement, and compared the outcomes of those who followed up to the outcomes of those who did not. MATERIALS AND METHODS: We reviewed the charts of 217 patients who underwent mid urethral synthetic sling placement. Telephone interviews including the Patient Global Impression of Improvement and the Medical, Epidemiological, and Social Aspects of Aging questionnaires were conducted for patients lacking 3-month followup. RESULTS: Based on the Patient Global Impression of Improvement of the 48 patients who responded 13 (27.1%) were failures. The overall failure rate of patients with at least 3-month followup was 19% (23 of 124). CONCLUSIONS: In our study success rates for patients lost to followup were similar to the rates for those who had routine followup. However, it is uncertain if these data can be applied to other study populations, especially in a randomized controlled trial.

Melanoma MicroRNA signature predicts post-recurrence survival.

PURPOSE: To identify a melanoma microRNA (miRNA) expression signature that is predictive of outcome and then evaluate its potential to improve risk stratification when added to the standard-of-care staging criteria. EXPERIMENTAL DESIGN: Total RNA was extracted from 59 formalin-fixed paraffin-embedded melanoma metastases and hybridized to miRNA arrays containing 911 probes. We then correlated miRNA expression with post-recurrence survival and other clinicopathologic criteria. RESULTS: We identified a signature of 18 miRNAs whose overexpression was significantly correlated with longer survival, defined as more than 18 months post-recurrence survival. Subsequent cross-validation showed that a small subset of these miRNAs can predict post-recurrence survival in metastatic melanoma with an estimated accuracy of 80.2% (95% confidence interval, 79.8-80.6%). In contrast to standard-of-care staging criteria, a six-miRNA signature significantly stratified stage III patients into "better" and "worse" prognostic categories, and a multivariate Cox regression analysis revealed the signature to be an independent predictor of survival. Furthermore, we showed that most miRNAs from the signature also showed differential expression between patients with better and worse prognoses in the corresponding paired primary melanoma. CONCLUSIONS: MiRNA signatures have potential as clinically relevant biomarkers of prognosis in metastatic melanoma. Our data suggest that molecularly based models of risk assessment can improve the standard staging criteria and support the incorporation of miRNAs into such models.

Increased shedding of HU177 correlates with worse prognosis in primary melanoma.

BACKGROUND: Increased levels of cryptic collagen epitope HU177 in the sera of melanoma patients have been shown to be associated with thicker primary melanomas and with the nodular histologic subtype. In this study, we investigate the association between HU177 shedding in the sera and clinical outcome in terms of disease-free survival (DFS) and overall survival (OS). METHODS: Serum samples from 209 patients with primary melanoma prospectively enrolled in the Interdisciplinary Melanoma Cooperative Group at the New York University Langone Medical Center (mean age = 58, mean thickness = 2.09 mm, stage I = 136, stage II = 41, stage III = 32, median follow-up = 54.9 months) were analyzed for HU177 concentration using a validated ELISA assay. HU177 serum levels at the time of diagnosis were used to divide the study cohort into two groups: low and high HU177. DFS and OS were estimated by Kaplan-Meier survival analysis, and the log-rank test was used to compare DFS and OS between the two HU177 groups. Multivariate Cox proportional hazards regression models were employed to examine the independent effect of HU177 category on DFS and OS. RESULTS: HU177 sera concentrations ranged from 0-139.8 ng/ml (mean and median of 6.2 ng/ml and 3.7 ng/ml, respectively). Thirty-eight of the 209 (18%) patients developed recurrences, and 34 of the 209 (16%) patients died during follow-up. Higher HU177 serum level was associated with an increased rate of melanoma recurrence (p = 0.04) and with increasing mortality (p = 0.01). The association with overall survival remained statistically significant after controlling for thickness and histologic subtype in a multivariate model (p = 0.035). CONCLUSIONS: Increased shedding of HU177 in the serum of primary melanoma patients is associated with poor prognosis. Further studies are warranted to determine the clinical utility of HU177 in risk stratification compared to the current standard of care.