Reexamining the Threshold for Reexcision of Histologically Transected Dysplastic Nevi.

Importance: Controversy persists regarding the appropriate management of incompletely excised, biopsy-proven, mild and moderate dysplastic nevi (DN). Objective: To determine long-term risk of associated melanoma in biopsied mild or moderate DN with positive histologic margins that were clinically observed vs reexcised with negative margins. Design, Setting, and Participants: Retrospective cohort study of mixed referral and community patients from an academic pigmented lesion clinic and dermatology clinics of the affiliated Veteran Affairs medical center with biopsy-confirmed DN with positive histologic margins diagnosed from May 15, 1991, to July 8, 2015, and followed up through May 30, 2016. A consecutive sample of 1473 histologically confirmed DN was identified using surgical pathology databases at the study sites; 590 cases in 498 patients met eligibility criteria. Main Outcomes and Measures: The primary outcome was the proportion of biopsied DN that progressed to histologically confirmed invasive or in situ melanoma. Secondary outcomes included local nevus recurrence and development of primary melanoma at other anatomic sites. Results: The 498 patients had a mean (range) age of 57.6 (14-93) years and 90% were male. Among 590 positive-margin DN, 191 were reexcised and 399 clinically observed without further surgery; 170 reexcised and 304 observed DN had available follow-up data, with mean (SD) follow-up of 5.5 (4.6) years. Cases in the observation group were more likely to demonstrate nevus recurrence than those that were reexcised (3.3% vs 0%; P = .02). Six of 304 (2.0%) observed DN subsequently developed melanoma at the same site, compared with 1 of 170 (0.06%) that were reexcised (P = .43). Five of 6 observed patients who developed melanoma initially underwent partial biopsy with grossly positive margins; 1 melanoma in situ evolved from an excisionally biopsied moderately dysplastic nevus 5 years later. Only 1 case of thin invasive melanoma (≤1 mm) was observed, and no deaths from melanoma arising from biopsy-proven DN occurred through the latest dermatology follow-up. New primary melanoma developed at other sites in 9.9% of excised and 9.4% of resected DN. Conclusions and Relevance: In cases of mild and moderate DN with microscopically positive margins and no concerning clinical residual lesion, observation, rather than reexcision, was a reasonable management option. Partial biopsies of pigmented lesions suspicious for melanoma may lead to delayed melanoma diagnosis and should be discouraged.

A fibrous papule with abundant CD34-immunoreactive ganglion-like multinucleated giant cells: a case report and review of the literature.

Fibrous papules present clinically as benign, asymptomatic, dome-shaped, flesh colored papules on the face. Histologically, fibrous papules are characterized by fibrous stroma with fibroblasts and dilated blood vessels. Multiple variants of fibrous papules have been reported. Although scattered multinucleated cells in fibrous papules have been well described, we report a fibrous papule with abundant multinucleated ganglion-like giant cells that were immunoreactive with CD34. Recognition of such fibrous papule variants is important to avoid misdiagnosis as potentially more worrisome and/or aggressive melanocytic, soft tissue, or neural lesions that may require more aggressive treatment. Indeed, fibrous papules do not commonly appear on the differential diagnosis for lesions with multinucleated giant cells or ganglion-like cells and consideration should be given to their inclusion in the appropriate clinical setting.

A phase II, multicenter, open-label, 3-cohort trial evaluating the efficacy and safety of vismodegib in operable basal cell carcinoma.

BACKGROUND: Vismodegib is approved for treatment of advanced basal cell carcinoma. OBJECTIVE: We sought to characterize vismodegib efficacy and safety in operable basal cell carcinoma. METHODS: Patients with new, operable, nodular basal cell carcinoma received vismodegib (150 mg/d) followed by excision and Mohs micrographic surgery to ensure clear margins. Cohort 1 received vismodegib for 12 weeks; cohort 2 received vismodegib for 12 weeks, then 24 weeks of observation before excision; and cohort 3 received vismodegib for 8 weeks on/4 weeks off/8 weeks on. RESULTS: In all, 24 patients enrolled in cohort 1, and 25 in cohorts 2 and 3. Complete histologic clearance was achieved by 42%, 16%, and 44% of patients in cohorts 1, 2, and 3, respectively. Muscle spasms (76%), alopecia (58%), and dysgeusia (50%) were the most frequent adverse events (AEs). Five (7%) patients discontinued treatment because of an AE. AE reversibility was evaluated in cohort 2 with 24 weeks of observation after treatment discontinuation. LIMITATIONS: Nonrandomized, small cohort sizes, and short observation durations for some patients are limitations. CONCLUSION: Primary efficacy end points were not met (predefined complete histologic clearance rate: >50% in cohorts 1 and 3; >30% in cohort 2). Safety was comparable when dosed continuously versus intermittently. Posttreatment reversibility of vismodegib-related AEs was demonstrated.

Imiquimod 5% cream as primary or adjuvant therapy for melanoma in situ, lentigo maligna type.

BACKGROUND: Surgical resection of lentigo maligna (LM) is complicated by noncontiguous, subclinical extension and actinic melanocytic hyperplasia in sun-damaged skin of older individuals. OBJECTIVE: We sought to determine the long-term effectiveness of imiquimod as primary or adjuvant therapy for LM. METHODS: Patients were retrospectively identified from January 1, 2003, to December 31, 2013, with LM, early/evolving LM, and LM melanoma who had used topical imiquimod 5% cream for either primary therapy after diagnostic biopsy, or adjuvant therapy after narrow-margin surgical resection or complete clinical but not histologic resection of LM. Follow-up occurred through December 31, 2014. RESULTS: In all, 63 cases were identified in 61 patients, mean (SD) age 71.1 (12.4) years; 58 were analyzed for local recurrence. Imiquimod was used as primary therapy in 22 of 63 (34.9%) and adjuvant therapy in 41 of 63 (65.1%) for mean duration of 11.7 (range 2-60) weeks. Fifty cases (86.2%) demonstrated clinical clearance at mean (SD) follow-up of 42.1 (27.4) months: 72.7% primary and 94.4% adjuvant at 39.7 (23.9) and 43.1 (28.9) months, respectively. LIMITATIONS: Retrospective cohort study and lack of standardized imiquimod application are limitations. CONCLUSION: Imiquimod cream appears to be a viable option for primary or adjuvant treatment of LM in older patients who are poor surgical candidates.

Acquired blue nevi in older individuals: retrospective case series from a Veterans Affairs population, 1991 to 2013.

IMPORTANCE: Apart from the atypical mole phenotype, development of new melanocytic nevi in older individuals is uncommon and considered worrisome for melanoma. We performed a retrospective case series in a Veterans Affairs population from 1991 to 2013 to characterize blue nevi (BN) by patient age at biopsy, location, self-reported duration, and relation to prior or subsequent development of cutaneous melanoma. OBSERVATIONS: A total of 204 BN were identified in 194 predominantly male patients (90.7%) who had a mean (SD) age of 62.8 (14.4) years. Clinical duration of 10 years or less was reported by 90.3% of patients with available data (32.0%). Histopathologic examination classified 74.0% of BN as common, 1.5% as cellular, and 24.5% as combined type. No malignant BN were identified; however, 18 primary melanomas were diagnosed, most (72.2%) prior to blue nevus biopsy, including 38.9% in situ and 61.1% with mean (SD) Breslow thickness of 1.02 (0.99) mm. CONCLUSIONS AND RELEVANCE: The later patient-reported onset of BN suggests a potential alternative mechanism of nevogenesis compared with common acquired nevi and differs from prior reports of BN development in younger adults. The lack of association with melanoma in older individuals suggests that most benign-appearing BN may be safely observed, even in a cohort at higher risk for skin cancer.

Chromhidrosis: a rare diagnosis requiring clinicopathologic correlation.

Chromhidrosis is a rare idiopathic disorder characterized by colored secretions most typically from the malar cheeks, axilla, or areolar regions. Histologically, chromhidrosis is notable for glandular structures with decapitation secretion indicating ectopic apocrine glands in the dermis, and the presence of lipofuscin pigments under ultraviolet fluorescence and in cytology smears. This case report describes a 26-year-old man who presented with a 2- to 3-year history of black-colored secretions on the bilateral malar cheeks, present on exertion or with squeezing of the cheeks. A 3-mm punch biopsy of the left cheek demonstrated histopathologic findings characteristic of chromhidrosis under hematoxylin and eosin staining and ultraviolet fluorescence. To our best knowledge, this is the second case report in the literature of an adult male being affected by chromhidrosis, and the first of an adult male with black-colored malar cheek secretions in chromhidrosis.

Recurrence rates associated with incompletely excised low-risk nonmelanoma skin cancer.

BACKGROUND: Reported recurrence rates for transected nonmelanoma skin cancer (NMSC) vary widely, and few studies have addressed recurrence of tumors followed clinically or treated with nonsurgical modalities. METHODS: Retrospective review of dermatopathology records from January 1999 to January 2005 was conducted to identify biopsies or excision specimens with histologically transected basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) which were not subsequently excised. Patient and tumor characteristics associated with recurrence were analyzed in a subgroup of patients with predominantly 'low-risk' and/or minimally transected NMSCs. Prospective follow up was performed through March 31, 2008. Data was analyzed with Chi-square and Fishers exact tests and multivariate logistic regression. RESULTS: Of 376 transected NMSCs, 27 (7.2%) recurred, including 20 (9%) of 223 BCCs and 7 (4.6%) SCCs in situ of 153 SCCs. The overall recurrence rate of the 124 minimally transected NMSCs was even lower (5.6%). Multivariate logistic regression identified three significant predictors of recurrence: tumor location on the head and neck (p = 0.041), tumor size (p = 0.00741) and superficial subtype of BCC (p = .035). CONCLUSIONS: Although surgical excision of NMSC remains the standard of care, observation or nonsurgical treatment may be acceptable in many cases of incompletely excised low-risk or minimally transected NMSCs.

Eyebrow papule in an elderly man.

A 70-year-old Caucasian man presented with a several-month history of a solitary, asymptomatic papule on the left eyebrow. His medical history included stage 1A lentigo maligna melanoma and multiple non-melanoma skin cancers. Physical examination demonstrated a solitary 5-mm smooth, dome-shaped skin colored papule with subtle central erosion on the left eyebrow. No overlying telangiectasias were noted. A biopsy of the lesion was performed. The lesion was composed of plump spindle cells arranged in a plexiform pattern in the background of thick, keloidal collagen bundles. The lesional cells were NKI/C3-positive and S-100-negative. A diagnosis of cellular neurothekeoma was made.

Cryolipolysis for noninvasive fat cell destruction: initial results from a pig model.

BACKGROUND: Liposuction is one of the most frequently performed cosmetic procedures in the United States, but its cost and downtime has led to the development of noninvasive approaches for adipose tissue reduction. OBJECTIVE: To determine whether noninvasive controlled and selective destruction of fat cells (Cryolipolysis) can selectively damage subcutaneous fat without causing damage to the overlying skin or rise in lipid levels. METHODS: Three Yucatan pigs underwent Cryolipolysis at 22 sites: 20 at cooling intensity factor (CIF) index 24.5 (-43.8 mW/cm(2)), one at CIF 24.9 (-44.7 mW/cm(2)), and one at CIF 25.4 (-45.6 mW/cm(2)). Treated areas were evaluated using photography, ultrasound, and gross and microscopic pathology. Lipids were at various times points. One additional pig underwent Cryolipolysis at various days before euthanasia. RESULTS: The treatments resulted in a significant reduction in the superficial fat layer without damage to the overlying skin. An inflammatory response triggered by cold-induced apoptosis of adipocytes preceded the reduction in the fat layer. Evaluation of lipids over a 3-month period following treatment demonstrated that cholesterol and triglyceride values remained normal. CONCLUSIONS: Cryolipolysis is worthy of further study because it has been shown to significantly decrease subcutaneous fat and change body contour without causing damage to the overlying skin and surrounding structures or deleterious changes in blood lipids.

A two-year, double-blind, randomized placebo-controlled trial of oral green tea polyphenols on the long-term clinical and histologic appearance of photoaging skin.

BACKGROUND: Green tea polyphenols (GTPs) have significant antioxidant and antiinflammatory activities, and prior short-term studies suggest that these compounds may improve photoaging skin. OBJECTIVES: To evaluate the long-term effects of oral GTPs on the clinical and histologic characteristics of photoaging skin. MATERIALS AND METHODS: Double-blind, placebo-controlled trial of 56 women aged 25 to 75 randomized to 250 mg GTPs or placebo twice daily for 2 years. A blinded dermatologist scored the appearance of photodamaged facial skin at 0, 6, 12, and 24 months. A blinded dermatopathologist scored the histologic characteristics of sun-exposed arm skin at 0 and 24 months. RESULTS: Clinical assessment of facial skin revealed that the GTP group had significant improvement in overall solar damage at 6 months (p=.02) and significant improvement in erythema and telangiectasias at 12 months (p=.02). The placebo group did not have significant improvements in these parameters at 6 months or 12 months. There were no statistically significant differences in other photoaging parameters at 6, 12, or 24 months in the GTP or placebo groups. Histopathologic analysis of sunexposed arm skin showed no statistically significant difference in photoaging parameters in the GTP group or the placebo group at 24 months. CONCLUSIONS: Long-term supplementation with oral GTPs was not superior to placebo in improving clinical or histologic photoaging parameters after 24 months of use.

Clinical efficacy of noninvasive cryolipolysis and its effects on peripheral nerves.

BACKGROUND: Cryolipolysis provides a method for noninvasive fat reduction that significantly reduces subcutaneous fat in a pig model without apparent damage to skin and surrounding structures. This study aimed to determine whether fat reduction in humans caused by cold exposure is associated with alteration in local sensory function or nerve fibers. METHODS: In this study, 10 subjects were treated with a prototype cooling device. Fat reduction was assessed in 9 of the 10 subjects via ultrasound before treatment and at the follow-up visit. Sensory function was assessed by neurologic evaluation (n = 9), and biopsies (n = 1) were collected for nerve staining. RESULTS: Treatment resulted in a normalized fat layer reduction of 20.4% at 2 months and 25.5% at 6 months after treatment. Transient reduction in sensation occurred in six of nine subjects assessed by neurologic evaluation. However, all sensation returned by a mean of 3.6 weeks after treatment. Biopsies showed no long-term change in nerve fiber structure. There were no lasting sensory alterations or observations of skin damage in any of the subjects evaluated. CONCLUSION: Noninvasive cryolipolysis results in substantial fat reduction within 2 months of treatment without damage to skin. The procedure is associated with modest reversible short-term changes in the function of peripheral sensory nerves.

A case of argyria after colloidal silver ingestion.

BACKGROUND: Argyria is often considered an entity of the past, one which has largely disappeared with the cessation of silver usage in oral medications. However, with the practice of colloidal silver ingestion in current "alternative health" treatments, argyria should be considered in the differential diagnosis of blue-gray hyperpigmentation. METHODS: A single case report with clinicopathological correlation. RESULTS: Histological examination of skin biopsy specimen, which showed perieccrine brown-black granules, verified that colloidal silver rather than a prescribed medication was the source of the patient's dyspigmentation.

Effects of monopolar radiofrequency treatment over soft-tissue fillers in an animal model.

BACKGROUND AND OBJECTIVES: Monopolar radiofrequency (RF) treatment is used by physicians to tighten and contour the skin of their patients. In many cases, patients have received prior treatment with other aesthetic modalities such as soft-tissue augmentation or they may wish to receive these treatment modalities simultaneously. Together, soft-tissue augmentation and monopolar RF treatment have the potential to restore tissue volume and improve facial laxity. To date, no published studies have documented the effects of RF treatment directly over soft-tissue fillers. STUDY DESIGN/MATERIALS AND METHODS: We examined the tissue interactions of monopolar RF heating with five commonly injected fillers in a juvenile pig model. This is the first part of a two-part study. In this study, the interaction of monopolar RF and filler substances was examined over a period of 4 months. The five soft-tissue fillers examined were cross-linked human collagen (Cosmoplast), hyaluronic acid (Restylane), calcium hydroxylapatite (Radiesse), polylactic acid (Sculptra), and liquid injectable silicone (Silikon 1000). RESULTS: There was no apparent increase in the risk of local burns and no observable effect of RF treatment on filler persistence in the tissue. With monopolar RF treatment, an increase in fibroplasia and collagen deposition surrounding Restylane, Radiesse, and Sculptra was observed. When scored in a blinded fashion, the increase in collagen deposition was statistically significant for Radiesse. CONCLUSIONS: In this animal study, RF treatment had no observed adverse effect on filler collagen responses or persistence. Filler presence did not increase the risk of undesirable thermal effects with monopolar RF treatment. Further clinical studies are required to evaluate the effect of monopolar RF treatment over dermal fillers with respect to aesthetic outcome.

Increasing incidence of lentigo maligna melanoma subtypes: northern California and national trends 1990-2000.

Worldwide, lentigo maligna melanoma (LMM) comprises 4%-15% of cutaneous melanoma and occurs less commonly than superficial spreading or nodular subtypes. We assessed the incidence of melanoma subtypes in regional and national Surveillance, Epidemiology, and End Results (SEER) cancer registry data from 1990 to 2000. Because 30%-50% of SEER data were not classified by histogenetic type, we compared the observed SEER trends with an age-matched population of 1024 cases from Stanford University Medical Center (SUMC) (1995-2000). SEER data revealed lentigo maligna (LM) as the most prevalent in situ subtype (79%-83%), and that LMM has been increasing at a higher rate compared with other subtypes and to all invasive melanoma combined for patients aged 45-64 and > or =65 y. The SUMC data demonstrated LM and LMM as the only subtypes increasing in incidence over the study period. In both groups, LM comprised > or =75% of in situ melanoma and LMM > or =27% of invasive melanoma in men 65 y and older. Regional and national SEER data suggest an increasing incidence of LM and LMM, particularly in men > or =age 65. An increased incidence of LM subtypes should direct melanoma screening to heavily sun-exposed sites, where these subtypes predominate.

Histologic similarities between lentigo maligna and dysplastic nevus: importance of clinicopathologic distinction.

BACKGROUND: Lentigo maligna (LM) can histologically simulate dysplastic nevus (DN). Partial biopsy of LM may lead to misdiagnosis. METHODS: One hundred and fourteen cases of LM and LM melanoma (LMM) were diagnosed at the Veterans Affairs Palo Alto Health Care System (1993-2002). Biopsy and excision specimens for 68 in situ and 28 invasive melanomas were classified as having predominant classical LM features, predominant DN-like morphology, or a mixed pattern. RESULTS: Biopsy specimens demonstrated a predominant classical pattern in 38% (25/65) LM and 36% (10/28) LMM, predominant DN-like features in 43% (28/65) LM and 25% (7/28) LMM, and mixed pattern in 15% (10/65) LM and 29% (8/28) LMM. Most LM and LMM biopsies were partial. Significant DN-like features were present in 51% LM and 57% LMM excision specimens. Median age was 72 years for LM and 73 years for LMM, mean lesion diameters were 1.3 and 1.7 cm for LM and LMM, respectively, and 85% of LM and 75% of LMM cases were located on heavily sun-exposed sites. CONCLUSIONS: Misdiagnosis of LM or LMM as DN could have devastating results. Large pigmented lesions on sun-damaged skin in elderly individuals should warrant consideration of LM/LMM diagnosis, even in the setting of DN-like features histologically. Excisional biopsy may help to avoid misdiagnosis.