Primary bilateral uveal melanoma: a population-based study and systematic review.

IMPORTANCE: Primary bilateral uveal melanoma (UM) is a rare and incompletely described entity. It is not known how these patients compare to those with unilateral UM. BACKGROUND: We sought to comprehensively characterize and compare patients with primary bilateral and unilateral UM. DESIGN: Retrospective, population-based and systematic review. PARTICIPANTS: Patients with bilateral (n = 52) and unilateral UM (n = 8915). METHODS: We analysed cases of primary bilateral UM from three data sources: (i) the University Hospitals Cleveland Medical Center pathology database from 1996 to 2016 (n = 1); (ii) the Surveillance, Epidemiology and End-Results (SEER)-18 database from 1973 to 2013 (n = 5) and (iii) a systematic review of the English language literature (n = 46). Cases of unilateral UM were obtained from the SEER-18 database from 1973 to 2013 for comparison (n = 8915). MAIN OUTCOME MEASURES: Demographics, clinicopathological characteristics, treatments and survival. RESULTS: There were no differences in sex, race, mean age at diagnosis, site of uveal involvement, metastases at diagnosis, or treatment among patients with bilateral as compared to unilateral UM. Additionally, there were no clinicopathological differences between the two UMs in each patient with bilateral disease. Overall survival did not differ between unilateral and bilateral UM patients, or between bilateral UM patients who presented with, or subsequently developed, bilateral disease. CONCLUSIONS AND RELEVANCE: Bilateral and unilateral UM patients share similar demographics, clinicopathological characteristics, treatments and prognoses. Moreover, the development of bilateral disease does not portend a poorer prognosis and patients should be treated similarly to those with unilateral disease.

Epidemiology of genitourinary melanoma in the United States: 1992 through 2012.

BACKGROUND: Primary melanoma arising in the genitourinary tract is rare and poorly characterized. OBJECTIVES: We sought to describe the epidemiology of genitourinary melanoma in the United States. METHODS: Incident case and population data were obtained for genitourinary melanoma from the Surveillance, Epidemiology, and End Results 13 Registries Database between 1992 and 2012. RESULTS: A total of 817 patients with genitourinary melanoma were identified; most cases occurred in the vulva. The incidence of genitourinary melanoma was much higher in women (1.74/1 million person-years) than men (0.17/1 million person-years). The highest rates occurred among non-Hispanic white women aged 85 years and older. Five-year melanoma-specific and overall survival were poor at 52.4% and 36.3%, respectively. Predictors of poor survival were increasing age, black race, and female sex. LIMITATIONS: The study population is small, therefore some rates reported may be unstable. In addition, cutaneous, mucosal, and other extracutaneous surfaces of the genitourinary tract cannot be reliably distinguished in Surveillance, Epidemiology, and End Results. Furthermore, melanomas may be underreported to cancer registries. CONCLUSION: From 1992 to 2012, genitourinary melanoma was 10 times more common in women than men. Survival was poor in women compared with men, which is different from cutaneous melanoma where women have a survival advantage.

Cutaneous manifestations associated with melanoma.

Melanoma is a malignancy most commonly arising from the skin; therefore, primary melanoma characteristics are usually the first cutaneous manifestations of melanoma. Cutaneous metastases, which can occur locally or diffusely, are important to detect in a timely manner as treatments for advanced melanoma that impact survival are now available. Melanoma can be associated with local or diffuse pigmentation changes, including depigmentation associated with the leukodermas and hyperpigmentation associated with diffuse melanosis cutis. The leukodermas occur frequently, illustrate the immunogenic nature of melanoma, and may impact prognosis. Paraneoplastic syndromes in association with melanoma are rare, though can occur.

Parotid melanoma of unknown primary.

PURPOSE: Rarely, melanoma is discovered in the parotid gland without an identifiable primary site. It is not known how patients with parotid melanoma of unknown primary (PMUP) compare to those with a known primary (PMKP). As such, we describe the largest series of patients with PMUP to date and compare them to patients with PMKP. METHODS: We analyzed cases from three sources: (1) the University Hospitals Case Medical Center pathology database (n = 45), (2) the Surveillance, Epidemiology, and End Results 18 database (n = 33), and (3) a comprehensive literature search (n = 32). RESULTS: PMUP patients were predominately male and presented at a mean age of 56 years. When compared to PMKP, PMUP cases were more likely to be diagnosed in the parotid parenchyma, present with stage IV disease, and develop distant metastases during follow-up in a shorter amount of time. However, there was no difference in overall survival between patients with PMUP and PMKP presenting with stage-matched disease. CONCLUSIONS: Overall survival is similar for stage-matched patients with parotid melanoma presenting with an unknown and known primary site.

An observational case series on dermatoscopic patterns of fading melanocytic naevi.

BACKGROUND/OBJECTIVES: The prevalence of melanocytic naevi falls with age. It has been postulated that this could be due to spontaneous involution (fading). Our objective was to provide dermatoscopic evidence of fading naevi and to describe the patterns of fading observed. METHODS: Serial dermatoscopic images of naevi demonstrating fading were collected from a set of 25 000 images. Any naevi that showed significant fading, as compared to previous imaging of the same lesion, were included in the analysis. RESULTS: A total of 47 naevi in 21 patients were found to have significantly faded over a span of 2-11 years. The dermatoscopic fading was observed to occur in two patterns. The most common pattern observed was generalised fading (n = 45), where fading was present over all the naevus. There were two cases of focal fading (n = 2) where fading was present only over one area of the naevus. CONCLUSIONS: Fading melanocytic naevi are uncommon. Melanocytic naevi fade in recognisable patterns, with generalised fading most commonly observed in our series.

A systematic review and meta-analysis of animal-type melanoma.

BACKGROUND: Animal-type melanoma is a rare subtype of melanoma with heavily pigmented dermal epithelioid and spindled melanocytes. Its classification as a subtype of melanoma versus a borderline melanocytic tumor is debated. OBJECTIVES: Our primary objective was to characterize the demographics, clinical presentation, histopathology, management, and outcomes of patients with animal-type melanoma. METHODS: We performed a systematic review and meta-analysis of the English-language literature on animal-type melanoma. RESULTS: We identified 190 cases of animal-type melanoma. They occurred equally in men and women, with Caucasians (53.7%) most commonly affected. The median Breslow depth was 3.8 mm; ulceration was reported present in 15.8%; and dermal mitoses greater than or equal to 1/mm(2) was reported in 27.4%. The most common initial management was wide local excision with sentinel lymph node biopsy (55.7%). In all, 78 patients underwent sentinel lymph node biopsy with 41.0% positivity rate. A total of 32 patients underwent completion lymph node dissection with 34.4% positivity rate. Locoregional recurrence was reported in 15 patients, recurrence with distant metastases in 6 patients, and death in 5 patients. LIMITATIONS: Data were obtained from small studies with limited follow-up. There is no universally accepted definition of animal-type melanoma. CONCLUSION: Prospective studies with complete staging information and molecular profiling may allow further characterization of this tumor.

Cutaneous Malignant Neoplasms in Hematopoietic Cell Transplant Recipients: A Systematic Review.

IMPORTANCE: Hematopoietic cell transplantation has increased the survival of patients with several types of malignant hematologic disease and hematologic disorders; however, these patients have an increased risk of posttransplant cutaneous malignant neoplasms. Physicians should be aware of associated risk factors to provide appropriate patient screening and long-term care. OBJECTIVE: To identify the incidence and risk factors for cutaneous malignant neoplasms following hematopoietic cell transplantation. EVIDENCE REVIEW: A systematic review was conducted using Medline and Cochrane databases from January 1995 to December 2013. Retrospective and prospective reviews containing at least 100 patients who underwent hematopoietic cell transplantation reporting skin cancer as a primary outcome were included. Information regarding the entire cohort, data for the subset who developed cutaneous malignant neoplasms, and cutaneous malignant neoplasm risk factors were extracted from included articles. The level of evidence for each study was assessed using the Strength of Recommendation Taxonomy scale. FINDINGS: Patients who underwent hematopoietic cell transplantation had an increased risk of squamous cell carcinoma, basal cell carcinoma, and melanoma. Factors such as primary disease, chronic graft-vs-host disease, prolonged immunosuppression, radiation exposure, light skin color, sex, and T-cell depletion are risk factors for cutaneous malignant neoplasms. CONCLUSIONS AND RELEVANCE: Given the increased risk of cutaneous malignant neoplasms in hematopoietic cell transplant recipients, this population should be educated on skin self-examination and pursue regular follow-up with dermatologists.

Squamous cell carcinoma of the scrotum: A look beyond the chimneystacks.

Despite the low incidence, squamous cell carcinoma (SCC) remains the most common scrotal malignancy with a propensity for recurrence and metastasis. In recent years there has been a significant change in the epidemiology of scrotal SCC. Surgery is the mainstay of treatment for resectable disease. Sentinel lymph node dissection adapted from experience with penile SCC can reduce the morbidity of routine lymph node dissection. Emerging treatments for advanced and metastatic SCC are at the cusp of significantly changing management of this disease. We have performed a comprehensive review of scrotal SCC with a focus on these topics.

Improved stroke care processes and outcomes following the institution of an acute stroke unit at a New Zealand district general hospital.

AIMS: To examine whether stroke care processes and outcomes are improved following the institution of an acute stroke unit (ASU) at a medium-sized New Zealand hospital. METHODS: Two retrospective audits over 12-month periods were carried out at Hutt Valley Hospital before and after the institution of a 6-bed ASU. Data was collected on demographics, length of stay, stroke type, investigations, processes of care and outcomes. RESULTS: 139 strokes pre ASU and 155 strokes post ASU were studied. 86.8% of strokes received stroke unit care in the 2009 audit. There were more intracerebral haemorrhages in 2006 (17.2% vs. 9.0%). Significant improvements were seen between 2006 and 2009 in time to aspirin administration (52.7 versus 14.5 hours), swallow assessment within 24 hours (88.5% versus 96.1%), lag time to carotid Doppler studies (21 days versus 4.5 days), pressure risk assessments (19.6%, versus 87.2%) and urinary infection rates (10.8% versus 2.0% ). Total length of stay (TLOS) and mortality were reduced but the difference was not statistically significant. (20.5 days versus 18.3 days p=0.34, Inpatient mortality 16.2% versus 10% p=0.12). CONCLUSIONS: The introduction of an ASU has resulted in improvements in several key processes of stroke care. Overall mortality and total length of stay showed a trend to improvement after the establishment of an ASU.

Influence of ABCB1 (P-glycoprotein) haplotypes on nortriptyline pharmacokinetics and nortriptyline-induced postural hypotension in healthy volunteers.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: A single nucleotide polymorphism in ABCB1, which encodes P-glycoprotein, has retrospectively been associated with symptoms of nortriptyline-induced postural hypotension in depressed patients. This finding needs to be replicated in independent studies before recommendations regarding pharmacogenetic testing can be made. WHAT THIS STUDY ADDS: In a prospective study of healthy volunteers homozygous for ABCB1 (1236-2677-3435, TTT/TTT or CGC/CGC), a single dose of nortriptyline was administered, plasma exposure was determined and blood pressure and heart rate were monitored during posture change. No differences between ABCB1 haplotype groups were found in plasma exposure of nortriptyline and its active metabolites, E- and Z-10-hydroxynortriptyline. The heart rate response to posture change was increased with nortriptyline, whereas there was no difference in blood pressure response. However, no differences between haplotype groups were observed except that the pre dose heart rate response to standing was greater in the TTT than CGC homozygotes. The association between ABCB1 polymorphisms and nortriptyline-induced postural hypotension found in a previous study could not be confirmed. The results raise the possibility of a predisposition in heart rate response in the TTT homozygotes rather than an effect of nortriptyline. AIMS To investigate the influence of ABCB1 (1236-2677-3435) polymorphisms on nortriptyline pharmacokinetics and nortriptyline-induced postural hypotension in healthy volunteers. METHODS: Genetic screening of 67 healthy volunteers identified eight CGC homozygotes and nine TTT homozygotes of ABCB1 (1236-2677-3435), who were administered a single dose of nortriptyline 25 mg. Plasma exposure of nortriptyline and its active metabolites, E- and Z-10-hydroxynortriptyline, was determined over 72 h. Heart rate and blood pressure responses to posture change (active standing and passive head-up tilt) were measured continuously using finger plethysmography. RESULTS: There were no differences in plasma exposure between ABCB1 haplotype groups, as the geometric mean (95% CI) AUC(0,72 h) ratios were 0.98 (0.94, 1.03), 1.02 (0.96, 1.09) and 0.95 (0.80, 1.10) for nortriptyline, E- and Z-10-hydroxynortriptyline, respectively. The pre dose heart rate response to standing was greater in the TTT than CGC homozygotes (mean (95% CI) difference 7.4 (1.5, 13.4) beats min(-1) , P = 0.02). At t(max) at 8 h post dose, nortriptyline increased the heart rate response to posture change in all subjects with mean (95% CI) Δ heart rate values of 7.4 (3.6, 11.3) beats min(-1) on active standing (P = 0.0009) and 4.8 (2.0, 7.6) beats min(-1) on head-up tilt (P = 0.002), but no difference was observed between haplotype groups. There was no difference in blood pressure response to posture change in either group. CONCLUSION: The association between ABCB1 polymorphisms and nortriptyline-induced postural hypotension found in the previous study could not be confirmed. The results raise the possibility of a predisposition in heart rate response in the TTT homozygotes rather than an effect of nortriptyline.