Practical implementation of noninvasive ventilation in Amyotrophic Lateral Sclerosis: lessons learned from a clinical case series.

PURPOSE: Noninvasive ventilation (NIV) may improve survival and quality of life in Amyotrophic Lateral Sclerosis (ALS) patients. There is a surprising paucity of practical guidelines for office-based implementation and management of NIV outside of tertiary ALS centers. We saw the need for a clinical protocol to allow feasible and consistent NIV management in this patient population. METHODS: We created a clinical protocol for office-based initiation of NIV implemented on consecutive ALS patients referred from our regional ALS multidisciplinary clinic. The protocol provided initial empiric settings using a bilevel device in volume-assured pressure support mode. A respiratory therapist (RT) initiated NIV in an office setting and made adjustments according to patient tolerance and therapy targets outlined in the protocol. Later setting changes were performed at patient or provider request. We evaluated patient adherence and efficacy via device download at 30 days and 1 year. RESULTS: We present data from a case series of the first 14 consecutive patients initiated on NIV over a 20-month period. Our protocol underwent iterative modification based on clinical experience and patient feedback. Early challenges included the significant time and resource burden required to coordinate device downloads and patient follow-up. Early 30-day NIV adherence was variable (median 20 out of 30 days), while 1-year NIV adherence was excellent (median 27.5 out of 30 days). CONCLUSIONS: Our RT-driven clinical NIV protocol was feasible but labor intensive. Achieving real-world adherence of NIV in our ALS patients required iterative protocol adjustment, significant RT provider time, and tele-based follow-up.

Novel findings of left ventricular non-compaction cardiomyopathy, microform cleft lip and poor vision in patient with SMC1A-associated Cornelia de Lange syndrome.

Relatively few patients with Cornelia de Lange syndrome (CdLS) due to SMC1A mutation have been reported, limiting understanding of the full extent of the phenotype. Compared to children with classic NIPBL-associated CdLS, patients with SMC1A-associated CdLS have a milder physical phenotype with prominent intellectual disability, high rate of cleft palate and absence of limb reductions. We present a patient with SMC1A-associated CdLS who had typical features including developmental delay, seizure disorder, feeding difficulties, hirsutism, and cleft palate. She also was found to have three novel features: (i) left ventricular non-compaction (LVNC) cardiomyopathy; (ii) microform cleft lip; and (iii) severe hyperopia and astigmatism. These features have implications regarding potential insight into the pathogenesis of the disorder, screening, and medical management. Hypertrophic cardiomyopathy has previously been reported in SMC1A-associated CdLS, but to our knowledge this is the first reported child with LVNC. Previous reports have included children with isolated clefts of the palate without involvement of the lip. When cleft palate alone is associated with a disorder, the underlying pathophysiology for clefting is sometimes secondary due to mechanical blocking of the fusion of the palatal shelves with the developing tongue. The presence of microform cleft lip in this patient suggests that the pathophysiology of clefting in SMC1A is primary rather than secondary. Few studies report ophthalmologic findings specific to SMC1A. Based on these findings, LVNC cardiomyopathy and cleft lip should be considered features of SMC1A-associated CdLS. All patients should receive echocardiogram and undergo thorough ophthalmologic evaluation as part of routine CdLS care. © 2016 Wiley Periodicals, Inc.

Sleep Architecture in Mechanically Ventilated Pediatric ICU Patients Receiving Goal-Directed, Dexmedetomidine- and Opioid-based Sedation.

This single-center prospective observational study aimed to evaluate sleep architecture in mechanically ventilated pediatric intensive care unit (PICU) patients receiving protocolized light sedation. We enrolled 18 children, 6 months to 17 years of age, receiving mechanical ventilation and standard, protocolized sedation for acute respiratory failure, and monitored them with 24 hours of limited (10 channels) polysomnogram (PSG). The PSG was scored by a sleep technician and reviewed by a pediatric sleep medicine physician. Sixteen children had adequate PSG data for sleep stage scoring. All received continuous opioid infusions, 15 (94%) received dexmedetomidine, and 7 (44%) received intermittent benzodiazepines. Total sleep time was above the age-matched normal reference range (median 867 vs. 641 minutes, p = 0.002), attributable to increased stage N1 and N2 sleep. Diurnal variation was absent, with a median of 47% of sleep occurring during night-time hours. Rapid eye movement (REM) sleep was observed as absent in most patients ( n = 12, 75%). Sleep was substantially disrupted, with more awakenings per hour than normal for age (median 2.2 vs. 1.1, p = 0.008), resulting in a median average sleep period duration (sleep before awakening) of only 25 minutes (interquartile range [IQR]: 14-36) versus normal 72 minutes (IQR: 65-86, p = 0.001). Higher ketamine and propofol doses were associated with increased sleep disruption. Children receiving targeted, opioid-, and dexmedetomidine-based sedation to facilitate mechanical ventilation for acute respiratory failure have substantial sleep disruption and abnormal sleep architecture, achieving little to no REM sleep. Dexmedetomidine-based sedation does not ensure quality sleep in this population.

A surface electrode adjacent to vagal nerve stimulator lead can aid in characterizing vagal nerve stimulator-mediated pediatric sleep-disordered breathing: a case series of 7 patients.

STUDY OBJECTIVES: The vagal nerve stimulator (VNS) is a nonpharmacological treatment for refractory epilepsy. A side effect of the VNS is sleep-disordered breathing. The purpose of this study was to demonstrate how a surface electrode placed over the VNS lead can help distinguish whether sleep-disordered breathing is due to VNS discharge. METHODS: Seven pediatric patients (aged 7.7 ± 2.2 years) with a VNS underwent a polysomnogram with an additional surface electrode on the left anterolateral neck to detect VNS discharge. The VNS-associated apnea-hypopnea index was calculated by determining the number of hypopneas and apneas occurring during VNS discharge. We evaluated the veracity of the VNS electrode by comparing signal duration and total number to those expected by programmed settings. We compared these findings to chin electromyogram signal change. RESULTS: Three patients had an obstructive pattern with VNS discharge, and 3 had an increase in respiratory rate without gas exchange abnormalities, including 1 with both patterns; 1 patient experienced no respiratory abnormalities. The mean obstructive apnea-hypopnea index was 8.2 ± 8.3 events/h. The mean VNS-associated apnea-hypopnea index was 4.8 ± 6.2 events/h and accounted for 46.9 ± 30.2% of the total obstructive apnea-hypopnea index. The additional electrode captured a statistically high percentage of expected discharges (94.7 ± 6.5%) compared to chin electromyogram (36.1 ± 35.8%; P < .05). CONCLUSIONS: We demonstrated that a surface electrode on the VNS lead can temporally coregister VNS discharges and enabled us to attribute sleep-disordered breathing to VNS stimulation in 4 patients. We propose that this sensor be standard procedure in patients with VNS undergoing polysomnogram. CITATION: Chan JHM, DelRosso LM, Ruth C, Wrede JE. A surface electrode adjacent to vagal nerve stimulator lead can aid in characterizing vagal nerve stimulator-mediated pediatric sleep-disordered breathing: a case series of 7 patients. J Clin Sleep Med. 2022;18(8):1973-1981.

Actigraphy in mechanically ventilated pediatric ICU patients: comparison to PSG and evaluation of behavioral circadian rhythmicity.

Sleep disruption is common in pediatric intensive care unit (PICU) patients, but measuring sleep in this population is challenging. We aimed to evaluate the utility of actigraphy for estimating circadian rhythmicity in mechanically ventilated PICU patients and its accuracy for measuring sleep by comparing it to polysomnogram (PSG). We conducted a single-center prospective observational study of children 6 months - 17 years of age receiving mechanical ventilation and standard, protocolized sedation for acute respiratory failure, excluding children with acute or historical neurologic injury. We enrolled 16 children and monitored them with up to 14 days of actigraphy and 24 hours of simultaneous limited (10 channel) PSG. Daily actigraphy-based activity profiles demonstrated that patients had a high level of nighttime activity (30-41% of total activity), suggesting disrupted circadian activity cycles. Among n = 12 patients with sufficient actigraphy and PSG data overlap, actigraphy-based sleep estimation showed poor agreement with PSG-identified sleep states, with good sensitivity (94%) but poor specificity (28%), low accuracy (70%,) and low agreement (Cohen's kappa = 0.2, 95% CI = 0.08-0.31). Using univariate linear regression, we identified that Cornell Assessment of Pediatric Delirium scores were associated with accuracy of actigraphy but that other clinical factors including sedative medication doses, activity levels, and restraint use were not. In this population, actigraphy did not reliably discern between sleep and wake states. However, in select patients, actigraphy was able to distinguish diurnal variation in activity patterns, and therefore may be useful for evaluating patients' response to circadian-oriented interventions.

Polysomnographic characteristics and sleep-disordered breathing in Schaaf-Yang syndrome.

INTRODUCTION: Schaaf-Yang syndrome (SYS) is a genetic disorder caused by truncating variants in the MAGEL2 gene located in the maternally imprinted Prader-Willi syndrome (PWS) region at 15q11-13. The SYS phenotype shares features with PWS, a syndrome with known high incidence of sleep disorders. However, the spectrum of sleep-disorders in SYS has not been described. METHODS: We performed a retrospective analysis of polysomnograms from 22 patients in an international SYS cohort. Sleep characteristics for individuals with the common c.1996dupC variant (n = 10) were compared to other truncating variants (n = 11). RESULTS: We collected 33 sleep study reports from 22 patients, ages 2 months - 18.5 years (mean 6.5 years). Mean sleep efficiency was 70.5% (range 45%-93%) with arousal index 14.1/h (1.2-45/h). The mean apnea-hypopnea index (AHI) was 19.1/h (0.9-49/h) with mean obstructive AHI (oAHI) of 16.3/h (0.6-49/h). Mean central apnea index was 2.8/h (0-14/h). Mean oxygen desaturation index was 20.8/h (range 0-85/hr). Obstructive sleep apnea (OSA) was diagnosed in 81%, and 62% had moderate or severe OSA. Elevated central apnea index occurred in 9.5%. Comparison by genotype groups and age did not reveal any difference in OSA findings. Periodic limb movement index (PLMI) was elevated in 4/15 (26%). CONCLUSION: OSA is frequently identified on polysomnography in patients with SYS. The mean PLMI is elevated compared to normative data. Patients with SYS should have routine polysomnography screening due to high risk of sleep disorders.

Determinants of ferritin response to oral iron supplementation in children with sleep movement disorders.

STUDY OBJECTIVES: To identify children who respond to oral iron supplementation as evidenced by increased ferritin levels and to identify factors that correlate with improvement in ferritin levels in those who respond. METHODS: A retrospective chart review of the PLMS/RLS/RSD database at Seattle Children's Hospital was carried out. Data collected included nocturnal polysomnography parameters, age, sex, initial and follow-up ferritin level and date of collection, and presence of restless legs syndrome (RLS), periodic limb movements of sleep (PLMS)/PLM disorder (PLMD), restless sleep disorder (RSD), obstructive sleep apnea (OSA), neurologic, psychiatric, neurodevelopmental, or medical comorbidity. Oral iron therapy was evaluated by side effects (none; constipation; bad taste/nausea), subjective outcome in symptoms (resolved, improved, no change), and adherence to therapy (poor, fair, good). RESULTS: Seventy-seven children were included in this study of whom 42 were classified as responders (increase in ferritin of ≥10 µg/L) and 35 were nonresponders. Age and sex were not different between groups. Adherence was the only significant predictor of an increase in ferritin of ≥10 µg/L. Constipation was seen in 7.1% of responders vs. 45.8% of nonresponders. No change in symptoms was reported in 26.2% of responders vs. 71.4% in nonresponders. A significant correlation was found between treatment duration and ferritin level change in responders but not in nonresponders. CONCLUSIONS: Side effects hinders adherence to oral iron supplementation in children. Responders to oral iron show improvement in ferritin levels and symptoms, while nonresponders show no improvement in ferritin levels despite a long-lasting treatment, at least in part of them.

Comorbidities in children with elevated periodic limb movement index during sleep.

STUDY OBJECTIVES: Little is known about comorbidities in children who have elevated periodic limb movement index (PLMI) during overnight polysomnogram (PSG). The aim of this study is to identify comorbidities in children with elevated PLMI (PLMI > 5) versus children with PLMI < 5 presenting to a pediatric sleep center. METHODS: This study was a retrospective review of all clinically indicated PSGs obtained consecutively from 3/2017-3/2019 at Seattle Children's Sleep Disorders Center. Data collected included demographics, clinical presentation, medications, medical history, family history specifically for restless legs syndrome (RLS), ferritin levels, and PSG metrics. Characteristics between those with (cases) elevated PLMI (AASM criteria) and without (controls) were summarized. RESULTS: We identified 148 subjects with elevated PLMI (67% male, mean age 7.95 years, range 1-20), yielding a PLMI > 5 prevalence of 5%. There were 188 controls included (58% male, mean age 8.0 years, range 1-19). Neither sex (chi-square = 2.8, NS) nor age (Mann-Whitney U = 1339.5, NS) differed between groups. Case subjects had a higher prevalence of RLS, snoring, insomnia, mood disorders, behavioral problems, morning headaches, chronic kidney disease, epilepsy, and chronic heart disease. Similarly, the use of antidepressants, antipsychotics, antiseizure medication, and other medications was statistically more frequent in children with elevated PLMS. The prevalence of PLMI > 5 was 5% and the prevalence of periodic limb movement disorder (PLMD) was 0.3% in children referred to polysomnography. Ferritin levels did not differ. CONCLUSIONS: We identified the prevalence of PLMD in a sleep medicine-referred population. We have also identified comorbidities and medications associated with elevated PLMI in children.No clinical trial.

Case of an In-Laboratory Vagal Nerve Stimulator Titration for Vagal Nerve Stimulator-Induced Pediatric Obstructive Sleep Apnea.

None: We present the case of a 12-year-old girl with medically refractory epilepsy and a vagal nerve stimulator (VNS), who experienced severe obstructive sleep apnea (OSA) with respiratory events closely matching her VNS settings. We demonstrated a real-time decrease in OSA through an in-laboratory VNS titration study, decreasing her VNS frequency from 20 Hz to 10 Hz. We were able to demonstrate a baseline level of OSA by turning off the VNS. We then effectively treated her residual OSA with continuous positive airway pressure (CPAP). Novel to our case is that this in-laboratory VNS titration did not result in any subsequent increase in seizure frequency. After 5 months, her seizure frequency had decreased. Our case demonstrates that in-laboratory VNS titration can be an efficient tool for optimizing treatment of VNS-induced OSA and assert that polysomnography before VNS placement is important for guiding future care.

A Novel Treatment for Nasolacrimal Air Regurgitation Into the Eye With CPAP: The Total Face Mask.

ABSTRACT: We present a patient who experienced insufflation of air under the left eyelid when using continuous positive airway pressure (CPAP) via an oronasal mask. The patient had a lacrimal stent in place for many years, which was a predisposing factor for this complication. Lacrimal stents are frequently used in the treatment of epiphora (excessive tearing) secondary to obstruction of the lacrimal drainage system. In this case, we review the pathophysiology of air regurgitation into the eye with CPAP use and methods previously described to address this rare complication. We also present a novel intervention for this rare complication, the total face mask. By additionally covering the eyes, a total face mask allows equalization of pressure on both sides of the lacrimal system. With a total face mask, our patient was able to successfully use CPAP.

Introduction to Obstructive Sleep Apnea for the Internist.

Introduction: The prevalence of sleep-disordered breathing is increasing, and there are insufficient sleep medicine specialists to meet the clinical demand of caring for these patients. One way to meet this clinical need is to train primary care and internal medicine physicians to provide some of the care. However, trainees in these specialties often receive very little training on practical aspects of the management of obstructive sleep apnea (OSA). We developed an experiential workshop to address this need at our institution. Methods: For approximately 60 internal medicine residents, we ran a 2.5-hour workshop consisting of two 20-minute didactic presentations to the whole audience and two 40-minute breakout sessions, led by eight facilitators. During the breakout sessions, the residents interacted with equipment such as positive airway pressure (PAP) devices and interfaces, reviewed sleep testing and PAP download reports, and participated in guided small-group discussions. Results: We received 40 evaluation surveys with at least partial responses. Only 50% of respondents had received prior formal instruction on PAP devices. Both subjective and objective knowledge scores improved on the postworkshop questions compared to the preworkshop questions. Trainee comments were extremely positive, indicating that they enjoyed the format of the session. Discussion: This curriculum provides an interactive educational session focused on practical aspects of OSA management relevant to primary care physicians and internists. It was well received and could be adapted to suit other time frames and other groups of learners.

Overview of Sleep and Sleep Disorders in Infancy and Childhood.

Sleep in children is an important and dynamic process, affecting numerous aspects of health and development. Problems with sleep are relatively common but often can be challenging to recognize. This article reviews the fundamental aspects of sleep in children from infancy to adolescence, and the most common and relevant sleep disorders likely to be encountered in a general pediatric practice. Where available, current evidence-based recommendations for management are discussed, including indications for referral to a sleep specialist. [Pediatr Ann. 2017;46(4):e133-e138.].

Diagnosis, treatment, and outcomes of infantile spasms in the Trisomy 21 population.

PURPOSE: To determine if there are differences in the timing of diagnosis and response to treatment between infants with infantile spasms (IS) and Trisomy 21 (T21) and those with idiopathic IS. METHOD: This was a retrospective study evaluating the time from onset of IS to diagnosis, treatment of IS, time from treatment to resolution of IS, and development of epilepsy in children with T21 and IS compared to children with idiopathic IS. RESULTS: Thirteen children with T21 and IS were identified over a 10 year period and compared to 32 children in the control group. There was no significant difference in age of onset, time between onset and diagnosis, or acute response to treatment. However, the children with idiopathic IS were more likely to go on to develop epilepsy than those with T21 and IS (41% vs. 0, p=0.006). CONCLUSION: The children with T21 and IS were diagnosed and treated similarly to those patients with idiopathic IS. There were no significant differences in the age of onset, time between the onset and diagnosis of IS, or acute treatment response of IS between the T21 and control groups. However those with T21 and IS had a lower risk of subsequent epilepsy following IS than those with idiopathic IS. IS in the T21 population appears to be inherently different from IS of unknown etiology.

American Academy of Sleep Medicine Position Paper for the Use of a Home Sleep Apnea Test for the Diagnosis of OSA in Children.

INTRODUCTION: The purpose of this position paper is to establish the American Academy of Sleep Medicine's (AASM) position on the use of a home sleep apnea test (HSAT) for the diagnosis of obstructive sleep apnea (OSA) in children (birth to 18 years of age). METHODS: The AASM commissioned a task force of 8 experts in sleep medicine to review the available literature on the use of an HSAT to diagnose OSA in children. The task force developed the position statement based on a thorough review of these studies and their clinical expertise. The AASM Board of Directors approved the final position statement. POSITION STATEMENT: Use of a home sleep apnea test is not recommended for the diagnosis of obstructive sleep apnea in children. The ultimate judgment regarding propriety of any specific care must be made by the clinician, in light of the individual circumstances presented by the patient, available diagnostic tools, accessible treatment options, and resources.

Low-grade B-Cell lymphomas with plasmacytic differentiation lack PAX5 gene rearrangements.

The chromosomal translocation t(9;14)(p13;q32) has been reported in association with lymphoplasmacytic lymphoma (LPL). Although this translocation involving the paired homeobox-5 (PAX5) gene at chromosome band 9p13 and the immunoglobulin heavy chain (IgH) gene at 14q32 has been described in approximately 50% of LPL cases, the actual number of cases studied is quite small. Many of the initial cases associated with t(9;14)(p13;q32) were actually low-grade B-cell lymphomas with plasmacytic differentiation other than LPL. Thus, we analyzed a series of low-grade B-cell lymphomas for PAX5 gene rearrangements. We searched records from the Department of Pathology, Stanford University Medical Center for low-grade B-cell lymphomas, with an emphasis on plasmacytic differentiation, that had available paraffin blocks or frozen tissue. We identified 37 cases, including 13 LPL, 18 marginal zone lymphomas (nodal, extranodal, splenic, and alpha-heavy chain disease), and 6 small lymphocytic lymphomas. A novel dual-color break-apart bacterial artificial chromosome probe was designed to flank the PAX5 gene, spanning previously described PAX5 breakpoints, and samples were analyzed by interphase fluorescence in situ hybridization. All cases failed to demonstrate a PAX5 translocation, indicating that t(9;14)(p13;q32) and other PAX5 translocations are uncommon events in low-grade B-cell lymphomas with plasmacytic differentiation. This study also confirms recent reports that found an absence of PAX5 rearrangements in LPL, suggesting the reassessment of PAX5 rearrangements in LPL.

Mitochondrial DNA Copy Number in Sleep Duration Discordant Monozygotic Twins.

STUDY OBJECTIVES: Mitochondrial DNA (mtDNA) copy number is an important component of mitochondrial function and varies with age, disease, and environmental factors. We aimed to determine whether mtDNA copy number varies with habitual differences in sleep duration within pairs of monozygotic twins. SETTING: Academic clinical research center. PARTICIPANTS: 15 sleep duration discordant monozygotic twin pairs (30 twins, 80% female; mean age 42.1 years [SD 15.0]). DESIGN: Sleep duration was phenotyped with wrist actigraphy. Each twin pair included a "normal" (7-9 h/24) and "short" (< 7 h/24) sleeping twin. Fasting peripheral blood leukocyte DNA was assessed for mtDNA copy number via the n-fold difference between qPCR measured mtDNA and nuclear DNA creating an mtDNA measure without absolute units. We used generalized estimating equation linear regression models accounting for the correlated data structure to assess within-pair effects of sleep duration on mtDNA copy number. MEASUREMENTS AND RESULTS: Mean within-pair sleep duration difference per 24 hours was 94.3 minutes (SD 62.6 min). We found reduced sleep duration (ß = 0.06; 95% CI 0.004, 0.12; P < 0.05) and sleep efficiency (ß = 0.51; 95% CI 0.06, 0.95; P < 0.05) were significantly associated with reduced mtDNA copy number within twin pairs. Thus every 1-minute decrease in actigraphy-defined sleep duration was associated with a decrease in mtDNA copy number of 0.06. Likewise, a 1% decrease in actigraphy-defined sleep efficiency was associated with a decrease in mtDNA copy number of 0.51. CONCLUSIONS: Reduced sleep duration and sleep efficiency were associated with reduced mitochondrial DNA copy number in sleep duration discordant monozygotic twins offering a potential mechanism whereby short sleep impairs health and longevity through mitochondrial stress.

Chromosomal aberrations in a case of synchronous extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type and bronchogenic adenocarcinoma.

We present the chromosomal aberrations in a case of synchronous extranodal marginal zone B-cell lymphoma and bronchogenic adenocarcinoma with bronchioloalveolar features. Using fluorescence in situ hybridization, we identified deletion of the immunoglobulin heavy chain gene in the lymphomatous component, but not the carcinomatous component. The presence of differing genetic compositions suggests a biclonal environment composed of 2 distinct neoplastic processes.

Fluorescence in situ hybridization investigation of cutaneous lesions in acute promyelocytic leukemia.

Cutaneous manifestations of acute promyelocytic leukemia are rare but well documented. Skin biopsies of leukemia can be difficult to confirm using morphology alone, and paraffin section immunophenotyping is not specific in separating acute promyelocytic leukemia from other acute myeloid leukemias involving the skin or inflammatory conditions, such as Sweet's syndrome and all-trans retinoic acid-associated genital ulcers, which may mimic leukemia cutis. Fluorescence in situ hybridization has been shown to be a fast and effective method of detecting the PML/RARA fusion gene characteristic of acute promyelocytic leukemia in fresh blood and bone marrow samples. Fluorescence in situ hybridization has also been demonstrated to be effective in detecting other chromosomal rearrangements in paraffin-embedded tissue. This retrospective study of cutaneous lesions from four patients with acute promyelocytic leukemia evaluates the utility of performing fluorescence in situ hybridization to confirm the presence of cutaneous manifestations of acute promyelocytic leukemia in formalin-fixed, paraffin-embedded skin biopsies. All patients had previous bone marrow findings of acute promyelocytic leukemia with characteristic morphology, immunophenotype, and cytogenetic studies, which detailed the presence of the t(15;17)(q22;q12) rearrangement. Two skin biopsies showed an infiltrate of blastic cells involving the dermis in a diffuse pattern and one biopsy had a perivascular/periadnexal pattern. The fourth case, involving the scrotum, showed a predominant neutrophilic infiltrate diffusely involving the dermis and epidermis with a subset of blastic cells. Nuclei were extracted from core biopsies of the formalin-fixed paraffin-embedded tissue and fluorescence in situ hybridization was performed using a dual color, dual fusion PML / RARA probe. All cases showed evidence of the t(15;17) rearrangement, with 90, 79, 51 and 16% positive signal patterns, each well above background limits. Fluorescence in situ hybridization appears to be a robust technique to detect cutaneous manifestations of acute promyelocytic leukemia in formalin-fixed paraffin-embedded skin biopsies.