The Bare Necessities: Uncovering Essential and Condition‐Critical Genes with Transposon Sequencing

Summary

Querying gene function in bacteria has been greatly accelerated by the advent of transposon sequencing (Tn‐seq) technologies (related Tn‐seq strategies are known as TraDIS, INSeq, RB‐TnSeq and HITS). Pooled populations of transposon mutants are cultured in an environment and next‐generation sequencing tools are used to determine areas of the genome that are important for bacterial fitness. In this review we provide an overview of Tn‐seq methodologies and discuss how Tn‐seq has been applied, or could be applied, to the study of oral microbiology. These applications include studying the essential genome as a means to rationally design therapeutic agents. Tn‐seq has also contributed to our understanding of well‐studied biological processes in oral bacteria. Other important applications include in vivo pathogenesis studies and use of Tn‐seq to probe the molecular basis of microbial interactions. We also highlight recent advancements in techniques that act in synergy with Tn‐seq such as CRISPR interference and microfluidic chip platforms.

This article is protected by copyright. All rights reserved.

http://bit.ly/2DpnJDG

Papular Spreaded Necrobiosis Lipoidica: a rare clinical presentation of this pathology

Abstract

A 69‐year‐old Caucasian woman suffering from long‐term diabetes mellitus type II was referred to our dermatology department with cutaneous lesions that appeared 3 years before. They were itchy and non‐tender, and spreaded progressively, with no history of previous trauma. Examination revealed multiple erythematous to yellowish papules on the lower legs, which merged in plaques, of varying shapes and sizes (Fig.1).

This article is protected by copyright. All rights reserved.

http://bit.ly/2TGpKSN

Papular Spreaded Necrobiosis Lipoidica: a rare clinical presentation of this pathology

Abstract

A 69‐year‐old Caucasian woman suffering from long‐term diabetes mellitus type II was referred to our dermatology department with cutaneous lesions that appeared 3 years before. They were itchy and non‐tender, and spreaded progressively, with no history of previous trauma. Examination revealed multiple erythematous to yellowish papules on the lower legs, which merged in plaques, of varying shapes and sizes (Fig.1).

This article is protected by copyright. All rights reserved.

http://bit.ly/2TGpKSN

A Brief History of Circannual Time

Abstract

The tenet of this review is that innate circannual timing is an ancestral trait that first evolved in free‐living eukaryotic cells some 2000My ago. Marine algae of the genus Allexandrium provide a living unicellular model. This species shows the primitive trait of 'alternation of generations' where the organism alternates between fast replicating vegetative cells in summer, and a dormant cystic cell over winter. The resistant cysts sink into the cold ocean sediments. Remarkably, excystment in spring is governed by an endogenous circannual timing mechanism. Thus, a tiny, short‐lived unicell can utilize a circannual clock as part of the species' life history program. Innate timing allows for major adjustments in physiology and behavior in anticipation of the seasons, and provides an internalized sense of seasonal time for the many species where standard environmental cues are weak or ambiguous. This is a highly adaptive strategy irrespective of the organism's size and longevity. Circannual rhythms are expressed by a diverse range of organisms from flowering plants,to mammals, interwoven into each species life‐history program – the consequence of fore‐ever living in a periodic world. In complex vertebrates, the early division of the zygote potentially carries circannual timer genes into all progeny cells and into all tissues. This supports the concept of a 'clock shop' where cell‐autonomous long‐term rhythms are generated in each tissue, orchestrated by a central circannual pacemaker system. This is analogous to the organization of the circadian timing system. For the circannual time‐scale, specialized thyrotrope cells located in the pars tuberalis (PT) of the pituitary gland and adjacent tanycyte cells located in the ependymal wall of the third cerebral ventricle (3rdV) of the brain act as putative central circannual pacemakers. At a molecular level epigenetically regulated, cyclical remodeling of chromatin, that determines whether specific circannual timer genes are transcriptionary active, or not, is thought to drive the oscillation between the summer and winter phenotypes.

This article is protected by copyright. All rights reserved.

http://bit.ly/2Spza8H

Surgical site infections after parotidectomy: management and benefits of an antibiotic prophylaxis protocol.

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Surgical site infections after parotidectomy: management and benefits of an antibiotic prophylaxis protocol.

Acta Otorhinolaryngol Ital. 2018 Dec 29;:

Authors: Meccariello G, Montevecchi F, D'Agostino G, Zeccardo E, Al-Raswashdeh MFH, De Vito A, Vicini C

Abstract
The use of perioperative prophylactic antibiotics in uncontaminated head and neck surgery is still controversial. The aim of this study was to assess the efficacy of an institutional antibiotic prophylactic protocol in preventing surgical site infection after parotidectomy. The medical charts of 448 patients who underwent parotidectomy were reviewed. Patients were divided in two groups according the use of perioperative administration of intravenous cefazolin or post-operative week course of antibiotics. Surgical site infection was registered in 29 (6.5%) cases, 16 (5.7%) within the group before the application of protocol and 13 (7.9%) within the antibiotic prophylaxis protocol group. The univariate and multivariate logistic regression analyses showed that predictors for surgical site infection were the amount of drain output ≥ 50 ml in the first post-operative 24 hours (OR: 4.86; 1.59-14.82 95% CI; p < 0.01) and history of a previous parotid acute infection (OR: 13.83; 5.31-36 95% CI; p < 0.01). The majority of post-surgical infections (82%) were treated with intravenous antibiotic therapy. The remnants were treated surgically. Perioperative antibiotic treatment is recommended for patients undergoing parotid gland surgery and intravenous antibiotics during the post-operative course are highly suggested in case of history of previous acute parotid infection and drain output ≥ 50 ml in first 24 hours.

PMID: 30632521 [PubMed - as supplied by publisher]

http://bit.ly/2RnDUuS

Oculorespiratory Reflex During Repair of an Orbital Fracture.

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Oculorespiratory Reflex During Repair of an Orbital Fracture.

JAMA Otolaryngol Head Neck Surg. 2019 Feb 07;:

Authors: Dang RP, Bhatt NK, Rizzi CJ, Chi JJ

PMID: 30730542 [PubMed - as supplied by publisher]

http://bit.ly/2GuWz14

Association of Chronic Rhinosinusitis With Depression and Anxiety in a Nationwide Insurance Population.

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Association of Chronic Rhinosinusitis With Depression and Anxiety in a Nationwide Insurance Population.

JAMA Otolaryngol Head Neck Surg. 2019 Feb 07;:

Authors: Kim JY, Ko I, Kim MS, Yu MS, Cho BJ, Kim DK

Abstract
Importance: Chronic rhinosinusitis (CRS) is associated with a decreased quality of life, affecting physical and emotional aspects of daily function, the latter of which could manifest as depression and anxiety.
Objective: To evaluate the risk of depression and anxiety in CRS, depending on the CRS phenotype (CRS without nasal polyps [CRSsNP] and CRS with nasal polyps [CRSwNP]).
Design, Setting, and Participants: This retrospective nationwide cohort study used population-based insurance data (consisting of data from approximately 1 million patients). The study population included 16 224 patients with CRS and 32 448 individuals without CRS, with propensity score matching between groups according to sociodemographic factors and enrollment year. Data were collected from January 1, 2002, through December 31, 2013, and analyzed from July 1 through November 15, 2018.
Main Outcomes and Measures: Survival analysis, the log-rank test, and Cox proportional hazards regression models were used to calculate the incidence, survival rate, and hazard ratio (HR) of depression and anxiety for each group.
Results: Among the 48 672 individuals included in the study population (58.8% female), the overall incidence of depression during the 11-year follow-up was 1.51-fold higher in the CRS group than in the non-CRS group (24.2 vs 16.0 per 1000 person-years; adjusted HR, 1.54; 95% CI, 1.48-1.61). The incidence of anxiety was also higher in the CRS group than in the comparison group (42.2 vs 27.8 per 1000 person-years; adjusted HR, 1.57; 95% CI, 1.52-1.62). Moreover, the adjusted HRs of developing depression (CRSsNP, 1.61 [95% CI, 1.54-1.69]; CRSwNP, 1.41 [95% CI, 1.32-1.50]) and anxiety (CRSsNP, 1.63 [95% CI, 1.57-1.69]; CRSwNP, 1.45 [95% CI, 1.38-1.52]) were greater in patients with CRSsNP than in those with CRSwNP.
Conclusions and Relevance: This observational study suggests that CRS is associated with an increased incidence of depression and anxiety. Specifically, findings from this study found that patients without nasal polyps showed a higher risk of developing depression and anxiety than those with nasal polyps.

PMID: 30730537 [PubMed - as supplied by publisher]

http://bit.ly/2E1DBxB

The Centers for Medicare & Medicaid Services' Overhaul of Office-Visit Payments-What's the Bottom Line for Otolaryngology?

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The Centers for Medicare & Medicaid Services' Overhaul of Office-Visit Payments-What's the Bottom Line for Otolaryngology?

JAMA Otolaryngol Head Neck Surg. 2019 Feb 07;:

Authors: Rathi VK, Varvares MA, Naunheim MR

PMID: 30730534 [PubMed - as supplied by publisher]

http://bit.ly/2GxG0lc

Does Chronic Rhinosinusitis Lead to Psychiatric Disease?

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Does Chronic Rhinosinusitis Lead to Psychiatric Disease?

JAMA Otolaryngol Head Neck Surg. 2019 Feb 07;:

Authors: McCoul ED

PMID: 30730532 [PubMed - as supplied by publisher]

http://bit.ly/2RTCiV8

Gezielte Exposition versus Allergenmeidung

http://bit.ly/2SE9Gn9

Schlechte Bewertungen im Internet: dulden oder löschen lassen?

Arztbewertungsportale im Internet erfreuen sich zunehmender Beliebtheit. Leider äußern sich dort aber vor allem unzufriedene Patienten. Vernichtende Kritik wirkt im Internet jedoch als Blickfang: Schon einige wenige solcher Bewertungen können die Leistung eines Arztes in ein völlig falsches Licht rücken. Ein Blick auf die rechtlichen Hintergründe zum Umgang mit solchen Bewertungen.

http://bit.ly/2SDTyC3

Allergologie unter Druck

http://bit.ly/2MZvftk

So sicher ist die intranasale Glukokortikoidtherapie

Auch wenn die intranasale Glukokorikoidtherapie als sicher gilt, befürchten manche systemische Nebenwirkungen, wie sie von einer oralen Anwendung bekannt sind. Bisher gab es keine Metaanalysen, mit deren Hilfe dies geklärt werden konnte. HNO-Ärzte aus den USA konnten diese Lücke nun schließen.

http://bit.ly/2N2f7r2

Weitergabe von Daten und Datenübertragung — nur mit Einwilligung?

Durch die Datenschutzgrundverordnung (DSGVO) ist in der Ärzteschaft Verunsicherung darüber entstanden, unter welchen Voraussetzungen Patientendaten an Dritte weitergegeben werden dürfen. Es besteht oftmals die Sorge, für jede Weitergabe von Patientendaten eine schriftliche Einwilligung des Patienten zu benötigen und so im Papierwust zu ersticken. Im Fokus steht dabei die Weitergabe von Daten an weiter- oder nachbehandelnde Ärzte, an Labore sowie an Abrechnungsgesellschaften. Doch auch außerhalb des Praxisalltags ist der Thematik Beachtung zu schenken.

http://bit.ly/2SE9xjB

Defizite in der Anaphylaxietherapie

http://bit.ly/2MXEtpH

Lesenswerte Therapiebegleitung für Tumorpatienten

http://bit.ly/2MYTZBJ

Akupunktur bei allergischen Erkrankungen — wann ist sie sinnvoll?

http://bit.ly/2MVqv7M

Skin, Body Dysmorphic Disorder, and Other Syndromes

C. Martínez-González
Actas Dermosifiliogr.2019;110:1

Full Text - PDF

http://bit.ly/2Smcypj

Is the Current Classification of Urethritis as Gonococcal or Nongonoccal Becoming Obsolete?

V.M. Leis-Dosil
Actas Dermosifiliogr.2019;110:2-3

Full Text - PDF

http://bit.ly/2SlWkwx

Psoriasis and Depression: The Role of Inflammation

S. González-Parra, E. Daudén
Actas Dermosifiliogr.2019;110:12-9

Abstract - Full Text - PDF

http://bit.ly/2Smcwhb

Medical Malpractice Issues in Dermatology: Clinical Safety and the Dermatologist

J. Arimany Manso, C. Martin Fumadó, J.M. Mascaró Ballester
Actas Dermosifiliogr.2019;110:20-7

Abstract - Full Text - PDF

http://bit.ly/2Drw89n

Screening for Body Dysmorphic Disorders in Acne Patients: A Pilot Study

S.E. Marron, T. Gracia-Cazaña, A. Miranda-Sivelo, S. Lamas-Diaz, L. Tomas-Aragones
Actas Dermosifiliogr.2019;110:28-32

Abstract - Full Text - PDF

http://bit.ly/2Sp2XOy

The Super Shaving Technique to Correct the Trapdoor Effect in Nasal Flaps

J. Correa, J. Magliano, I. Peres, C. Bazzano
Actas Dermosifiliogr.2019;110:33-7

Abstract - Full Text - PDF

http://bit.ly/2Dqu4hY

Haemophilus Species Isolated in Urethral Exudates as a Possible Causative Agent in Acute Urethritis: A Study of 38 Cases

J. Magdaleno-Tapial, C. Valenzuela-Oñate, M.M. Giacaman-von der Weth, B. Ferrer-Guillén, Á. Martínez-Domenech, M. García-Legaz Martínez, J.M. Ortiz-Salvador, D. Subiabre-Ferrer, P. Hernández-Bel
Actas Dermosifiliogr.2019;110:38-42

Abstract - Full Text - PDF

http://bit.ly/2SkJTRI

Granulomatous Reaction in a Patient With Metastatic Melanoma Treated With Ipilimumab: First Case Reported With Isolated Cutaneous Findings

J. Cervantes, A. Rosen, L. Dehesa, G. Dickinson, J. Alonso-Llamazares
Actas Dermosifiliogr.2019;110:43-9

Abstract - Full Text - PDF

http://bit.ly/2DuG7Ls

Erythematous Papules on the Dorsum of the Hand

C. Maldonado Seral, C. Gómez de Castro, B. Vivanco Allende
Actas Dermosifiliogr.2019;110:e1-e2

Full Text - PDF

http://bit.ly/2DAhD3t

Recurrent Facial Edema

J. Sabater Abad, C. Lloret Ruiz, E. Quecedo Estébanez
Actas Dermosifiliogr.2019;110:e3-e4

Full Text - PDF

http://bit.ly/2SkAF8b

Scratch-Induced Lesions…Without the Scratching

J.L. Ramírez-Bellver, A. Alegre-Sánchez
Actas Dermosifiliogr.2019;110:e5

Full Text - PDF

http://bit.ly/2Smc2I4

Granulocyte Colony-Stimulating Factor (G-Csf)–Producing Giant Squamous Cell Carcinoma of the Scrotum

M. Takako, K. Yasunobu, Y. Toshiyuki
Actas Dermosifiliogr.2019;110:57-9

Full Text - PDF

http://bit.ly/2SkAw4D

Advanced-Stage Thymoma Associating Multiple Paraneoplastic Syndromes with Good Response to Oral Corticosteroids and Topical Tacrolimus

S. Sánchez-Pérez, C. Monteagudo-Castro, J.M. Martín-Hernández, M.D. Ramón-Quiles
Actas Dermosifiliogr.2019;110:60-2

Full Text - PDF

http://bit.ly/2DsANYT

Dermatomyositis-like Eruption in a Woman Treated With Hydroxyurea

E. Moreno-Artero, J.J. Paricio, J. Antoñanzas, A. España
Actas Dermosifiliogr.2019;110:64-7

Full Text - PDF

http://bit.ly/2DuROS2

Big Data Research in Neuro-Ophthalmology: Promises and Pitfalls

Background: Big data clinical research involves application of large data sets to the study of disease. It is of interest to neuro-ophthalmologists but also may be a challenge because of the relative rarity of many of the diseases treated. Evidence Acquisition: Evidence for this review was gathered from the authors' experiences performing analysis of large data sets and review of the literature. Results: Big data sets are heterogeneous, and include prospective surveys, medical administrative and claims data and registries compiled from medical records. High-quality studies must pay careful attention to aspects of data set selection, including potential bias, and data management issues, such as missing data, variable definition, and statistical modeling to generate appropriate conclusions. There are many studies of neuro-ophthalmic diseases that use big data approaches. Conclusions: Big data clinical research studies complement other research methodologies to advance our understanding of human disease. A rigorous and careful approach to data set selection, data management, data analysis, and data interpretation characterizes high-quality studies. Address correspondence to Heather E. Moss, MD, PhD, Department of Ophthalmology, Stanford University, Spencer Center for Vision Research, 2370 Watson Court, MC 5349, Palo Alto, CA 94303; E-mail: hemoss@stanford.edu National Institutes of Health (Bethesda, MD) grants R21 EY027447 (to S. Roth), K23 EY 024345 (to Moss), P30 EY 026877 to the Department of Ophthalmology at Stanford University, P30 EY001792 to the Department of Ophthalmology at the University of Illinois at Chicago, unrestricted grants from Research to Prevent Blindness, Inc. (New York, NY) to the Stanford Department of Ophthalmology and to the University of Illinois at Chicago Department of Ophthalmology and Visual Sciences, and by the Michael Reese Foundation (Chicago, IL) Pioneers Award to Dr. Roth. The authors report no conflicts of interest. © 2019 by North American Neuro-Ophthalmology Society

http://bit.ly/2G7MMxL

Neuro-Ophthalmology Virtual Education Library (NOVEL) 2019 Update: North American Neuro-Ophthalmology Society's Neuro-Ophthalmology Examination Techniques (NExT) and Illustrated Curriculum are Online

No abstract available

http://bit.ly/2G7MNSl

Neuro-Ophthalmology in Canada

No abstract available

http://bit.ly/2FRqcu0

Acute Posterior Multifocal Placoid Pigment Epitheliopathy Complicated by Fatal Cerebral Vasculitis

Abstract: A 21-year-old man experienced unilateral vision loss associated with multiple atrophic chorioretinal lesions. He was treated for a presumptive diagnosis of acute retinal necrosis, but his vision did not improve with antiviral therapy. Over the course of several weeks, his symptoms progressed to involve both eyes. The fellow eye showed characteristic yellow-white placoid lesions, prompting treatment with oral corticosteroids for acute posterior multifocal placoid pigment epitheliopathy (APMPPE). Despite high-dose therapy with prednisone 80 mg daily, the patient developed the acute onset of mental status changes within the next several days. Neuroimaging revealed multifocal large-vessel strokes associated with cerebral edema; these infarcts led to herniation and death. Postmortem histopathologic examination confirmed granulomatous inflammation in both ocular and cerebral vasculatures. Together with findings from multimodal imaging obtained throughout this patient's clinical course, our findings support the notion that granulomatous choroiditis is the mechanism of the ocular lesions seen in APMPPE. This granulomatous inflammation can also affect cerebral vessels, leading to strokes. Address correspondence to Gregory P. Van Stavern, MD, Washington University in St. Louis, St. Louis, MO; E-mail: vanstaverng@wustl.edu The authors report no conflicts of interest. R. N. Maamari and L. Stunkel contributed equally to this work. © 2019 by North American Neuro-Ophthalmology Society

http://bit.ly/2CKTnee

Petroclival Meningioma Presenting With an Ipsilateral Sixth Nerve Palsy and a Contralateral Homonymous Quadrantanopia: A Unique and Topographically Localizing Syndrome

Abstract: An 84-year-old woman reported onset of headaches, diplopia, and blurred vision. On examination, she was found to have a left sixth nerve palsy and an incongruous right homonymous hemianopia. Brain MRI demonstrated a left petroclival meningioma, causing this unusual combination of clinical findings. The patient was treated with radiation therapy and has remained stable over 4 years of follow-up. Address correspondence to Andrew G. Lee, MD, Blanton Eye Institute, Houston Methodist Hospital, 6560 Fannin Street Suite 450, Houston, TX 77030; E-mail: aglee@houstonmethodist.org The authors report no conflicts of interest. © 2019 by North American Neuro-Ophthalmology Society

http://bit.ly/2FJvwyJ

Ocular Tilt Reaction in Compensated Vestibular Schwannoma

No abstract available

http://bit.ly/2RHT9yg

A Tough NUT to Crack: A 47-Year-Old With Diplopia From a Rare Malignancy

No abstract available

http://bit.ly/2HaFN9u

Peripapillary Vessel Density Measured by Optical Coherence Tomography Angiography in Idiopathic Intracranial Hypertension

Background: Although alterations in the peripapillary retinal nerve fiber layer (RNFL) in patients with idiopathic intracranial hypertension (IIH) have been characterized using optical coherence tomography (OCT), there are little data regarding the peripapillary vasculature in this patient population. Our aim was to evaluate findings of OCT angiography (OCT-A) in the peripapillary region in addition to the RNFL measurements on OCT in patients with IIH. Methods: Thirty-eight eyes of 19 patients with IIH and 42 eyes of 21 healthy controls were enrolled in our study. Papilledema was graded according to the Frisen scale. Peripapillary RNFL and vessel density were evaluated with OCT and OCT-A, respectively. Results: RNFL thickness was found to be increased with OCT, but this was statistically significant only in the inferior location in IIH patients when compared with the control group. There was a significant decrease in mean peripapillary vessel density measured with OCT-A in IIH patients with papilledema when compared with the control group (P

http://bit.ly/2CLmHmp

Minocycline-Induced Vasculitis Presenting as a Third Nerve Palsy

No abstract available

http://bit.ly/2GBt8wb

Monocular Single Saccadic Pulses

No abstract available

http://bit.ly/2RlOAcR

Do Most Patients With a Spontaneous Cerebrospinal Fluid Leak Have Idiopathic Intracranial Hypertension?

Background: The association between cerebrospinal fluid (CSF) leaks at the skull base and raised intracranial pressure (ICP) has been reported since the 1960s. It has been suggested that spontaneous CSF leaks might represent a variant of idiopathic intracranial hypertension (IIH). We review the evidence regarding the association between spontaneous CSF leaks and IIH, and the role of ICP in the pathophysiology of nontraumatic skull base defects. We also discuss the management of ICP in the setting of CSF leaks and IIH. Evidence Acquisition: References were identified by searches of PubMed from 1955 to September 2018 with the terms "idiopathic intracranial hypertension" and "cerebrospinal fluid leak." Additional references were identified using the terms "pseudotumor cerebri," "intracranial hypertension," "benign intracranial hypertension," and by hand search of relevant articles. Results: A CSF leak entails the egress of CSF from the subarachnoid spaces of the skull base into the surrounding cavitary structures. Striking overlaps exist regarding demographic, clinical, and radiological characteristics between IIH patients and those with spontaneous CSF leaks, suggesting that some (if not most) of these patients have IIH. However, determining whether a patient with spontaneous CSF leak may have IIH may be difficult, as signs and symptoms of raised ICP may be obviated by the leak. The pathophysiology is unknown but might stem from progressive erosion of the thin bone of the skull base by persistent pulsatile high CSF pressure. Currently, there is no consensus regarding the management of ICP after spontaneous CSF leak repair when IIH is suspected. Conclusions: IIH is becoming more widely recognized as a cause of spontaneous CSF leaks, but the causal relationship remains poorly characterized. Systematic evaluation and follow-up of patients with spontaneous CSF leaks by neuro-ophthalmologists will help clarify the relation between IIH and spontaneous CSF leaks. Address correspondence to Valérie Biousse, MD, Neuro-Ophthalmology Unit, Emory Eye Center, The Emory Clinic, 1365-B Clifton Road NE, Atlanta, GA 30322; E-mail: vbiouss@emory.edu Supported in part by an unrestricted departmental grant (Department of Ophthalmology) from Research to Prevent Blindness, Inc., New York, and by NIH/NEI core grant P30-EY06360 (Department of Ophthalmology). N. J. Newman received the Research to Prevent Blindness Lew R. Wasserman Merit Award. J. M. Levy is supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Numbers UL1TR002378 and KL2TR002381. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors report no conflicts of interest. © 2019 by North American Neuro-Ophthalmology Society

http://bit.ly/2tfQaiK

Black and Brown Oro-facial Mucocutaneous Neoplasms

Abstract

Black and brown-colored mucocutaneous lesions present a differential diagnostic challenge, with malignant melanoma being the primary clinical concern. The vast majority of pigmented lesions in the head and neck region are the result of benign, reactive factors such as post-inflammatory melanosis. However, it is not uncommon to discover a range of muco-cutaneous black and brown neoplasms in the oro-facial area. The majority of black/brown pigmented neoplasms are melanocytic in origin; these are neoplasms of neural crest derivation. Melanocytic nevi are a diverse group of benign neoplasms that are the result of specific oncogenic mutations. They are common on cutaneous surfaces but can manifest in mucosal sites. Currently, nevi are classified based on clinical and histological criteria. The most common cutaneous and oral mucosal nevus is the acquired melanocytic nevus; nevi do not pose an increased risk for the development of malignant melanoma. Emerging information on specific genetic differences supports the notion of biologically distinct nevi. This article will review the classic clinical and microscopic features of nevi commonly found in the head and neck region, and discuss emerging concepts in nevus pathogenesis and taxonomy. Melanoma is a malignant melanocytic neoplasm and is a result of cumulative genetic deregulation. The etiology of malignant melanoma (MM) is multifactorial and includes underlying genetic susceptibility, UV radiation, skin-type, and race. The majority of MM occurs on cutaneous surfaces and less commonly on mucosal and extra-cutaneous visceral organs. Regardless of location, MM exhibits clinical-pathological features that relate to horizontal or vertical tumor spread. Cutaneous and mucosal MM typically present as asymmetrical, irregularly bordered, large (> 0.5 cm), heterogeneous brown-black lesions with foci of erythema, atrophy or ulceration. As with melanocytic nevi, advances in melanomagenesis research have revealed primary oncogenic BRAF and NRAS mutations associated with cutaneous MM. Unlike their cutaneous counterparts, mucosal melanomas exhibit primary oncogenic alterations in c-KIT and other genes. This article will discuss the role of specific primary oncogenic and secondary/tertiary genetic defects in differential clinical presentation, anatomic distribution, future classification changes, and targeted therapy of melanoma. The clinical and microscopic features of mucosal melanomas and a summary of management guidelines will be discussed. Additionally, this article will cover the salient features of melanocytic neuroectodermal tumor of infancy, a neoplastic entity that can involve the oro-facial region, and the clinical-pathological features of selected, commonly occurring pigmented ectodermally-derived neoplasms that are often part of the clinical differential diagnosis of black–brown pigmented lesions.

http://bit.ly/2G6YR6q

Adamantinoma-Like Ewing Sarcoma of the Thyroid: A Case Report and Review of the Literature

Abstract

Currently considered a variant of Ewing sarcoma, adamantinoma-like Ewing sarcoma is a rare malignancy that shows classic Ewing sarcoma-associated gene fusions but also epithelial differentiation. Here we present the 6th reported case of adamantinoma-like Ewing sarcoma involving the thyroid gland. Sections of the thyroid tumor from a 20-year old woman showed sheets, lobules and trabeculae of primitive, uniform, small round blue cells that diffusely expressed pankeratin, p40 and CD99. Fluorescent in situ hybridization revealed an EWSR1 gene rearrangement and an EWSR1-FLI1 fusion was detected by RT-PCR. Neck lymph nodes were not involved, and the patient was treated with a Ewing sarcoma chemotherapy protocol and radiation and is disease free 7 months after surgery. The unusual histology and immunohistochemical profile of adamantinoma-like Ewing sarcoma makes diagnosis and classification very challenging. We also present a literature review of adamantinoma-like Ewing sarcoma involving the thyroid.

http://bit.ly/2E0qHzS

A Guide to Yellow Oral Mucosal Entities: Etiology and Pathology

Abstract

When faced with an uncertain clinical pathosis in the oral cavity, identifying the color of the mucosal lesion helps to narrow down a differential diagnosis. Although less common than red and white lesions, yellow lesions encompass a small group of distinct mucosal pathologic entities. Adipose tissue, lymphoid tissue, and sebaceous glands are naturally occurring yellow constituents of the oral cavity and become apparent with associated developmental or neoplastic lesions. Reactive and inflammatory lesions can create a yellow hue due to purulence, necrosis, and calcification. Some systemic diseases are known to deposit yellow bi-products such as amyloid or bilirubin into the oral mucosa of an affected person, and while not always yellow, unusual entities like verruciform xanthoma and granular cell tumor fall under the umbrella of yellow lesions given their occasional propensity to demonstration the color. This chapter aims to explore the unique group that is yellow lesions presenting in the oral mucosa.

http://bit.ly/2TfsKp2

Ulcerated Lesions of the Oral Mucosa: Clinical and Histologic Review

Abstract

Ulcerated lesions of the oral cavity have many underlying etiologic factors, most commonly infection, immune related, traumatic, or neoplastic. A detailed patient history is critical in assessing ulcerative oral lesions and should include a complete medical and medication history; whether an inciting or triggering trauma, condition, or medication can be identified; the length of time the lesion has been present; the frequency of episodes in recurrent cases; the presence or absence of pain; and the growth of the lesion over time. For multiple or recurrent lesions the presence or history of ulcers on the skin, genital areas, or eyes should be evaluated along with any accompanying systemic symptoms such as fever, arthritis, or other signs of underlying systemic disease. Biopsy may be indicated in many ulcerative lesions of the oral cavity although some are more suitable for clinical diagnosis. Neoplastic ulcerated lesions are notorious in the oral cavity for their ability to mimic benign ulcerative lesions, highlighting the essential nature of biopsy to establish a diagnosis in cases that are not clinically identifiable or do not respond as expected to treatment. Adjunctive tests may be required for final diagnosis of some ulcerated lesions especially autoimmune lesions. Laboratory tests or evaluation to rule out systemic disease may be also required for recurrent or severe ulcerations especially when accompanied by other symptoms. This discussion will describe the clinical and histopathologic characteristics of a variety of ulcerated lesions found in the oral cavity.

http://bit.ly/2FZue3A

Erythematous and Vascular Oral Mucosal Lesions: A Clinicopathologic Review of Red Entities

Abstract

Erythematous lesions of the oral mucosa are common and can reflect a variety of conditions, ranging from benign reactive or immunologically-mediated disorders to malignant disease. Together with vascular abnormalities, which can vary from reddish to bluish-purple in color, the differential diagnosis for erythematous oral mucosal change is quite diverse. This review focuses on salient clinical features and histopathologic findings of selected conditions which clinically present as red or vascular-like oral mucosal alterations, including oral vascular malformations and neoplasms, pyogenic granuloma, localized juvenile spongiotic gingival hyperplasia, denture stomatitis, benign migratory glossitis (geographic tongue), orofacial granulomatosis, granulomatosis with polyangiitis (Wegener granulomatosis), megaloblastic anemia, and erythroplakia. Recognition of the characteristic clinical features of these conditions, in conjunction with thorough patient history, will allow clinicians to narrow the differential diagnosis and guide appropriate clinical decision making, including the need for tissue biopsy, in order to complete the diagnostic process and initiate optimal patient care.

http://bit.ly/2G7qUmo

Non-HPV Papillary Lesions of the Oral Mucosa: Clinical and Histopathologic Features of Reactive and Neoplastic Conditions

Abstract

Excluding human papillomavirus (HPV)-driven conditions, oral papillary lesions consist of a variety of reactive and neoplastic conditions and, on occasion, can herald internal malignancy or be part of a syndrome. The objectives of this paper are to review the clinical and histopathological features of the most commonly encountered non-HPV papillary conditions of the oral mucosa. These include normal anatomic structures (retrocuspid papillae, lingual tonsils), reactive lesions (hairy tongue, inflammatory papillary hyperplasia), neoplastic lesions (giant cell fibroma), lesions of unknown pathogenesis (verruciform xanthoma, spongiotic gingival hyperplasia) and others associated with syndromes (for instance Cowden syndrome) or representing paraneoplastic conditions (malignant acanthosis nigricans). Common questions regarding differential diagnosis, management, and diagnostic pitfalls are addressed, stressing the importance of clinico-pathologic correlation and collaboration.

http://bit.ly/2FUqLDk

A Rainbow of Colors and Spectrum of Textures: An Approach to Oral Mucosal Entities

http://bit.ly/2FZ9zNl

Candidiasis: Red and White Manifestations in the Oral Cavity

Abstract

Candidiasis is a very common malady in the head neck region. This review will concentrate on intraoral, pharyngeal and perioral manifestations and treatment. A history of the origins associated with candidiasis will be introduced. In addition, oral conditions associated with candidiasis will be mentioned and considered. The various forms of oral and maxillofacial candidiasis will be reviewed to include pseudomembranous, acute, chronic, median rhomboid glossitis, perioral dermatitis, and angular cheilitis. At the end of this review the clinician will be better able to diagnose and especially treat candidal overgrowth of the oral facial region. Of particular interest to the clinician are the various treatment modalities with appropriate considerations for side effects.

http://bit.ly/2G7qMmO

Lumps and Bumps of the Gingiva: A Pathological Miscellany

Abstract

Lesions of the gingivae are amongst the commonest lesions seen in patients and the vast majority are reactive hyperplasias, related to a number of chronic irritant stimuli. However, there are a number of entities that have a predilection for the gingivae, which are much less common in other parts of the oral cavity. The purpose of this paper is to discuss the clinical and histological differential diagnoses when presented with a lump on the gingivae, including the approach to diagnosis and diagnostic pitfalls.

http://bit.ly/2FWagql

HPV-Related Papillary Lesions of the Oral Mucosa: A Review

Abstract

Human papillomaviruses (HPVs) are causative of a group of clinically papillary lesions. The HPV-related lesions of the oral cavity include squamous papilloma, condyloma acuminatum, verruca vulgaris, and multifocal epithelial hyperplasia. Benign entities, such as verruciform xanthoma or giant cell fibroma, as well as malignancies, such as papillary squamous cell carcinoma and verrucous carcinoma, may be considered in the clinical and/or histologic differential diagnoses of these lesions. Mechanisms of infection, epidemiology, clinical presentations, histologic features, and differential diagnoses of the HPV-related oral pathologies are discussed. Current concepts of viral transmission, especially as pertaining to lesions in pediatric patients, and the impacts of HPV vaccination are reviewed.

http://bit.ly/2FYoPtE

Tongue Lumps and Bumps: Histopathological Dilemmas and Clues for Diagnosis

Abstract

Exophytic lesions of the tongue encompass a diverse spectrum of entities. These are most commonly reactive, arising in response to local trauma but can also be neoplastic of epithelial, mesenchymal or miscellaneous origin. In most cases, the microscopic examination is likely to provide a straightforward diagnosis. However, some cases can still raise microscopic diagnostic dilemmas, such as conditions that mimic malignancies, benign tumors with overlapping features and anecdotal lesions. A series of "lumps and bumps" of the tongue are presented together with suggested clues that can assist in reaching a correct diagnosis, emphasizing the importance of the clinico-pathological correlations.

http://bit.ly/2G7qH2u

Frictional Keratosis, Contact Keratosis and Smokeless Tobacco Keratosis: Features of Reactive White Lesions of the Oral Mucosa

Abstract

White lesions of the oral cavity are quite common and can have a variety of etiologies, both benign and malignant. Although the vast majority of publications focus on leukoplakia and other potentially malignant lesions, most oral lesions that appear white are benign. This review will focus exclusively on reactive white oral lesions. Included in the discussion are frictional keratoses, irritant contact stomatitis, and smokeless tobacco keratoses. Leukoedema and hereditary genodermatoses that may enter in the clinical differential diagnoses of frictional keratoses including white sponge nevus and hereditary benign intraepithelial dyskeratosis will be reviewed. Many products can result in contact stomatitis. Dentrifice-related stomatitis, contact reactions to amalgam and cinnamon can cause keratotic lesions. Each of these lesions have microscopic findings that can assist in patient management.

http://bit.ly/2U9yVL4

Lichenoid Characteristics in Premalignant Verrucous Lesions and Verrucous Carcinoma of the Oral Cavity

Abstract

Verrucous hyperkeratosis (VH), verrucous carcinoma (VC) and the relentless, truly pre-malignant variant proliferative verrucous leukoplakia often exhibit lichenoid histologic features that may create a diagnostic dilemma for pathologists. This study aims to evaluate and categorize the frequency and the histopathologic patterns of lichenoid features seen in these lesions. Following IRB approval, cases of VH and VC from 1994 to 2014 were retrieved from the archives of UF Oral Pathology Biopsy Service. A panel of 4 board-certified oral and maxillofacial pathologists reviewed and scored the presence or absence of 5 lichenoid features: band-like infiltrate (BLI), saw tooth rete ridges (STRR), interface stomatitis (IS), civatte bodies (CB), and basement membrane degeneration (BMD). Cases not fulfilling the stringent selection criteria were excluded. A total of 70 cases of VH and 56 cases of VC were included. Approximately 25% of both VH and VC cases exhibited 3 or more lichenoid features. By Chi square testing, BLI (p = 0.000), IS (p = 0.005), and CB (p = 0.026) were significantly more common in VC than VH. Gingival lesions had significantly less frequent BLI (p = 0.004) and IS (p = 0.024) versus other sites. However, STRR was significantly more common in VH than VC (p = 0.000) in the gingiva. (p = 0.002). Statistical analysis revealed that the only significant valid association was the increased presence of band-like infiltrate in VC over VH (p = 0.001). Lichenoid features are common in both VH and VC and may represent a nonspecific inflammatory response to the dysplasia or malignancy rather than concomitant lichenoid disease. This could lead to significant under diagnoses of these premalignant or potentially malignant lesions by pathologists.

http://bit.ly/2U87q4B

Black and Brown: Non-neoplastic Pigmentation of the Oral Mucosa

Abstract

Black and brown pigmentation of the oral mucosa can occur due to a multitude of non-neoplastic causes. Endogenous or exogenous pigments may be responsible for oral discoloration which can range from innocuous to life-threatening in nature. Physiologic, reactive, and idiopathic melanin production seen in smoker's melanosis, drug-related discolorations, melanotic macule, melanoacanthoma and systemic diseases are presented. Exogenous sources of pigmentation such as amalgam tattoo and black hairy tongue are also discussed. Determining the significance of mucosal pigmented lesions may represent a diagnostic challenge for clinicians. Biopsy is indicated whenever the source of pigmentation cannot be definitively identified based on the clinical presentation.

http://bit.ly/2DsEw9V

Development and Characterization of a Novel Monoclonal Antibody Against Chitinase-like Protein CHID1 Applicable for Immunohistochemistry on Formalin Fixed Paraffin-Embedded Sections

Monoclonal Antibodies in Immunodiagnosis and Immunotherapy, Ahead of Print.


http://bit.ly/2tfTF8Q

Epitope Mapping of Antidiacylglycerol Kinase α Monoclonal Antibody DaMab-2

Monoclonal Antibodies in Immunodiagnosis and Immunotherapy, Ahead of Print.


http://bit.ly/2UQJ7sq

The Diagnostic Tests for Detection of Helicobacter pylori Infection

Monoclonal Antibodies in Immunodiagnosis and Immunotherapy, Ahead of Print.


http://bit.ly/2teYmzN

Respiratory Syncytial Virus

Viral Immunology, Ahead of Print.


http://bit.ly/2UNxUJ3

Penalized Supervised Star Plots: Example Application in Influenza-Specific CD4+ T Cells

Viral Immunology, Ahead of Print.


http://bit.ly/2tewdIU

Serological and T Cell Responses After Varicella Zoster Virus Vaccination in HIV-Positive Patients Undergoing Renal Dialysis

Viral Immunology, Ahead of Print.


http://bit.ly/2US6VMn

Unrecognized Pseudohypoparathyroidism Type 1A as a Cause of Hypocalcemia and Seizures in a 64-Year-Old Woman.

Related Articles

Unrecognized Pseudohypoparathyroidism Type 1A as a Cause of Hypocalcemia and Seizures in a 64-Year-Old Woman.

Case Rep Endocrinol. 2019;2019:8456239

Authors: Del Monte P, Cuttica CM, Marugo A, Foppiani L, Audenino D, Godowicz TT, Elli FM, Mantovani G, Di Maria E

Abstract
Pseudohypoparathyroidism type 1A (PHP1A) is usually diagnosed in childhood or early adulthood. We describe the case of a 64-year-old woman admitted to the Neurological Unit for recurrent episodes of loss of consciousness and seizures. Glycemia and ECG were normal, while hypocalcemia was noted. Clinical history revealed carpo-pedal spasm since the age of 30 years, cognitive impairment, hypothyroidism since early adulthood, and menopause at 30 years. She was taking oral calcium and cholecalciferol for chronic hypocalcemia. Physical features suggested Albright's osteodystrophy. Blood calcium was confirmed low, with increased parathyroid hormone, moderate 25OH-vitamin D deficiency, and normal creatinine. Brain CT scan revealed calcifications of the basal ganglia, cortical and subcortical white matter, and cerebellum. Therapy was switched to oral calcitriol, with normalization of calcium levels; levetiracetam was started and no further seizures occurred. The clinical diagnosis of PHP1A was confirmed by molecular analysis, which demonstrated the heterozygous c.568_571del mutation of the GNAS gene. Our report illustrates the natural history of a patient with PHP1A, which went undiagnosed until the age of 64 years, with multi-hormonal resistance and clinical sequelae evolving throughout life, and underlines the importance of diagnosing this rare disease, which has a great impact on patients and their family life.

PMID: 30729047 [PubMed]

http://bit.ly/2SmrDYi

Diabetic Ketoacidosis Revealing a Severe Hypertriglyceridemia and Acute Pancreatitis in Type 1 Diabetes Mellitus.

Related Articles

Diabetic Ketoacidosis Revealing a Severe Hypertriglyceridemia and Acute Pancreatitis in Type 1 Diabetes Mellitus.

Case Rep Endocrinol. 2019;2019:8974619

Authors: Zaher FZ, Boubagura I, Rafi S, Elmghari G, Elansari N

Abstract
Diabetic ketoacidosis (DKA) is a life-threatening acute metabolic complication occurring in patients with diabetes, especially in patients with type 1 diabetes (T1D), due to an insulin deficiency. Moderate hypertriglyceridemia is commonly observed in DKA but severe hypertriglyceridemia with a triglyceride level exceeding 10g/L is very rarely reported. We report a case of a 14-year-old boy who had type 1 diabetes for 4 years treated with insulin therapy, also having adrenal insufficiency treated with hydrocortisone who presented with ketoacidosis and excruciating abdominal pain. Investigations revealed hypertriglyceridemia at 64g/L, lipasemia at 1000 U/L, and stage E pancreatitis on abdominal CT. The patient was treated with intravenous insulin, rehydration, and fenofibrate with good clinical and biological evolution. Severe hypertriglyceridemia causing pancreatitis in type 1 diabetes mellitus is a rare but very serious complication of DKA in children.

PMID: 30723557 [PubMed]

http://bit.ly/2GegRge

Randomized, Controlled, Multicentered, Double-Blind Investigation of Injectable Poly-L-Lactic Acid for Improving Skin Quality

BACKGROUND Poly-L-lactic acid (PLLA) is an injectable filler used for restoring facial fat volume loss. OBJECTIVE To evaluate the effect of repeated PLLA injections on skin quality. METHODS Forty healthy women were enrolled in this randomized, controlled, double-blind, multicenter study. Eligible subjects received 3 treatments every 4 weeks with either PLLA (treatment group) or saline (control group) injections, into both sides of the face. Follow-up visits were at 6, 9, and 12 after the last treatment. Assessments included biophysical measuring instruments, live ratings, patient questionnaires, and rating of standardized pictures by a blinded evaluator. RESULTS At the 12-month follow-up, there was a statistically significant increase of skin elasticity and hydration in PLLA-treated subjects and a decrease in transepidermal water loss in both groups. Pigmentation, erythema, and pore size were significantly decreased, whereas radiance and smoothness were significantly increased at 12 months per blinded investigator rating in this group. No treatment-related adverse events occurred. CONCLUSION Repeated PLLA treatments may improve skin quality in a time-dependent manner. Address correspondence and reprint requests to: Neil S. Sadick, MD, Sadick Dermatology, 911 Park Avenue, New York, NY 10075, or e-mail: nssderm@sadickdermatology.com Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (http://bit.ly/2bw6lgr). The authors received funding for this research from Galderma who also provided the PLL. The authors have indicated no significant interest with commercial supporters. © 2019 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.

http://bit.ly/2ULn3PK

Treatment of Facial Telangiectases With Glycerin Sclerotherapy

BACKGROUND Sclerotherapy is used to treat varicosities and telangiectases. Glycerin is a sclerosing agent that has been used off-label for years with a favorable adverse effect profile. However, the treatment of facial telangiectases with sclerotherapy is controversial given the potential for necrosis and embolization in relation to the complex vascular anatomy of the face. OBJECTIVE To determine the safety and efficacy of glycerin sclerotherapy for the treatment of facial telangiectases. MATERIALS AND METHODS The authors report a series of 8 patients with facial telangiectases treated with glycerin sclerotherapy. Glycerin mixed with lidocaine and epinephrine was used. The telangiectases were measured and identified as targets for treatment. RESULTS The patients ranged in age from 45 to 88 years. Between 0.5 and 1 mL was used to treat telangiectases of the nose and malar cheek area per session. Five of the patients achieved satisfactory results after 1 treatment, whereas patients with more extensive telangiectases required up to 3 sessions with 4-week intervals between each session. Injection site pain was the only reported adverse effect, and no evidence of necrosis or blindness was observed. CONCLUSION Glycerin sclerotherapy seems to be a safe and effective modality for the treatment of facial telangiectases. Address correspondence and reprint requests to: Sean McGregor, DO, PharmD, Department of Dermatology, Wake Forest Baptist Health, 4618 Country Club Road, Winston-Salem, NC 27104, or e-mail: smcgrego@wakehealth.edu The authors have indicated no significant interest with commercial supporters. Use of this product as discussed has not been approved by the Food and Drug Administration. © 2019 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.

http://bit.ly/2UNxdPX

Efficacy of Microneedling and Photodynamic Therapy in Vitiligo

No abstract available

http://bit.ly/2te88C1

The Frequency of Auricular Cartilage Invasion by Nonmelanoma Skin Cancer

No abstract available

http://bit.ly/2UOM7Wb

How We Do It: Use of Reinforced Adhesive Skin Closures as a “Ripstop” Medium for Suturing Fragile Skin: A Video Demonstration of Technique

No abstract available

http://bit.ly/2te884Z

Cellular Dermatofibroma: Clinicopathologic Review of 218 Cases of Cellular Dermatofibroma to Determine Clinical Recurrence Rate

BACKGROUND Cellular dermatofibromas, a variant of dermatofibroma, are reported to recur at rates of 26% to 50%. OBJECTIVE To determine whether there are distinct clinical or histological differences between cellular dermatofibromas that recur versus those that do not. To determine recurrence rates in a real-world clinical setting. MATERIALS AND METHODS A retrospective analysis of the medical records and skin biopsies of cellular dermatofibroma in the University of Utah Health system between December 2011 and 2016. Clinical and dermatopathological features were evaluated to find distinct differences between the cellular dermatofibromas that recurred compared with those that did not. RESULTS There were no significant differences in histology between the primary lesions in recurrent and nonrecurrent cases. One factor that seemed to be associated with a greater likelihood of recurrence was an initial lesion size greater than 1 cm. The authors' data suggest that if the margins are involved on initial biopsy, there is a 10% chance of recurrence. This percentage is far less than the 26% to 50% reported in the past literature. CONCLUSION If a patient presents with a cellular dermatofibroma larger than 1 cm and positive margins at initial biopsy, a careful discussion should be had between the provider and patient about the low risk of local recurrence. Address correspondence and reprint requests to: Keith Duffy, MD, Department of Dermatology, 30 N 1900 East, 4A330, Salt Lake City, UT 84132, or e-mail: keith.duffy@hsc.utah.edu The authors have indicated no significant interest with commercial supporters. © 2019 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.

http://bit.ly/2UOMMa7

Suture Treatment for Pincer Nail Deformity: An Inexpensive and Simple Technique

No abstract available

http://bit.ly/2tdptLp

Use of Insulin Syringes for Precision Filler in Periocular and Rhinoplasty Procedures

No abstract available

http://bit.ly/2USH4US

A Diagnostic Challenge: Changes in Histopathologic Tumor Diagnosis of Atypical Squamous Proliferations After Surgical Removal

BACKGROUND Biopsy-proven "atypical squamous proliferations" (ASPs) may prove difficult to diagnose histologically because of partial sampling, lack of complete criteria for definitive diagnosis, or overlap of histopathological features with other neoplasms. There are no guidelines concerning the management of ASPs. OBJECTIVE To retrospectively clarify the diagnosis of biopsy-proven ASPs after surgical removal, specifically, to ascertain what fraction represent malignant tumors. METHODS Medical records of patients who underwent surgical removal of biopsy-proven ASPs in an academic dermatologic surgical unit from June 2008 to July 2013 were examined. The resultant histopathologic diagnosis of these lesions after surgical removal, along with other demographic data, was obtained. RESULTS Of the 71 biopsy-proven ASPs that were treated by surgical removal in the study period, 54.9% exhibited resultant pathologic diagnosis of nonmelanoma skin cancer (NMSC). CONCLUSION Biopsy-proven ASPs present a therapeutic challenge. The authors' data illustrate the importance of subsequent tissue sampling, as these lesions often represent NMSCs. Address correspondence and reprint requests to: Ashley G. Rubin, MD, 2683 Via De La Valle STE G-710, Del Mar, CA 92014, or e-mail: Rubindermatology@gmail.com The authors have indicated no significant interest with commercial supporters. © 2019 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.

http://bit.ly/2tcJKRr

Assessment of Skin Physiology Change and Safety After Intradermal Injections With Botulinum Toxin: A Randomized, Double-Blind, Placebo-Controlled, Split-Face Pilot Study in Rosacea Patients With Facial Erythema

BACKGROUND Botulinum toxin (BTX) has been used cosmetically with good clinical efficacy and tolerable safety. OBJECTIVE This randomized, double-blind, split-face clinical study aimed to investigate the efficacy and safety of intradermal BTX in patients with rosacea. MATERIALS AND METHODS Twenty-four participants were enrolled and randomly given intradermal injections of BTX and normal saline in both cheeks. Clinician Erythema Assessment (CEA) score, Global Aesthetic Improvement Scale (GAIS) score, skin hydration, transepidermal water loss (TEWL), melanin content, erythema index, elasticity, and sebum secretions were evaluated at baseline and 2, 4, 8, and 12 weeks. RESULTS On the BTX-treated side, the CEA score significantly decreased and the GAIS score significantly increased. The erythema index decreased at Weeks 4 and 8. Skin elasticity was improved at Weeks 2 and 4 and skin hydration, at Weeks 2, 4, and 8. However, TEWL and sebum secretion did not show significant differences. CONCLUSION Intradermal BTX injections significantly reduced the erythema on both cheeks and improved skin elasticity and hydration, but not TEWL and sebum secretion. Intradermal BTX injections reduced erythema and rejuvenated the skin effectively and safely in patients with rosacea. Address correspondence and reprint requests to: Yang W. Lee, MD, PhD, Department of Dermatology, Konkuk University School of Medicine, 120-1 Neungdong-ro, Gwangjin-gu, Seoul 05030, Korea, or e-mail: 20050078@kuh.ac.kr Supported by the Basic Science Research Program of the National Research Foundation of Korea (NRF) and funded by the Ministry of Science, ICT, and Future Planning (NRF-2016R1D1A1A09918488). Daewoong Pharmaceutical provided the research funds and drugs used in this clinical trial (prabotulinumtoxinA; NABOTA, Daewoong Pharmaceutical, Seoul, Korea). This study protocol was approved by the International Review Board of Konkuk University Hospital, Seoul, South Korea (KUH 1120075), and informed consent was obtained from all subjects before study enrollment. Assessment of Skin Physiology Change and Safety After Intradermal Injections With Botulinum Toxin: A Single-Center, Randomized, Double-Blind, Placebo-Controlled, Split-Face Pilot Study in Rosacea Patients With Facial Erythema. The authors have indicated no significant interest with commercial supporters. © 2019 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.

http://bit.ly/2UQIi2O

Objective and Subjective Evaluation of Lipoinjection for Correction of Temporal Depression

BACKGROUND Temporal depression is commonly found among people. OBJECTIVE Objective and subjective evaluation of lipoinjection for correction of temporal depression. METHODS From November 2012 to January 2018, 34 healthy female subjects underwent temporal augmentation by lipoinjection on both sides. Efficacy was assessed by objective and subjective parameters. The quantitative measurement of the temporal defect was obtained using molded plasticine preoperatively and 12 months after treatment. The subjective assessment consisted of excellent, good, fair, and poor results based on the patients' self-evaluations. The adverse events were recorded. RESULTS The follow-up period ranged from 12 to 36 months. It was found that a statistically significant difference existed between the preoperative and postoperative defect on both temples. Regarding the patients' self-evaluations, 17 patients (50.0%) reported feeling excellent, 15 patients (44.1%) as good, and 2 patients (5.9%) as fair, and no patient as poor. After the statistical analysis, it was found that the volumetric restoration rate of the grafted fat decreased as the temporal defect generally increased during the aging process. Injection-site swelling and bruising were commonly found complications; other complications were not found. CONCLUSION Autologous fat is inexpensive and readily available. Fat grafting is an alternative for correction of temporal depression. Address correspondence and reprint requests to: Xiaogen Hu, MD, Plastic Surgery Department, China Japan Friendship Hospital, Beijing 100029, China, or e-mail: huxiaogeng78@qq.com The authors have indicated no significant interest with commercial supporters. © 2019 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.

http://bit.ly/2tniKih

Cutaneous Metastasis of Malignant Peripheral Nerve Sheath Tumor Arising From the Pancreas: A Rarity

No abstract available

http://bit.ly/2UQIhvM

Novel Classifications for Muscular Contraction of the Lower Face and Neck

BACKGROUND Currently, there are no scales that address lower-face muscular contraction patterns, and there is only one that addresses platysmal bands. OBJECTIVE The goal of this article is to create scales to classify the strength and contraction patterns of the lower face and neck based on (1) the muscular anatomy and contraction patterns of the platysma and (2) the strength of the depressor anguli oris (DAO). METHODS Three hundred sixty patients participated in the study. Standardized photogarphs were taken in an effort to characterize muscle contraction patterns. RESULTS A novel classification measuring the strength of the DAO is presented. For the DAO, 4 different contraction patterns were observed: Type 1 (38%), Type 0 (26.3%), Type 2 (25.2%), and Type 3 (8.6%). The remainder (1.9%) used asymmetric contraction. For platysmal bands, 3 different contraction patterns were observed: complete contraction (64.53%), lateral contraction (19.83%), and central contraction pattern (11.73%). A small percentage of patients (3.91%) had an asymmetric contraction pattern. CONCLUSION Categorization of contraction of the DAO and platysmal bands into these proposed classifications provides objective measurements that can be helpful for designing treatment protocols and assessing response to treatment. Address correspondence and reprint requests to: Berta E. Alcalá, MD, Roger de flor 2907, 512 Las Condes, Santiago, Chile 7550201, or e-mail: berta.alcala@gmail.com The authors have indicated no significant interest with commercial supporters. B.S.F. Bravo is a speaker for Allergan. © 2019 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.

http://bit.ly/2tbRfrG

Repair of a Large Dorsal Hand Defect After Mohs Micrographic Surgery

No abstract available

http://bit.ly/2UOMeB5

Institution of a Double-Dosing Protocol Using Cyanoacrylate Glue for the Larger Diameter Refluxing Superficial Truncal Vein

No abstract available

http://bit.ly/2tfSRRm

Satellite and In-Transit Metastatic Disease in Melanoma Skin Cancer: A Retrospective Review of Disease Presentation, Treatment, and Outcomes

BACKGROUND Satellitosis and in-transit metastases (SITM) are uncommon in cutaneous melanoma and are associated with poor prognosis. However, the disease- and treatment-specific variables that predict outcomes among patients with SITM are poorly defined. OBJECTIVE To identify factors that predict prognosis among patients with SITM. MATERIALS AND METHODS Retrospective chart review of patients treated for melanoma at a large academic medical center in central Pennsylvania between 2000 and 2012. Patients with pathology reports containing "satellite lesions" or "in-transit metastases" were selected for analysis. Data were collected regarding tumor stage, the timing of SITM discovery, treatment, recurrence-free survival after SITM discovery, and overall survival (OS). RESULTS We identified SITM in 32 (1.9%) of 1,650 patients with pathology-diagnosed melanoma over the study period. Reduced recurrence-free survival after SITM discovery was associated with higher pathologic stage, metastatic disease, lymph node dissection, and use of adjuvant chemotherapy. Reduced OS was associated with higher T, N, M, and overall prognostic stage; positive surgical margins; disease recurrence; and SITM on initial presentation. CONCLUSION Our data support previous findings that higher stage disease confers a worse prognosis among patients with SITM. Patients with SITM on initial presentation had worse outcomes, suggesting SITM is indicative of more aggressive disease. Address correspondence and reprint requests to: Genevieve Andrews, MD, Department of Surgery, Division of Otolaryngology—Head and Neck Surgery, Milton S. Hershey Medical Center, The Pennsylvania State University, 500 University Drive, Mail Code H091, Hershey, PA 17033-0850, or e-mail: gigi.andrews76@gmail.com The authors have indicated no significant interest with commercial supporters. © 2019 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.

http://bit.ly/2UKb598

Squamous Cell Carcinoma of the Nail Unit: A Clinical Histopathologic Study and a Proposal for Classification

BACKGROUND There is no consensus on the classification, grading, and the treatment of nail squamous cell carcinoma (NSCC). OBJECTIVE The aim of the study was to propose a possible classification of NSCC. MATERIALS AND METHODS Nail squamous cell carcinoma referred from January 2006 till December 2014 was included. On the basis of the clinical presentation, patients with NSCC were divided in 2 groups. Group A tumors presented as nodular or ulcerated masses of the nail bed, whereas Group B tumors presented as hyperkeratotic bands. In these 2 groups, differences in proportions (sex, histopathologic grading, and treatment performed) were evaluated with the chi-square test. RESULTS Forty-one NSCCs were included. The groups of NSCC differed regarding: (1) the age of the patients, (2) histopathology, and (3) surgical approach. CONCLUSION Nail squamous cell carcinomas may originate from 2 different epithelia, presenting a diverse clinical behavior. The correct identification and diagnosis of each subgroup of NSCC could be helpful in standardizing management of this tumor. Future studies considering human papillomavirus subtyping and including a major number of tumors should be performed to confirm or reject the authors' hypothesis. Limitations This is a retrospective study, presenting the data and the experience of a single institute. Address correspondence and reprint requests to: Emi Dika, MD, PhD, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, V. Massarenti 1, 40138 Bologna, Italy, or e-mail: emi.dika3@unibo.it The authors have indicated no significant interest with commercial supporters. © 2019 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.

http://bit.ly/2thYPAU

Permanent Cutaneous Adverse Events After Injection With Deoxycholic Acid

No abstract available

http://bit.ly/2UMMznS

Cryolipolysis for Noninvasive Contouring of the Periumbilical Abdomen With a Nonvacuum Conformable-Surface Applicator

BACKGROUND Although most cryolipolysis treatments are performed with vacuum applicators, some patients may have areas of fibrous, nonpinchable fat or find vacuum suction to be uncomfortable. OBJECTIVE This study evaluates a nonvacuum conformable-surface applicator for cryolipolysis of the periumbilical abdomen. METHODS/MATERIALS Twenty subjects with periumbilical subcutaneous fat were treated with a nonvacuum cryolipolysis applicator in this prospective, single-center, open-label clinical trial. Each subject underwent a single treatment cycle with an optional second treatment 10 weeks later. Efficacy was evaluated by blinded review of digital photographs. Subject satisfaction was assessed at 10-week follow-up. RESULTS Twenty subjects completed one treatment, of which 6 underwent the optional retreatment. Independent review demonstrated 77% correct identification of baseline photographs after one treatment, which improved to 100% after a second treatment. Patient questionnaires after one treatment revealed 50% satisfaction, with 60% willing to recommend the procedure and 60% reporting visible fat reduction. After second treatment, however, 100% were satisfied, 83% were willing to recommend, and 100% reported visible fat reduction. CONCLUSION Cryolipolysis with a nonvacuum conformable-surface applicator is safe, effective, and well tolerated for noninvasive reduction of fibrous periumbilical abdominal fat. Efficacy and subject satisfaction is significantly greater with 2 treatments than with a single session. Address correspondence and reprint requests to: Daniel P. Friedmann, MD, FAAD, Westlake Dermatology Clinical Research Center, Westlake Dermatology and Cosmetic Surgery, 8825 Bee Cave Road, Austin, TX 78746, or e-mail: daniel@westlakedermatology.com Supported in part by a research grant from ZELTIQ Aesthetics. The author is a consultant and investigator for Allergan North America, Inc. © 2019 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.

http://bit.ly/2tiGRhH

Cutaneous Sarcomatoid Squamous Cell Carcinoma of the Ear and the Use of Immunohistochemical Staining as a Diagnostic Aid

No abstract available

http://bit.ly/2UMMwbG

Cerebrovascular pathology in cerebral amyloid angiopathy presenting as intracerebral haemorrhage

Abstract

Cerebral amyloid angiopathy (CAA) is the second most common cause of non-traumatic intracerebral haemorrhage (ICH) accounting for 12–15% of lobar haemorrhages in the elderly. Definitive diagnosis of CAA requires histological evaluation. We aimed to evaluate the spectrum of cerebrovascular changes in CAA-related ICH. Between 2011 and 2015, biopsy-confirmed cases of CAA were retrieved and clinical, radiological and pathological features were reviewed. The spectrum of vascular alterations was evaluated and amyloid deposition was graded in accordance with the Greenberg and Vonsattel scale. Seven cases of sporadic CAA [5 males and 2 females] were diagnosed, none of whom were suspected to have CAA pre-operatively. Six presented with large intracerebral haematoma (ICH) requiring neurosurgical intervention (age range: 56–70 years) and one had episodic headache and multiple microhaemorrhages requiring a diagnostic brain biopsy (45 years). In the presence of large ICH, vascular amyloid deposits were of moderate to severe grade (grade 4 in 4, grades 2 and 3 in 1 case each) with predominant involvement of medium (200–500 μm) to large (> 500 μm) leptomeningeal vessels. Fibrinoid necrosis was noted in four. Two were hypertensive and on antiplatelet agents. β-Amyloid plaques were detected in two, one of whom had symptomatic dementia. MRI performed in 3 of 6 cases with ICH did not reveal any microhaemorrhages. Amyloid deposits in small (50–200 μm) to medium (200–500 μm) calibre intracortical vessels produced parenchymal microhemorrhages. Histopathological examination of ICH is essential for diagnosing CAA. The vascular calibre rather than grade of amyloid deposits dictates size of the bleed. Presence of co-morbidities such as antiplatelet agents may predispose to haemorrhage.

http://bit.ly/2BpeNxB

Role of epithelial–mesenchymal transition factors in the histogenesis of uterine carcinomas

Abstract

Several subtypes of high-grade endometrial carcinomas (ECs) contain an undifferentiated component of non-epithelial morphology, including undifferentiated and dedifferentiated carcinomas and carcinosarcomas (CSs). The mechanism by which an EC undergoes dedifferentiation has been the subject of much debate. The epithelial–mesenchymal transition (EMT) is one of the mechanisms implicated in the transdifferentiation of high-grade carcinomas. To improve our understanding of the role of EMT in these tumors, we studied a series of 89 carcinomas including 14 undifferentiated/dedifferentiated endometrial carcinomas (UECs/DECs), 49 CSs (21 endometrial, 29 tubo-ovarian and peritoneal), 17 endometrioid carcinomas (grade 1–3), and 9 high-grade serous carcinomas of the uterus, using a panel of antibodies targeting known epithelial markers (Pan-Keratin AE1/AE3 and E-cadherin), mesenchymal markers (N-cadherin), EMT transcription factors (TFs) (ZEB1, ZEB2, TWIST1), PAX8, estrogen receptors (ER), progesterone receptors (PR), and the p53 protein. At least one of the three EMT markers (more frequently ZEB1) was positive in the sarcomatous component of 98% (n = 48/49) of CSs and 98% (n = 13/14) of the undifferentiated component of UEC/DEC. In addition, 86% of sarcomatous areas of CSs and 79% of the undifferentiated component of UEC/DEC expressed all three EMT-TFs. The expression of these markers was associated with the loss of or reduction in epithelial markers (Pan-keratin, E-cadherin), PAX8, and hormone receptors. In contrast, none of the endometrioid and serous endometrial carcinomas expressed ZEB1, while 6% and 36% of endometrioid and 11% and 25% of serous carcinomas focally expressed ZEB2 and TWIST1, respectively. Although morphologically different, EMT appears to be implicated in the dedifferentiation in both CSs and UEC/DEC. Indeed, we speculate that the occurrence of EMT in a well differentiated endometrioid carcinoma may consecutively lead to a dedifferentiated and undifferentiated carcinoma, while in a type II carcinoma, it may result in a CS.

http://bit.ly/2TFboSv

Acknowledgement to reviewers 2018

http://bit.ly/2BwYA9P

Comprehensive analysis of PD-L1 expression, HER2 amplification, ALK/EML4 fusion, and mismatch repair deficiency as putative predictive and prognostic factors in ovarian carcinoma

Abstract

Most ovarian carcinomas (OC) are characterized by poor prognosis, particularly the most frequent type high-grade serous carcinoma. Besides PARP inhibitors, target-based therapeutic strategies are not well established. We asked the question which other therapeutic targets could be of potential value and, therefore, analyzed a large cohort of OC for several predictive factors. Two hundred eighty-eight (288) cases of OC including the major histological types were analyzed by immunohistochemistry for PD-L1HER2, ALK, and the mismatch repair (MMR) proteins MLH1, PMS2, MSH2, and MSH6. HER2 amplification and ALK/EML4 fusion were assessed by fluorescence in situ hybridization. The most frequent finding was PD-L1 expression ≥ 1% in 19.5% of the cases, which correlated with a significantly better overall survival in multivariate analysis (p < 0.001). HER2 amplification was detected in 11 cases (4%), all high-grade serous carcinomas. Amplification of HER2 did not correlate with patients' survival. ALK/EML4 fusion was found in two cases (0.74%): one high-grade serous and one endometrioid carcinoma. MMR deficiency was only present in one case of stage IV high-grade serous carcinoma. Subsets of high-grade serous carcinomas show PD-L1 expression and HER2 amplification, respectively, and, therefore, could qualify for immune checkpoint inhibitor therapy or anti HER2 therapy. PD-L1 is also of prognostic impact. ALK/EML4 fusion is very rare in OC and not a putative therapeutic target.

http://bit.ly/2TFbklJ

Compact buds with biphasic differentiation and calcitonin-expressing neuroendocrine cells—previously unrecognized structures of thyroglossal duct unveiled by immunohistochemistry

Abstract

Immunophenotype of thyroglossal duct (TGD) cysts, including lining epithelium and thyroid remnants, is scarcely addressed in the literature. There is indirect evidence that C cells may be derived from progenitor cells of the midline thyroid primordium. This is supported by the recent concept of the endodermal origin of lateral thyroid anlagen and several case reports. We aimed to search for neuroendocrine cells in TGD cysts and to characterize immunophenotype of the thyroid follicles and epithelial lining of TGD. Out of 98 TGD cysts, 70% contained both cyst-lining epithelium and thyroid follicles, whereas 30% possessed only cyst-lining epithelium. Specimens eligible for immunohistochemistry (n = 61) were stained for thyroid-specific and neuroendocrine markers. Thyroid remnants were positive for thyroid transcription factor 1 (TTF-1) and other thyroid tissue-specific markers and negative for calcitonin. TGD epithelium showed strong p63 positivity. We found that respiratory epithelium in 9.8% of TGDs contained neuroendocrine cells positive for calcitonin, chromogranin A, and synaptophysin but negative for carcinoembryonic antigen. In 44.2% of the cases, we detected compact buds, microscopic structures appearing as nests of epithelial cells with a biphasic population of basal (p63+) and central (TTF-1+) cells. Thyroid remnants in TGD expressed full spectrum of thyroid-specific markers and contained no C cells. Instead, calcitonin-expressing neuroendocrine cells were found among the respiratory epithelium of TGD. These cells can be a potential source of neuroendocrine tumors mimicking medullary carcinoma in median anlage derivatives. We also discovered precursor compact buds with dual immunophenotype and proposed a concept of their morphogenesis.

http://bit.ly/2BtAEnQ

A mismatch repair-deficient and HPV-negative anorectal squamous cell carcinoma

Abstract

Invasive primary squamous cell carcinomas involving the anorectal region are challenging to manage. Microsatellite instability has been shown to impact clinical courses and outcomes of patients affected by many types of carcinomas. To the best of our knowledge, there are no reports on microsatellite instability in anorectal squamous cell carcinomas. Here, we report a HPV-negative anorectal squamous cell carcinoma which, despite cisplatin-based chemoradiation therapy, showed progression. Interestingly, after identification of its mismatch repair-deficiency (MLH1/PMS2-absent, MSH2/MSH6-intact), pembrolizumab-based immunotherapy was initiated, leading to a marked clinical response. This unique case illustrates that microsatellite instability testing and immunotherapy targeting immune checkpoint blockade should be considered for managing anorectal squamous cell carcinomas that fail conventional chemoradiation therapies or when patients are non-surgical candidates. This report provides the first evidence of microsatellite instability in anorectal squamous cell carcinomas and supports the role for microsatellite instability testing in this cancer type to optimize patient management.

http://bit.ly/2TBF8zI

National multicentric evaluation of quality of pathology reports for rectal cancer in France in 2016

Abstract

The quality of pathologic assessment of rectal cancer specimens is crucial for treatment efficiency and survival. The Royal College of Pathologists (RCP) recommends evaluating the quality of the pathology report in routine practice using three quality indicators (QIs): the number of lymph nodes (LNs) analyzed (≥ 12), the rate of venous invasion (VI ≥ 30%), and peritoneal involvement (pT4a ≥ 10%). In this study, we evaluated the three QIs of the French national pathology reports and compared them with British guidelines and assessed the influence of neoadjuvant radiochemotherapy on QIs. From January 1 to December 31, 2016, all pathology reports for rectal adenocarcinoma were collected from French departments. Neoadjuvant radiochemotherapy included long-course radiotherapy with concomitant 5-FU-based chemotherapy. A total of 983 rectal cancer pathology reports were evaluated. A median of 15 LNs were analyzed and 81% of centers had ≥ 12 LNs. The rate of VI was 30% and 41% of centers had ≥ 30% VI. The rate of pT4a was 4% and 18% of centers reported ≥ 10% pT4a. None of the centers reached the threshold for the three QIs. All three QIs were lower after radiochemotherapy compared to surgery alone. In conclusion, in French routine practice, the values of two of the three QIs (LNs analyzed and VI) were globally in line with RCP guidelines. However, the rate of pT4a was very low, particularly after radiochemotherapy, suggesting its low value in rectal cancer.

http://bit.ly/2BvCsfU

European follow-up of incorrect biomarker results for colorectal cancer demonstrates the importance of quality improvement projects

Abstract

Biomarker analysis for colorectal cancer has been shown to be reliable in Europe with 97% of samples tested by EQA participants to be correctly classified. This study focuses on errors during the annual EQA assessment. The aim was to explore the causes and actions related to the observed errors and to provide feedback and assess any improvement between 2016 and 2017. An electronic survey was sent to all laboratories with minimum one genotyping error or technical failure on ten tumor samples. A workshop was organized based on 2016 survey responses. Improvement of performance in 2017 was assessed for returning participants (n = 76), survey respondents (n = 13) and workshop participants (n = 4). Survey respondents and workshop participants improved in terms of (maximum) analysis score, successful participation, and genotyping errors compared to all returning participants. In 2016, mostly pre- and post-analytical errors (both 25%) were observed caused by unsuitability of the tumor tissue for molecular analysis. In 2017, most errors were due to analytical problems (50.0%) caused by methodological problems. The most common actions taken (n = 58) were protocol revisions (34.5%) and staff training (15.5%). In 24.1% of issues identified no action was performed. Corrective actions were linked to an improved performance, especially if performed by the pathologist. Although biomarker testing has improved over time, error occurrence at different phases stresses the need for quality improvement throughout the test process. Participation to quality improvement projects and a close collaboration with the pathologist can have a positive influence on performance.

http://bit.ly/2THIUrd

Analysis of the prognostic relevance of sex-steroid hormonal receptor mRNA expression in muscle-invasive urothelial carcinoma of the urinary bladder

Abstract

Muscle-invasive urothelial carcinoma of the urinary bladder (UCB) often recurs following radical cystectomy (RC). An altered expression of sex-steroid hormone receptors has been associated with oncological outcomes of UCB and may represent therapeutic targets. Here the expression of different hormone receptors was measured on mRNA levels in patients treated by RC and associated with outcomes. Androgen receptor (AR), estrogen receptor 1 (ESR1), and progesterone receptor (PGR) mRNA expression was assessed by quantitative reverse transcription polymerase chain reaction (RT-qPCR) in RC samples of 87 patients with a median age of 66 (39–88) years. Univariate and multivariate analyses were performed to test associations with pathological and clinical characteristics as well as recurrence-free (RFS) and disease-specific survival (DSS). AR mRNA expression was lower in comparison with ESR1 and PGR expression (p < 0.0001). In univariate analysis, high expression levels of AR were associated with reduced RFS (HR 2.8, p = 0.015) and DSS (HR 2.8, p = 0.010). High AR mRNA expression and a positive lymph node status were independent predictors for reduced RFS (HR 2.5, p = 0.0049) and DSS (HR 3.4, p = 0.009). In patients with low AR mRNA expression, an increased ESR1 and PGR mRNA expression were associated with reduced RFS and DSS. High expression levels of AR are significantly associated with adverse outcome in patients with muscle-invasive UCB following RC. ESR1 and PGR expression status can further stratify patients with low AR expression into subgroups with significantly reduced RFS and DSS. Therapeutic targeting of AR may influence outcomes in patients with UCB.

http://bit.ly/2BrNO4P

Acute Epstein–Barr virus-positive cytotoxic T cell lymphoid hyperplasia in the upper aerodigestive tract, mimicking extranodal natural killer/T cell lymphoma, nasal type

Abstract

To describe the clinicopathological features of nine patients with acute Epstein–Barr virus (EBV)-positive cytotoxic T cell lymphoid hyperplasia (EBV+TLH) in the upper aerodigestive tract, in which initial findings led to a preliminary misdiagnosis of extranodal NK/T cell lymphoma, nasal type (ENKTL). A series of nine cases of EBV+TLH in one Chinese institution over a 9-year interval was retrospectively analyzed. Median age was 16 years (range 5–29 years) with a M:F ratio of 5:4. All patients were previously healthy with an acute onset period of < 1 month. Six patients (66%) presented with masses or polypoid protrusions in the upper aerodigestive tract. Nasopharyngeal symptoms, cervical lymphadenopathy, and fever were found in 89%, 78%, and 56% of patients, respectively. In seven cases, morphology mainly showed small-sized irregular cells and in two cases medium-to-large cells. In all cases, the cells diffusely expressed cytoplasmic CD3 and at least one marker for cytotoxic granules, but were negative for CD56. CD5 expression was detected in eight cases (8/9, 89%). In all cases, double staining for CD3 and EBER indicated that most T cells were infected with EBV. T cell receptor gene rearrangement was performed in five cases and all showed polyclonal results. All patients achieved complete remission within 1 month after diagnosis without any chemoradiotherapy and were followed up 19–124 months without recurrent disease. EBV+TLH in the upper aerodigestive tract is occasionally observed in China. The histopathologic features of EBV+TLH can mimic ENKTL. EBV+TLH should be taken into consideration as a potential diagnosis when the disease duration is short, spontaneous remission is achieved without intervention, and when histology shows infiltration with EBV-infected T lymphocytes.

http://bit.ly/2TNSE3a

Targeted sequencing with a customized panel to assess histological typing in endometrial carcinoma

Abstract

The two most frequent types of endometrial cancer (EC) are endometrioid (EEC) and serous carcinomas (SC). Differential diagnosis between them is not always easy. A subset of endometrial cancers shows misleading microscopical features, which cause problems in differential diagnosis, and may be a good scenario for next-generation sequencing. Previous studies have assessed the usefulness of targeted sequencing with panels of generic cancer-associated genes in EC histological typing. Based on the analysis of TCGA (The Cancer Genome Atlas), EEC and SC have different mutational profiles. In this proof of principle study, we have performed targeted sequencing analysis with a customized panel, based on the TCGA mutational profile of EEC and SC, in a series of 24 tumors (16 EEC and 8 SC). Our panel comprised coding and non-coding sequences of the following genes: ABCC9, ARID1A, ARID5B, ATR, BCOR, CCND1, CDH19, CHD4, COL11A1, CSDE1, CSMD3, CTCF, CTNNB1, EP300, ERBB2, FBXW7, FGFR2, FOXA2, KLLN, KMT2B, KRAS, MAP3K4, MKI67, NRAS, PGAP3, PIK3CA, PIK3R1, PPP2R1A, PRPF18, PTEN, RPL22, SCARNA11, SIN3A, SMARCA4, SPOP, TAF1, TP53, TSPYL2, USP36, and WRAP53. Targeted sequencing validation by Sanger sequencing and immunohistochemistry was performed in a group of genes. POLE mutation status was assessed by Sanger sequencing. The most mutated genes were PTEN (93.7%), ARID1A (68.7%), PIK3CA (50%), and KMT2B (43.7%) for EEC, and TP53 (87.5%), PIK3CA (50%), and PPP2R1A (25%) for SC. Our panel allowed correct classification of all tumors in the two categories (EEC, SC). Coexistence of mutations in PTEN, ARID1A, and KMT2B was diagnostic of EEC. On the other hand, absence of PTEN, ARID1A, and KMT2B mutations in the presence of TP53 mutation was diagnostic of SC. This proof of concept study demonstrates the suitability of targeted sequencing with a customized endometrial cancer gene panel as an additional tool for confirming histological typing.

http://bit.ly/2TFZWpV

In this issue

http://bit.ly/2BpeKlp

Validation of the pathological prognostic staging system proposed in the revised eighth edition of the AJCC staging manual in different molecular subtypes of breast cancer

Abstract

The authors investigated the clinical utility of the revised prognostic staging system proposed in the eighth edition of the American Joint Committee on Cancer (AJCC) staging manual in breast cancer (BC) patients. We retrospectively reviewed the data of 714 BC patients that received surgical treatment and standard adjuvant therapy from January 2005 to December 2007. All patients were restaged for anatomic TNM stage and pathological prognostic (PP) stage as defined in the revised eighth edition of the AJCC manual. Compared with anatomic stage, PP stage was different from anatomic stage in 325 (45.5%) patients, 254 were down-staged and 71 were upstaged. There were significant differences in overall survival (OS) and disease-free survival (DFS) according to different anatomic stages or PP stages (all, p < 0.001). In anatomic stage I patients, OS was significantly different between PP stages IA and IB (p < 0.001), but no significant difference was observed between anatomic stages IA and IB (p = 0.413). PP stages exhibited significant OS differences in anatomic stage IIB (p = 0.011), but survival differences according to PP stages were not observed in anatomic stage IIA, IIIA, or IIIC. PP stages were found to have prognostic value with respect to OS and DFS for luminal (p < 0.001 and p < 0.001), HER2-positive (p = 0.001 and p = 0.013), and triple-negative (p = 0.008 and p = 0.03) subtypes. The prognostic staging system proposed in the eighth edition of the AJCC more accurately predicts the clinical outcomes of BC patients than the traditional anatomic staging system.

http://bit.ly/2TGeyFP

Evaluation of tumor-infiltrating lymphocytes in osteosarcomas of the jaws: a multicenter study

Abstract

The aim of the present study was to investigate the profile of tumor-infiltrating lymphocytes (TIL) in osteosarcomas of the jaws (OSJ). A total of 21 OSJ samples were analyzed in a retrospective and cross-sectional multicenter study. Immunohistochemistry was performed to determine the recognition of TIL such as CD4⁺, CD8⁺, granzyme B⁺ (GrB), programmed cell death protein⁺ (PD-1), and cytotoxic T lymphocyte-associated antigen 4⁺ (CTLA-4) in intratumoral and peripheral (stromal) regions. Positivity was determined based on the percentage and density of TIL⁺ per square millimeter [1 = absent (< 25 cells/mm²), 2 = low (25 to 130 cells/mm²), and 3 = high (> 130 cells/mm²)]. The association of TIL density with clinicopathologic data was determined by the Mann-Whitney test (p < 0.05). OSJ were positive for CD8⁺ cells in 45% (n = 9) of cases, for CD4⁺ cells in 30% (n = 6) of cases, and for CTLA-4⁺ in 4.8% (n = 1) of cases, with a score of 2 (low TIL) in all cases. All cases were negative for GrB and PD-1 (score 1). No association was observed between immune infiltrate and clinicopathologic findings. OSJ showed a microenvironment with low TIL, including failure of effectiveness of the antitumor immune response (absence of GrB⁺ cells), and few cells exhibited immunotherapeutic targets, such as CTLA-4 and PD-1.

http://bit.ly/2BqxIs4

The impact of exercise on asthma

Purpose of review Asthma is one of the most common chronic diseases in children and adults in developed countries around the world. Despite international treatment guidelines, poor asthma control remains a frequent problem leading to missed school and work, and emergency room visits and hospitalizations. Many patients with asthma report exercise as a trigger for their asthma, which likely leads to exercise avoidance as a means to control symptoms. Evolving research has suggested that routine exercise may actually help improve some aspects of asthma control. This review discusses the recent research addressing how routine exercise affects important asthma-related outcomes including symptoms, lung function and quality of life. Recent findings Several systematic reviews and meta-analyses have been conducted in recent years, which strongly support the safety of routine exercise in children and adults with asthma. Exercise appears to favor improvements in aerobic fitness, asthma symptoms and quality of life, but results so far are less consistent in demonstrating improvements to lung function and airway hyperresponsiveness. Summary In addition to routine management guidelines, clinicians should recommend for their patients with asthma routine exercise for its general health benefits and likely improvement in asthma symptoms and quality of life. Correspondence to Jason E. Lang, MD, MPH, Division of Allergy/Immunology and Pulmonary Medicine, Duke Children's Hospital and Health Center, MSRB-1 203 Research Drive Rm 127, Durham, North Carolina, USA. Tel: +1 919 684 8657; fax: +1 919 684 2292; e-mail: jason.lang@duke.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

http://bit.ly/2RjRtuy

Use of population data for assessing trends in work-related asthma mortality

Purpose of review Work-related asthma has been associated with poorer asthma control and frequent unscheduled healthcare visits, and can be fatal. Case reports of work-related asthma deaths are rare, but can initiate efforts to prevent additional cases. We reviewed relevant literature and data sources to evaluate whether analyzing mortality data at the population level can help identify potential sources of exposures that contribute to work-related asthma. Recent findings A limited number of population-based studies have addressed work-related asthma mortality. Data on asthma mortality are derived from death certificates using the International Classification of Diseases (ICD) as a standard for coding cause. However, no discrete code for work-related asthma is available. Analysis of asthma mortality relative to industries and occupations appears to identify high-risk jobs that were not identified by analyzing asthma morbidity data. Summary Beyond recognized work-related asthma deaths, it is possible that occupational exposures have contributed to other asthma deaths that have gone unnoticed and could potentially be identified by the analysis of mortality data at the population level. Such analyses in the United States appear to assist in recognizing high-risk occupations and industries. Additional analyses would be possible if a work-related asthma ICD code were available. Correspondence to Jacek M. Mazurek, MD, MS, PhD, Respiratory Health Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention (CDC), Mailstop HG908, 1095 Willowdale Road, Morgantown, WV 26505, USA. Tel: +1 304 285 5983; e-mail: jmazurek1@cdc.gov Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

http://bit.ly/2GI3SEx

Phenotypes of wheezing and asthma in preschool children

Purpose of review The purpose of this review is to provide an overview of the identified phenotypes of preschool wheezing. Recent findings Early life wheezing patterns have been described in multiple populations, with several commonalities found between cohorts. Early life environmental exposures have been found to be differentially associated with preschool wheezing phenotypes and their future trajectories. These include allergen and microbe exposure, environmental tobacco smoke exposure, and maternal stress and depression. Elevated IgE in early life may also influence future asthma risk. Summary Preschool wheezing phenotypes are heterogeneous and complex, with trajectories that are related to factors including environmental exposures. More research is needed to characterize these relationships, hopefully leading to targeted prevention strategies. Correspondence to Leonard B. Bacharier, MD, Campus Box 8116, 660 S. Euclid Ave., St. Louis, MO 63110, USA. Tel: +1 314 454 2694; e-mail: Bacharier_l@wustl.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

http://bit.ly/2QGvlpU

Management of acute loss of asthma control: yellow zone strategies

Purpose of review Asthma exacerbations are associated with a significant burden to both the individual patient and to the healthcare system. Patients often step-up home therapies in response to increased asthma symptoms, and the asthma action plan was created to empower patients to self-manage their asthma care. The yellow (intermediate) zone of the asthma action plan is frequently poorly defined, and current Expert Panel Report 3 guideline recommendations are not effective for all patients. This article reviews the evidence behind various recommended yellow zone intervention strategies. Recent findings There are many potential methods of delivering yellow zone therapy, and recent studies have assessed preventive efficacy of a scheduled increase in controller medication(s), reliever medication(s), or a symptom-driven combination of both. The literature suggests that, in certain asthma subpopulations, some methods may be more efficacious than others. Summary Multiple yellow zone approaches may be beneficial, and the yellow zone is not a 'one size fits all' narrative. Correspondence to Brooke I. Polk, MD, Division of Allergy, Immunology, and Pulmonary Medicine, St. Louis Children's Hospital, Washington University in St. Louis School of Medicine, 1 Children's Place, Campus Box 8116, St. Louis, MO 63110, USA. Tel: +1 314 454 2694; fax: +1 314 454 2694; e-mail: bpolk@wustl.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

http://bit.ly/2R0AGIz

How guideline can shape clinical practice globally: the diagnosis and rationale for action against cow's milk allergy experience

Purpose of review Allergic diseases are increasing worldwide and are considered an important public health problem causing severe and even life-threatening reactions. The creation of guidelines aims to help clinicians improving the quality of diagnosis and management of such diseases. Clinical practice guidelines alone are not sufficient and there is a need for implementation strategies for their introduction into daily practice. We report here the main international allergy guidelines with a more focused look on the Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) guidelines and their effect on clinical practice. Recent findings DRACMA guidelines have clearly modified the approach to cow's milk allergy (CMA) from its diagnosis to treatment tailoring the choices for each patient. Although they strongly recommend oral food challenge for diagnosing CMA, they also indicate that it may not be necessary in many cases with the introduction of the pretest probability of CMA. Studies on the implementation of DRACMA guidelines show how they influenced the formula market, making appropriate treatments more affordable. Summary DRACMA reconciled international differences in the diagnosis and management of CMA. They introduced the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology in the field of food allergy and highlighted the importance for meta-analyses to be able to adapt recommendations to the local context. Correspondence to Alessandro Fiocchi, MD, Division of Allergy, University Department of Pediatrics, Pediatric Hospital Bambino Gesù, Rome, Vatican City. Tel: +39 06 6859 4777; e-mail: Agiovanni.fiocchi@opbg.net Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

http://bit.ly/2Fpio1v