Characteristic Cochlear Hypoplasia in Patients with Walker-Warburg Syndrome: A Radiologic Study of the Inner Ear in alpha-Dystroglycan-Related Muscular Disorders

BACKGROUND AND PURPOSE: Walker-Warburg syndrome, muscle-eye-brain disease, and Fukuyama congenital muscular dystrophy are α-dystroglycan–related muscular disorders associated with brain malformations and eye abnormalities in which no structural inner ear abnormality has been described radiologically. We collected patients from 6 tertiary pediatric hospitals and reported the radiologic features and frequency of inner ear dysplasias. MATERIALS AND METHODS: Patients previously diagnosed clinicoradiologically with Walker-Warburg syndrome, muscle-eye-brain disease, or Fukuyama congenital muscular dystrophy were included. We recorded the pathogenic variant, when available. Brain MR imaging and/or CT findings were reviewed in consensus, and inner ear anomalies were classified according to previous description in the literature. We then correlated the clinicoradiologic phenotype with the inner ear phenotype. RESULTS: Thirteen patients fulfilled the criteria for the Walker-Warburg syndrome phenotype, 8 for muscle-eye-brain disease, and 3 for Fukuyama congenital muscular dystrophy. A dysplastic cochlea was demonstrated in 17/24. The most frequent finding was a pronounced cochlear hypoplasia type 4 with a very small anteriorly offset turn beyond the normal-appearing basal turn (12/13 patients with Walker-Warburg syndrome and 1/11 with muscle-eye-brain disease or Fukuyama congenital muscular dystophy). Two of 8 patients with muscle-eye-brain disease, 1/3 with Fukuyama congenital muscular dystrophy, and 1/13 with Walker-Warburg syndrome showed a less severe cochlear hypoplasia type 4. The remaining patients without Walker-Warburg syndrome were healthy. The vestibule and lateral semicircular canals of all patients were normal. Cranial nerve VIII was present in all patients with diagnostic MR imaging. CONCLUSIONS: Most patients with the severe α‐dystroglycanopathy Walker-Warburg syndrome phenotype have a highly characteristic cochlear hypoplasia type 4. Patients with the milder variants, muscle-eye-brain disease and Fukuyama congenital muscular dystrophy, more frequently have a normal cochlea or milder forms of hypoplasia

Imaging of temporal bone inflammations in children: a pictorial review

Purpose: Understanding the underlying pathophysiology and the patterns of disease spread is crucial in accurate image interpretation. In this pictorial review, the common and important inflammatory processes of the temporal bone in children will be discussed, and key computed tomography (CT) and magnetic resonance imaging (MRI) features described. Methods: Inflammatory processes are categorized by anatomical location: the petrous apex and the inner, middle and outer ear. A complete review of the literature is provided. Results: Cholesteatoma, cholesterol granuloma and mucoceles are inflammatory processes that occur across the anatomical subsites of the temporal bone, whilst site-specific inflammatory processes include labyrinthitis ossificans in the inner ear and keratosis obturans in the external ear. Infection is a key cause of inflammation in the temporal bone, and specific infections include petrous apicitis, otitis media and necrotizing otitis externa. Finally, important mimics and do-not-touch lesions are considered. CT and MRI are complementary in assessing these disorders, as two of the most important diagnostic clues are the presence of bone erosion, best appreciated on CT, and true diffusion restriction as seen on MRI. Flow charts to assist in the diagnosis of paediatric temporal bone inflammatory disease are also provided. Conclusion: Paediatric temporal bone inflammatory processes are common and can have severe clinical sequelae. Timely intervention, facilitated by correct radiological diagnosis, can often prevent progression of disease, loss of hearing and systemic illness

Beta-adrenergic activation of Epithelial-Mesenchymal Transition in ovarian cancer

The Epithelial-Mesenchymal Transition (EMT) is a key process in cancer metastasis whereby epithelial cells lose their polarity and cell-to-cell adhesion, and undergo morphologic changes, giving them a mesenchymal phenotype that allows them to migrate and invade other tissues. Our previous research has shown that beta-adrenergic signaling stimulates pathways involved in ovarian tumor progression, but the underlying mechanisms are not fully understood. We performed genome-wide transcriptome profiling of advanced stage ovarian carcinomas from 98 patients and compared those above versus below the median split on tumor norepinephrine level (NE) (median: 1.05pg/mg tumor). Patients were matched on age, BMI, cancer grade, stage, and histology. High-NE tumors showed increased expression of 694 genes by at least 25% and 124 by at least 50%. These included multiple genes related to EMT, as well as decreased expression of a variety of anti-metastatic genes. In ovarian cancer cell lines (SKOV3ip1 and HeyA8), exposure to stress-concentrations of NE increased transcription of SNAI2 and IL6, both of which regulate EMT. In an in vivo orthotopic mouse model of ovarian cancer, 3weeks of restraint stress significantly decreased the epithelial marker E Cadherin, increased mesenchymal markers N Cadherin and Vimentin, and up-regulated EMT mediators Snai1, Snai2, and Twist1. These results identify an additional pathway by which beta-adrenergic signaling can promote ovarian cancer progression by stimulating EMT gene expression programs that mediate metastasis

Urethral lichen sclerosus under the microscope: a survey of academic pathologists.

INTRODUCTION:Given the poor understanding of the pathophysiology of genital lichen sclerosus (GLS) and a lack of accepted definitive diagnostic criteria, we proposed to survey pathologists regarding their understanding of GLS. We hypothesized that significant disagreement about GLS will exist. MATERIALS AND METHODS:All urologists participating in the Trauma and Urologic Reconstruction Network of Surgeons identified genitourinary (GUP) and dermatopathologists (DP) at their respective institutions who were then invited to participate in an online survey regarding their experience with diagnosing GLS, GLS pathophysiology and its relationship to urethral stricture disease. RESULTS:There were 23 (12 DP, 11 GUP) pathologists that completed the survey. The most agreed upon criteria for diagnosis were dermal collagen homogenization (85.7%), loss of the normal rete pattern (33.3%) and atrophic epidermis (28.5%). No pathologists believed GLS had an infectious etiology (19% maybe, 42% unknown) and 19% believed GLS to be an autoimmune disorder (42% maybe, 38% unknown); 19% believed LS to be premalignant, but 52% believed it was associated with cancer; 80% believed that LS could involve the urethra (DP (92%) versus GUP (67%); p = 0.272). Of those diagnosing urethral GLS, 80% of DUP believed that GLS must first involve the glans/prepuce before involving the urethra, while all GUP believed that urethral disease could exist in isolation (p = 0.007). CONCLUSIONS:There was significant disagreement in this specialized cohort of pathologists when diagnosing GLS. A logical first step appears to be improving agreement on how to best describe and classify the disease. This may lead to improve treatments

Urethral lichen sclerosus under the microscope: a survey of academic pathologists.

INTRODUCTION:Given the poor understanding of the pathophysiology of genital lichen sclerosus (GLS) and a lack of accepted definitive diagnostic criteria, we proposed to survey pathologists regarding their understanding of GLS. We hypothesized that significant disagreement about GLS will exist. MATERIALS AND METHODS:All urologists participating in the Trauma and Urologic Reconstruction Network of Surgeons identified genitourinary (GUP) and dermatopathologists (DP) at their respective institutions who were then invited to participate in an online survey regarding their experience with diagnosing GLS, GLS pathophysiology and its relationship to urethral stricture disease. RESULTS:There were 23 (12 DP, 11 GUP) pathologists that completed the survey. The most agreed upon criteria for diagnosis were dermal collagen homogenization (85.7%), loss of the normal rete pattern (33.3%) and atrophic epidermis (28.5%). No pathologists believed GLS had an infectious etiology (19% maybe, 42% unknown) and 19% believed GLS to be an autoimmune disorder (42% maybe, 38% unknown); 19% believed LS to be premalignant, but 52% believed it was associated with cancer; 80% believed that LS could involve the urethra (DP (92%) versus GUP (67%); p = 0.272). Of those diagnosing urethral GLS, 80% of DUP believed that GLS must first involve the glans/prepuce before involving the urethra, while all GUP believed that urethral disease could exist in isolation (p = 0.007). CONCLUSIONS:There was significant disagreement in this specialized cohort of pathologists when diagnosing GLS. A logical first step appears to be improving agreement on how to best describe and classify the disease. This may lead to improve treatments