Biopsy In Childhood Research Articles

Germ Cell Neoplasia in Situ and Preserved Fertility Despite Suppressed Gonadotropins in a Patient With Testotoxicosis

Testotoxicosis is an autosomal-dominant, male-limited disorder. Activating mutations in the luteinizing hormone receptor gene (LHCGR) cause high autonomous testosterone secretion, resulting in early-onset peripheral precocious puberty. Little is known about long-term consequences of testotoxicosis. We present a rare case of a patient followed for 25 years with two remarkable outcomes: preserved fertility and germ cell neoplasia in situ (GCNIS). He presented with precocious puberty at 10 months of age and was diagnosed with testotoxicosis due to a de novo heterozygous Asp578Tyr mutation in LHCGR. Testicular biopsy in childhood showed Leydig cell hyperplasia with altered cell maturation. From infancy throughout adulthood, elevated testosterone and estradiol, low inhibin B and anti-Müllerian hormone, and completely suppressed follicle-stimulating hormone and luteinizing hormone were noted. Height acceleration and advanced bone age resulted in a reduced final height. Semen analysis revealed ongoing spermatogenesis, and the patient fathered a child by natural conception. Ketoconazole treatment decreased circulating testosterone in childhood, supported by experimental suppression of testosterone production in his adult testis tissue cultured ex vivo. At 25 years of age, ultrasound revealed a testicular tumor, identified as a Leydig cell adenoma, but unexpectedly with GCNIS present in adjacent seminiferous tubules. The case illustrates that absence of gonadotropins but high intratesticular testosterone concentration is sufficient for spermatogenesis and to allow fatherhood. Our study is also the first description, to our knowledge, of GCNIS in a patient with testotoxicosis. We recommend regular clinical examination and ultrasonic evaluation of the testes in these patients due to potential increased risk of malignancy.

Muscle histopathology in nebulin-related nemaline myopathy: ultrastrastructural findings correlated to disease severity and genotype

Nemaline myopathy (NM) is a rare congenital myopathy characterised by hypotonia, muscle weakness, and often skeletal muscle deformities with the presence of nemaline bodies (rods) in the muscle biopsy. The nebulin (NEB) gene is the most commonly mutated and is thought to account for approximately 50% of genetically diagnosed cases of NM. We undertook a detailed muscle morphological analysis of 14 NEB-mutated NM patients with different clinical forms to define muscle pathological patterns and correlate them with clinical course and genotype. Three groups were identified according to clinical severity. Group 1 (n = 5) comprises severe/lethal NM and biopsy in the first days of life. Group 2 (n = 4) includes intermediate NM and biopsy in infancy. Group 3 (n = 5) comprises typical/mild NM and biopsy in childhood or early adult life. Biopsies underwent histoenzymological, immunohistochemical and ultrastructural analysis. Fibre type distribution patterns, rod characteristics, distribution and localization were investigated. Contractile performance was studied in muscle fibre preparations isolated from seven muscle biopsies from each of the three groups. G1 showed significant myofibrillar dissociation and smallness with scattered globular rods in one third of fibres; there was no type 1 predominance. G2 presented milder sarcomeric dissociation, dispersed or clustered nemaline bodies, and type 1 predominance/uniformity. In contrast, G3 had well-delimited clusters of subsarcolemmal elongated rods and type 1 uniformity without sarcomeric alterations. In accordance with the clinical and morphological data, functional studies revealed markedly low forces in muscle bundles from G1 and a better contractile performance in muscle bundles from biopsies of patients from G2, and G3.In conclusion NEB-mutated NM patients present a wide spectrum of morphological features. It is difficult to establish firm genotype phenotype correlation. Interestingly, there was a correlation between clinical severity on the one hand and the degree of sarcomeric dissociation and contractility efficiency on the other. By contrast the percentage of fibres occupied by rods, as well as the quantity and the sub sarcolemmal position of rods, appears to inversely correlate with severity. Based on our observations, we propose myofibrillar dissociation and changes in contractility as an important cause of muscle weakness in NEB-mutated NM patients.

ESPR uroradiology task force and ESUR Paediatric Work Group—Imaging recommendations in paediatric uroradiology, part VI: childhood renal biopsy and imaging of neonatal and infant genital tract

The European Society of Paediatric Radiology Uroradiology Task Force and the ESUR Paediatric Work Group jointly publish guidelines for paediatric urogenital imaging. Two yet unaddressed topics involving patient safety and imaging load are addressed in this paper: renal biopsy in childhood and imaging of the neonatal genital tract, particularly in girls. Based on our thorough review of literature and variable practice in multiple centers, procedural recommendations are proposed on how to perform renal biopsy in children and how to approach the genital tract in (female) neonates. These are statements by consensus due to lack of sufficient evidence-based data. The procedural recommendation on renal biopsy in childhood aims at improving patient safety and reducing the number of unsuccessful passes and/or biopsy-related complications. The recommendation for an imaging algorithm in the assessment of the neonatal genital tract focuses on the potential of ultrasonography to reduce the need for more invasive or radiating imaging, however, with additional fluoroscopy or MRI to be used in selected cases. Adherence to these recommendations will allow comparable data and evidence to be generated for future adaptation of imaging strategies in paediatric uroradiology.

P.9.7 Skeletal muscle biopsy reappraisal in nebulin-related nemaline myopathy

Nemaline myopathy (NM) is a congenital disorder associating muscle weakness with rods in muscle biopsy. Clinical presentation is variable spanning from severe to mild forms. Seven genes are associated with NM. The nebulin (NEB) gene is the most commonly mutated accounting for 50% of cases. We performed a muscle morphological analysis of thirteen NEB-mutated patients with different clinical forms to define pathological patterns and clinical-morphological correlations. Four groups were identified according to clinical severity and age at biopsy. Group 1 ( n = 4) comprises severe/lethal NM and biopsy in first days. Group 2 ( n = 3) comprehends severe NM and biopsy after one month. Group 3 ( n = 3) comprises typical NM and biopsy in childhood, and group 4 ( n = 2) patients with mild NM and biopsy in adulthood. Molecular diagnosis was done using dHPLC/Sanger-sequencing in six patients and next-generation sequencing in seven. Biopsies underwent histoenzymological, immunohistochemical and ultrastructural analysis. Fiber type distribution, rod characteristics, distribution and localization were investigated. All patients presented NEB mutations consistent with AR inheritance. G1 showed type 2 predominance and scattered squared rods in 1/3 of fibers. Ultrastructural analysis revealed high percentage of fibers with sarcomeric disarray. G2 showed a variable pattern of fiber type distribution spanning from slight type 2 predominance to type 1 uniformity. Rods presented variable distribution and shape. Ultrastructural analysis revealed rare fibers with sarcomeric disarray. In contrast, G3 and G4 presented a homogeneous type 1 uniformity associated with well-delimited subsarcolemmal and/or cytoplasmic elongated rods without sarcomeric alterations. In conclusions we (1) identified an unreported association of type 2 predominance in muscle biopsy of patients presenting severe NEB-related NM; (2) suggest a direct correlation between the association of sarcomeric disarray and clinical severity.

Increased Risk of Death for Patients With Celiac Disease-Related Disorders

New research indicates that patients with lesser degrees of celiac disease-related symptoms, such as intestinal inflammation or latent celiac disease, have a modestly increased risk of death, according to a study in the September 16, 2009 issue of JAMA. Although most research has shown an increased risk of death in celiac disease, less is known about the long-term consequences of nonspecific small intestinal inflammation without villous atrophy. Research on other inflammatory disorders suggests that inflammation may be associated with increased mortality, but this has not been investigated for nonspecific inflammation in the small intestine. Jonas F. Ludvigsson, MD, PhD, of Örebro University Hospital, örebro, Sweden, and colleagues used nationwide histopathology data collected from biopsies taken between July 1969 and February 2008 in Sweden to examine overall mortality risk in individuals with celiac disease and inflammation. Data from the biopsies was divided into three groups: celiac disease (Marsh stage 3, villous atrophy; n = 29,096 individuals); inflammation (Marsh stage 1–2; n = 13,306); and individuals with latent celiac disease (n = 3719). Latent celiac disease was defined as positive celiac disease serology in individuals with normal intestinal mucosa. Through linkage with the Swedish Total Population Register, the researchers estimated the risk of death through August 2008, compared with age- and gender-matched controls from the general population. The data indicated there were 3049 deaths among patients with celiac disease, 2967 deaths in patients with inflammation, and 183 deaths with latent celiac disease. The study found mortality risk was increased in all 3 groups, with patients with inflammation having a 72% increased risk; patients with celiac disease, a 39% increased risk; and patients with latent celiac disease having a 35% increased mortality risk. The risk of death was highest in the first year of follow-up, with celiac disease associated with a 2.8-fold increased risk of death, inflammation with a 4.7-fold increase, and latent celiac disease with a 1.8-fold increase. After the first year of follow-up, these figures decreased. Mortality risk also decreased with age at diagnosis, with risk being higher for those diagnosed before age 20. “In conclusion, we found increased [risks] for death in individuals with biopsy-verified celiac disease, inflammation, and latent celiac disease, although absolute risks were small” the authors note. “Individuals undergoing small-intestinal biopsy in childhood had increased [risks] for death. Cardiovascular disease and malignancy were the main causes of death in celiac disease.” Peter H. R. Green, MD, of Columbia University College of Physicians and Surgeons, New York, writes in an accompanying editorial that this study provides important information on the risks associated with celiac disease. “Until recently, gluten sensitivity has received little attention in the traditional medical literature, although there is increasing evidence for its presence in patients with various neurological disorders and psychiatric problems. The study by Ludvigsson and colleagues reinforces the importance of celiac disease as a diagnosis that should be sought by physicians. It also suggests that more attention should be given to the lesser degrees of intestinal inflammation and gluten sensitivity.” See: JAMA 2009;302:1171–1178 and 1225–1226.

Electromyography (EMG) Accuracy Compared to Muscle Biopsy in Childhood

Reports show wide variability of electromyography (EMG) in detecting pediatric neuromuscular disorders. The study's aim was to determine EMG/nerve conduction study accuracy compared to muscle biopsy and final clinical diagnosis, and sensitivity for myopathic motor unit potential detection in childhood. Of 550 EMG/nerve conduction studies performed by the same examiner from a pediatric neuromuscular service, 27 children (ages 6 days to 16 years [10 boys; M:F, 1:1.7]) with muscle biopsies and final clinical diagnoses were compared retrospectively. Final clinical diagnoses were congenital myopathies (5 of 27,18%), nonspecific myopathies (biopsy myopathic, final diagnosis uncertain; 6 of 27, 22%), congenital myasthenic syndrome (3 of 27, 11%), juvenile myasthenia gravis (1 of 27, 4%), arthrogryposis multiplex congenita (2 of 27, 7%), hereditary motor and sensory neuropathy (1 of 27, 4%), bilateral peroneal neuropathies (1 of 27, 4%), and normal (8 of 27, 30%). There were no muscular dystrophy or spinal muscular atrophy patients. EMG/nerve conduction studies had a 74% agreement with final clinical diagnoses and 100% agreement in neurogenic, neuromuscular junction, and normal categories. Muscle biopsies concurred with final diagnoses in 87%, and 100% in myopathic and normal categories. In congenital myasthenic syndrome, muscle biopsies showed mild variation in fiber size in 2 of 3 children and were normal in 1 of 3. EMG sensitivity for detecting myopathic motor unit potentials in myopathies was 4 of 11 (36%), greater over 2 years of age (3 of 4, 75%), compared to infants less than 2 years (1 of 7, 14%), not statistically significant (P = .0879). EMGs false-negative for myopathy in infants < 2 years of age were frequently neurogenic (3 of 6, 50%). In congenital myopathies EMG detected myopathic motor unit potentials in 40%, with false-negative results neurogenic (20%) or normal (40%). Because our study has no additional tests for active myopathies, for example Duchenne muscular dystrophy genetic testing, our sensitivity for myopathies is lower than if we used a more global view. In conclusion, EMG detection rate of myopathic motor unit potentials at a young age was low, improving in children over 2 years of age. In neurogenic and neuromuscular junction disorders, the EMG has a very high detection rate. In children with mild to moderate neurogenic EMG findings and normal nerve conduction, a myopathy should always be considered.

An approach to the paediatric renal biopsy

Although the principles the pathologist uses to assess renal biopsies are similar when reporting adult and paediatric biopsies, the interpretation of the findings may differ owing to relative differences in the frequencies of particular diagnoses in childhood versus adulthood, as well as age-related changes in normal histological appearances. In addition, there are a range of conditions that are either unique to or much more frequent in childhood compared with adult practice, for example congenital nephrotic syndrome subtypes, whereas other conditions, such as hypertensive renal disease or diabetic nephropathy, remain a significant component of adult renal pathology practise but are almost never encountered in childhood. The renal biopsy plays a central role in the management of many paediatric conditions presenting to the nephrologist, and percutaneous ultrasound-guided renal biopsy in children appears safe, with a low frequency (<1%) of serious complications. The most common indication for renal biopsy in childhood is nephrotic syndrome, either in the first year of life, in which the differential diagnoses are usually relatively specific to this age group, or in later childhood, when the major differential diagnoses are minimal-change nephropathy (minimal-change disease) and focal segmental glomerulosclerosis. Other entities that may be encountered commonly in paediatric renal biopsy practise include congenital disorders of the glomerular capillary basement membrane, such as Alport nephropathy, and a range of cystic diseases of the kidney. This review will provide an overview of these issues, focusing predominantly on those issues and entities specific to paediatric practise.

Effect of testicular biopsy in childhood on spermatogenesis, fertility, and paternity in adulthood—A mouse model study

Objectives To study the effect of testicular biopsy in childhood on spermatogenesis, fertility, and paternity in subsequent adulthood using an animal model. Considerable controversy exists as to whether testicular biopsy should be performed in children. Methods Four-week-old male ICR mice were subjected to unilateral testicular biopsy (group 1), bilateral biopsy (group 2), or a sham operation (group 3). At 8 weeks of age, the testicular weight, seminiferous tubular diameter, and manifestation of apoptosis were examined. The motility of sperm obtained from the epididymides of the same testes was also examined. Fertility and paternity was assessed in each mouse by housing it with 2 age-matched females for 2 weeks. Results No significant differences were found in the testicular weight, mean seminiferous tubular diameter, or number of apoptotic germ cells between the biopsied and unbiopsied side in group 1 or between groups 2 and 3. No significant differences were noted in the average sperm motility rate between the biopsied (30.5% ± 14.5%) and unbiopsied side (35.8% ± 19.2%) in group 1, or between groups 2 (37.6% ± 18.0%) and 3 (39.3% ± 10.0%). All females who coupled with the male mice in all groups became pregnant. The average number of offspring from the 2 female mice was not significantly different among the three groups (group 1, 13.1 ± 2.3; group 2, 12.3 ± 2.0; and group 3, 11.3 ± 3.0). Conclusions The spermatogenesis, fertility, and paternity of mature mice were unaffected by testicular biopsy in childhood.

Recognition of Crohn disease on incidental gastric biopsy in childhood.

The role of gastric biopsy in the diagnosis of Crohn disease (CD) in the pediatric population has not been well described. We assessed the use of gastric biopsies in the diagnosis of CD using specific histopathologic parameters: granulomata, focal gland injury with neutrophils (glandulitis or glandular abscesses), and/or focal concomitant eosinophilic infiltrates. Multiple (438) consecutive pediatric biopsies with inflammation spanning a 5-year period were identified from archival material in patients ages 2 months to 16 years. A total of 56 CD cases were confirmed using colon biopsies and clinical and radiologic data as the gold standards of diagnosis. Review of hematoxylin and eosin (H&E) slides and Diff-Quik stained slides (negative for Helicobacter pylori) isolated 53 cases which suggested CD on gastric biopsy: 20 cases with granulomata, 14 cases with focal glandulitis and glandular abscesses, and 19 cases of focal glandulitis/glandular abscesses with eosinophilic infiltrates. Seventy-seven percent (43/56) were correctly identified as patients with CD. Twenty-three percent (13/56) of CD cases were not identified primarily because of concurrent H. pylori infection identified on Diff-Quik stain with a superimposed nonspecific diffuse gastritis. The use of Diff-Quik stain to identify H. pylori cases after all other factors are considered was significant (P = 0.0145); a negative stain, combined with the identified histopathologic features indicative of CD, significantly increased the accuracy of CD diagnosis. CD was mimicked by other gastric granulomatous diseases (actinomyces, 1 case; chronic granulomatous disease of childhood, 1 case). Gastric biopsy can be used to identify or support the diagnosis of CD in children in the appropriate clinicopathologic setting.

Images in cardiovascular medicine. Myocardial fibrosis in glycogen storage disease type III.

A 32-year-old man was referred with exertional chest pain. He had been diagnosed with glycogen storage disease type IIIa (GSDIIIa) by liver biopsy in childhood. Cine cardiovascular magnetic resonance (CMR) demonstrated profound symmetrical hypertrophy (483 g) with impaired systolic function. Gadolinium-diethylene triamine penta-acetic acid (DTPA) rest perfusion demonstrated multifocal first pass mid-myocardial defects and late imaging demonstrated …

Cardiac biopsy in childhood.

Endomyocardial biopsy was attempted in 18 children aged 5 months to 15 years with 82% success. Biopsies obtained from 15 children were examined by light and electron microscope making positive morphological diagnoses in 3 cases. The biopsy findings were actively helpful in 7 other cases, which contrasts with experience in adult biopsy series. This is a low risk procedure which does not add to the hazards of cardiac catheterization in children.

Premedication for jejunal biopsy in childhood using intravenous diazepam and metoclopramide.

Premedication for jejunal biopsy in childhood using intravenous diazepam and metoclopramide.

Intestinal biopsy in childhood.

Intestinal biopsy in childhood.

6) "Technique of renal biopsy in childhood"

6) "Technique of renal biopsy in childhood"

Percutaneous renal biopsy in childhood.

Percutaneous renal biopsy in childhood.

Small intestine suction biopsy in childhood: technic complications, importance in diagnosis of intestinal diseases

Small intestine suction biopsy in childhood: technic complications, importance in diagnosis of intestinal diseases

Jejunal Biopsy in Childhood

Jejunal Biopsy in Childhood

JEJUNAL BIOPSY IN CHILDHOOD.

JEJUNAL BIOPSY IN CHILDHOOD.

Jejunal Biopsy in Childhood

Jejunal Biopsy in Childhood

Jejunal Biopsy in Childhood

Jejunal Biopsy in Childhood