Submucosal Nerve Diameter in the Rectum Increases With Age: An Important Consideration for the Diagnosis of Hirschsprung Disease

2021 ◽  
pp. 109352662110496
Author(s):  
Miriam R Conces ◽  
Sarah Beach ◽  
Christopher R Pierson ◽  
Vinay Prasad
Keyword(s):  
Hirschsprung Disease ◽  
Average Diameter ◽  
Rectal Biopsies ◽  
Effect Of Age

Introduction Hypertrophic submucosal nerves, defined as ≥40 µm in diameter, are considered supportive of a diagnosis of HSCR, but the effect of age on nerve diameter has not been well-studied. We sought to determine the distribution of the largest nerve diameter in ganglionic rectal biopsies and the significance of hypertrophic submucosal nerves in the diagnosis of Hirschsprung disease (HSCR) based on age. Methods Rectal biopsies performed in the evaluation of HSCR were retrospectively reviewed from 179 patients (151 ganglionic biopsies, 28 aganglionic biopsies), and the diameter of the largest submucosal nerve was measured. Results In non-Hirschsprung disease (non-HSCR) biopsies, submucosal nerve diameter increased with age. In patients <1 year, the average diameter was 34.1 ± 11.6 µm but increased to 50.8 ± 17.3 µm after 1 year of age. Submucosal nerves ≥40 µm in diameter were significantly associated with HSCR across all ages [HSCR = 25/28 (89.3%) vs non-HSCR = 59/151 (39.1%), p < 0.0001] and remained significant in patients <1 year of age [HSCR = 22/24 (91.7%) vs non-HSCR = 19/91 (20.9%), p < 0.0001]. Conclusions The diameter of submucosal nerves increases with age, and ≥40 µm nerves are common after 1 year of age.

Calretinin Immunohistochemistry versus Acetylcholinesterase Histochemistry in the Evaluation of Suction Rectal Biopsies for Hirschsprung Disease

2009 ◽  
Vol 12 (1) ◽  
pp. 6-15 ◽  
Author(s):  
Raj P. Kapur ◽  
Robyn C. Reed ◽  
Laura S. Finn ◽  
Kathleen Patterson ◽  
Judy Johanson ◽  
...  
Keyword(s):  
Hirschsprung Disease ◽  
Acetylcholinesterase Histochemistry ◽  
Rectal Biopsies

Submucosal Supernumerary Smooth Muscle Coat: A Common Histologic Finding in Mowat–Wilson Syndrome With or Without Hirschsprung Disease

2020 ◽  
Vol 23 (5) ◽  
pp. 372-379
Author(s):  
Mariko Suchi ◽  
Casey M Calkins ◽  
Ashish Chogle ◽  
Jesse Steffan Bond ◽  
Raj P Kapur
Keyword(s):  
Smooth Muscle ◽  
Circular Muscle ◽  
Hirschsprung Disease ◽  
Clinical Information ◽  
Pathological Feature ◽  
Glass Slides ◽  
Intestinal Pseudo Obstruction ◽  
System Disorder ◽  
Rectal Biopsies ◽  
Muscle Coat

Background Mowat–Wilson syndrome (MWS) is a multiorgan system disorder caused by ZEB2 (zinc finger E-box-binding homeobox 2) mutations or deletions. One common manifestation is constipation, and approximately half of the patients have Hirschsprung disease (HSCR). In addition to classic histologic features of HSCR, an unusual supernumerary intestinal muscle coat was recently reported in a patient of MWS with HSCR. A similar smooth muscle alteration, segmental additional circular muscle coat, had been described in the specimens from patients with intestinal pseudo-obstruction without MWS or HSCR. Method Rectal biopsies and rectosigmoidectomy specimens from MWS patients were identified by retrospective reviews of surgical pathology records. Routinely prepared glass slides were examined to determine whether any smooth muscle structural alteration was present. Clinical information was obtained by chart review. Results Six MWS patients were identified. A supernumerary smooth muscle coat in the submucosa was present in 3 of them, including 2 of the 4 patients with HSCR. Conclusion The structural anomaly, termed submucosal supernumerary smooth muscle coat, is not a syndrome-specific pathological feature. However, it appears to be more common than expected in MWS and is consistent with contemporary models for the roles of ZEB2 and related cell signaling pathways in the patterning of intestinal musculature during embryonic development.

Selective Demonstration of Mural Nerves in Ganglionic and Aganglionic Colon by Immunohistochemistry for Glucose Transporter-1

2000 ◽  
Vol 124 (9) ◽  
pp. 1314-1319 ◽  
Author(s):  
Yutaka Kakita ◽  
Kiyohiko Oshiro ◽  
D. Sean O'Briain ◽  
Prem Puri
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Glucose Transporter ◽  
Growth Factor Receptor ◽  
Hirschsprung Disease ◽  
Nerve Fibers ◽  
Nerve Growth Factor Receptor ◽  
Nerve Growth ◽  
Glut 1 ◽  
Rectal Biopsies

Abstract Objective.—Hypertrophic nerves have long been considered a histopathologic feature of the aganglionic segment in Hirschsprung disease, but they remain incompletely explained. The purpose of this study was to define the nature and diagnostic importance of hypertrophic nerves in Hirschsprung disease and to clarify their relation to nearby smaller nerve fibers. Methods.—We used an immunoperoxidase staining technique to compare the distribution of 2 nerve markers—erythrocyte-type glucose transporter (GLUT-1), a marker of perineurium, and nerve growth factor receptor, a marker of both nerve fibers and perineurium—in aganglionic tissue (12 resected specimens and 4 rectal biopsies) and control tissue (6 autopsy specimens and 17 rectal biopsies) of children. Results.—In control ganglionic tissue, the myenteric and submucosal areas contained only occasional GLUT-1–positive nerves (usually less than 50 μm in diameter), but extramural extrinsic (serosal) nerves were invariably positive for GLUT-1. In aganglionic tissue, GLUT-1–positive nerves in the myenteric and submucosal areas were frequent and included both large (50–150 μm) and small (&lt;50 μm) diameter nerves. Nerve growth factor receptor–positive fibers were frequent in all layers of all tissue studied. In aganglionic bowel, a distinct perineurium could be identified in the largest nerves, but nerve growth factor receptor had poor discrimination for small perineurium-sheathed nerves. Conclusion.—Most nerves, of both large and small diameter, in the myenteric and submucosal plexus of aganglionic bowel are GLUT-1 positive. Serosal extrinsic nerves stain identically, supporting the interpretation that the mural nerves are of extrinsic origin. Mural GLUT-1–positive nerves, when they are multiple and especially when they are greater than 50 μm in diameter (a figure which may be used as a threshold for hypertrophic nerves), are suggestive of Hirschsprung disease.

Rectal biopsies for Hirschsprung disease: Patient characteristics by diagnosis and attending specialty

2016 ◽  
Vol 51 (4) ◽  
pp. 573-576 ◽  
Author(s):  
Camille L. Stewart ◽  
Ann M. Kulungowski ◽  
Suhong Tong ◽  
Jacob C. Langer ◽  
Jason Soden ◽  
...  
Keyword(s):  
Disease Patient ◽  
Hirschsprung Disease ◽  
Patient Characteristics ◽  
Rectal Biopsies

Does Calretinin Immunohistochemistry Reduce Inconclusive Diagnosis in Rectal Biopsies for Hirschsprung Disease?

2014 ◽  
Vol 58 (5) ◽  
pp. 603-607 ◽  
Author(s):  
Pedro L.T. de Arruda Lourenção ◽  
Bonifácio K. Takegawa ◽  
Erika V.P. Ortolan ◽  
Simone A. Terra ◽  
Maria A.M. Rodrigues
Keyword(s):  
Hirschsprung Disease ◽  
Rectal Biopsies

Choline Transporter Immunohistochemistry

2017 ◽  
Vol 20 (4) ◽  
pp. 308-320 ◽  
Author(s):  
Raj P Kapur ◽  
Philipp W Raess ◽  
Samuel Hwang ◽  
Conrad Winter
Keyword(s):  
Frozen Section ◽  
Hirschsprung Disease ◽  
Observer Agreement ◽  
Routine Practice ◽  
Cholinergic Nerves ◽  
Predictive Values ◽  
Choline Transporter ◽  
Ffpe Tissues ◽  
Mucosal Innervation ◽  
Rectal Biopsies

Acetylcholinesterase enzymatic histochemistry (AChE EHC), which highlights abnormal cholinergic nerves in the mucosa of aganglionic bowel, has been used for decades to evaluate rectal biopsies for Hirschsprung disease (HSCR). While useful diagnostically, AChE EHC is not compatible with conventional formalin-fixed and paraffin-embedded (FFPE) tissues and is not widely available. The choline transporter (ChT) is a putative alternative marker of cholinergic nerves. ChT immunohistochemistry (IHC) was investigated using FFPE biopsies and resections from patients with confirmed HSCR, as well as appropriate non-HSCR controls. ChT immunostaining was effective at identifying cases with HSCR and qualitatively similar to AChE EHC on frozen section. Among 3 pathologists, the diagnostic positive and negative predictive values based on ChT IHC ranged from 0.84–0.94 and 0.85–0.89, respectively, with good inter-observer agreement (Cohen kappa = 0.70–0.90). ChT IHC was useful in unusual scenarios in which calretinin (CR) IHC failed to correctly identify patients with HSCR. In 10 cases of short-segment HSCR, abnormal ChT+ mucosal innervation was present through the entire aganglionic segment and into portions of the TZ with submucosal nerve hypertrophy. In contrast, mucosal CR IHC was retained in the TZ and adjacent aganglionic bowel, which could lead to misinterpretation of a biopsy as ganglionic bowel. Indeed, 6 such patients were identified with paradoxical CR-positive mucosal innervation in their diagnostic biopsies. ChT IHC was interpreted as unequivocal HSCR in these cases, and HSCR was confirmed on resection. In summary, ChT IHC in FFPE tissue demonstrates high positive and negative predictive values for HSCR, is superior to CR IHC in a subset of cases, and can be incorporated into routine practice without the need for specialized techniques.

scholarly journals Comparative study between use of calretinin and synaptophysin immunostaining in diagnosis of Hirschsprung disease

2019 ◽  
Vol 6 (3) ◽  
pp. 658
Author(s):  
Mahmoud Sheir ◽  
Rehab M. Samaka ◽  
Tamer Fakhry ◽  
Ayman A. Albatanony
Keyword(s):  
Ganglion Cells ◽  
Hirschsprung Disease ◽  
Rectal Biopsy ◽  
Diagnostic Value ◽  
Immunohistochemical Expression ◽  
University Hospitals ◽  
Female Ratio ◽  
Hematoxylin And Eosin ◽  
Rectal Biopsies ◽  
Male To Female

Background: Hirschsprung disease (HD) is diagnosed by absence of ganglion cells in rectal biopsy. In some cases, standard methods fail to diagnose agangliosis. The aim of this study is to assess the diagnostic value of immunohistochemistry (IHC) of calretinin and synaptophysin compared to standard methods.Methods: This prospective cross section study was conducted in Menoufia University hospitals, Egypt spanning the period between October 2017 to December 2018. Rectal biopsies of the clinically suspected HD patients stained with calretinin and synaptophysin and their results compared to the standard hematoxylin and eosin (H&E) stained sections.Results: A total of 30 patients aged from 3 days to 2 years with a male to female ratio 11:4 were examined for rectal biopsies. Sections of 9 cases were diagnosed HD. In inadequate specimens, sensitivity and specificity of calretinin and synpatophysin (100%, 80%) and (100%, 85.71%) respectively were superior to the sensitivity (40%) and specificity (14%) of H&E. However, in adequate specimens, results of H&E, calretinin and synaptophysin were the same.Conclusions: Immunohistochemical expression of calretinin and synaptophysin were conclusive, diagnostic and superior to the results of H&E stained section in inadequate. However, in adequate specimens calretinin and synaptophysin were consistent and confirmatory to the results of H&E sections.

A useful panel for the diagnosis of Hirschsprung disease in rectal biopsies: calretinin immunostaining and acetylcholinesterase histochesmistry

2013 ◽  
Vol 17 (4) ◽  
pp. 352-356 ◽  
Author(s):  
Pedro Luiz Toledo de Arruda Lourenção ◽  
Bonifácio Katsunori Takegawa ◽  
Erika Veruska Paiva Ortolan ◽  
Simone Antunes Terra ◽  
Maria Aparecida Marchesan Rodrigues
Keyword(s):  
Hirschsprung Disease ◽  
Rectal Biopsies

scholarly journals Are We Underdiagnosing Hirschsprung Disease?

2019 ◽  
Vol 23 (1) ◽  
pp. 60-71
Author(s):  
Raj P Kapur ◽  
Lusine Ambartsumyan ◽  
Caitlin Smith
Keyword(s):  
Transition Zone ◽  
Ganglion Cells ◽  
Hirschsprung Disease ◽  
Rectal Biopsy ◽  
Cholinergic Innervation ◽  
Short Segment ◽  
Recent Improvement ◽  
Recent Trends ◽  
Mucosal Innervation ◽  
Rectal Biopsies

Hirschsprung disease (HSCR) is conventionally defined as aganglionosis of the distal rectum and a variable length of proximal contiguous bowel with a transition zone of ganglionic, but neuroanatomically abnormal, bowel located immediately upstream. Recent improvement in our understanding of the pathology and genetics of HSCR and relevant animal models indicates highly variable expressivity. The spectrum of intestinal neuropathology includes patients with very short-segment aganglionosis, limited to the distal 1 to 2 cm of the rectum, and possibly patients with no true aganglionic segment, but nonphysiological transition zone pathology in their distal rectums. The presence or absence of submucosal ganglion cells in a rectal biopsy is not sufficient to exclude these patients, in whom submucosal nerve hypertrophy and/or abnormal cholinergic mucosal innervation may be the only diagnostic clues. In addition, diagnosis or exclusion of HSCR by rectal biopsy now relies in part on mucosal patterns of calretinin immunohistochemistry, with less emphasis on submucosal tissue adequacy and assessment of cholinergic innervation. These recent trends in the surgical pathology approach to rectal biopsies may miss patients at the phenotypically milder end of the malformation spectrum, with profound implications for subsequent management, prognosis, and genetic counseling.

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