Appendicular Biopsy in Total Colonic Aganglionosis

Background The reliability of intraoperative evaluation of ganglion cells in the appendix as a guide to a diagnosis of total colonic aganglionosis is unclear. Objective To evaluate the diagnostic utility of appendicular innervation in colonic Hirschsprung disease (HD) and TCA. Methods Prospective, systematic study of ganglion cells and the neural plexii in appendices from cases (HD and TCA) and age matched controls with frozen and paraffin sections, rapid acetylcholinesterase (AChE) and immunohistochemistry. Results A total of 48 appendices (28 controls, 20 cases; 19 frozen) were evaluated. Of these 48, 30 were neonates. Ganglion cell clusters were smaller in controls (28) and HD (6) than those in the rectum, distorted at places and mimicked lymphocytes and endothelial cells, especially in neonates. Complete study of 13 appendices in TCA showed absence of ganglion cells, hypertrophic nerves, AChE activity, and calretinin staining. In 2/13 TCA, an erroneous frozen section identification of ganglia was later corrected based on AChE histochemistry and a panel of IHC stains. Ileal biopsies guided the placement of a ganglionic ileostomy in all. One case each of skip segment aganglionosis in a TCA and variable hypoganglionosis in long segment colonic HD is reported. Conclusion Intraoperative characterization of appendicular innervation as a guide to the diagnosis of TCA is unreliable, in part because of the possibility of skip segment disease/variable hypoganglionosis. We propose terminal ileal biopsies for diagnosis and leveling of aganglionosis. AChE on frozen/calretinin on paraffin tissue is the best approach to avoid diagnostic errors.

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Total Colonic Aganglionosis: Case Report, Practical Diagnostic Approach and Pitfalls

Archives of Pathology & Laboratory Medicine ◽

10.5858/2010-0279-cr.1 ◽

2010 ◽

Vol 134 (10) ◽

pp. 1467-1473 ◽

Cited By ~ 3

Author(s):

Raja Rabah

Keyword(s):

Transition Zone ◽

Ganglion Cells ◽

Hirschsprung Disease ◽

Rectal Biopsy ◽

Nerve Fibers ◽

Submucosal Plexus ◽

Total Colonic Aganglionosis ◽

Biopsy Specimens ◽

Suction Rectal Biopsy ◽

Acetylcholinesterase Staining

Abstract Hirschsprung disease remains a challenging diagnosis for many pathologists. The disease is characterized by a lack of ganglion cells in the myenteric and submucosal plexus, associated with increased numbers of acetylcholinesterase-positive nerve fibers. Hypertrophic nerve fibers are present in most but not all patients. Total colonic aganglionosis (TCA) is an uncommon form of Hirschsprung disease with clinical, histologic, and genetic differences and is even more difficult to diagnose and manage. This case illustrates some of the difficulties frequently faced by the pathologists dealing with total colonic aganglionosis. Suction rectal biopsy specimens often lack significant nerve hypertrophy and positive acetylcholinesterase staining, which aid in the diagnosis. Pathologists have to depend mainly on the lack of ganglion cells in adequate submucosa to establish the diagnosis. Transition zone is often long in total colonic aganglionosis and interpretation of frozen sections can be difficult. The presence of several uniformly distributed clusters of mature ganglion cells and lack of nerve hypertrophy are required to avoid connections at the transition zone.

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Reoperation for Hirschsprung Disease: Pathology of the Resected Problematic Distal Pull-Through

Pediatric and Developmental Pathology ◽

10.2350/11-02-0977-oa.1 ◽

2012 ◽

Vol 15 (1) ◽

pp. 30-38 ◽

Cited By ~ 38

Author(s):

Alexander Coe ◽

Margaret H. Collins ◽

Taiwo Lawal ◽

Emily Louden ◽

Marc A. Levitt ◽

...

Keyword(s):

Transition Zone ◽

High Power ◽

Ganglion Cells ◽

Frozen Section ◽

Hirschsprung Disease ◽

Postoperative Outcome ◽

Surgical Removal ◽

High Power Field ◽

Pull Through ◽

Poor Outcomes

Hirschsprung disease, which consists of aganglionosis of the rectum and sometimes more proximal bowel, requires surgical removal of the aganglionic bowel and creation of ganglionated neorectum using proximal normally innervated bowel. The border between aganglionic and ganglionic bowel is irregular; the transition zone features variable quantities of ganglion cells and numerous large nerves. We report the histopathology of pull-through bowel segments resected because of poor postoperative outcome from 30 patients (22 boys, 8 girls). The most common indication for reoperation was severe constipation/obstruction. Transition zone (bowel with at least two nerves ≥40 μm diameter per 400× high-power field, and ganglion cells) or aganglionic bowel (bowel with at least two nerves ≥40 μm per high-power field diameter, but without ganglion cells) was found in 19/30 (63%) resections. In colons resected because of familial adenomatous polyposis, rare high-power fields showed two enlarged nerves; the mean age of those patients (135 ± 49.4 months) was significantly higher than that of the patients undergoing redo pull-through surgery (67.9 ± 42.8 months). Additional pathology included stricture and enterocolitis. Although there are multiple causes for poor outcomes following surgical therapy for Hirschsprung disease, abnormal innervation of the bowel used for pull-through is common. We recommend that intraoperative consultation at primary pull-through procedure include frozen section evaluation of the circumference of the bowel to be used for pull-through to confirm histologically the presence of both ganglion cells and normal-caliber nerves. The criteria used in this study are most suitable for infants and young children.

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A Retrospective Cohort Study of Total Colonic Aganglionosis: Is the Appendix a Reliable Diagnostic Tool?

Journal of Neonatal Surgery ◽

10.21699/jns.v5i4.460 ◽

2016 ◽

Vol 5 (4) ◽

pp. 44 ◽

Cited By ~ 4

Author(s):

Thomas Joseph O'Hare ◽

Michael McDermott ◽

Maureen O'Sullivan ◽

Pat Dicker ◽

Brice Antao

Keyword(s):

Cohort Study ◽

Retrospective Cohort Study ◽

Retrospective Cohort ◽

Ganglion Cells ◽

Frozen Section ◽

Histopathological Analysis ◽

Total Colonic Aganglionosis ◽

Term Outcome ◽

Long Term Outcome ◽

Pull Through

Background: Hirschsprung’s disease (HD) is characterized by a lack of ganglion cells in the myenteric and submucosal plexus, associated with increased numbers of acetyl cholinesterase (AChE) positive nerve fibres. In approximately 10% of patients with HD the entire colon will be affected; a condition known as Total Colonic Aganglionosis (TCA). Aganglionosis of the appendix has long been considered to be an important finding in a patient in whom TCA is suspected, but its reliability for diagnosis has seldom been discussed. The aim of our study was to assess the reliability of the appendix as a histological specimen for the diagnosis of TCA, and to evaluate the long-term outcome of TCA.Methods: A retrospective cohort study was performed of all pathological specimens of patients with confirmed HD in our institution between March 2006 and April 2016.Results: Out of a total of 91 patients identified, 15 patients also had histopathological analysis of the appendix. Nine of these cases were confirmed as having TCA. The remaining 6 patients had HD involving the rest of the bowel up to the ascending colon, with normal ganglion present in the caecum. The appendix was removed in all the 15 cases. All 9 patients with confirmed TCA had aganglionosis of the appendix as well. The remaining 6 cases of short and long segment HD not involving the caecum, demonstrated normal ganglion cells within the appendix.Conclusion: Aganglionosis of the appendix is a reliable tool in the diagnosis of TCA. The authors recommend that at the time of levelling biopsies, if aganglionosis extends to the mid-transverse colon, an ileostomy be performed and appendix sent for definitive confirmation of TCA. However, at the time of definitive surgery, a frozen section of pull-through segment of bowel is recommended to confirm the presence of ganglion cells.

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CASE REPORT: RARE FORM OF HIRSCHPRUNG’S DISEASE

10.35988/sm-hs.2020.118 ◽

2020 ◽

Vol 30 (5) ◽

pp. 82-84

Author(s):

Ilja Skalskis

Keyword(s):

Down Syndrome ◽

Case Report ◽

Clinical Symptoms ◽

Hirschsprung Disease ◽

Distal Colon ◽

Total Colonic Aganglionosis ◽

Sphincter Function ◽

Anal Sphincter Function ◽

History Of ◽

High Index Of Suspicion

Hirschsprung disease (HD) is a developmental disorder characterized by the absence of ganglia in the distal colon, resulting in a functional obstruction. Incidence of total colonic aganglionosis (TCA) is 1 in 500 000 and it accounts for 5-10% of all cases of HD. HD should be suspected in patients with typical clinical symptoms and a high index of suspicion is appropriate for infants with a predisposing condition such as Down Syndrome (DS), or for those with a family history of HD. The treatment of choice for HD is surgical, such as Swenson, Soave, and Duhamel procedures. The goals are to resect the affected segment of the colon, bring the normal ganglionic bowel down close to the anus, and preserve internal anal sphincter function. We present a clinical case report of TCA in a child with Down syndrome (DS) and review of literature.

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Characterization of Ground Squirrel Retinal Ganglion Cells

10.21236/ada230311 ◽

1990 ◽

Author(s):

N. Lugo-Garcia ◽

R. E. Blanco ◽

Ivonne Santiago

Keyword(s):

Retinal Ganglion Cells ◽

Ground Squirrel ◽

Ganglion Cells ◽

Retinal Ganglion

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Autopsy Study of Calretinin Immunohistochemistry in the Anorectal Canal in Young Infants and Potential Implications for Rectal Biopsy Approach in the Neonatal Period

Pediatric and Developmental Pathology ◽

10.1177/10935266211030172 ◽

2021 ◽

pp. 109352662110301

Author(s):

Heather Rytting ◽

Zachary J Dureau ◽

Jose Velazquez Vega ◽

Beverly B Rogers ◽

Hong Yin

Keyword(s):

Neonatal Period ◽

Ganglion Cells ◽

Hirschsprung Disease ◽

Rectal Biopsy ◽

Autopsy Study ◽

Pathologic Diagnosis ◽

Young Infants ◽

Autopsy Specimens ◽

Pectinate Line ◽

Age Range

Background Absent submucosal ganglion cells in biopsies 1-3 cm above the pectinate line establishes the pathologic diagnosis of Hirschsprung Disease (HD). Calretinin stains both ganglion cells and their mucosal neurites and has gained importance in HD diagnosis. Absent calretinin positive mucosal neurites in biopsies at the appropriate level above the pectinate line is highly specific for HD. Whether this applies to lower biopsies is uncertain. To address this, we studied anorectal canal autopsy specimens from infants. Methods We performed an autopsy study of infant anorectal canal specimens to describe calretinin staining in this region. Calretinin staining was correlated with histologic and gross landmarks. Results In all 15 non-HD specimens, calretinin positive mucosal neurites were present in glandular mucosa up to the anorectal line where neurites rapidly diminished. Age range was preterm 26 weeks to 3 months. Conclusions Calretinin positive mucosal neurites are present in glandular mucosa up to the anorectal line in young infants. This is potentially important regarding neonatal HD biopsy level and diagnosis. Positive calretinin staining at the anorectal line favors normal innervation making HD unlikely. Absent calretinin positive neurites in glandular mucosa is worrisome for HD in young infants, regardless of location.

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Characterization of GABA- and glycine-induced currents of solitary rodent retinal ganglion cells in culture

Neuroscience ◽

10.1016/0306-4522(88)90230-8 ◽

1988 ◽

Vol 27 (1) ◽

pp. 193-203 ◽

Cited By ~ 43

Author(s):

D.L. Tauck ◽

M.P. Frosch ◽

S.A. Lipton

Keyword(s):

Retinal Ganglion Cells ◽

Ganglion Cells ◽

Retinal Ganglion ◽

Cells In Culture ◽

Induced Currents

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Cytokeratin on Frozen Sections of Sentinel Node May Spare Breast Cancer Patients Secondary Axillary Surgery

Pathology Research International ◽

10.1155/2012/802184 ◽

2012 ◽

Vol 2012 ◽

pp. 1-5 ◽

Cited By ~ 2

Author(s):

Elisabeth Specht Stovgaard ◽

Tove Filtenborg Tvedskov ◽

Anne Vibeke Lænkholm ◽

Eva Balslev

Keyword(s):

Breast Cancer ◽

Sentinel Node ◽

Predictive Value ◽

Frozen Section ◽

Axillary Lymph ◽

Breast Cancer Patients ◽

Frozen Sections ◽

Paraffin Sections ◽

Significant Difference ◽

Diagnostic Values

Background. The feasibility and accuracy of immunohistochemistry (IHC) on frozen sections, when assessing sentinel node (SN) status intraoperatively in breast cancer, is a matter of continuing discussion. In this study, we compared a center using IHC on frozen section with a center not using this method with focus on intraoperative diagnostic values. Material and Methods. Results from 336 patients from the centre using IHC intraoperatively were compared with 343 patients from the center not using IHC on frozen section. Final evaluation on paraffin sections with haematoxylin-eosin (HE) staining supplemented with cytokeratin staining was used as gold standard. Results. Significantly more SN with isolated tumor cells (ITCs) and micrometastases (MICs) were found intraoperatively when using IHC on frozen sections. There was no significant difference in the number of macrometastases (MACs) found intraoperatively. IHC increased the sensitivity, the negative predictive value, and the accuracy of the intraoperative evaluation of SN without decreasing the specificity and positive predictive value of SN evaluation. Conclusions. IHC on frozen section leads to the detection of more ITC and MIC intraoperatively. As axillary lymph node dissection (ALND) is performed routinely in some countries when ITC and MIC are found in the SN, IHC on frozen section provides valuable information that can lead to fewer secondary ALNDs.

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