Diagnostic Role of Calretinin in Suspicious Cases of Hirschsprung’s Disease

Singh, Sanjeev Kumar; Gupta, Umesh Kumar; Aggarwal, Ramesh; Rahman, Rafey Abdul; Gupta, Nitin; Verma, Vandana

doi:10.7759/cureus.13373

Cited by 4 publications

(3 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…23,24 With a male-to-female ratio of 3.6:1, which is analogous to the universal ratio of 2.9: 1 to 4.5: 1, the current study demonstrated that males were more afflicted than females, 25 75% of our HD-positive patients were suffering from chronic constipation which is compatible with other published studies. 23,26 The second most frequent symptom was delayed meconium passage, while 10% of children reported intestinal obstruction, and our clinical assessment was consistent with the clinical findings in the literature. 24 Rectal biopsy continues to be the gold standard for definitively diagnosing HD.…”

Section: Discussionsupporting

confidence: 88%

Hirschsprung’s Disease Diagnosis: A Comparison of Calretinin and CD56 Immunohistochemistry

Aldeen,

Al-rawi,

Hamad Amen

2024

Adv.med.j.

View full text Add to dashboard Cite

Background & objectives: Hirschsprung’s disease is attributable to the congenital lack of ganglion cells in the far intestine. Rectal biopsy is deemed critical for its testing. In some instances, regular techniques fail to detect it. This study aims to evaluate the testing role of calretinin and CD56 immunohistochemistry and correlate the results to routine hematoxylin & eosin stained samples. Methods: This retrospective study was conducted in Rizgary Teaching Hospital, Erbil, Kurdistan region, Iraq. Rectal biopsies and colonic resection specimens of the clinically suspected Hirschsprung’s disease patients were collected and stained with calretinin and CD56 then their findings were compared to the hematoxylin and eosin stained sections during the period between February 2016 to October 2021. Results: Fifty patients aged from 3 days to 8 years with a male-to-female ratio of 3.6:1 were examined for rectal and colonic biopsies. Forty out of 50 cases were detected as HD by H&E staining. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy rate of calretinin were coherent with that of H&E-stained samples (100%), the likelihood ratio was 50 and the kappa test was 1, were superior to CD56 results with sensitivity (100%), specificity (90%), positive predictive value (97.5%), negative predictive value (100%), accuracy rate (98%), likelihood ratio was 27.77 and kappa test was 0.805. Conclusions: Immunohistochemical expression of calretinin is more specific and accurate than CD56 in HD diagnosis. Calretinin is a trustworthy, additional diagnostic tool for better morphological evaluation of ganglion cells and thereby assists in making a reliable diagnosis of HD.

show abstract

Section: Discussionsupporting

confidence: 88%

Hirschsprung’s Disease Diagnosis: A Comparison of Calretinin and CD56 Immunohistochemistry

Aldeen,

Al-rawi,

Hamad Amen

2024

Adv.med.j.

View full text Add to dashboard Cite

show abstract

“…Jorge et al reported an average of 2.7 months (approximately 80 days) in their sample with only calretinin IHC diagnostics [1]. Singh et al were able to diagnose 73% of all HD patients within the first 28 days of life using calretinin IHC [17]. Calretinin enables the diagnosis of HD to be made at any time.…”

Section: Discussionmentioning

confidence: 99%

Clinical Relevance of Pathological Diagnosis of Hirschsprung’s Disease with Acetylcholine-Esterase Histochemistry or Calretinin Immunohistochemistry

Romero,

Burger,

Wennberg

et al. 2024

Children

View full text Add to dashboard Cite

Introduction: Hirschsprung disease (HD) manifests as a developmental anomaly affecting the enteric nervous system, where there is an absence of ganglion cells in the lower part of the intestine. This deficiency leads to functional blockages within the intestines. HD is usually confirmed or ruled out through rectal biopsy. The identification of any ganglion cells through hematoxylin and eosin (H&E) staining rules out HD. If ganglion cells are absent, further staining with acetylcholine-esterase (AChE) histochemistry or calretinin immunohistochemistry (IHC) forms part of the standard procedure for determining a diagnosis of HD. In 2017, our Institute of Pathology at University Hospital of Heidelberg changed our HD diagnostic procedure from AChE histochemistry to calretinin IHC. In this paper, we report the impact of the diagnostic procedure change on surgical HD therapy procedures and on the clinical outcome of HD patients. Methods: We conducted a retrospective review of the diagnostic procedures, clinical data, and postoperative progress of 29 patients who underwent surgical treatment for HD in the Department of Pediatric Surgery, University of Heidelberg, between 2012 and 2021. The patient sample was divided into two groups, each covering a treatment period of 5 years. In 2012–2016, HD diagnosis was performed exclusively using AChE histochemistry (AChE group, n = 17). In 2017–2021, HD diagnosis was performed exclusively using calretinin IHC (CR group, n = 12). Results: There were no significant differences between the groups in sex distribution, weeks of gestation, birth weight, length of the aganglionic segment, or associated congenital anomalies. Almost half of the children in the AChE group, twice as many as in the CR group, required an enterostomy before transanal endorectal pull-through procedure (TERPT). In the AChE group, 4 patients (23.5%) required repeat bowel sampling to confirm the diagnosis. Compared to the AChE group, more children in the CR group suffered from constipation post TERPT. Discussion: Elevated AChE expression is linked to hypertrophied extrinsic cholinergic nerve fibers in the aganglionic segment in the majority of patients with HD. The manifestation of increased AChE expression develops over time. Therefore, in neonatal patients with HD, especially those in the first 3 weeks of life, an increase in AChE reaction is not detected. Calretinin IHC reliably identifies the presence or absence of ganglion cells and offers multiple benefits over AChE histochemistry. These include the ability to perform the test on paraffin-embedded tissue sections, a straightforward staining pattern, a clear binary interpretation (negative or positive), cost-effectiveness, and utility regardless of patient age. Conclusions: The ability of calretinin IHC to diagnose HD early and time-independently prevented repeated intestinal biopsies in our patient population and allowed us to perform a one-stage TERPT in the first months of life, reducing the number of enterostomies and restoring colonic continuity early. Patients undergoing transanal pull-through under the age of 3 months require a close follow-up to detect cases with bowel movement problems.

show abstract

“…They reported sensitivity of calretinin as 100%, specificity as 68.75%, and positive and negative predictive values as 85.33% and 100%, respectively. 9 Under light microscopy the ganglion cells are identified by their classic cytological features. They have sufficient cytoplasm, nucleus is to one side and it is round and have a prominent nucleolus.…”

Section: Discussionmentioning

confidence: 99%

Is nerve bundle hypertrophy a reliable criteria for diagnosing Hirschsprung disease? A case control study using Calretinin as an adjunct tool for confirming Hirschsprung disease.

Sarwar

Qaiser

Mumtaz

et al. 2022

TPMJ

View full text Add to dashboard Cite

Objective: To determine the frequency of nerve bundle hypertrophy in aganglionic segments in relation to the site of biopsy, along with the assessment of value of Calretinin immunostaining in the diagnosis of suspected cases of Hirschsprung disease. Study Design: Cross Sectional study. Setting: Department of Pathology, Pakistan Institute of Medical Sciences (PIMS) Islamabad. Period: September 2018 to March 2019. Material & Methods: After routine tissue processing colonic biopsies were examined for presence of ganglion cells and hypertrophic nerve presence or absence. Diagnosis of Hirschsprung disease was based on the absence of ganglion cells in submucosal and myenteric plexus, the presence or absence of hypertrophic nerves (more than 4 nerves >30 µm thick/×200 field or more than 2 nerves >40 µm thick/×200 field) was also noted in all cases of Hirschsprung disease (aganglionic segments). Calretinin immunostaining was applied to all the cases and controls and findings were recorded as positive or negative staining. Statistical Analysis: Data was analyzed using SPSS version 23. Qualitative data was calculated as frequencies and percentages. Pearson Chi square test was used to establish the association of nerve bundle hypertrophy with the site of biopsy. Results: Total biopsies were 60; 30 each from ganglionic and aganglionic segments. Calretinin sensitivity in our study was 90%, specificity 83.3%. In 30 cases of aganglionosis hypertrophic nerves were present in 13(21.7%) and they were absent in 17 (28.3%). No significant association (p value= 0.447) was seen in nerve bundle hypertrophy and site of biopsy. Conclusion: Calretinin immunohistochemistry can be used as a reliable ancillary technique in the diagnosis of HD. Aganglionosis may not always be associated with submucosal nerve hypertrophy which alone should not be used as a criteria for HD diagnosis but instead adjunct methods like Calretinin immunostaining must be utilized to confirm presence or absence of ganglion cells. There is no association of nerve hypertrophy with site of biopsy.

show abstract

Diagnostic Role of Calretinin in Suspicious Cases of Hirschsprung’s Disease

Cited by 4 publications

References 20 publications

Hirschsprung’s Disease Diagnosis: A Comparison of Calretinin and CD56 Immunohistochemistry

Hirschsprung’s Disease Diagnosis: A Comparison of Calretinin and CD56 Immunohistochemistry

Clinical Relevance of Pathological Diagnosis of Hirschsprung’s Disease with Acetylcholine-Esterase Histochemistry or Calretinin Immunohistochemistry

Is nerve bundle hypertrophy a reliable criteria for diagnosing Hirschsprung disease? A case control study using Calretinin as an adjunct tool for confirming Hirschsprung disease.

Contact Info

Product

Resources

About