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

Dalya Sabah  Najm Aldeen; Rafal Abdulrazaq  Al-rawi; Kalthuma Salih  Hamad Amen

doi:10.56056/amj.2024.238

Authors

Dalya Sabah Najm Aldeen
Rafal Abdulrazaq Al-rawi
Kalthuma Salih Hamad Amen

DOI:

https://doi.org/10.56056/amj.2024.238

Keywords:

Hirschsprung’s disease, Ganglion cells, Immunohistochemistry, Calretinin, and CD56

Abstract

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.

Downloads

Download data is not yet available.

References

Langer JC. Hirschsprung Disease. In: Mattei P, editor. Fundamentals of pediatric surgery. New York (NY): Springer; 2011; 475-84.

Singh S, Croaker G, Manglick P, et al. Hirschsprung's disease: the Australian Paediatric Surveillance Unit's experience. Pediatr Surg Int. 2003; 19:247-50.

Parahita IG, Makhmudi A. Comparison of Hirschsprung-associated enterocolitis following Soave and Duhamel procedures. J Pediatr Surge. 2018; 53:1351-4.

Zain AZ, Fadhil SZ. Hirschsprung's Disease: a Comparison of Swenson's and Soave's Pull-through Methods. Iraqi J Med Sci. 2012; 10:69-74.

Alnajjar SM, Omer JT, Ali SA. Retrospective study of Hirschsprung's disease in Erbil city/Iraq during 2004–2016. Med J Babylon. 2020; 17:177.

Fukuzawa M. Progress in the treatment of and research on Hirschsprung's disease. Nihon Geka Gakkai Zasshi. 2014; 115:312-6.

Jiang M, Li K, Li S, et al. Calretinin, S100 and protein gene product 9.5 immunostaining of rectal suction biopsies in the diagnosis of Hirschsprung disease. Am J Transl Res. 2016;8: 3159.

Gonzalo DH, Plesec T. Hirschsprung disease and use of calretinin in inadequate rectal suction biopsies. Archives of Pathology and Laboratory Medicine. 2013; 137:1099-102.

Pradhan P, Pal P, Rath G. Role of Calretinin Immunohistochemical Stain in Evaluation of Hirschsprung’s Disease. J Clin Diagn Res. 2021;15: EC08-EC11

Kapur RP. Can we stop looking? Immunohistochemistry and the diagnosis of Hirschsprung disease. Oxford University Press Oxford, UK; 2006. p. 9-12.

Pacheco MC, Bove KE. Variability of acetylcholinesterase hyperinnervation patterns in distal rectal suction biopsy specimens in Hirschsprung disease. Pediatric and Developmental Pathology. 2008; 11:274-82.

Guinard-Samuel V, Bonnard A, De Lagausie P, et al. Calretinin immunohistochemistry: a simple and efficient tool to diagnose Hirschsprung disease. Mod Pathol. 2009; 22:1379-84.

Bjørn N, Rasmussen L, Qvist N, Detlefsen S, Ellebæk MB. Full-thickness rectal biopsy in children suspicious for Hirschsprung's disease is safe and yields a low number of insufficient biopsies. J Pediatr Surg. 2018; 53:1942-4.

Skog MS, Nystedt J, Korhonen M, et al. Expression of neural cell adhesion molecule and polysialic acid in human bone marrow-derived mesenchymal stromal cells. Stem Cell Research & Therapy. 2016; 7: 1-12.

Cohavy O, Targan SR. CD56 marks an effector T cell subset in the human intestine. J Immunol. 2007; 178:5524-32.

Yoshimaru K, Taguchi T, Obata S, et al. Immunostaining for Hu C/D and CD56 is useful for a definitive histopathological diagnosis of congenital and acquired isolated hypoganglionosis. Virchows Archiv. 2017; 470:679-85.

Kapur RP, Reed RC, Finn LS, Patterson K, Johanson J, Rutledge JC. Calretinin immunohistochemistry versus acetylcholinesterase histochemistry in the evaluation of suction rectal biopsies for Hirschsprung disease. Pediatr Dev Pathol. 2009; 12:6-15.

Musa ZA, Qasim BJ, Ghazi HF, Al Shaikhly AW. Diagnostic roles of calretinin in hirschsprung disease: A comparison to neuron-specific enolase. Saudi J Gastroenterol. 2017; 23:60.

Mukhopadhyay B, Mukhopadhyay M, Mondal KC, Sengupta M, Paul A. Hirschsprung’s disease in neonates with special reference to calretinin immunohistochemistry. J clin Diagnostic Res. 2015; 9:EC06.

Takawira C, D’Agostini S, Shenouda S, Persad R, Sergi C. Laboratory procedures update on Hirschsprung disease. J Pediatr Gastroenterol Nutr. 2015; 60:598-605.

Goldstein A, Hofstra R, Burns A. Building a brain in the gut: development of the enteric nervous system. Clinical genetics. 2013; 83:307-16.

Yadav L, Kini U, Das K, Mohanty S, Puttegowda D. Calretinin immunohistochemistry versus improvised rapid Acetylcholinesterase histochemistry in the evaluation of colorectal biopsies for Hirschsprung disease. Indian J Pathol Microbiol. 2014; 57: 369.

Ziad F, Katchy KC, Al Ramadan S, Alexander S, Kumar S. Clinicopathological features in 102 cases of Hirschsprung disease. Ann Saudi Med. 2006; 26:200-4.

Anbardar MH, Geramizadeh B, Foroutan HR. Evaluation of Calretinin as a new marker in the diagnosis of Hirschsprung disease. Iran J Pediatr. 2015; 25.

Ekenze S, Ngaikedi C, Obasi A. Problems and outcome of Hirschsprung’s disease presenting after 1 year of age in a developing country. World J Surg. 2011; 35:22-6.

Singh SK, Gupta UK, Aggarwal R, Rahman RA, Gupta NK, Verma V. Diagnostic Role of Calretinin in Suspicious Cases of Hirschsprung’s Disease. Cureus. 2021; 13.

Cinel L, Ceyran B, Güçlüer B. Calretinin immunohistochemistry for the diagnosis of Hirschprung disease in rectal biopsies. Pathol Res Pract. 2015; 211:50-4.

Barshack I, Fridman E, Goldberg I, Chowers Y, Kopolovic J. The loss of calretinin expression indicates aganglionosis in Hirschsprung’s disease. J Clin Pathol. 2004; 57:712-6.

Ma?dyk J, Rybczy?ska J, Piotrowski D, Kozielski R. Evaluation of calretinin immunohistochemistry as an additional tool in confirming the diagnosis of Hirschsprung disease. Pol J Pathol. 2014; 65:34-9.

Fakhry T, Samaka RM, Sheir M, Albatanony AA. Comparative study between use of calretinin and synaptophysin immunostaining in diagnosis of Hirschsprung disease. Int Surg J. 2019; 6:658-63.

Hiradfar M, Sharifi N, Khajedaluee M, Zabolinejad N, Jamshidi ST. Calretinin immunohistochemistery: an aid in the diagnosis of Hirschsprung’s disease. Iran J Basic Med Sci. 2012; 15:1053.

Zuikova V, Franckevica I, Strumfa I, Melderis I. Immunohistochemical diagnosis of Hirschsprung's disease and allied disorders. Acta Chirurgica Latviensis. 2015; 15:50.

Park S-H, Min H, Chi JG, Park KW, Yang HR, Seo JK. Immunohistochemical studies of pediatric intestinal pseudo-obstruction: bcl2, a valuable biomarker to detect immature enteric ganglion cells. Am J Surg pathol. 2005; 29:1017-24.