Evaluation of the Diagnostic Value of Calretinin Immunohistochemistry Assay in the Superficial Rectal Biopsy of Children Suspected of Hirschsprung's Disease

Document Type : Original Article

Authors

1 Department of Pathology, Isfahan University of Medical Sciences, Isfahan, Iran

2 Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

Background: Hirschsprung's disease (HD) is the most common cause of colon obstruction in neonates. Lack of calretinin immunohistochemistry (IHC) in colon lamina propria could be associated with aganglionosis.
Methods: This cross-sectional retrospective study examined 64 patients suspicious of HD and conducted on collected-demographic data and Hematoxylin/Eosin (H & E) results of the surgical rectal biopsy from the archive of Imam Hossein Hospital, Isfahan, Iran. Calretinin IHC was achieved for all the specimens, and the results of the two methods were compared. The receiver operating characteristic (ROC) chart shows sensitivity changes according to (1-specificity). Moreover, sensitivity, specificity, as well as the positive and negative predictive values (PPV and NPV) of calretinin staining in lamina propria and muscularis mucosa, compared to H & E staining, was calculated in this study.
Results: The number of males and females was the same in this study (n=32; 50%). The age of the patients ranged from 1 month to 156 months (13 years). Out of 64 patients, 8 cases were diagnosed with HD, and calretinin staining was negative in 7 patients; moreover, only one case showed weak positive staining. In 56 patients, who were not HD, two patients with negative calretinin staining had a positive H&E staining report. The current study aimed to check the diagnostic value of calretinin IHC in lamina propria of patients suspicious of HD. Compared to H&E staining, which is the routine method in thick wall biopsies, the statistics show that calretinin IHC has a high diagnostic value (P<0.001), sensitivity of 87%, specificity of 96%, PPV of 77%, and NPV of 98%.
Conclusion: In conclusion, calretinin IHC utilized in specimens seems superficial and inadequate; moreover, the association with the high specificity percentage (96%) could help physicians with less invasive biopsy methods, such as endoscopic rectal biopsy.
 
 

Keywords

References

  1. Mukhopadhyay B, Mukhopadhyay M, Mondal KC, Sengupta M, Paul A. Hirschsprung’s disease in neonates with special reference to calretinin immunohistochemistry. J Clin Diagn Res. 2015;
    9(7):EC06-9.
  2. Tran VQ, Lam KT, Truong DQ, Dang MH, Doan TTP, Segers V, et al. Diagnostic value of rectal suction biopsies using calretinin immunohistochemical staining in Hirschsprung's disease. J Pediatr Surg. 2016;51(12):2005-9.
  3. Guinard-Samuel V, Bonnard A, De Lagausie P, Philippe-Chomette P, Alberti C, El Ghoneimi A, et al. Calretinin immunohistochemistry: a simple and efficient tool to diagnose Hirschsprung disease.
  4. Najjar S, Ahn S, Kasago I, Zuo C, Umrau K, Ainechi S, et al. Image processing and analysis of mucosal calretinin staining to define the transition zone in Hirschsprung disease: a pilot study. Eur J Pediatr Surg. 2019;29(02):179-87.
  5. Rakhshani N, Araste M, Imanzade F, Panahi M, Tameshkel FS, Sohrabi MR, et al. Hirschsprung disease diagnosis: Calretinin marker role in determining the presence or absence of ganglion cells. Iran J Pathol. 2016;11(4):409-15.
  6. Haricharan RN, Georgeson KE. Hirschsprung disease. Semin Pediatr Surg. 2008;17(4):266-75.
  7. Muise ED, Cowles RA. Rectal biopsy for Hirschsprung's disease: a review of techniques, pathology, and complications. World J Pediatr. 2016;12(2):135-41.
  8. Kruger GM, Mosher JT, Tsai Y-H, Yeager KJ, Iwashita T, Gariepy CE, et al. Temporally distinct requirements for endothelin receptor B in the generation and migration of gut neural crest stem cells. Neuron. 2003;40(5):917-29.
  9. de Lorijn F, Kremer LC, Reitsma JB, Benninga M. Diagnostic tests in Hirschsprung disease: a systematic review. J Pediatr Gastroenterol Nutr. 2006;42(5):496-505.
  10. Halleran DR, Ahmad H, Lehmkuhl H, Baker P, Wood RJ, Levitt MA, et al. Suction Rectal Biopsy Is Accurate in Late Preterm Infants with Suspected Hirschsprung Disease. J Pediatr Surg. 2020;55(1):67-70.
  11. Ambartsumyan L, Smith C, Kapur RP. Diagnosis of Hirschsprung Disease. Pediatr Dev Pathol. 2020;
    23(1):8-22.
  12. Musa ZA, Qasim BJ, Ghazi HF, Al Shaikhly AWA. Diagnostic roles of calretinin in hirschsprung disease: A comparison to neuron-specific enolase. Saudi J Gastroenterol. 2017;23(1):60-66.
  13. Jeong H, Jung HR, Hwang I, Kwon SY, Choe M, Kang YN, et al. Diagnostic Accuracy of Combined Acetylcholinesterase Histochemistry and Calretinin Immunohistochemistry of Rectal Biopsy Specimens in Hirschsprung’s Disease. Int J Surg Pathol. 2018;26(6):507-13.
  14. Agrawal R, Kakkar N, Vasishta R, Kumari V, Samujh R, Rao K, et al. Acetylcholinesterase histochemistry (AChE)-A helpful technique in the diagnosis and in aiding the operative procedures of Hirschsprung disease. Diagn Pathol. 2015;10(1):1-8.
  15. Taguchi T, Tanaka K, Ikeda K. Immunohistochemical study of neuron specific enolase and S-100 protein in Hirschsprung's disease. Virchows Arch A Pathol Anat Histopathol. 1985;405(4):399-409.
  16. Kawana T, Nada O, Ikeda K, Goto S, Hirose R, Taguchi T, et al. Distribution and localization of glia fibrillary acidic protein in colons affected by Hirschsprung's disease. J Pediatr Surg.1989;24(5):448-52.
  17. Nakao M, Suita S, Taguchi T, Hirose R, Shima Y. Fourteen-year experience of acetylcholinesterase staining for rectal mucosal biopsy in neonatal Hirschsprung's disease. J Pediatr Surg. 2001;36(9):
    1357-63.
  18. Burtelow MA, Longacre TA. Utility of microtubule associated protein-2 (MAP-2) immunohistochemistry for identification of ganglion cells in paraffin-embedded rectal suction biopsies. Am J Surg Pathol. 2009;33(7):1025-30.
  19. Park S-H, Min H, Chi JG, Park KW, Yang HR, Seo JK, et al. Immunohistochemical studies of pediatric intestinal pseudo-obstruction: bcl2, a valuable biomarker to detect immature enteric ganglion cells. Am J Surg Pathol. 2005;29(8):1017-24.
  20. Gonzalo DH, Plesec T. Hirschsprung disease and use of calretinin in inadequate rectal suction biopsies. Arch Pathol Lab Med. 2013;137(8):1099-102.
  21. Muller CO, Hobeika C, Montalva L, Berrebi D, Bonnard A. Calretinin Variant in Hirschsprung Disease: Pretransitional Sign and Surgical Planning. Eur J Pediatr Surg. 2016;26(05):449-53.
  22. Russo P, Ruchelli ED, Piccoli DA. Pathology of pediatric gastrointestinal and liver disease: Springer. 2014.
  23. Kapur RP. Can we stop looking? Immunohis-tochemistry and the diagnosis of Hirschsprung disease. Am J Clin Pathol. 2006;126(1):9-12.
  24. Holland SK, Ramalingam P, Podolsky RH, Reid-Nicholson MD, Lee JR. Calretinin immunostaining as an adjunct in the diagnosis of Hirschsprung disease. Ann Diagn Pathol. 2011;15(5):323-8.
  25. 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(5):1053-9.
  26. Małdyk J, Rybczyńska 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(1):34-9.

 

 

Iranian Journal of Neonatology
Volume 13, Issue 1
January 2022
Pages 25-29

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