doi: 10.25005/2074-0581-2023-25-4-466-477


1Faculty of Medicine and Health Sciences, Universiti Malaysia Sarawak, Kota Samarahan, Malaysia
2Saint James School of Medicine, Valley, Anguilla
3Volgograd State Medical University, Volgograd, Russian Federation
4Municipal Clinical Emergency Hospital № 7, Volgograd, Russian Federation
5Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh, Malaysia

Objective: To compare the immunohistochemical (IHC) characteristics of appendices removed from children with acute appendicitis and chronic pain syndrome (CP) in the right lower quadrant of the abdomen (RLQA), as well as to define clinical and morphological correlations.

Methods: The structure of fifty-one appendices of children aged 5-14 years who underwent appendectomy for chronic appendicitis/CP in the RLQA (24 patients, Group 1) and acute appendicitis (27 patients, Group 2) was assessed. Image analysis of histological sections stained with hematoxylin-eosin and immunohistochemically for S100 protein and proliferating cell nuclear antigen (PCNA) was performed.

Results: Image analysis showed the presence of a significantly higher volume density (VD) and numerical density (ND) (p<0.05) of immunoreactive cells when stained for S100 protein, as well as the ND of intramural ganglia (p<0.05) against the background of minimal histological changes in the wall of the appendix in patients of Group 1 compared to Group 2. On the contrary, the ND of PCNA-immunoreactive cells was significantly higher in patients of Group 2 against the background of pronounced inflammatory changes in the appendix (p<0.01). In the biopsy samples of the Group 1 patients, a significantly higher ND of the lymphoid nodule germinal centers was also noted (p<0.05), while the ND of tingible body macrophages was higher in Group 2 patients (p<0.001). These results demonstrate differences in neuroimmune parameters in the appendices in the two described nosologic groups and indicate the possible role of the appendiceal neural component as a prerequisite for developing CP in the RLQA in children

Keywords: Appendix, Schwann cell, S100 protein, PCNA, appendicitis, chronic abdominal syndrome.

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  1. Di Sebastiano P, Fink T, di Mola FF, Weihe E, Innocenti P, Friess H, et al. Neuroimmune appendicitis. Lancet. 1999;354(9177):461-6. https://doi. org/10.1016/S0140-6736(98)10463-4
  2. Zdichavsky M, Gögele H, Blank G, Kraulich M, Meile T, von Feilitzsch M, et al. Histological characterization of appendectomy specimens with intraoperative appearance of vascular injection. Surg Endosc. 2013;27(3):849-53. https://doi. org/10.1007/s00464-012-2523-x
  3. Peisl S, Burckhardt O, Egger B. Neurogenic appendicopathy: An underestimated disease-systematic review of the literature. Int J Colorectal Dis. 2021;36(9):1995- 2005. https://doi.org/10.1007/s00384-021-03901-1
  4. Hussein MRA, Al Bshabshe A, Elhakeem AA, Elsamman MK. Neurogenic appendicitis: A reappraisal of the clinicopathological features and pathogenesis. Diagnostics (Basel). 2022;12(6):1386. https://doi.org/10.3390/ diagnostics12061386
  5. Kaya A, Karaman K, Aziret M, Ercan M, Köse E, Kahraman YS, et al. The role of hematological parameters in distinguishing acute appendicitis from lymphoid hyperplasia. Ulus Travma Acil Cerrahi Derg. 2022;28(4):434-9. https://doi. org/10.14744/tjtes.2020.69027
  6. Dohner E, Kierdorf F, Moreno P, Langer R, Zuber M, Fahrner R. Neurogenic appendicopathy: A rare differential diagnosis of acute appendicitis. J Visc Surg. 2023:S1878-7886(23)00035-8. https://doi.org/10.1016/j.jviscsurg.2023.02.006
  7. Güller U, Rosella L, McCall J, Brügger LE, Candinas D. Negative appendicectomy and perforation rates in patients undergoing laparoscopic surgery for suspected appendicitis. Br J Surg. 2011;98:589-95.
  8. Sesia SB, Mayr J, Bruder E, Haecker FM. Neurogenic appendicopathy: Clinical, macroscopic, and histopathological presentation in pediatric patients. Eur J Pediatr Surg. 2013;23(3):238-42. https://doi.org/10.1055/s-0032-1333119
  9. Franke C, Gerharz CD, Böhner H, Ohmann C, Heydrich G, Krämling HJ, et al. Neurogenic appendicopathy in children. Eur J Pediatr Surg. 2002;12(1):28-31. https://doi.org/10.1055/s-2002-25092
  10. Xiong S, Puri P, Nemeth L, O'Briain DS, Reen DJ. Neuronal hypertrophy in acute appendicitis. Arch Pathol Lab Med. 2000;124(10):1429-33. https://doi. org/10.5858/2000-124-1429-NHIAA
  11. Partecke LI, Thiele A, Schmidt-Wankel F, Kessler W, Wodny M, Dombrowski F, et al. Appendicopathy – a clinical and diagnostic dilemma. Int J Colorectal Dis. 2013;28(8):1081-9. https://doi.org/10.1007/s00384-013-1677-x
  12. Amber S, Mathai AM, Naik R, Pai MR, Kumar S, Prasad K. Neuronal hypertrophy and mast cells in histologically negative, clinically diagnosed acute appendicitis: A quantitative immunophenotypical analysis. Indian J Gastroenterol. 2010;29(2):69-73.
  13. Petroianu A, Barroso TVV, Buzelin MA, Theobaldo BM, Tafuri LSA. Neuroendocrine appendicopathy in morphologically normal appendices of patients with diagnosis of acute appendicitis: Diagnostic study. Ann Med Surg (Lond). 2020;60:344-51. https://doi.org/10.1016/j.amsu.2020.10.044
  14. Seifarth FG, Barry JN, Forse CL, Plesec TP, Worley S, Mahajan L. Appendiceal follicular hyperplasia: A possible indicator for chronic appendicitis in children. J Laparoendosc Adv Surg Tech A. 2023 Jun 16. https://doi.org/10.1089/ lap.2023.0026
  15. Xu Y, Jeffrey RB, DiMaio MA, Olcott EW. Lymphoid hyperplasia of the appendix: A potential pitfall in the sonographic diagnosis of appendicitis. AJR. 2016;206(1):189-94. https://doi.org/10.2214/AJR.15.14846
  16. Phillips AW, Jones AE, Sargen K. Should the macroscopically normal appendix be removed during laparoscopy for acute right iliac fossa pain when no other explanatory pathology is found? Surg Laparosc Endosc Percutan Tech. 2009;19:392-4.
  17. van Rossem CC, Treskes K, Loeza DL, van Geloven AA. Laparoscopic appendectomy for chronic right lower quadrant abdominal pain. Int J Colorectal Dis. 2014 Oct;29(10):1199-202. doi: 10.1007/s00384-014-1978-8.
  18. Villar Barroso TV, Petroianu A. Neuroimmunoendocrine peptides on inflammed a ndmorphologicallynormalappendicesremoveddue toclinicalacuteappendicitis. Int J Surg. 2019;67:76-8. https://doi.org/10.1016/j.ijsu.2019.05.017
  19. Akbulut S, Tas M, Sogutcu N, Arikanoglu Z, Basbug M, Ulku A, Semur H, et al. Unusual histopathological findings in appendectomy specimens: A retrospective analysis and literature review. World J Gastroenterol. 2011;17(15):1961-70. https://doi.org/10.3748/wjg.v17.i15.1961
  20. Kubikova E, Sivakova I, Falougy HE, Perzelova A. Subserosal localization of myenteric ganglia in normal human appendix: Immunostaining with neuronal and glial markers. Bratisl Lek Listy. 2018;119(12):743-6. https://doi.org/10.4149/ BLL_2018_135
  21. Ucar Karabulut K, Erinanc H, Yonar A, Kisinma A, Ucar Y. Correlation of histological diagnosis and laboratory findings in distinguishing acute appendicitis and lymphoid hyperplasia. Ann Surg Treat Res. 2022;103(5):306-11. https://doi. org/10.4174/astr.2022.103.5.306
  22. Gupta G, Srivastava SK, Mathur SK, Gupta V. Histomorphometric characteristics of human vermiform appendix with special reference to lymphoid tissue. J Morphol Sci. 2012;29(3):135-9.
  23. Swischuk LE, Chung DH, Hawkins HK, Jadhav SP, Radhakrishnan R. Nonfecalith-induced appendicitis: Etiology, imaging, and pathology. Emerg Radiol. 2015;22(6):643-9. https://doi.org/10.1007/s10140-015-1338-1
  24. Trivedi N, Gupta D, Sood R, Singh A, Tewari A, Agarwal Sh, et al. A review on placental tuberculosis. Journal of Advances in Medicine and Medical Research. 2020;32(15):42-7. https://doi.org/10.9734/jammr/2020/v32i1530605
  25. Heerema-McKenney A. Defense and infection of the human placenta. Journal of Pathology, Microbiology and Immunology. 2018;126(7):570-88. https://doi. org/10.1111/apm.12847

Author information:

Kapitonova Marina,
MD, PhD, Professor, Professor of Anatomy, Faculty of Medicine and Health Sciences, Universiti Malaysia Sarawak

Researcher ID: Y-6429-2018
Scopus ID: 8854275100
ORCID ID: 0000-0001-6055-3123
SPIN: 5647-3218
Author ID: 121504
E-mail: kmarina@unimas.my

Brohi Imam Bux,
MD, Associate Professor of the Family Medicine, Faculty of Medicine and Health Sciences, Universiti Malaysia Sarawak
ORCID ID: 0000-0001-7574-2154
E-mail: bimam@unimas.my

Gupalo Sergey,
MD, MS, Associate Professor of Pathology, Saint James School of Medicine
Scopus ID: 56657520000
ORCID ID: 0000-0002-8487-1409
E-mail: sgupalo@mail.sjsm.org

Smirnov Aleksey Vladimirovich,
MD, PhD, Professor, Head of Pathology Department, Volgograd State Medical University
Scopus ID: 57213379797
ORCID ID: 0000- 0001-5351-6105
E-mail: alexey-smirnov@rambler.ru

Petrenyuk Vyacheslav Savvovich,
MD, General Surgeon, Head of the 1st Children’s Surgical Department, Municipal Clinical Emergency Hospital № 7 (died in May, 2023)
Scopus ID: 6505949589

Ahmad Azhar,
BSc, MSc, Researcher, Institute of Medical Molecular Biotechnology, Faculty of Medicine, Universiti Teknologi MARA
Scopus ID: 57212513419
ORCID ID: 0000- 0001-5456-079X
E-mail: biotech.azhar@gmail.com

Information about support in the form of grants, equipment, medications

The study was supported by grant of the Malaysian Ministry of Higher Education FRGS/2/2013/SKK01/UITM/01/4/. The authors did not receive financial support from manufacturers of medicines and medical equipment

Conflicts of interest: No conflict

Address for correspondence:

Gupalo Sergey,
MD, MS Associate Professor of Pathology, Saint James School of Medicine

A-1, Albert Lake Dr, The Quarter 2640, Anguilla

Tel.: +6017 6205710

E-mail: sgupalo@mail.sjsm.org

Materials on the topic: