Skip to main content

Advertisement

SpringerLink
Log in

Chronic intestinal pseudo-obstruction: systematic histopathological approach can clinch vital clues

  • Original Article
  • Published:
Virchows Archiv Aims and scope Submit manuscript

Abstract

The histopathological approach of chronic intestinal pseudo-obstruction (CIP) is critical, and the findings are often missed by the histopathologists for lack of awareness and nonavailability of standard criteria. We aimed to describe a detailed histopathological approach for working-up cases of CIP by citing our experience. Eight suspected cases of CIP were included in the study to determine and describe an approach for reaching the histopathological diagnosis collected over a period of the last 1.5 years. The Hirschsprung’s disease was put apart from the scope of this study. A detailed light microscopic analysis was performed along with special and immunohistochemical stains. Transmission electron microscopy was carried out on tissue retrieved from paraffin embedded tissue blocks. Among the eight cases, three were neonates, one in the pediatric age group, two adolescent, and two adults. After following the described critical approach, we achieved the histological diagnoses in all the cases. The causes of CIP noted were primary intestinal neuronal dysplasia (IND) type B (in 4), mesenchymopathy (in 2), lymphocytic myenteric ganglionitis (in 1), and duplication of myenteric plexus with leiomyopathy (in 1). Desmosis was noted in all of them along with other primary pathologies. One of the IND patients also had visceral myopathy, type IV. Histopathologists need to follow a systematic approach comprising of diligent histological examination and use of immunohistochemistry, immunocytochemistry, and electron microscopy in CIP workup. Therapy and prognosis vary depending on lesions identified by pathologists. These lesions can be seen in isolation or in combinations.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Ogilvie H (1948) Large-intestine colic due to sympathetic deprivation. Br Med J 2(4579):671–673

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  2. Dudley HO, Sinclair IS, McLaren IF, McNair TJ, Newsam JE (1958) Intestinal pseudo-obstruction. J R Coll Surg Edinb 3:206–217

    CAS  PubMed  Google Scholar 

  3. Neely J, Catchpole BN (1967) An analysis of the autonomic control of gastrointestinal motility in the cat. Gut 8(3):230–241

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  4. Saunders MD (2004) Acute colonic pseudo-obstruction. Curr Gastroenterol Rep 6(5):410–416

    Article  PubMed  Google Scholar 

  5. Fazel A, Verne GN (2005) New solutions to an old problem: acute colonic pseudo-obstruction. J Clin Gastroenterol 39(1):17–20

    PubMed  Google Scholar 

  6. Antonucci A, Fronzoni L, Cogliandro L et al (2008) Chronic intestinal pseudo-obstruction. World J Gastroenterol 14(19):2953–2961

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Bandopadhyay R, Chatterjee U, Bandyopadhyay SK, Basu AK (2011) Migration and maturation pattern of fetal enteric ganglia: a study of 16 cases. Indian J Pathol Microbiol 54(2):269–272

    Article  Google Scholar 

  8. Knowles C, Giogio RD, Kapur RP et al (2010) The London classification of the gastrointestinal neuromuscular pathology: report on behalf of the Gastro 2009 International Working Group. Gut 59:882–887

    Article  PubMed  Google Scholar 

  9. Kapur PR (2003) Neuronal dyaplasia: a controversial pathological correlate of intestinal pseudo-obstruction. Am J Med Genet 122A:287–293

    Article  PubMed  Google Scholar 

  10. Meier-Ruge WA, Bruder E, Kapur RP (2006) Intestinal neuronal dysplasia: one giant ganglion is not enough. Pediatr Dev Pathol 9:444–452

    Article  PubMed  Google Scholar 

  11. Rodrigues CA, Shepherd NA, Lennard-Jones JE et al (1989) Familial visceral myopathy: a family with at least six involved members. Gut 30:1285–1292

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Koh A, Bradley RF, French SW, Farmer DG, Cortina G (2008) Congenital visceral myopathy with a predominant hypertrophic pattern treated by multivisceral transplantation. Hum Pathol 39(6):970–974

    Article  PubMed  Google Scholar 

  13. Wiswell T, Rawlings J, Wilson J et al (1979) Megacystis microcolon- intestinal hypoperistalsis syndrome. Pediatrics 63:805–808

    CAS  PubMed  Google Scholar 

  14. Byearne W, Cipel L, Euler A et al (1977) Chronic idiopathic intestinal pseudo-obstruction syndrome in children—clinical characteristics and prognosis. J Pediatr 90:585–589

    Article  Google Scholar 

  15. Sieber WK, Girdany BR (1963) Functional intestinal obstruction in newborn infants with morphologically normal gastrointestinal tracts. Surgery 53:357–361

    CAS  PubMed  Google Scholar 

  16. Faulk DL, Anuras L, Christensen J (1978) Chronic intestinal pseudo-obstruction. Gastroenterology 74:922

    CAS  PubMed  Google Scholar 

  17. Isaacson C, Wainwright HC, Hamilton DG, Ou Time L (1985) Hollow visceral myopathy in black South Africans. A report of 14 cases. S Afr Med J 67:1015–1017

    CAS  PubMed  Google Scholar 

  18. Kimpinski K, Iodice V, Vernio S, Sandroni P, Low PA (2009) Association of N-type calcium channel autoimmunity in patients with autoimmune autonomic ganglionopathy. Auton Neurosci 150(1–2):136–139

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. King PH, Redden D, Palmgren JS, Nabors LB, Lennon VA (1999) Hu antigen specificities of ANNA-I autoantibodies in paraneoplastic neurological disease. J Autoimmun 13(4):435–443

    Article  CAS  PubMed  Google Scholar 

  20. Caras SD, McCallum HR, Brashear HR, Smith TK (1996) The effect of human antineuronal antibodies on the ascending excitatory reflex and peristalsis in isolated guinea pig ileum: “Is the paraneoplastc syndrome a motor neuron disorder?”. Gastroenterology 110:A643

    Article  Google Scholar 

  21. Basilisco G, Gebbia C, Peracchi M et al (2005) Cerebellar degeneration and hearing loss in a patient with idiopathic myenteric ganglionitis. Eur J Gastroenterol Hepatol 17(4):449–452

    Article  PubMed  Google Scholar 

  22. Veress B, Nyberg B, Törnblom H, Lindberg G (2009) Intestinal lymphocytic epithelioganglionitis: a unique combination of inflammation in bowel dysmotility: a histopathological and immunohistochemical analysis of 28 cases. Histopathology 54(5):539–549

    Article  PubMed  Google Scholar 

  23. Schäppi MG, Smith VV, Milla PJ, Lindley KJ (2003) Eosinophilic myenteric ganglionitis is associated with functional intestinal obstruction. Gut 52(5):752–755

    Article  PubMed Central  PubMed  Google Scholar 

  24. Accarino A, Colucci R, Barbara G et al (2007) Mast cell neuromuscular involvement in patients with severe gastrointestinal motility disorders. Gut 39:A18

    Google Scholar 

  25. Meier-Ruge W (1971) Über ein Erkrankungsbild des Colons mit Hirschsprung-Symptomatik. Verh Dtsch Ges Pathol 55:506–510

    CAS  PubMed  Google Scholar 

  26. Meier ruge WA, Bruder E (2005) Immaturity of enteric nervous system. Pathobiology 72:34–36

    Article  Google Scholar 

  27. Schmittenbecher PP, Sacher P, Cholewa D et al (1999) Hirschsprung's disease and intestinal neuronal dysplasia—a frequent association with implications for the postoperative course. Pediatr Surg Int 15(8):553–558

    Article  CAS  PubMed  Google Scholar 

  28. Borchard F, Malfertheiner P, Von Herbay A et al (1992) [Classification of erosions of the stomach. Results of a meeting of the Study Group of Gastroenterologic Pathology of the German Society of Pathology 23 November 1991 in Frankfurt/Main]. Pathologe 13(5):249–251

    CAS  PubMed  Google Scholar 

  29. Cord-Udy CL, Smith VV, Ahmed S, Risdon RA, Milla PJ (1997) An evaluation of the role of suction rectal biopsy in the diagnosis of intestinal neuronal dysplasia. J Pediatr Gastroenterol Nutr 24(1):1–6

    Article  CAS  PubMed  Google Scholar 

  30. Kapur RP (2003) Neuronal dysplasia: a controversial pathological correlate of intestinal pseudo-obstruction. Am J Med Genet A 122A(4):287–293

    Article  PubMed  Google Scholar 

  31. Koletzko S, Jesch I, Faus-Kebetaler T et al (1999) Rectal biopsy for diagnosis of intestinal neuronal dysplasia in children: a prospective multicentre study on interobserver variation and clinical outcome. Gut 44(6):853–861

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Meier-Ruge W, Gambazzi F, Käufeler RE, Schmid P, Schmidt CP (1994) The neuropathological diagnosis of neuronal intestinal dysplasia (NID B). Eur J Pediatr Surg 4(5):267–273

    Article  CAS  PubMed  Google Scholar 

  33. Montedonico S, Acevedo S, Fadda B (2002) Clinical aspects of intestinal neuronal dysplasia. J Pediatr Surg 37(12):1772–1774

    Article  PubMed  Google Scholar 

  34. Kobayashi H, Hirakawa H, Puri P (1996) Is intestinal neuronal dysplasia a disorder of the neuromuscular junction? J Pediatr Surg 31:575–579

    Article  CAS  PubMed  Google Scholar 

  35. Nogueira A, Campos M, Soares-Oliveira M et al (2001) Histochemical and immunohistochemical study of the intrinsic innervation in colonic dysganglionosis. Pediatr Surg Int 17:144–151

    Article  CAS  PubMed  Google Scholar 

  36. Moore SW, Rode H, Millar AJ, Albertyn R, Cywes S (1991) Familial aspects of Hirschsprung’s disease. Eur J Pediatr Surg 1:97–101

    Article  CAS  PubMed  Google Scholar 

  37. Kobayashi H, Mahomed A, Puri P (1996) Intestinal neuronal dysplasia in twins. J Pediatr Gastroenterol Nutr 22:398–401

    Article  CAS  PubMed  Google Scholar 

  38. Tou JF, Li MJ, Guan T, Li JC, Zhu XK, Feng ZG (2006) Mutation of RET proto-oncogene in Hirschsprung's disease and intestinal neuronal dysplasia. World J Gastroenterol 12(7):1136–1139

    CAS  PubMed  Google Scholar 

  39. Meier-Ruge WA, Bruder E (2012) Histopathology of chronic constipation. Karger AG, Basel.

  40. Jain D (2004) Neuromuscular disorders of the GI tract. In: Odze RD, Goldblum JR, Crawford JM (eds) Surgical pathology of the GI tract, liver, biliary tract, and pancreas. Elsevier, Philadelphia (Pa), pp 105–119

    Google Scholar 

  41. Kapur RP, Correa H (2009) Architectural malformation of the muscularis propria as a cause for intestinal pseudo-obstruction: two cases and a review of literature. Pediatr Dev Pathol 12:156–164

    Article  PubMed  Google Scholar 

  42. Kapur RP, Robertson SP, Hannibal MC et al (2010) Diffuse abnormal layering of small intestinal smooth muscle is present in patients with FLNA mutations and x-Linked intestinal pseudo-obstruction. Am J Surg Pathol 34:1528–1543

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

We are thankful to the HOD, Department of Pathology, AIIMS, for providing us facilities for working of index cases. The help extended by all laboratory staffs are also acknowledged.

Conflict of interest

The authors declare no conflict of interest.

Author information

Authors and Affiliations

  1. Departments of Pathology, Gastroenterology, Neonatology, Pediatric and Gastrointestinal Surgery, All India Institute of Medical Sciences, New Delhi, India

    Saumyaranjan Mallick, Das Prasenjit, Kinra Prateek, Panda S. Shasanka, Yadav Rajni, Jindal Gaurav, Maneesh K. Vijay, Kumar V. Arun, Agarwala Sandeep, Dash Nihar Ranjan & Datta Gupta Siddhartha

  2. Department of Pediatric Surgery, Post Graduate Institute of Medical Education and Research, Chandigarh, India

    Sekhon Virender & J. K. Mahajan

  3. Department of Pathology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India

    Das Prasenjit

Authors
  1. Saumyaranjan Mallick
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Das Prasenjit
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kinra Prateek
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Panda S. Shasanka
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sekhon Virender
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yadav Rajni
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jindal Gaurav
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Maneesh K. Vijay
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Kumar V. Arun
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. J. K. Mahajan
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Agarwala Sandeep
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Dash Nihar Ranjan
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Datta Gupta Siddhartha
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Das Prasenjit.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Suppl Figure 1

Photomicrographs show small intestine with normal appearance of fibrous sling in muscularis propria [A, Sirius Red (SR) x40]. The arms of this sling (black arrows) run parallel to each other within inner circular muscle layer [A & B, SR; A x40; B x100]. Near the myenteric plexus there is horizontal condensation of this sling (yellow arrows) and the limbs of this sling run at an 45º angle to the arms in longitudinal muscle layer (white arrow) and also an interweaving fibrous network around individual muscle fibers is noted in outer longitudinal layer [C, SR x200]. (JPEG 96 kb)

High resolution image (TIFF 4283 kb)

Suppl Figure 2

Photomicrograph of intestine shows thickened muscle layers [A, IHC for SMA x40]. Sirius red and MT stains show partial desmosis with loss of arms of fibrous slings within circular muscle layer (arrow) [B & C, SR & MT x40]. Bcl2 stain shows lightly stained mature ganglion cells (white arrow) and darkly stained immature ganglion cells (blue arrow) [D, IHC for Bcl2 x200]. CD117 stain shows loss of cells of Cajal both around myenteric plexus and within muscle layers. Inset shows presence of normal population of cells of Cajal in normal control [E, IHC for CD117 x100; inset x200]. Ultrastructure shows immature ganglion cells (yellow arrows) in comparison to mature ganglion cells (black arrow inset) [F, TEM]. (JPEG 73 kb)

High resolution image (TIFF 3532 kb)

Suppl Figure 3

Photomicrographs show giant ganglia in the submucosal and myenteric plexus [A-C, H & E (A & B); A x40; B x100; C (MT) x100]. MT stain also shows loss of fibers in outer longitudinal layer with basket weave fibrosis [C, MT x100]. SMA stain shows loss of staining of inner circular muscle (black arrow), except a peripheral stained rim (brown arrow). Outer longitudinal layer confirms loss of muscle fibers [D, IHC for SMA x100]. Sirius red stain shows disorganized fibrous sling (brown arrow) with loss of condensation of fibrous layer around myenteric plexus (black arrow) [E, SR x100]. Computer assisted image analysis (Media Cybernetics, USA) shows thickened inner circular muscle layer [F, IA x40]. (JPEG 85 kb)

High resolution image (TIFF 4968 kb)

Suppl Figure 4

Photomicrographs show giant ganglia with numerous mature (black arrow) and immature ganglion cells (brown arrow) [A, H&E x100; Inset- IHC for Bcl2 x 200]. SR and MT stains show complete desmosis and loss of muscle fibers [B, SR x40; MT x100]. Ultrastructural photographs show vacuolation and degeneration of neurons [C, TEM], mature ganglion cells with loss of cytoplasmic organelles (arrow) [D, TEM] and degeneration of muscle fibers (arrow) [E, TEM]. (JPEG 69 kb)

High resolution image (TIFF 2773 kb)

Suppl Figure 5

Photomicrographs show myenteric plexus ganglia with dense lymphocytic infiltrate (arrow) [A, H&E x200], with degeneration of nerve fibers and ganglion cells (arrow) [B, H&E x200], infiltration by a population of CD3 positive T cells (arrow) [C, IHC for CD3 x200] and peripheral condensation of CD20 positive B cells (arrow) [D, IHC for CD20 x200]. SMA stain shows normal staining pattern of muscle fibers [E, IHC for SMA x40]. Sirius red stain shows complete desmosis with complete distortion of ‘H’ like fibrous sling (arrows) [A, SR x100]. (JPEG 98 kb)

High resolution image (TIFF 4603 kb)

Suppl Figure 6

Photograph shows normal distribution of ganglia in myenteric plexus (arrows) [A, IHC for S100 x 40]. CD117 stain shows loss of cells of Cajal (arrow) [B, IHC for CD117 x 100]. SR stain shows loss of fiber arms in inner circular muscles (arrow) [C, SR x 40]. CD117 stain in case 8 shows complete absence of cells of Cajal (arrow) [D, IHC for CD117 x 100]. SR stain also shows partial desmosis with focal loss of tendinous arms within inner circular muscle [E & F, SR E x 40; F x100]. Outer longitudinal layer also shows focal disorganization of obliquely arranged limbs of fibrous sling (arrow) [E, SR x 40]. (JPEG 76 kb)

High resolution image (TIFF 4057 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mallick, S., Prasenjit, D., Prateek, K. et al. Chronic intestinal pseudo-obstruction: systematic histopathological approach can clinch vital clues. Virchows Arch 464, 529–537 (2014). https://doi.org/10.1007/s00428-014-1565-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00428-014-1565-y

Keywords

Search

Navigation