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Surgical Pathology Criteria

Rejection of Transplanted Small Intestine


  • Immune mediated injury against transplanted small intestine manifested by crypt epithelial injury

Diagnostic Criteria

  • Increased apoptotic bodies in crypts
    • >6 bodies / 10 crypts
  • Crypt injury
    • Cytoplasmic basophilia
    • Nuclear enlargement and hyperchromasia
    • Mucin depletion
    • Loss of Paneth cells
  • Distortion of villous and crypt architecture
  • Mucosal ulceration in severe cases


  • Indeterminate
    • Up to 6 apoptotic bodies per 10 crypts
  • Mild
    • >6 apoptotic bodies per 10 crypts
  • Moderate
    • Confluent apoptosis
    • Increased inflammation
    • Epithelial injury
  • Severe /Exfoliative
    • Features of moderate rejection plus mucosal ulceration
    • May have arteritis
    • Must be distinguished from CMV ulcers
    • Poor prognosis

Neeraja Kambham MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342

Original posting : May 9, 2007

Supplemental studies

  • Anti-viral immunohistological stains are useful to rule out other causes
    • CMV
    • Adenovirus
    • Herpes simplex
    • These can coexist with rejection

Differential Diagnosis

Nonspecific enteritis

  • Features favoring rejection
    • Crypt apoptosis
    • Activated lymphocytes
    • Increased number of eosinophils reported in patients pretreated with thymoglobulin or alemtuzumab
  • Lymphocytic cryptitis is not specific for rejection
  • Acute neutrophilic cryptitis suggests infection
  • Specific viral infections must be ruled out



  • Inclusions may be too small to be diagnostic on H&E stain
    • Immunohistologic stain may demonstrate specific inclusions
  • Background may range from lack of infiltrate to typical features of infectious enteritis



  • More common in pediatric patients
  • Features may overlap with rejection
    • Inflammation, crypt apoptosis and regenerative epitihelia changes may be seen
  • Viral inclusions in surface enterocytes (smudge cells)
    • Immunohistologic stain may specifically identify the inclusions


Herpes simplex virus

  • Histologic findings may overlap
  • Identification of inclusions useful
    • Ground glass nuclei
    • Margination of chromatin
    • Immunohistologic staining is useful


Post-transplant lymphoproliferative disorder

  • Infiltrate of atypical large lymphocytes
    • CD20+
  • May form a mass lesion


  • Signs and symptoms
    • Abdominal pain
    • Fever, nausea, vomiting
    • Increased stomal output
    • Septic shock if severe
  • Endoscopic findings
    • Edema, hyperemia
    • Granularity
    • Loss of fine mucosal vascular pattern
    • Mucosal ulceration


  • Wu T, Abu-Elmagd K, Bond G, Nalesnik MA, Randhawa P, Demetris AJ. A schema for histologic grading of small intestine allograft acute rejection. Transplantation. 2003 Apr 27;75(8):1241-8.
  • Ruiz P, Bagni A, Brown R, Cortina G, Harpaz N, Magid MS, Reyes J. Histological criteria for the identification of acute cellular rejection in human small bowel allografts: results of the pathology workshop at the VIII International Small Bowel Transplant Symposium. Transplant Proc. 2004 Mar;36(2):335-7.
  • Wu T, Bond G, Martin D, Nalesnik MA, Demetris AJ, Abu-Elmagd K. Histopathologic characteristics of human intestine allograft acute rejection in patients pretreated with thymoglobulin or alemtuzumab. Am J Gastroenterol. 2006 Jul;101(7):1617-24.
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