Table of Contents
Definition / general | Essential features | ICD coding | Epidemiology | Sites | Pathophysiology | Etiology | Clinical features | Diagnosis | Radiology description | Prognostic factors | Case reports | Treatment | Clinical images | Microscopic (histologic) description | Microscopic (histologic) images | Virtual slides | Negative stains | Sample pathology report | Differential diagnosis | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Moreno G, Hagen CE. Graft versus host disease. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/colongvhd.html. Accessed December 22nd, 2024.
Definition / general
- Complication of allogeneic stem cell transplantation in which T cells from the donor recognize the recipient tissue as foreign, leading to organ damage
- May also occur in some autologous stem cell transplant patients (Mod Pathol 2011;24:117)
Essential features
- Complication of stem cell transplantation in which T cells from the donor recognize the recipient tissue as foreign, leading to organ damage
- Histologically characterized by crypt apoptosis, crypt dropout and ulceration
- Infection (especially cytomegalovirus) and drug induced injury are the most common differential considerations
ICD coding
- ICD-10: D89.813 - graft versus host disease, unspecified
Epidemiology
- Occurs in 30 - 70% of allogeneic stem cell transplant patients (Biol Blood Marrow Transplant 2015;21:389)
- M:F = 1.2:1 (Blood 2012;119:296, Bone Marrow Transplant 2013;48:587)
- Median age: 36 - 43 years (Blood 2012;119:296, Bone Marrow Transplant 2013;48:587)
Sites
- Skin > gastrointestinal tract > liver
- Other sites: mouth, eyes, lungs
Pathophysiology
- Tissue injury occurs following myeloablative or conditioning chemotherapy regimens in preparation for stem cell transplantation and leads to antigen upregulation on host tissues
- Donor T cells recognize host tissue antigens as foreign
- T cell activation and cytokine storm lead to end organ damage (Am J Clin Pathol 2016;145:591)
- Alteration of the microbiome is likely a contributing factor (Biol Blood Marrow Transplant 2018;24:1322)
- In autologous stem cell transplant patients, it is hypothesized to result from failure of self tolerance (Mod Pathol 2011;24:117)
Etiology
- Risk factors: human leukocyte antigen mismatch, age, sex disparity, stem cell source and intensity of the conditioning regimen (N Engl J Med 2017;377:2167)
Clinical features
- Clinically divided into classic acute graft versus host disease (occurring within 100 days of transplant), persistent / recurrent / late onset acute graft versus host disease (occurring > 100 days posttransplant) and chronic graft versus host disease (defined by presence of diagnostic clinical signs and symptoms; no specific features are diagnostic of chronic colonic GVHD)
- Histologic distinction of these groups not possible (Biol Blood Marrow Transplant 2015;21:589)
- Gastrointestinal symptoms: dysphagia, anorexia, nausea, vomiting, diarrhea (watery to mucoid / bloody), weight loss and failure to thrive (Nat Rev Gastroenterol Hepatol 2017;14:711)
- Coexisting skin graft versus host disease is often present, causing diffuse maculopapular rash
- Endoscopic findings range from edema and mild erythema to mucosal erosions, ulceration and denudation (Nat Rev Gastroenterol Hepatol 2017;14:711)
Diagnosis
- Combination of clinical, endoscopic and histologic features
- Biopsy is essential when the clinical presentation is atypical and helps exclude alternative diagnoses
Radiology description
- Bowel wall thickening with mucosal enhancement, mesenteric edema and vascular engorgement (AJR Am J Roentgenol 2017;209:33)
Prognostic factors
- Severity predicts treatment response and mortality (Biol Blood Marrow Transplant 2015;21:389)
- Gastrointestinal tract staging is based on severity of diarrhea and extent of weight loss
Case reports
- 23 year old man with defecation of a colon cast (Ann Saudi Med 2009;29:231)
- 44 year old woman with cytomegalovirus infection (World J Gastroenterol 2013;19:597)
- 56 year old man with idelalisib induced colitis and skin eruption (Clin J Gastroenterol 2017;10:14)
- 63 and 74 year old men with multiple myeloma and hematopoietic stem cell transplantation (Gastroenterology Res 2018;11:52)
- 3 patients with Epstein-Barr virus associated posttransplant lymphoproliferative disorder (Eur J Haematol 2019;103:519)
Treatment
- Increased immunosuppression
Microscopic (histologic) description
- Characteristic histologic features include crypt apoptosis, crypt dropout and ulceration (Biol Blood Marrow Transplant 2015;21:589)
- Inflammation is generally sparse
- Endocrine cell nests may be seen (Am J Surg Pathol 2013;37:1319)
- Fibrosis and crypt architectural changes are markers of longstanding disease but not specific features of chronic graft versus host disease (Am J Clin Pathol 2016;145:591)
- Apoptosis in the colon is not specific to graft versus host disease and the lower diagnostic threshold is debated
- National Institute of Health proposes ≥ 1 apoptotic body per biopsy fragment (Biol Blood Marrow Transplant 2015;21:589)
- Others propose > 6 apoptotic bodies per 10 contiguous crypts for definitive diagnosis of graft versus host disease (Am J Surg Pathol 2013;37:539)
- Cases with ≤ 6 apoptotic bodies per 10 contiguous crypts are considered indeterminate for graft versus host disease (Histopathology 2016;69:802)
- Utility of histologic grading is questionable because of poor correlation with patient outcome
- When grading is performed, the Lerner system is most commonly utilized
- Grade I: crypt apoptosis without crypt dropout
- Grade II: single crypt dropout
- Grade III: contiguous crypt dropout
- Grade IV: diffuse crypt dropout with ulceration
- When grading is performed, the Lerner system is most commonly utilized
- Graft versus host disease in autologous stem cell transplant patients shows more prominent crypt apoptosis but is otherwise histologically identical to allogeneic graft versus host disease (Mod Pathol 2018;31:1619)
- Histologic examination of at least 8 serial sections is recommended to avoid missing rare apoptotic bodies (Biol Blood Marrow Transplant 2015;21:589)
Microscopic (histologic) images
Virtual slides
Negative stains
- Cytomegalovirus IHC, PAS and Giemsa negative for microorganisms (though their presence does not rule out coincident graft versus host disease)
Sample pathology report
- Colon, biopsy:
- Colonic mucosa with increased crypt apoptosis and crypt dropout (see comment)
- Comment: Given the patient's history of allogeneic stem cell transplant, the findings likely represent graft versus host disease.
Differential diagnosis
- Cytomegalovirus colitis:
- Presence of characteristic viral inclusions via immunohistochemistry or on H&E; always helpful to rule out in cases of suspected graft versus host disease
- Chemotherapy or radiation related changes:
- Usually resolve within 20 days
- Epithelial flattening with regenerative atypia, mucin depletion and crypt apoptosis
- Mycophenolate mofetil:
- Increased eosinophils in the lamina propria and fewer neuroendocrine cell nests (Am J Surg Pathol 2013;37:1319)
- Cryptosporidiosis:
- Identification of organisms attached to mucosal surface, Giemsa or PAS stains can highlight organisms; prominent neutrophilic inflammation (Hum Pathol 2010;41:918)
Board review style question #1
A 55 year old man undergoes peripheral blood stem cell transplant for multiple myeloma. 70 days after the transplant, he complains of mucoid to bloody diarrhea 3 - 5 times per day. Colonoscopy shows multiple ulcerations and biopsies are obtained. What is the most likely diagnosis?
- Chemotherapy induced injury
- Crohn's disease
- Graft versus host disease
- Ischemic colitis
- NSAID related injury
Board review style answer #1
Board review style question #2
What is the most characteristic histologic feature of colonic graft versus host disease?
- Architectural distortion
- Crypt apoptosis
- Eosinophilic inflammation
- Lamina propria hyalinization
- Neutrophilic inflammation
Board review style answer #2