Cardiac Path Online

Reporting of Endomyocardial Biopsy -

Diagnosis and Grading of Rejection after Heart  Transplantation 

Dr Sampurna Roy MD





Histological examination of endomyocardial biopsy (EMB) still is the most reliable method to detect and monitor rejection after heart transplantation.

Multiple serial sections stained with haematoxylin and eosin are usually adequate for the diagnosis of rejection.

In some cases, endomyocardial biopsies taken to assess rejection may show evidence of recurrent disease like amyloidosis or haemochromatosis in the cardiac allograft.

Clinical details of the patient:

Age and sex of the patient ; time since transplant ; whether clinical features of rejection are present  ; current anti-rejection therapy ; histological findings on previous endomyocardial biopsies  ;  Findings of microbiological and virological  investigations.

The pathologist should comment on the following features in the histopathology report:

- Comment on whether the specimen is adequate :   The International Society for Heart and Lung Transplantation (ISHLT) Grading system requires that there are four or more fragments ; Assessment of the adequacy of the biopsy sample is important and at least half of each fragments should be free from fibrosis. Clinically significant rejection cannot be excluded if sampling is inadequate.

- Comment on whether only granulation tissue is present in  any of the fragments indicating the site of a recent biopsy ;

- Comment on the ischaemic changes, indicated by focal myocyte necrosis, particularly beneath the endocardium, without the lymphoid infiltrate that characterizes rejection.

This may be seen early, around the time of transplantation, or late in relation to coronary occlusive disease;

- Comment on whether epicardial tissue is present ; whether it shows inflammation;  whether it is granulomatous indicating  fat necrosis;

- Comment on the evidence of infective organisms such as Toxoplasma cysts or viral inclusions.

In these cases, a lymphoid infiltrate may not be due to rejection.

The pathologist should be cautious before making  an interpretation;

- Whether atypical lymphoid cells are present (particularly in the endocardium) which may indicate post-transplant lymphoproliferative disease.

- Changes in the endocardium:

Lymphoid infiltrate :  Solitary or multiple ; Well-defined or more florid with encroachment on underlying myocardium (Quilty lesion) ;   

Fibrosis :  Whether this extends into the underlying myocardium.

- Changes in the myofibres:

Damage :  Vacuolation , basophilia , myocytolysis.

Necrosis :

Nuclei : Pleomorphism, presence of bizarre forms.

- Changes in the interstitium:

Inflammation : Type, location and severity ; Eosinophils may  be seen in any of the rejection grades but more frequent in higher grades;

Oedema :

Fibrosis : Distribution and extent.

Special stains and procedures on cardiac biopsies:

 The following stains may be useful in cardiac biopsies:

- van Gieson’s or trichrome method for collagen : 

Connective tissue stains may help in the assessment of myocyte damage and fibrosis.

- Congo red for amyloid :

- Stain for elastic fibres :

- Pearls’ stain for haemosiderin :

- The following immunostains are useful in some cases: 

- Cytomegalovirus, other herpesviruses, adenoviruses, when viral infection is suspected.

- Lymphoid markers when atypical lymphoid cells are present.

- Electron microscopy is useful in some cases:  

In suspected anthracycline toxicity : To look for loss of myofibrillary components from myocytes and dilatation of sarcoplasmic reticulum to form large membrane-bound spaces.


Further reading:

Pathologic classification of antibody-mediated rejection correlates with donor-specific antibodies and endothelial cell activation.

Usefulness of routine surveillance endomyocardial biopsy 6 months after heart transplantation.

An approach to endomyocardial biopsy interpretation

Current Status of Endomyocardial Biopsy

Endomyocardial biopsy in heart transplantation: schedule or event?

Diagnosis of rejection after heart transplantation

A comparative analysis between survivors and nonsurvivors with antibody mediated cardiac allograft rejection.

The role of immunological biomarkers in cardiac rejection.

Gene expression profiling for cardiac rejection surveillance is not predictive of post-transplantation skin cancer.




Dr Sampurna Roy  MD

Consultant  Histopathologist (Kolkata - India)







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