PATHOLOGY MCQs

Heart transplantation has become a life-saving procedure for many patients with end-stage heart disease. Post-transplant care involves meticulous monitoring for rejection, a common and serious complication. Histopathology plays a crucial role in this process, differentiating between types of rejections and other findings such as Quilty lesions. Let’s explore the nuances of acute cellular rejection (ACR), antibody-mediated rejection (AMR), and Quilty lesions in the context of heart transplant biopsies.

Acute Cellular Rejection (ACR)

ACR is the classical form of rejection and is characterized histologically by the infiltration of T lymphocytes into the cardiac tissue. On a biopsy, you might see interstitial and perivascular infiltration by mononuclear cells, often with associated myocyte damage.

This T-cell-mediated response can lead to endothelialitis—inflammation and damage of the blood vessel walls within the heart muscle, which, if unchecked, can lead to fibrin deposition, necrosis, and ultimately, graft failure. Clinically, ACR correlates with symptoms of graft dysfunction, and it’s typically treated with increased immunosuppression.

Antibody-Mediated Rejection (AMR)

AMR, on the other hand, involves the heart’s vasculature and is characterized by the presence of antibodies against the donor heart. Histologically, it presents as capillary injury, with evidence of intravascular macrophages and deposition of complement components, most notably C4d.

AMR can be particularly insidious as it may occur even in the absence of clinical symptoms. Unlike ACR, the treatment for AMR targets antibody production and involves therapies like intravenous immunoglobulin (IVIG), plasmapheresis, and rituximab to lower the levels of circulating antibodies.

Quilty Lesions

Quilty lesions are somewhat of a red herring in the world of transplant pathology. These are benign nodular endocardial infiltrates of lymphocytes that mimic the appearance of rejection on biopsies but are not associated with graft dysfunction.

They do not show the myocyte damage typical of ACR or the capillary destruction characteristic of AMR. CD 4, CD8 and CD 20 are positive.

Importantly, Quilty lesions require no treatment, and recognizing them is vital to avoid unnecessary immunosuppressive therapy.

Differentiation is Key

The histopathological differentiation between these entities is critical:

• ACR demands an increase in immunosuppression to protect the graft.
• AMR calls for specific antibody-targeted therapies.
• Quilty lesions, while important to identify, do not alter the management of the patient.

Feature	Acute Cellular Rejection (ACR)	Antibody-Mediated Rejection (AMR)	Quilty Lesion
Histological Findings	Interstitial and perivascular infiltration of mononuclear cells, often with associated myocyte damage	Capillary injury with intravascular macrophages, neutrophils, or hemorrhage; deposition of complement components such as C4d	Nodular endocardial infiltrates of lymphocytes without myocyte damage
Vascular Changes	Endothelialitis with inflammation of vessel walls, possibly leading to fibrin deposition and necrosis	Often involves microvascular inflammation with endothelial cell swelling and capillary fragmentation	No vascular changes typical of rejection
Immunological Cells	Predominantly T lymphocytes (CD3+, CD8+)	Presence of natural killer cells, macrophages, and plasma cells, with complement deposition (C4d+)	Lymphocytes, similar to those seen in lymphoid follicles, without aggressive features
Presence of Antibodies	Not characterized by antibodies	Diagnostic hallmark includes circulating donor-specific antibodies (DSA)	No antibodies involved
Tissue Staining	No specific staining; myocyte necrosis may be observed	Positive staining for C4d in capillaries is supportive of diagnosis	No specific staining pattern related to rejection
Clinical Correlation	Correlates with clinical signs of graft dysfunction	May occur even in the absence of graft dysfunction symptoms; diagnosed through biopsy and serological findings	Not correlated with graft dysfunction; incidental finding
Treatment	Increased immunosuppression, such as corticosteroids and antithymocyte globulin	Targeted therapies like IVIG, plasmapheresis, and anti-CD20 antibodies to reduce antibody levels	No treatment required as it is a benign finding

Conclusion

The role of the pathologist in reviewing heart transplant biopsies is not just diagnostic but has direct therapeutic implications. Understanding the differences between ACR, AMR, and Quilty lesions can significantly impact patient management and long-term outcomes. As we continue to refine our diagnostic techniques, the hope is that we can further tailor treatments to ensure the best possible results for heart transplant patients.

Try to answer this MCQ

Correct answer is D: QUILTY lesion

CLUES: No myocyte injury, endocardial location and CD 20 and CD 3 positive.