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Difficulty: HardPathology and Biopsy Interpretation

A 48-year-old man who underwent a deceased-donor renal transplantation 7 months ago is evaluated during a routine follow-up visit. He feels well and reports no fever, dysuria, or decreased urine output. His current medications include tacrolimus, mycophenolate mofetil, and prednisone. His blood pressure is 138/86 mmHg, and his temperature is 37.1°C (98.8°F). Physical examination of the allograft reveals no tenderness. Laboratory studies show a serum creatinine level of 2.6 mg/dL, which has increased from a baseline of 1.3 mg/dL three months ago. A renal ultrasound demonstrates normal graft size, no hydronephrosis, and normal resistive indices. An ultrasound-guided percutaneous needle biopsy of the allograft is performed. Light microscopy reveals a dense interstitial infiltrate predominantly composed of lymphocytes and macrophages, with greater than 10 mononuclear cells per tubular cross-section (severe tubulitis). Several small arteries exhibit subendothelial mononuclear inflammatory cells with lifting of the endothelial layer (intimal arteritis). Immunohistochemical staining for C4d is negative in the peritubular capillaries. Staining for SV40 T antigen is also negative. Based on the histopathologic findings, which of the following is the most likely diagnosis?

  1. Acute T-cell-mediated rejectionAnswer
  2. B
    Acute antibody-mediated rejection
  3. C
    Calcineurin inhibitor nephrotoxicity
  4. D
    BK polyomavirus nephropathy
  5. E
    Interstitial fibrosis and tubular atrophy

Answer

Acute T-cell-mediated rejection
The patient's biopsy demonstrates the classic features of acute T-cell-mediated (cellular) rejection. According to the Banff classification of renal allograft pathology, acute cellular rejection is characterized by tubulointerstitial inflammation, specifically an interstitial infiltrate of mononuclear cells accompanied by tubulitis (lymphocytes invading the tubular epithelium). The presence of intimal arteritis (subendothelial mononuclear cells in arteries, also known as endothelialitis) indicates a more severe form of acute cellular rejection (Banff Type II or III). The negative C4d stain effectively rules out acute antibody-mediated rejection, and the negative SV40 stain effectively rules out BK polyomavirus nephropathy.

Step-by-Step Solution

1
Analyze the clinical presentation.
The patient has an asymptomatic rise in serum creatinine 7 months post-renal transplant with a normal ultrasound, prompting a biopsy to rule out rejection or toxicity.
Establishing the clinical context helps interpret the subsequent biopsy results.
2
Interpret the light microscopy findings from the pathology report.
The biopsy shows a dense interstitial lymphocytic infiltrate, severe tubulitis (>10 mononuclear cells per tubular cross-section), and intimal arteritis (subendothelial infiltration).
These are the hallmark Banff criteria features for diagnosing acute cellular (T-cell-mediated) rejection.
3
Evaluate the immunohistochemical staining results.
Negative C4d staining rules out acute antibody-mediated rejection. Negative SV40 staining rules out BK polyomavirus nephropathy.
Immunohistochemistry is essential to differentiate cellular rejection from antibody-mediated rejection and viral nephropathy, which can present with similar clinical timelines.
4
Synthesize the findings to confirm the diagnosis.
The combination of severe tubulitis and intimal arteritis in the absence of C4d and SV40 staining definitively points to Acute T-cell-mediated rejection.
Finalizing the diagnosis requires integrating positive morphologic findings with the exclusion of key alternative diagnoses through special stains.

Key Concept

Interpretation of renal allograft biopsy to differentiate acute T-cell-mediated rejection from antibody-mediated rejection, drug toxicity, and viral nephropathy based on distinct histopathologic and immunohistochemical features.
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Topics

Pathology and Biopsy Interpretation

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