Case of the Month
A 70-year-old woman with multiple medical problems presented with abdominal pain. Upper endoscopy was performed and gastric biopsies showed histologic abnormalities as displayed in the representative images below.
Which of the following diagnoses is most likely?
a. Mucosal calcinosis
b. Doxycycline-induced gastric injury
c.Strongyloides infection
d. Gastric antral vascular ectasia
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The Case of the Month series is curated by Anamarija M. Perry, University of Michigan.
B. Polyoma BK virus
The clinical scenario and histologic findings are most consistent with BK virus nephropathy (BKVN), a diagnosis supported by nuclear immunostaining with antibody to simian virus 40 (SV40). In clinical practice, the antibody to SV40 is used for demonstrating BK virus (BKV) because the two viruses share 70 percent homology.
BKV is a non-enveloped, icosahedral, double-stranded DNA polyomavirus. More than 90 percent of people show BKV seroconversion by age 23, with most children seropositive by 10 years old. The virus spreads by respiratory and oral-enteric transmission. Primary infection is most often seen in children aged two to five and is typically asymptomatic or with nonspecific flu-like symptoms. BKVN is a major complication in renal transplant patients and most often occurs secondary to reactivation of latent BKV infection of renal tubular epithelial cells and urothelium. Infected cells can be shed in urine and are described as decoy cells on cytology due to their “malignant-like” appearance. Risk factors for BKVN include pre-transplantation BKV seronegativity (most significant, usually pediatric patients), high-dose immunosuppression, and urothelial injury (i.e., ureteral stent). After viral infection, viremia precedes BKVN, causing renal interstitial inflammation, fibrosis, and tubular atrophy. This progresses to allograft failure and end-stage renal disease in approximately 50–80 percent of patients. Treatment is aimed at reducing immunosuppression to allow the immune system to control the virus.
Histologically, BKV cytopathic effects are usually seen in renal tubular epithelial cells as 40–45 nm intranuclear inclusion bodies. They may also be observed in Bowman’s capsule parietal epithelial cells. Associated lymphoplasmacytic tubulointerstitial inflammation is present in the biopsy if the patient has enough immune cells to mount a response. Prolonged infection progresses to interstitial fibrosis, with both inflammation and fibrosis being prognostically significant. Routine BKV load assessment and examination during surveillance biopsy is important for early detection. Immunohistochemical staining with SV40 can be used to aid detection, especially in cases with lymphoplasmacytic inflammation, possible nuclear inclusions, and/or high clinical suspicion.
Submitted by Amanda Kitson, House Officer IV, University of Michigan, Ann Arbor, Michigan, USA.
Further Reading
1. D Sawinski, J Trofe-Clark, Clin J Am Soc Nephrol, 13, 1893 (2018). PMID: 30242026.
2. P Acott, H Hirsch, Pediatr Nephrol, 22, 1243 (2007). PMID: 17377822.
3. B Nankivell et al., Am J Transplant, 17, 2065 (2017). PMID: 28371308.
4. A Zarauza Santoveña et al., Transplant Proc, 47, 62 (2015). PMID: 25645771.
