Definition/General
Introduction:
Viral changes in urine cytology represent viral cytopathic effects in urothelial cells
Most commonly caused by polyomaviruses (BK and JC virus)
These changes can mimic high-grade urothelial carcinoma
Recognition is crucial to avoid misdiagnosis and unnecessary interventions.
Origin:
Viral changes originate from viral infection of urothelial cells
Polyomaviruses are the most common cause
BK virus predominantly affects kidney transplant patients
JC virus more commonly causes neurological disease
Cytomegalovirus and adenovirus less commonly involved.
Classification:
Classified by viral etiology
Polyomavirus changes (BK virus, JC virus)
Cytomegalovirus cytopathic effects
Adenovirus changes
Herpes simplex virus (rare)
Papillomavirus effects (extremely rare in urine).
Epidemiology:
Most common in immunocompromised patients
Particularly frequent in kidney transplant recipients (BK virus)
Bone marrow transplant patients at risk
HIV patients with low CD4 counts
Occasional in immunocompetent individuals
Higher prevalence in males.
Clinical Features
Presentation:
Often asymptomatic in early stages
Hematuria (microscopic or gross)
Dysuria and urinary frequency
Renal dysfunction in transplant patients
Ureteral stenosis may develop
Allograft dysfunction in kidney transplant patients
Progressive nephropathy possible.
Symptoms:
Urinary symptoms (frequency, urgency, dysuria)
Hematuria (blood in urine)
Lower abdominal pain
Flank pain (in nephritis cases)
Systemic symptoms rare
Asymptomatic viruria common
Fever may be absent.
Risk Factors:
Immunosuppression (transplant recipients)
Chemotherapy or immunosuppressive drugs
HIV infection
Chronic kidney disease
Diabetes mellitus
Advanced age
Male gender
Immunodeficiency syndromes.
Screening:
Routine surveillance in transplant patients
Quarterly urine cytology screening
Quantitative PCR for viral load
Plasma viral PCR monitoring
Renal biopsy when indicated
Cystoscopy in symptomatic patients.
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Gross Description
Appearance:
Clear to turbid urine specimen
May show hematuria (pink to red)
Usually normal appearance in early stages
Proteinuria may be present
Minimal sediment in many cases
Foamy urine if proteinuria significant.
Characteristics:
Increased cellularity may be present
Cellular debris in background
Normal color and odor typically
Crystal formation possible
Blood clots rare unless severe hemorrhage
Adequate cellular yield for cytological examination.
Microscopic Description
Immunohistochemistry
Positive Markers:
Polyomavirus T antigen (nuclear staining)
VP1 capsid protein
SV40 T antigen (cross-reactive)
p53 (wild-type pattern)
CK7 and CK20 (urothelial origin)
Uroplakin (umbrella cells).
Negative Markers:
High-risk HPV markers (E6/E7)
p16 (usually negative)
CEA (negative)
TTF-1 (negative)
CK5/6 (may be negative in infected cells)
PSA (negative in males).
Diagnostic Utility:
Polyomavirus immunostains confirmatory
Essential for diagnosis in equivocal cases
SV40 T antigen widely available
VP1 more specific but less available
p53 shows wild-type (not overexpressed)
Cell cycle markers may be altered.
Molecular/Genetic
Differential Diagnosis
Similar Entities:
High-grade urothelial carcinoma
Reactive atypia
Radiation cystitis
Drug-induced changes
Other viral infections
Decoy cells (polyomavirus).
Distinguishing Features:
Viral changes: Specific inclusions, immunostains positive
Urothelial carcinoma: Irregular chromatin, high N:C ratio, negative viral markers
Reactive atypia: Inflammation present, smaller nuclei
Radiation: Bizarre cells, multinucleation
Drugs: History of exposure.
Diagnostic Challenges:
Distinguishing from high-grade malignancy
Severe viral changes very concerning morphologically
Mixed infections complicate interpretation
Partial viral effects may be subtle
Technical factors affecting immunostains.
Sample Pathology Report
Template Format
Sample Pathology Report
Complete Report: This is an example of how the final pathology report should be structured for this condition.
Specimen Information
Urine specimen, [collection method], [volume] ml
Specimen Adequacy
Adequate for cytological evaluation
Viral Cytopathic Changes
Urothelial cells showing viral cytopathic effects with [specific features]
Nuclear Inclusions
[present/absent]. If present: [type and characteristics]
Immunohistochemistry
Polyomavirus immunostain: [positive/negative]
Viral Identification
[Viral type] identified by [method]
Diagnosis
Viral cytopathic changes consistent with [viral type] infection
Clinical Correlation
Correlate with immunosuppressive status and clinical findings
Recommendations
Viral load monitoring. Consider immunosuppression adjustment. Follow-up cytology.