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Infectious Disease Pathology
Wednesday, March 2, 2005 - 7:30 PM
Convention Center, Room Room 006 C,D
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Moderator:
Gary W. Procop
Cleveland Clinic Foundation
Cleveland, OH
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Clinical histories are printed below.
Click on the case numbers for text and references of each case.
Click on each slide thumbnail image for an enlarged view
Submitted by:
Elizabeth C. Burton
Baylor University Medical Center
Dallas, TX
A 50 year old African American female underwent a cadaveric renal transplant for end stage renal
disease secondary to hypertension and diabetes. She was readmitted (19 days post-transplantation) for an
increased creatinine level, hydronephrosis and mild acute cellular rejection. Her immunosuppressive
therapy was adjusted and she was discharged home four days later with a nephrostomy tube in place. Four
days following discharge (27 days post-transplantation), she was readmitted to the hospital for
abdominal/right flank pain that had worsened over the preceding two days. Admission laboratory data were
significant for: hemoglobin of 11.2 g/dL, hematocrit of 33.7%, red cell distribution width—coefficient
of variation (RDW-CV) of 16.6%, glucose level of 290 mg/dL, blood urea nitrogen (BUN) of 48 md/dL,
creatinine of 1.2 mg/dL, globulin 4.0 g/dL, total bilirubin 1.0, aspartate aminotransferase (AST) 61 U/L,
alanine aminotransferase (ALT) 88 U/L, and her urine culture was positive for Enterococcus faecalis. Her white blood cell count, remaining blood cell indices,
and remaining chemistries were within normal limits. She underwent an appendectomy on the day following
admission for presumed acute appendicitis. Postoperatively, her temperature was decreased at 95.8°
Fahrenheit and a warming blanket was placed. She continued to complain of abdominal, right flank pain
and itching in the right flank area. She became increasingly restless, agitated and developed seizure
activity. A computed tomography (CT) scan of the head was obtained and showed no evidence of acute
abnormality. An electroencephalogram (EEG) study was significant for mild to moderate generalized
slowing. Over the next 36 to 48 hours, she became increasingly disoriented with hallucinations and
developed hypotension, bradycardia and right bundle branch block requiring temporary pacemaker
placement. She was transferred to the intensive care unit where she developed respiratory failure and
was intubated (postoperative day 3). Her cyclosporine level increased to 809 ng/mL (reference 150-400
ng/mL) and her cyclosporine was held. Over the next few days, she became increasingly obtunded with
increased respiratory/oral secretions, continuous eye movements and facial grimacing. By postoperative
day 7, she continued to have seizure activity and a repeat CT scan of the head again showed no acute
abnormalities. Within the next 8 hours, she progressed to coma with absent brainstem reflexes. A repeat
CT scan was now significant for generalized edema with brainstem herniation. A "do not resuscitate
order" was placed and the following morning, she developed ventricular arrythmias/asystole and died.
Autopsy Findings
Autopsy examination was significant for an organized hematoma surrounding the pelvic transplant kidney
which had patent and intact vascular and ureteral anastomoses and microscopic evidence of acute tubular
injury, early microangiopathy, non-specific chronic interstitial nephritis, and perihilar neuritis. The
native kidneys were remarkable for end stage renal disease. There was also acute bilateral
bronchopneumonia with early organization and a mild bilateral lymphocytic adrenalitis. Gross examination
of the central nervous system (CNS) found marked cerebral edema with bilateral tonsillar and
transtentorial herniation. Selected microscopic images from the CNS are below.
Submitted by:
David H. Myerson
Fred Hutchinson Cancer Research Center
University of Washington
Seattle, Washington
A 56 year old male, 163 days post-marrow transplant for refractory follicular lymphoma. He was
prepared with fludarabine, total body irradiation (TBI), and cyclophosphamide, and engrafted from his HLA
haplo-identical brother. His course was complicated by bacterial, viral, metabolic and neoplastic
disease. Ten days post-transplant he developed microscopic hematuria, with urine BK polyomavirus
detected at 9x107 copies/ml. Thirty-eight days post-transplant his condition deteriorated
with gross hematuria and passage of clots. Concurrent urine BKV level was 8 x 108 genomes/ml.
He became free of gross hematuria after a month, with a urine BKV level of 3 x 105 genomes/ml.
Serum PCR detected 2400, 390, and 1100 BK genomes/ml respectively. Renal function remained slightly
compromised but adequate, with a creatinine up to 2.0. Other complications included graft-versus-host
disease (GVHD). Ultimately recurrent malignancy and a Zygomycetes intervened. The kidney was obtained
at autopsy.
Case 2 - Figure 1 - BKV nephropathy. Several hyperchromatic enlarged nuclei are present in the tubular epithelium of a single isolated tubule.
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Case 2 - Figure 2 - In situ hybridization with digoxigenin-labeled BKV probe shows the same tubule with heavily staining cells, indicating many copies of BKV. The same result is seen under stringent conditions, avoiding potential detection of other polyomaviruses (e.g. JCV, SV40).
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Submitted by:
Thomas A. Sporn
Duke University School of Medicine
Durham, NC
The patient was a 2 year old girl diagnosed at 18 months of age with acute monocytic leukemia
(French-American-British M5). Following establishment of remission with standard chemotherapy and
subsequent intensification and consolidation phases, the child suffered bone marrow relapse, which was
treated with non-related umbilical cord blood transplant. The child developed progressive pulmonary
infiltrates and alveolar opacities with hypoxic respiratory failure and death on post-transplant day 36,
despite therapies directed against graft-versus-host disease, and bacterial, fungal and viral pathogens.
An autopsy was performed, with findings notable for heavy lungs whose cut surface exuded pale yellow
fluid. Microscopic examination of the lungs demonstrated alveolar filling with granular eosinophilic
PAS-positive material. The lung parenchyma featured scant interstitial inflammation and fibrosis, and
numerous syncytial-type giant cells. Alveolar epithelial differentiation for these cells was suggested
on the basis of positive immunostaining with anti-cytokeratin antibodies. Ultrastructural examination of
the alveolar exudate was notable for electron-dense granular material, cell debris and lamellar bodies
with closely packed circumscribed membranes. Immunofluorescent staining of the giant cells and
corroborative cultures identified the etiologic agent.
Case 3 - Figure 1 - Chest radiograph taken two day prior to death demonstrates bilateral patchy opacities consistent with consolidation.
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Case 3 - Figure 2 - The lungs at the postmortem examination showed multiple foci of consolidation.
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Case 3 - Figure 3 - The alveoli were distended by eosinophilic granular material that was Periodic-acid Schiff positive.
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Case 3 - Figure 4 - The alveoli were distended by eosinophilic granular material that was Periodic-acid Schiff positive.
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Case 3 - Figure 5 - Giant cells with complex configurations and multiple nuclei were also seen.
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Case 3 - Figure 6 - Giant cells with complex configurations and multiple nuclei were also seen.
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Submitted by:
Christopher D. Paddock
Centers for Disease Control and Prevention
Atlanta, GA
A 40 year-old-woman with alcoholic cirrhosis complicated by encephalopathy and hepatopulmonary
syndrome was admitted to a Wisconsin hospital during November 2003. An orthoptopic liver transplant was
performed. On postoperative day 5 the patient developed fever. On day 8 she developed elevated hepatic
transaminase levels and leukopenia. Liver biopsies showed focal centrilobular necrosis and changes
consistent with mild rejection but no evidence of viral cytopathic changes. Immunohistochemical stains
of the biopsy specimens were negative for herpes simplex virus, adenovirus, and cytomegalovirus. The
patient's condition deteriorated and she developed mental status changes and a focal petechial rash
around the surgical incision on day 14. The patient subsequently developed multiple bleeding diatheses
around indwelling lines and incisional and biopsy sites. She died on postoperative day 18. An autopsy
was performed. Histopathologic findings included multiple foci of necrosis, hemorrhage, and mild
mononuclear cell infiltrates in the liver (Figures 1, 2), diffuse alveolar damage of the lungs (Figure
3), and necrosis and hemorrhage of the adrenal glands (Figure 4). No specific etiologic diagnosis was
obtained; however, 3 additional organ recipients who received kidneys and lungs from the same donor died
9-76 days following transplantation. Selected biopsy or autopsy tissues from the donor and each of the 4
recipients were sent to the Centers for Disease Control and Prevention for evaluation.
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