Invasive aspergillosis extensively involving the brain and multiple organs in a bone marrow transplant patient
D Feng, R Heffner, J Wright
D Feng, R Heffner, J Wright. Invasive aspergillosis extensively involving the brain and multiple organs in a bone marrow transplant patient. The Internet Journal of Pathology. 2007 Volume 7 Number 2.
We report here a 16-year-old Caucasian male with an 8 years history of acute lymphoblastic leukemia who died of an acute invasive systemic aspergillosis 163 days after allergenic bone marrow transplantation. One week prior to death, he had drowsiness, lethargy, and fever. Both CT scan and MRI of the head demonstrated multiple ring enhancing lesions consistent with intracerebral abscesses. Autopsy showed extensive brain involvement of aspergillosis in the frontal cortex, occipital cortex, hippocampus, basal ganglia, medulla, ponds, and cerebellum. Aspergillosis also presented in multiple organs including heart, lungs, liver, kidney, thyroid gland, and lymph nodes.
Invasive aspergillosis is a serious opportunistic disease among immunocompromised and immunosupressed patients (1,2,3).
The patient was a 16 year-old white male with a history of acute lymphoblastic leukemia (ALL), which was diagnosed 8 years back. He was then treated with extensive chemotherapy, but his ALL was relapsed twice. Therefore, he received allogenic bone marrow transplantation. His graft versus host disease (largely limited to the skin) was well controlled with high dose of immunosuppression medication including high doses of steroids. Two weeks prior to death, he was very weak and presented to the hospital on wheelchair for a checkup. His parents informed that he had fallen on the floor on several occasions at home. On the same day he was admitted to the hospital for severe myopathy, and depression.
On admission, his vital signs were stable, and lab tests showed a white blood cell count of 17,000, hemoglobin 7, platelets 24,000, BUN 23, creatinine 0.6, glucose 278, alkaline phosphatase 134, total bilirubin 1.7, aspartate aminotransferase (AST) 45, alanine aminotransferase (ALT) 147, and lactate dehydrogenase (LDH) 1826. He had steroid-related diabetes, and appeared emotionally depressed associated with his disease and steroids. He had had pancytopenia for a few weeks. During his admission, he was treated with physical therapy for his myopathy, and was given multiple prophylactic antibiotics including amoxicillin, acyclovir, pentamisine, and caspofungin. He was also blood transfusion and growth factor (G-CSF) dependant. Five days after admission, the patient was noted to have change in mental status including drowsiness and lethargy. He complained of fatigue and weakness. Three days later, the patient became febrile and his blood culture revealed
The patient presented a typical appearance of Cushing's syndrome including moon face, truncal obesity, buffalo hump, hirsutism, multiple abdominal purple striae. He had bruises over his external body surface, and petechial hemorrhages on skin of his lower extremities. There was straw-colored fluid in the bilateral pleural cavities (right side100 ml and left 220 ml), pericardial (120 ml) and peritoneal cavities (320 ml).
On gross examination, the brain was diffusely edematous and enlarged with flattened gyri and sulci. Multiple foci of recent hemorrhagic infarct and nodules, varying in size from 1 to 3 cm in diameter, were present in the frontal and occipital cortex, hippocampus, basal ganglia, medulla, ponds and cerebellum. Two foci showed recent hemorrhages draining into bilateral ventricles, which were enlarged and asymmetric (Figure1). Bilateral pulmonary lobes showed multiple white to yellow, irregularly shaped demarcated, firm nodules varying in size with central necrosis. There were also similar nodules present in the heart, liver, spleen, left and right kidneys, thyroid, cecum, and lymph nodes.
Microscopically, numerous thin septate Aspergillus hyphae with 45 degree branching were identified in every portion of the brain on random sections. Vascular invasion by Aspergillus associated with extensive thrombosis, hemorrhage, infarct and edema were seen in bilateral cerebral hemispheres. Aspergillus was present in virtually every organ microscopically, including heart, lungs, liver, kidneys, thyroid gland, and lymph nodes on random sections. Aspergillus invading vessels with associated extensive thrombosis, hemorrhage and infarct were present in lungs (Figure 2), spleen, and kidneys. Bilateral lungs also showed necrotizing pneumonia, and edema. The liver exhibited diffuse necrosis and hemorrhage often adjacent to portal triads. There were cytopathic effects consistent with viral hepatitis. In the thyroid gland, multiple aspergillus fungal balls were noted spreading into adjacent follicles.
Aspergillosis is a serious infectious complication in immunocompromised patients. Other commonly affected patients include those with neutropenia from hematologic malignancy or chemotherapy, those with AIDS, and those on chronic corticosteroids (1,2,3). Life-threatening invasive aspergillosis is dramatically increasing, and commonly occurs in immunocompromised or immunosuppressed patients via inhalation of fungal spores (mold conidia) causing pulmonary infection (4,5). Clues to pulmonary infection are development of pleuritic chest pain and elevation of serum LDH (4,5,6).
Systemic mycoses affecting severely immunocompromised patients often have acute or subacute presentations with rapidly progressive pneumonia, fungemia, and manifestations of extrapulmonary dissemination. Disseminated aspergillosis is associated with a mortality rate of greater than 90% (10,11). Treatment of invasive aspergillosis including early high doses of amphotericin B may be life-saving (4,5).
Authors wish to thank Dr. G. Brink for review of the manuscript.