The patient was an 85-year-old man who had undergone a total gastrectomy because of gastric cancer 8 years prior and had been diagnosed with myelodysplastic syndrome (RAEB-T, IPSS-IR 8.5 points) 2 years prior. He was categorized as "high risk" when considering hematopoietic stem cell transplantation, therefore azacitidine therapy had been continued. Six months before the current hospitalization he was diagnosed with pulmonary tuberculosis and administered rifampicin, isoniazid and ethambutol for 2 months, then switched to maintenance therapy consisting of rifampicin and isoniazid. He developed thrombocytopenia due to myelodysplastic syndrome and rifampicin 4 months after treatment initiation. He was hospitalized with fever and left chest pain 5 months after treatment initiation and was diagnosed with aspiration pneumonia and pleuritis. Despite the administration of broad-spectrum antibiotics his symptoms deteriorated, in conjunction with gradually increasing oxygen demand. His sputum mycobacterial smear converted to positive, suggesting the possibility of tuberculosis recurrence.
Eleven days after the initiation of treatment contrast-enhanced chest CT revealed tumor-like consolidation without enhancement expanding from the left lower lobe, which was diagnosed as pulmonary abscess. He was treated with several broad-spectrum antibiotics including moxifloxacin in view of the possibility of Citrobacter and/or anaerobic bacteria. Acid-fast sputum culture collected 4 days before admission proved positive, prompting the addition of streptomycin to isoniazid to treat active pulmonary tuberculosis. When pleural effusion increased, a chest drainage tube was inserted into his left thorax in view of a possible empyema with fistula on hospitalization day 17.
His respiratory condition improved transiently after insertion of the chest drain tube, but fever and inflammation increased again a few days later. Contrast-enhanced chest CT on day 21 depicted massive tumor-like consolidation without enhancement expanding from the left lower lobe. Emboli were also detected in the left descending pulmonary artery (Fig. 1). Because he had developed disseminated intravascular coagulation and that was thought to be the cause of pulmonary embolism, anticoagulants were administered. They were discontinued 5 days thereafter however, due to hemoptysis.
On day 25, an exploratory puncture to the remaining abscess was performed. No pus was aspirated, but a small amount of bloody effusion was collected. Enterococcus faecium was cultured from the bloody clot, but no fungal species or mycobacteria were detected. Because the bacteria were repeatedly detected in sputum and pleural effusion and were thought to be the cause of the pulmonary abscess, vancomycin was administered. Despite intensive treatment he developed multiple organ failure and died 47 days after hospitalization.
Gross pathology of a lung autopsy specimen revealed left lower pulmonary arterial embolism (Fig. 2) and pulmonary infarction (Fig. 3). Acute myeloid leukemia with myelodysplasia-related changes was detected in the bone marrow. Histopathology of the necrotic lesion and the emboli revealed that mycelia had grown inside the mass and fungal emboli had spread from the pulmonary artery trunk over the left pulmonary artery proximal portion. The artery wall was destroyed by granulomatous inflammation and fungal invasion, which had also spread outside the artery. Pulmonary arterial embolism composed of invasive mycelia in conjunction with acute myeloid leukemia associated with myelodysplastic syndrome was deemed to be the direct cause of death. As well as the above, E. faecium was detected via necrotic lung tissue culture.
Real-time polymerase chain reaction (PCR) was performed to identify the species responsible for the mycosis. DNA was extracted from two samples cut from formalin-fixed paraffin-embedded specimens that had been obtained from a bacterial mass in a proximal portion of the pulmonary artery. A real-time PCR protocol designed to detect 15 types of fungi identified Mucor sp. genes in the specimens. Immunohistochemistry using a mouse anti-Rhizopus arrhizus antibody (clone WSSA-RA-1; BioRad, New York, USA) as the primary antibody revealed that the mold in the blood vessels of lung tissue was partially positive for the mucor antigen (Fig. 4).
Enhanced chest computed tomography (CT) images on the 21st day after admission. Pulmonary embolism of the left descending pulmonary artery was observed. . c. Ground-glass opacity, which is one of the typical CT finding in invasive fungal infection, was not observed in the pulmonary window setting.