Aspergillosis in a Patient Receiving Temozolomide for the Treatment of Glioblastoma
A 78-year-old woman was diagnosed 4 months before admission with a right frontal GBM with extension to the basal ganglia and temporal lobe. The patient underwent a frontal craniotomy and partial resection of the lesion, followed by hypofractionated radiation therapy (16 fractions of 250 cGy) with concomitant daily TMZ (75 mg/m2). During the concurrent phase, she developed grade 1 lymphopenia and grade 2 nausea, but the treatment was otherwise well tolerated. Two days after completing chemoradiation, the patient was admitted for dyspnea and asymmetrical lower extremity edema. At admission, she denied cough, sputum, hemoptysis or thoracic pain. She reported no fever, chills, sweats or weight loss. Neurologic symptoms were stable since her last assessment. She had a history of hypertension and controlled type 2 diabetes. Medications included omeprazole, amlodipine, metformin, gliclazide, sitagliptin and prophylactic sulfamethoxazole-trimethoprim. She was also taking dexamethasone 4 mg/day on a tapering scale.\nUpon physical examination, she had normal vital signs, with a respiratory rate of 18 breaths/min and oxygen saturation of 95% on room air. She had asymmetric edema of the lower limbs and, on auscultation, fine respiratory crackles bilaterally. Electrolytes, liver enzymes and renal function were normal. Blood counts were: hemoglobin 11.9 g/dl, platelets 67,000/mm3 and leukocytes 7,030/mm3, with an absolute lymphocyte count of 800/mm3. A venous duplex-scan of the lower extremities showed an extensive deep vein thrombosis involving the left common femoral vein. An angiotomography of the thorax diagnosed an acute pulmonary embolism and also revealed scattered lobulated nodules with areas of cavitation, measuring up to 2.7 cm, located predominately in the upper lobes, some with a surrounding ground-glass halo. There was no pleural effusion. Areas of peribronchial infiltrates and centrilobular nodules were also present (fig. ). Serum galactomannan levels, determined using an enzyme-linked immunosorbent assay, were elevated (optical density index = 6.7, optical density index ≥0.5 is considered a positive result). Blood samples obtained for culture and Cryptococcus neoformans and Histoplasma antigen assays were negative.\nA CT-guided pulmonary biopsy was then performed. Histochemical analysis (Gomori's silver stain) showed septate hyphal elements with acute-angle branching (fig. ), and culture of the pulmonary tissue was positive for Aspergillus fumigatus. The patient was promptly started on antifungal therapy with voriconazole and was discharged to complete the treatment as an outpatient. Chemotherapy with TMZ was resumed after 4 weeks of antifungal therapy. A control CT scan done approximately 30 days after admission revealed a reduction of the nodular lesions and ground-glass component previously identified (fig. ).\nWritten informed consent for publication of the clinical details and/or clinical images was obtained from the guardian/relative of the patient.