In 2015, a 39-year-old man presented to our hospital with a four-week history of headache and a two-week history of low-grade fever. He was previously healthy and had not been taking any medications. He was a current smoker (15 pack-years) and occasionally consumed alcohol. Although he had traveled to Hawaii in 2005, Dalian in China in 2008, and Hong Kong in 2010, he had no other history of overseas travel. He had been working as electrical engineering technician, and had not been exposed to any imported timber or animals.
A physical examination revealed mild neck stiffness and a low-grade fever of 37.2 C. A chest X-ray showed a tumor of approximately 50 mm in size in the right lower field, and a chest computed tomography (CT) scan showed a 48x35 mm tumor with spiculation and notching on the right S9/10 (Fig. 1a and b). A gadolinium-enhanced brain magnetic resonance imaging (MRI) scan showed multiple brain tumors with ring enhancement (Fig. 1c and d). The patient's white blood cell (WBC) and platelet counts were high [WBC, 12,900/mm2 (normal range 4,000-9,000/mm2); platelet, 444,000/mm2 (normal range 150,000-370,000/mm2)], and the blood chemistry findings were normal, including the levels of glucose, hemoglobin A1c, tumor markers, immunoglobulin, and autoimmune antibodies.
Based on the chest CT and brain MRI findings, we suspected lung cancer with multiple brain metastases, and performed a bronchoscopic examination. A histopathological examination of the transbronchial lung biopsy (TBLB) specimen from the right S9/10 revealed numerous fungal elements that appeared as encapsulated yeast with clear halos (Fig. 2a). The yeast was observed after periodic acid-Schiff and Grocott methenamine silver staining (Fig. 2b). A lumbar puncture had an elevated opening pressure (33 cm H2O), and the cerebrospinal fluid sample contained 264/mm2 cells, 84.1% of which were lymphocytes. India ink staining of the patients' cerebrospinal fluid revealed encapsulated Cryptococci as a halo against a black background (Fig. 2c). Additional serological tests revealed that the patient was negative for HIV-1/2 antibodies and positive for cryptococcal antigen; the CD4+ lymphocyte level in the patient's peripheral blood was normal. The cryptococcal strain isolated from the bronchial lavage and cerebrospinal fluid was identified as C. gattii genotype VGIIa using multi-locus sequence typing (MLST), based on a DNA sequence analysis of a set of polymorphic loci.
As a result, the patient was diagnosed with pulmonary and cerebral cryptococcosis induced by C. gattii genotype VGIIa infection. He was treated with liposomal amphotericin B (5 mg/kg/day for more than 8 weeks), flucytosine (6,000 mg/body for more than 8 weeks). Percutaneous lumbar drainage was performed more than 15 times within the first month to manage his increased intracranial pressure. His subjective symptoms and radiological abnormalities improved gradually. After induction therapy, we are planning consolidation therapy and maintenance therapy with oral fluconazole.