A Case of Pulmonary Cryptococcosis by Capsule-deficient Cryptococcus neoformans
A 25-year-old woman was admitted to our hospital with nonresolving pneumonia. The patient had felt well until two weeks before her admission, when she began to experience a dry cough, dyspnea and pleuritic pain. Her respiratory symptoms did not respond to a 5-day course of oral cephalosporin, and macrolide antibiotics had been prescribed before her admission. She was a non-smoker with unremarkable past medical history.\nOn admission the body temperature was 36.6℃, the heart rate was 84/min, the respiration rate was 20/minute and the blood pressure was 100/80 mmHg. On physical examination, the patient was alert and not in great discomfort. There was a crackle sound over the left lower lung zone. There was no organomegaly or lymphadenopathy. Detailed examination of the cardiovascular system and abdomen was unremarkable. Chest radiography disclosed a pneumonic infiltration on the left lower lung field and there was no cardiomegaly (). Computed tomography (CT) scanning of the chest revealed a consolidation with air-bronchogram in the left lower lobe and a small amount of pleural effusion (). The complete blood count showed a normal white cell count (8.4×109/L). There was no hypoxemia on the blood gas analysis (pH 7.4, PaCO2 37.2 mmHg, SaO2 98%) when she was breathing room air. The other laboratory investigations showed normal electrolytes and renal and liver function tests. The fasting glucose was normal. The serum anti-HIV antibody was negative. The serum immunoglobulin levels (including IgG, IgA and IgM) were normal. Pulmonary function testing showed a mild restrictive pattern (the forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) was 2.50/2.32L; the ratio was 93%), and there was a normal diffusion coefficient for carbon monoxide (DLco: 109%). The initial examination of the sputum for acid-fast bacilli with gram staining and culture did not reveal any organisms. The blood culture was sterile after 7 days incubation. We then conducted a bronchoscopic examination. There were no endobronchial abnormalities. Bronchoalveolar lavage (BAL) revealed the lymphodominant nature (a lymphocyte count of 70%, the macrophages were 28%). The BAL fluid culture was negative and there were neither acid-fast bacilli nor any pathogens.\nDuring the first six days of this patient's admission to our hospital, her annoying respiratory symptoms and lung consolidation did not improved for all the combination antibiotic treatment (intravenous cefuroxime and oral clarithromycin). We performed a subsequent computed tomography guided percutaneous needle biopsy on the sixth hospital day. The tissue pathology revealed granulomatous lesion including multinucleated giant cells and fungal spores. The specimens were stained with Hematoxilin-Eosin, mucicarmine, Gomori-Methenamine silver (GMS), and periodic-acid-Schiff (PAS). The Hematoxilin-Eosin and GMS stain showed granulomatous inflammation with numerous yeast-like organisms that were surrounded by clear halos, and these organisms were present within multinucleated giant cells and in the intercellular spaces (). Mucicarmine staining for capsular material was negative. With performing additional Fontana-Masson silver staining (FMS), the black color in the walls of the organism was disclosed (). This special stain pattern is a characteristic of C. neoformans, and especially for the capsule deficient form. Subsequently, the antibiotic regimen was replaced by 1-week of once-a-day intravenous fluconazole treatment and the patient was discharged on oral fluconazole. Further cultures of the lung specimen yielded moderate growth of Cryptococcus neoformans afterward. During the 6-months follow up period her respiratory symptoms and abnormal radiologic feature were markedly improved ().