A 65-year-old woman was diagnosed as a neurosarcoidosis and oral administration of prednisolone (PSL) 45 mg/day was started. Methotrexate (MTX) 8 mg/week was added 4 months after PSL administration. A month later, she complained of fever and productive cough. A chest computed tomography (CT) revealed an abnormal shadow in the right upper lobe of the lung and right pleural effusion. She was treated with oral levofloxacin, but her symptoms and abnormal chest shadow did not improve. She was referred to our hospital for further examination and treatment.
Vital signs were stable and no abnormality was noted in physical examination. Laboratory testing revealed a white blood cell count of 6,670 per mm3, erythrocyte sedimentation rate of 30mm/1h, C-reactive protein of 1.2mg/dl, immunoglobulin (Ig) G of 622 mg/dl. beta-D glucan and KL-6 were within normal limits. Chest radiograph showed infiltrative shadows in the upper right lobe and right pleural effusion. Chest CT revealed right dominant non-segmental infiltrative shadows, multiple nodules, and right pleural effusion (Fig. 1a). Although we suspected the possibility of MTX-induced interstitial lung disease and discontinued this treatment, her symptoms and chest radiograph became worse.
Considering the immunocompromised host and radiological OP pattern such as non-segmental infiltrative shadows, we had to differentiate between idiopathic, collagen diseases, infection, malignant tumors, and drug reaction as causes of OP, and therefore performed a bronchoscopy obtaining a transbronchial lung biopsy (TBLB) of the right S2 region. The biopsy specimens revealed diffuse lymphocytes in the alveolar wall, and some of the alveolar spaces contained Masson bodies, which was consistent with OP. Moreover, intra-alveolar granulomas and high fibrin precipitation and bleeding, which strongly indicated various degrees of inflammation, were revealed (Fig. 1b). Spherical fungi of large variation sizes of about several mum to 20 mum were revealed by Grocott's silver stain (Fig. 1c). According to the finding of Grocott's silver stain, we considered the possibility of Cryptococcus neoformans or Pneumocystis jirovecii. Mucicarmine staining, which stains the yeast capsule of Cryptococcus red, was negative. However, the tissue specimens also lacked the characteristic of Pneumocystis jirovecii such as size uniformity of 4-10 mum, crescent-shaped, helmet-shaped, and intracystic dots. In the culture test of bronchial wash, general bacteria, acid-fast bacteria and fungi were all negative. Furthermore, the serum cryptococcal antigen was positive. It is known that there is the capsule-deficient form of cryptococcus, which is negative of mucicarmine staining. Finally, we diagnosed her as secondary pulmonary cryptococcosis. After fluconazole treatment, her symptoms, chest radiograph and CT finding improved (Fig. 1d).