Occult pleural cryptococcosis in an immunocompromised patient

Abstract

Sir: Cryptococcosis is a rare opportunistic, invasive, fungal, lifethreatening infection, which occurs in both immunocompetent and immunocompromised patients. In immunocompromised patients, the signs of cryptococcosis can easily be confused by the symptoms of the primary disease, which may delay adequate treatment [1]. We recently treated a 47-year-old woman with a thymoma WHO type B1 in the left hemithorax treated with three cycles of cisplatin/etoposide. Simultaneously, she developed a recurrent right-sided pleural effusion, which was drained four times and tested by an India ink and gramstained smear, bacterial culturing, Cryptococcus serum and pleural punctuate antigen testing and a cytological stain, which were all negative for microorganisms including Cryptococcus neoformans. The broncheoalveolar lavage (BAL) material was also negative. The transudate contained lymphocytes and mesothelial cells. Eight days following the last cycle of chemotherapy, the patient was admitted because of fever, headache, neck pain, and cognitive changes during chemotherapyinduced pancytopenia. Three months after pleural effusion development, C. neoformans meningitis was diagnosed in the cerebral spinal fluid. The infection was successfully treated with amphotericin B (0.7 mg/kg/day) and flucytosine (100 mg/kg/day) for 2 weeks, followed by 8 weeks amfotericin B (0.7 mg/kg/day) with flucanozole (800 mg/kg/day). Despite the diagnosis of meningeal cryptococcosis, pleural abnormalities remained attributed to the thymoma. Two weeks after cryptococcosis diagnosis, the patient underwent surgery for staging. Histology of the right middle lobe and pleura revealed a granulomatous necrotizing infection with C. neoformans (Fig. 1). One month later, a thymectomy was performed with partial pericardectomy, followed by ICU admission for 1 month. In summary, our patient showed pulmonary cryptococcosis which, due to negative bacteriological testing, was not recognized as such. Pulmonary signs were, therefore, attributed to her thymoma. Despite repeated testing for fungi of the pleural effusion and BAL, these tests remained negative during a substantial part of the disease progression. Whether the initial pleural transuduate was caused by cryptococcal infection or that secondary infection of pre-existent pleural fluid occurred, remains unclear. Microbiologic examination of specimens for cryptococci is not always conclusive: the appearance of cryptococci may vary considerably