International Journal of Gerontology 10 (2016) 112e116 Contents lists available at ScienceDirect International Journal of Gerontology journal homepage: www.ijge-online.com Case Report Cryptococcemia in an Elderly Woman with Retroperitoneal Diffuse Large B-cell Lymphoma after Rituximab-containing Chemotherapy* Ming-Wei Cheng 1, Alice Ying-Jung Wu 1, Chang-Pang Liu 1, 2, 3, Ken-Hong Lim 2, 4, * Shu-Ling Weng 5, Hsiang-Kuang Tseng 1, 2, 3 1 Division of Infectious Diseases, Department of Internal Medicine, MacKay Memorial Hospital, Zhongshan District, Taipei City, 2 School of Medicine, MacKay Medical College, New Taipei, 3 Microbiology Section, Department of Medical Research, MacKay Memorial Hospital, 4 Division of Hematology and Oncology, Department of Internal Medicine, MacKay Memorial Hospital, 5 Department of Laboratory Medicine, MacKay Memorial Hospital, Taipei, Taiwan article info summary Article history: Cryptococcemia is a bloodstream fungal infection caused by encapsulated yeasts of Cryptococcus neo- Received 20 January 2015 formans. We reported an 88-year-old woman in whom C. neoformans colonies of smooth and mucoid Received in revised form phenotypes were sequentially cultured from the blood during treatment of retroperitoneal diffuse large 24 February 2015 B-cell lymphoma using rituximab-containing chemotherapy. The most likely cause was disease pro- Accepted 25 February 2015 gression of pulmonary cryptococcoma. She was successfully treated with optimal antifungal therapy. Available online 14 June 2016 Copyright © 2016, Taiwan Society of Geriatric Emergency & Critical Care Medicine. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ Keywords: cryptococcemia, licenses/by-nc-nd/4.0/). Cryptococcus neoformans, lymphoma, rituximab 1. Introduction Rituximab is a monoclonal antibody for CD20-positive B lympho- cyte. However, opportunistic infections have been reported due to Cryptococcus neoformans is the most common encapsulated the immunosuppressive effect of rituximab3,4. yeast that causes opportunistic cryptococcosis in immunocom- promised patients. The molecular type of C. neoformans can be 2. Case Report subdivided into VNI, VNII, VNB (C. neoformans var. grubii), VNIV (C. neoformans var. neoformans), and VNIII (a hybrid form of 2 va- An 88-year-old woman had a history of right breast cancer, rieties). The subtype VNI is the leading cause of cryptococcosis Stage IIA postmastectomy, and lymph node dissection in April 1 worldwide, including Taiwan . The morphology of Cryptococcus 2010. Since then she has received oral tamoxifen adjuvant ther- 2 colonies can be depicted as smooth (SM) or mucoid (MC) . Fries apy until December 2012. In December 2012, she presented with 2 et al described the morphology change between SM and MC as right flank and abdominal pain with weight loss of <10% of body phenotypic switching. It is a reversible process, in which colony weight (5 kg) within 3 months. A large soft tissue lesion morphology changes to another variant at a higher frequency than (9.3 cm  5.4 cm  9.3 cm) in the retroperitoneal aortocaval and would be expected from random somatic mutation. para-aortic region was found by abdominal computed tomogra- Rituximab-containing cyclophosphamide, hydroxydaunor- phy scan. Biopsy of the retroperitoneal mass revealed CD20- ubicin, oncovin, and prednisolone (CHOP) chemotherapy is one of positive diffuse large B-cell lymphoma. In addition, one 2-mm the regimens indicated for diffuse large B-cell lymphoma. peripheral nodule at the right upper lung and another 3-mm nodule at the left upper lung without definite characteristics on chest computed tomography scan (Figure 1A) were found * Conflicts of interest: All contributing authors declare that they have no conflicts during staging workup. Bone marrow needle biopsy showed no of interest. bone marrow involvement. Thus, her diffuse large B-cell lym- * Correspondence to: Dr Hsiang-Kuang Tseng, School of Medicine, MacKay phoma was classified as Stage IIA disease. Her Eastern Coopera- Medical College, Number 46, Section 3, Zhongzheng Road, Sanzhi District, New Taipei City 25245, Taiwan. tive Oncology Group performance score was 2. The level of E-mail address: [email protected] (H.-K. Tseng). lactate dehydrogenase was 261 IU/L. The International Prognostic http://dx.doi.org/10.1016/j.ijge.2015.02.005 1873-9598/Copyright © 2016, Taiwan Society of Geriatric Emergency & Critical Care Medicine. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Cryptococcemia in an Elderly Woman 113 Figure 1. (A) Chest computer tomography revealed two peripheral nodules (black arrows). (B) Summary of morphology change and antifungal treatment. AMB þ 5FC ¼ amphotericin B plus flucytosine; MC ¼ mucoid; MS-CNS ¼ methicillin-susceptible coagulase-negative Staphylococcus;SM¼ smooth. Index score was 3, which placed her in the higheintermediate was 1600/mL with 4% band, 64% neutrophil, and 26% lymphocyte. risk group. She was first treated with a prephase therapy con- She had a C-reactive protein level of 5.18 mg/dL, procalcitonin level taining dexamethasone plus vincristine in January 2013. One of 0.063 ng/mL, and creatinine level of 0.8 mg/dL. Granulocyte week later, she was treated with rituximab, cyclophosphamide, colony-stimulating factor was administered due to neutropenia. vincristine, and prednisolone combination chemotherapy. The Blood culture yielded methicillin-susceptible coagulase-negative dose of rituximab was 375 mg/m2 during treatment. Three weeks Staphylococcus; fever subsided gradually after adequate antibiotic later, she received a second course of treatment with rituximab use. However, her urine culture yielded yeast (Figure 1B). On March and prednisolone to minimize side effects. 4, 2013 (Day 13), we repeated blood cultures due to neutropenic On the third admission for chemotherapy, rituximab, vincris- fever. Three days later (Day 16), the preliminary report from blood tine, and prednisolone combination therapy was given on February culture revealed yeast. Initially, a 400-mg dose of intravenous flu- 19, 2013 (Day 0). Fever developed 8 days later, and she received conazole was administered empirically; the antifungal regimen was empirical antibiotics after obtaining urinalysis and blood culture then pre-emptively switched to micafungin 100 mg once daily on (BACTEC FX culture system; Becton Dickinson, Inc., Sparks, MD, the next day (Day 17) to cover clinically suspected azole-resistant USA). Laboratory data (Day 8) showed that white blood cells count Candida. 114 M.-W. Cheng et al. The yeasts from urine and blood cultures were subsequently with fluconazole 400 mg orally started after 2-week induction identified to be Cryptococcus species through positive India ink and therapy5. She recovered slowly without any neurological sequelae urease test. The morphology of Cryptococcus species was round and was discharged on Day 139 with a maintenance dose of flu- with smooth (SM) dome colony surface and thin capsule (Figure 2). conazole 200 mg/d orally. Due to old age and the deteriorated The antifungal regimen was thus switched to an induction therapy performance status of the patient, the family decided not to receive for cryptococcemia5, consisting of intravenous amphotericin B further chemotherapy, and the clinical course of the patient was (0.7 mg/kg/d) plus oral flucytosine 1000 mg/6 h for a 14-day course. uneventful after that. Eventually, she passed away 1 year later due The serum cryptococcal antigen titer was 1024-fold. Although there to an episode of respiratory infection at the age of 90 years. was a high concern for central nervous system invasion by Cryp- tococcus species (SM), she declined lumbar puncture due to per- 3. Discussion sonal reasons. In the beginning, Cryptococcus species (SM) in urine and blood culture was identified as Cryptococcus laurentii through In most developed countries including Taiwan, the aging pop- VITEK 2 system (bioMerieux, Marcy l'Etoile, France). C. laurentii,a ulation continues to grow to a larger percentage of the overall possible saprophyte from skin, has rarely been reported as a human population. It was generally agreed that older persons are prone to pathogen. infections. However, with adequate therapy, age may not be a sig- On March 7, 2013 (Day 16), we performed follow-up blood nificant predictor of mortality for sepsis, even in critically ill pa- culture and Cryptococcus species (SM) was reported again. Inter- tients7. The application of sepsis bundles including obtaining estingly, a few shiny and mucoid-appearing colonies (MC; Figure 3) routine culture before the administration of broad-spectrum anti- were found and identified as C. neoformans by VITEK 2 system. On biotics has been effective and has led to a substantial reduction in March 11, 2013 (Day 20), we carried out another blood culture; both hospital mortality8. In a cohort comparing clinical characteristics of SM and MC colonies were found. The antifungal susceptibility test cryptococcal meningitis in elderly patients (aged 65 years) with of SM and MC revealed no significant difference in amphotericin B, those in younger patients, there was no difference in mortality fluconazole, itraconazole, voriconazole, posaconazole, and flucy- rate9. We had successfully treated this 88-year-old woman for her tosine by a commercially prepared, dried colorimetric micro- cryptococcemia through proper blood