A 15-year-old Caucasian boy was diagnosed with B-NHL involving lymph nodes, mediastinum and bones. The patient was treated according to B-NHL-BFM (Berlin-Frankfurt-Munster) 1997 protocol combined with Rituximab.
Seven days after the fifth chemotherapy course, the patient was hospitalized for fever (37.9 C), severe cytopenia (white blood cell count 0.15 x 109/L, neutrophils 0 x 109/L, platelet count 23 x 109/L, Hb 96 g/L), elevated C-reactive protein [C-RP] (92 mg/l), but normal procalcitonin [PCT] (0.33 ng/ml) and vital signs (blood pressure 124/69 mmHg, heart rate 79 beats per minute [bpm], peripheral oxygen saturation [Sp02] 97%). After drawing blood cultures from central line and peripheral vein, an empiric antibiotic treatment with ceftazidime, amikacin and teicoplanin was promptly initiated together with granulocyte colony stimulating factor (GCSF), while prophylaxis with cotrimoxazole and fluconazole was continued. On day 4 tachypnea, dyspnea, hypoxemia (Sp02 80%), tachycardia (heart rate 150 bpm) and left hemithorax acute pain appeared together with an increase of CRP (440 mg/l) and PCT (3.13 ng/ml). On physical examination, lung auscultation revealed diminished breath sounds and rales over the left lung. The first set of blood cultures was negative as well as the second one and the blood samples for galactomannan (GM) and beta-d-glucan (BDG) antigens. Lung computerized tomography (CT) showed a left extensive consolidation associated with pleural effusion (Figure 1).
Considering a possible fungal origin of pneumonia and the profound B-lymphocytopenia, micafungin (100 mg/day) was started and, in order to enhance the innate immunity, a 3-day course of intravenous IgM-enriched immunoglobulins was administered. On day 6 the fever disappeared while the neutrophils recovered over 0.5 x 109/L. On day 7, BDG was markedly positive (> 523 pg/ml) while GM remained negative. On day 9, high fever reappeared associated with edema and hyperemia on the left neck. A second lung CT revealed a slight increment of the left lung consolidation (Figure 2). A neck ultrasound detected a swelling lesion in left thyroid lobe (19 x 19 mm) and an abdomen ultrasound found a nodule in the middle-superior part of the right kidney (25 x 22 mm). This nodular lesions, as well as the lung one, were intensely hypermetabolic on positron emission tomography (PET)-CT scan proving to have probably the same infectious origin. We performed a needle aspiration of the thyroid lesion showing only the presence of a suppurative process. Blood cultures and serum GM were again negative whereas serum BDG value returned into normal range.
The antifungal therapy was enhanced adding voriconazole to micafungin, while the antibiotic therapy was modified introducing metronidazole and replacing ceftazidime and amikacin with meropenem. Despite this, the fever persisted with a CRP rising to 425.8 mg/L on day 11. On day 17 the patient underwent a bronchoalveolar lavage (BAL) that resulted negative for bacteria, fungi, Mycobacterium tuberculosis, GM and BDG antigen.
The patient continued to experience evening fever peaks and cough. On day 32 we repeated a CT scan showing unaltered the left lung consolidations and the left thyroid lobe lesion and an increase of the multiple nodules at the right kidney. These radiological findings were discussed in a multidisciplinary meeting with radiologists, infectivologists and pediatric hematologists discovering that the main lung lesion was presenting the reverse halo sign from the beginning. Given the lack of improvement and the severe clinical conditions, on day 36 the patient underwent left superior lung lobectomy. No postoperative complications were observed and the patient was discharged home 13 days later. The histopathological examination was consistent with a fungal pneumonia for the presence of hyphae. The identification of fungal DNA was performed by sequencing the internal transcribed spacer (ITS) domain of the rDNA gene and D1-D2 region of ribosomal sub-unites, according to the method described by White et al. that revealed the presence of Lichtheimia corymbifera (Figure 3). Therefore, the patient suspended voriconazole and received antifungal therapy with liposomal amphotericin B (5 mg/kg three times a week) and posaconazole (3 x 200 mg/d) for 7 weeks.
Six days after discharge home the patient developed low grade fever (37.5 C), painful increase and hyperemia of the left emithyroid (60 x 50 mm), increased of CRP 125 mg/l and PCT 0.13 ng/ml) with normal blood count. The patient underwent an urgent hemithyroidectomy with surgical drainage with rapid clinical improvement. The cultural search for bacteria, fungi and Mycobacteria resulted negative.
The patient continued a secondary prophylaxis with posaconazole (3 x 200 mg/day) for 18 months. A lung CT, performed 6 months after surgery, showed only postoperative changes whereas the renal lesion disappeared after 12 months of posaconazole treatment.
CT lung scan showing the slight increment of the left lung consolidation (53 x 77 mm) appearing as an area of pulmonary opacity surrounded by normal parenchyma.