Leukemic Infiltration of Lung Mimicking Fungal Pneumonia

Abstract

Leukemic infiltration of lung may be seen in acute leukemia especially in those with high white cell counts. However, it is difficult to diagnose antemortem as it mimics infections or pulmonary hemorrhage which are much more common complications. We present an unusual patient who had a fatal outcome due to leukemic progression in the lung despite blood and marrow response to induction chemotherapy. Twenty-eight year old female presented with fever and lymphadenopathy for 4 weeks. Investigations: Hemoglobin: 6.7 g/dL; Thrombocyte count: 0.92 × 109/L; white blood cell (WBC) count: 4.1 × 109/L with 65 % blasts confirmed as precursor B acute lymphoblastic leukemia on bone marrow studies. At baseline, patient was afebrile with a normal chest radiograph (Fig. 1a). By day 7 of therapy (only Prednisolone 60 mg/m2 for the first 1 week as per BFM 95 protocol) her WBC count had dropped to 0.6 × 109/L and her peripheral blood had cleared blasts. However, she developed high grade fever and her general condition deteriorated; infection was suspected and empiric antibiotics were started. The day 8 chemotherapy was modified (only Vincristine was delivered, Daunorubicin was omitted). After initial stabilization, the patient had recurrent fever spikes and worsening respiratory status. Patient’s chest radiograph showed lung infiltrates and nodular shadows which made us suspect fungal pneumonia (Fig. 1b). A bone marrow exam was done which showed hypocellular marrow hence all leukemic therapy was withheld and we started her on 2nd line antibiotics and antifungal therapy (voriconazole). She continued to remain febrile and had persistent pancytopenia. Bleeding manifestations precluded any attempt at tissue diagnosis from lung lesions. Repeat chest imaging (Fig 1c) showed further worsening of pulmonary infiltrates. On day 22, she developed progressive respiratory failure and expired. Post mortem lung biopsy showed extensive leukemic infiltration of lung (Fig. 1d, e). No fungal pathogen/infection could be found. Fig. 1 Chest X-ray before starting chemotherapy (a). Chest X-ray showing path infiltrates in both lung fields (b).Chest X-ray showing progression of lung infiltrates (c). Low magnification (×20) view showing leukemic infiltrates in lung (d). Higher magnification ... Pulmonary involvement in acute leukemia can manifest as pulmonary leukostasis, leukemic infiltrates, alveolar hemorrhage, pulmonary nodules, or pleural infiltrates [1–3]. Clinical presentation can vary from asymptomatic pulmonary infiltrates on imaging to acute respiratory distress syndrome—like features. Various radiological findings based on computed tomography of lung have been described for pulmonary leukemic infiltrates [4] but we could not do any imaging other than chest X-ray as patient was too sick to be transferred. We suspected fungal pneumonia in our patient as she was profoundly neutropenic and was not responding to antibiotics. However, postmortem lung biopsy proved that it was leukemic pulmonary infiltrates rather than infection which caused death in our patient. Most of the reported literature of involvement of lung in leukemic patients is in cases of acute leukemia in pre-treatment setting. However postmortem series have shown pulmonary infiltrates in 31–66 %. It’s very intriguing that our patient had a dramatic response with clearance of blasts while the disease progressed in the lungs. The tissue diagnosis of pulmonary infiltrates in leukemic patients can bring about significant changes in management. However, the procedure can be risky especially where patients have significant bleeding tendencies, as in our patient. This led to empiric therapy which resulted in a negative outcome in our patient. We report this case to create awareness about the possibility of leukemic infiltrates being an important cause of respiratory failure during acute leukemia induction even when there is apparent response in the bone marrow.