A 62-year-old man who had been treated for severe persistent asthma for 10 years at a local hospital presented to our hospital with a 1-month history of wheezing and exertional dyspnea. At his local hospital, he had been treated with high-dose inhaled corticosteroid, an inhaled long-acting beta2-agonist, leukotriene receptor antagonist, xanthine and intermittent systemic corticosteroids at least once a month for half a year. At our hospital, his wheezing disappeared after the administration of oral corticosteroid, but his exertional dyspnea did not improve. He was admitted to our hospital for the investigation of dyspnea and pulse oximeter desaturation.
A physical examination was normal despite hypoxemia. Chest sounds were normal, and expiratory wheezing was no longer heard after bronchodilator administration. There were no skin lesions, lymphadenopathy or neurological findings. Laboratory findings showed elevated serum lactic dehydrogenase (LDH) (1,482 IU/L), aspartate aminotransferase (AST) (39 IU/L) and C-reactive protein (CRP) (1.6 mg/dL) levels. An arterial blood gas analysis at rest while breathing room air showed hypoxemia (PaO2 53.9 Torr) with an elevated alveolar-arterial oxygen difference (AaDO2) (60.9 Torr). The serum tumor markers were within normal limits, except for an elevated soluble interleukin-2 receptor level (sIL-2R) (1,570 U/mL). Although chest X-ray showed no abnormal findings, chest CT showed diffuse multiple small nodules in the lung fields, no mass and no lymphadenopathy in the thorax or the abdominal cavity (Fig. 1A). Respiratory function testing showed a decline in the pulmonary diffusing capacity for carbon monoxide (DLCO). Pulmonary blood flow scintigraphy showed decreased accumulation in both middle-lower lung fields. A diffuse pulmonary 18F-FDG PET-CT scan showed an increased diffuse FDG uptake in both middle-lower lung fields (Fig. 1B). The existence of malignant lymphoma, such as IVLBCL, without clinical findings was suspected because of the hypoxemia, the high levels of LDH and sIL-2R, the increased AaDO2, the decreased DLCO and the scintigraphic, CT and PET-CT findings. A random skin biopsy and TBLB were performed, and the pathological findings revealed atypical lymphoid cells located within the intravascular space of the capillary vessels and pulmonary artery. In immunohistochemical staining, these atypical lymphoid cells were positive for CD20 and CD79a, which are B-cell markers (Fig. 2), and demonstrated a high proliferation index, as revealed by MIB-1 (Ki-67) (data not shown). Based on these results, the patient was diagnosed as having IVLBCL with pulmonary involvement.
After transfer to the Department of Hematology, the patient was treated with prednisolone and vincristine to reduce the pulmonary tumor burden due to his worsening respiratory condition. After one week, his respiratory condition improved. Following prednisolone and vincristine administration, he was treated with R-CHOP chemotherapy, consisting of rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine and prednisolone. He achieved complete remission after eight cycles of R-CHOP chemotherapy with no severe adverse events, and the LDH and sIL-2R levels, the AaDO2 and chest CT and FDG-PET findings subsequently revealed no signs of lymphoma involvement (Fig. 3).
18F-FDG PET-CT. scans at the initial presentation, showing diffuse multiple small nodules in the lung fields and an increased diffuse FDG uptake in both middle-lower lung fields. FDG: fluorodeoxyglucose, PET: positron emission tomography.