A 72-year-old male with a long standing history of chronic lymphocytic leukemia (CLL) presented with upper respiratory symptoms including mild productive cough and dyspnea. An outpatient chest CT showed innumerable bilateral ill-defined solid pulmonary nodules in a peribronchovascular distribution, which were new from a prior scan 6 months earlier (Figure 1). Many of the lesions had a peripheral ground-glass halo. Nonenlarged mediastinal and bilateral axillary lymph nodes were suspected to be related to the patient's history of CLL. The pulmonary nodules were not a typical manifestation of CLL and other etiologies were considered such as atypical pulmonary infection, sarcoidosis, Kaposi sarcoma, and metastasis, even though patient had no other known malignancy. He was treated with antibiotics and steroids for his symptoms; however there was progressive clinical decline over several weeks and thus the patient was admitted for further work-up.
At the time of admission, vital signs showed exertional hypoxia, mild tachycardia in the low 100's, and a fever up to 102.4, which raised the concern for an infection and septic emboli. However, there were no significant pulmonary findings on exam. Skin examination revealed erythematous/purple skin papules on both lower extremities which broadened the differential to also include autoimmune and vascular etiologies.
Aside from normocytic anemia (Hb 11.6 mg/dL), initial laboratory evaluation with CBC and BMP showed no significant abnormalities. IgG levels were low. Blood and sputum cultures were negative. QuantiFERON was negative for tuberculosis. Serologies for aspergillus, blastomycosis, coccidioides, cryptococcus, histoplasma, HIV, and toxoplasma were negative. Bronchoalveolar lavage was negative for acid-fast bacilli, fungal organisms, and pneumocystis.
Immunologic evaluation was negative for ANCA, proteinase 3, and myeloperoxidase antibodies. This excluded granulomatosis with polyangiitis as a differential diagnosis. Bronchoalveolar lavage was negative for cytology.
Punch biopsy of one of the skin lesions demonstrated poorly circumscribed granulomas surrounding blood vessels and skin appendages, mild lymphocytic infiltration with no features to suggest cutaneous lymphoma, and no evidence of leukocytoclastic vasculitis. Stains for fungal and acid-fast bacilli were negative.
Left upper and lower lobe wedge biopsies of the nodules were taken through video-assisted thoracoscopic surgery (VATS) as the diagnosis was still unclear. The biopsies revealed EBV-positive DLBCL with features of LG grade 3 (Figure 2). The features that favor LG over DLBCL include a background that consisted predominantly of inflammatory cells with a minority of large B-cells and vascular invasion. In addition, lung involvement and EBV positivity are not exclusive to LG, but are almost always present in LG. Flow cytometry did not detect the large B-cells which are sometimes too fragile to survive flow cytometric processing, but did detect rare, small monoclonal B-cells with a CLL/small lymphocytic lymphoma (SLL) phenotype. The flow cytometric findings are compatible with the morphology as no significant CLL/SLL population could be identified with CD5 and CD23 immunostaining (Figure 3). In this case, the source of rare CLL cells is likely peripheral blood, either physiologically through the inflammatory response or contamination during resection. Features of secondary organizing pneumonia were also present.
The patient underwent PET-CT 4 weeks following the initial chest CT (Figure 4). This showed significant progression and confluence of bilateral peribronchovascular lung opacities. The lung opacities had diffuse FDG uptake with a maximum SUV of 22.3. The PET/CT also demonstrated intense uptake in the cutaneous lesions of the lower extremities.
Bone marrow biopsy was consistent with hypercellular marrow with 20-30% marrow involvement by CLL/SLL cells. The patient was started on R-CHOP chemotherapy with Neupogen support. IVIG was also given for hypogammaglobulinemia.