Pulmonary Opacities in a Patient With Essential Thrombocythemia

Todd R. Hazelton, MD, and Jin Seong Lee, MD


November 27, 2001


Since the HRCT findings in this case were not typical for nontuberculous mycobacterial pulmonary infection, the patient underwent thoracoscopic lung biopsy, which provided the diagnosis of pulmonary alveolar proteinosis (PAP). Due to this diagnosis and her history of a blood dyscrasia, a repeat bone marrow biopsy was done. From this biopsy, chronic myelogenous leukemia (CML) with Philadelphia chromosome was diagnosed. The patient's PAP progressed over six months, and she was treated with whole lung lavage. Her CML was treated with high-dose chemotherapy and an allogeneic bone marrow transplant. Eleven months after her initial presentation, she developed pulmonary aspergillosis, renal failure, and hepatic veno-occlusive disease. She ultimately died of these complications.

PAP is a rare disorder of uncertain etiology. It has been associated with hematologic and lymphatic malignancies, with a small number of cases reported in patients with either leukemia or lymphoma.[1] Pathologically, the disease is characterized by filling of the alveoli with lipid-rich, proteinaceous material that exhibits periodic acid-Schiff (PAS) stain positivity. The pulmonary interstitium appears relatively normal with only mild lymphocytic infiltration and minimal fibrosis.[2]

Common presenting symptoms include dyspnea and cough, with chest pain and hemoptysis occurring less frequently.[3,4] Although PAP can be diagnosed at bronchoscopy with bronchoalveolar lavage or transbronchial biopsy, many patients require open lung biopsy for definitive diagnosis.[4] In patients with significant left-to-right shunting and symptoms such as dyspnea on exertion, PAP is treated with bronchoalveolar lavage. While many patients remain in remission after their initial treatment, others relapse and require periodic therapeutic lavage.[5] Deaths due to PAP have been reported.[4]

Radiographically, the typical findings in PAP are diffuse or patchy bilateral airspace opacities in a perihilar or basal distribution. The classic radiographic pattern resembles noncardiogenic pulmonary edema, with a differential diagnosis including pneumonia, hemorrhage, and neoplasms such as bronchioloalveolar carcinoma or lymphoma. As in this case, the pattern can also consist of small, ill-defined nodular opacities. These small nodules may be confluent, or more discrete nodules may be evident in the periphery of the abnormal areas of confluent opacification.[6,7]

On HRCT, abnormal areas typically appear as ground glass opacification, although consolidation can be seen. The sharp demarcation of the involved lung from normal parenchyma yields a geographic appearance to the abnormal opacities. The distinct borders of the areas of opacification can be due to the secondary pulmonary lobular distribution, or there may be no apparent anatomic reason for the visible boundaries. In areas of ground glass opacification, HRCT often demonstrates smooth interlobular septal thickening that is not apparent radiographically. The presence of geographic areas of ground glass airspace abnormality with areas of smooth interlobular septal thickening results in an HRCT pattern that has been termed "crazy paving." This pattern, which is evident in this case, suggests the diagnosis of PAP. The primary differential diagnostic considerations include Pneumocystis carinii and cytomegalovirus pulmonary infections. In contrast to PAP, the HRCT findings in patients with nontuberculous mycobacterial pulmonary infection include bronchiectasis, nodules, consolidation, volume loss, and cavitation.[7]