Acute lymphoblastic leukemia presenting with an acute fibrinous and organizing pneumonia

The case

A 46-year-old woman with history of chronic anemia was admitted to a community hospital with fever, cough, and right pleuritic chest pain that had been present for 1 week. On admission, her temperature was 40.2°C (104.3°F), respiration rate was 20 breaths per minute, and oxygen saturation was 90% on room air.

Results of the lung examination demonstrated diminished breath sounds over the right lung. Other findings from the examination were unremarkable, with no adenopathy or organomegaly.

Admission laboratory tests showed the following results: hemoglobin, 7.1 g/dL; mean corpuscular volume, 77 fL; red cell distribution width, 23.5%; platelet count, 232,000/µL; and white blood cell count, 1000/µL, with 21% segmented neutrophils, 22% bands, but no blasts. A chest radiograph revealed primarily a right upper lobe infiltrate (Figure 1).

Community-acquired pneumonia was suspected. The patient was given azithromycin and ceftriaxone as well as a transfusion of packed red blood cells. During the hospi- tal course, the azithromycin was switched to doxycycline because a rash had developed, and oral fluconazole was started for the treatment of oropharyngeal candidiasis. Despite treatment with these antimicrobial agents, the patient had persistent fevers.

Blood cultures showed no growth; serologic tests for Coccidioides and HIV antigens yielded negative results; and there was no evidence of acute infection with human parvovirus B19, mycoplasma, or chlamydia. An echocardiogram showed no valvular vegetations. A CT scan of the chest revealed bilateral pulmonary infiltrates and pleural effusions (Figure 2).

Bronchoscopy was performed, and quantitative bacterial cultures yielded no growth. Cultures of the bronchoalveolar lavage fluid were negative for Legionella, fungi, acid-fast bacilli, and viruses. A transbronchial biopsy (TBB) specimen showed fibrinous acute lung injury with patchy airspace organization corresponding to AFOP (Figures 3 and 4).

Because of the patient's anemia, leukopenia, and persistent fevers, a bone marrow biopsy was performed on the 11th hospital day. The results revealed acute B-cell lymphoblastic leukemia.

The patient was given prednisone for her leukemia and to treat her lung condition after infectious causes had been ruled out. One week later, she was started on a regimen of standard ALL induction chemotherapy consisting of vincristine, daunorubicin, prednisone, cyclophosphamide, and l-asparaginase, and complete remission was induced.

She completed intrathecal methotrexate for CNS prophylaxis and then received maintenance chemotherapy. Serial CT scans showed gradual improvement (Figure 5) and near-complete resolution of the pulmonary infiltrates about 7 months after the initial diagnosis.

Discussion

ALL is uncommon in adults. About 1000 to 1300 cases of adult-onset ALL are diagnosed in the United States each year.¹ Like many leukemias, ALL is commonly associated with pulmonary infiltrates.² In about 60% to 80% of patients with leukemia, a pulmonary infiltrate will develop sometime during the course of their disease.³ Causes of such pulmonary infiltrates include infection, hemorrhage, leukemic involvement, adverse drug reactions, and congestive heart failure. Most pulmonary infiltrates in patients with leukemia are the result of infection.²

Our patient's TBB revealed AFOP, a recently described pattern of lung injury. First described by Beasley and associates,⁴ AFOP is characterized by intra-alveolar fibrin with a patchy distribution within the lung parenchyma and by organizing pneumonia composed of intraluminal connective tissue within the alveolar ducts and bronchioles. The pattern of AFOP does not meet the classic histologic criteria for diffuse alveolar damage, bronchiolitis obliterans with organizing pneumonia, or eosinophilic pneumonia.

Because AFOP has been described only recently, not much is known about it. In the original case series of 17 patients, Beasley and associates⁴ noted that patients with AFOP had symptoms that were typically acute or subacute. The most common symptoms were fever and shortness of breath.

On chest radiographs, AFOP is characterized by bilateral basilar infiltrates. Beasley and colleagues⁴ did not report upper lobe infiltrates. They noted several conditions or situations associated with AFOP, including collagen-vascular disease, zoologic work, coal mining, construction work, hairspray exposure, high-grade lymphoma, altered immune status, use of amiodarone, and infections caused by Haemophilus influenzae and Acinetobacter baumannii.⁴ Reports of AFOP with juvenile dermatomyositis and severe acute respiratory syndrome have also been described.^5,6 AFOP has not been reported in association with ALL.

AFOP appears to have 2 prognostic patterns: fulminate disease leading to death and a subacute, less fulminant form with recovery.⁴ There is no clear treatment for AFOP at this time. Our patient was initially treated with corticosteroids and induction chemotherapy, with clinical improvement and then resolution of her pulmonary infiltrates with consolidation chemotherapy and maintenance chemotherapy. Whether resolution of the pulmonary infiltrates was attributable to corticosteroids is unclear. The patient's pulmonary infiltrates may have improved because of chemotherapy.

In conclusion, AFOP is a recently described pattern of lung disease. In patients with ALL presenting with a localized infiltrate, AFOP should be considered in the differential diagnosis. The optimal treatment of AFOP is uncertain and warrants further investigation.

References:

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