A lymphocytic BAL pattern is commonly seen in granulomatous lung diseases, such as sarcoidosis and hypersensitivity pneumonitis (Fig. 16.1a, b), and in the context of immune reactions of the lung to some drugs. However, the number of lymphocytes and the CD4/CD8 ratio can be variable in sarcoidosis. The majority of sarcoidosis cases display an isolated BAL lymphocytosis, while a raised neutrophil count appears to correlate with more severe disease and need for therapy. In hypersensitivity pneumonitis, not only the number of lymphocytes but also the absolute neutrophil and eosinophil counts may be significantly increased. BAL lymphocytosis >50% generally raises a suspicion for the diagnosis of hypersensitivity pneumonitis, and patients with hypersensitivity pneumonitis may exhibit either decreased, normal, or increased CD4/CD8 ratio. BAL lymphocytosis may be present in methotrexate and amiodarone pneumonitis, as well as in beryllium disease. BAL lymphocytosis appears to be common in the cellular variant of nonspecific interstitial pneumonia (NSIP) too. Finally, a subclinical lymphocytic cellular pattern in BAL has been reported in Wegener’s granulomatosis, Crohn’s disease, and primary biliary cirrhosis.

A neutrophilic cellular pattern can be found in idiopathic pulmonary fibrosis (IPF), asbestosis, acute respiratory distress syndrome (ARDS), aspiration pneumonia, subacute hypersensitivity pneumonitis, and cryptogenic organizing pneumonia (COP), as well as in pulmonary infections. An increased neutrophil count may be unspecific but in the appropriate clinical setting is observed in the BAL of 70–90% of patients with IPF. The nonspecific nature of a BAL neutrophilia is illustrated by the difficult diagnostic problem of fibrotic nonspecific interstitial pneumonia (NSIP) too.

An eosinophilic cellular pattern of BAL is in the absence of asthma and parasitic infections highly suggestive of eosinophilic pneumonia. Differential diagnosis may be Churg–Strauss syndrome, allergic pulmonary aspergillosis, drug-induced lung disease, or Langerhans’ cell histiocytosis. The diagnosis of Langerhans’ cell histiocytosis can be made by the presence of more than 5% Langerhans’ cells in BAL, identified by monoclonal antibodies directed against the CD1a antigen or Langerin. Though, it can be an unspecific finding too, as in some cases of IPF, HP, and collagen vascular disease-associated pulmonary fibrosis. If eosinophilia exceeds 25%, eosinophilic pneumonia has to be considered.

Plasma cells are not present in normal BAL. If found, together with foamy macrophages and increased lymphocyte count, HP or drug-induced lung disease has to be suggested. Differential diagnoses are cryptogenic organizing pneumonia and chronic eosinophilic pneumonia. Mast cells appear in the process of lung inflammation and fibrosis. An increased number is sometimes observed in sarcoidosis, associated with advanced or progressive disease.

In addition, if mixed cellular patterns are present, the predominant cellular pattern might offer a hint to the diagnosis, although in these circumstances, invasive procedures such as lung biopsy (bronchoscopic transbronchial or surgical) may be required to make a specific diagnosis.