Bronchial-associated lymphoid tissue is an ordinary finding in bronchial biopsies, and benign lymphocytic infiltrates are very common in bronchial biopsies as a nonspecific reaction or as part of an infection or specific inflammatory disease. Therefore, benign reactive lymphoid infiltrates are relatively common on endobronchial and transbronchial biopsies, whereas lymphomas are uncommon.

The lung is rarely the site of primary hematologic malignancies. Primary pulmonary non-Hodgkin lymphomas are rare, making up <1% of primary pulmonary neoplasms, with extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) arising as the most common primary pulmonary hematologic malignancy. Lymphomatoid granulomatosis and large B-cell lymphomas may also occur infrequently. Hodgkin lymphoma and other non-Hodgkin lymphomas are rarely found as pulmonary primary malignancies. MALT lymphomas occur most commonly in older patients, many of whom are asymptomatic. The lesion may be composed of varying proportions of small lymphocytes and intermediate-size lymphocytes, plasmacytoid lymphocytes, and plasma cells. Although lymphocytic infiltration of bronchial mucosa, with the formation of lymphoepithelial lesions, is characteristic of MALT lymphoma, the feature is not specific and may be found in various reactive lesions. Primary large B-cell lymphoma of the lung occurs less frequently as a primary pulmonary neoplasm than MALT lymphoma, but nonetheless it may occasionally be encountered. It occurs over a wide range of ages, and diagnosis is often accompanied by symptoms such as dyspnea and chest pain. It typically consists of sheets of discohesive large cells that efface pulmonary architecture. Lymphomatoid granulomatosis is the term used for a T-cell-rich, large B-cell lymphoma with malignant B-cell immunopositivity with Epstein-Barr virus. It is associated with immunodeficiency. The differential diagnosis for lymphomatoid granulomatosis includes infections, Wegener granulomatosis, necrotizing sarcoidosis, and bronchocentric granulomatosis. Primary pulmonary Hodgkin lymphoma patients often present symptomatically, usually with multiple pulmonary lesions. Because of extensive associated granulomatous inflammation, differential diagnosis includes infection, large-cell non-Hodgkin lymphoma, and poorly differentiated carcinoma.

A MALT lymphoma may histologically show various morphologic features throughout the lesion. Lymphomatoid granulomatosis may have only focal diagnostic areas containing large cells. Features necessary to diagnose Hodgkin lymphoma, including the appropriate inflammatory background, may be widely or focally distributed throughout the lesion. Other hematologic neoplasms such as T-cell lymphomas frequently exhibit a polymorphous inflammatory background. As such, definitive diagnosis of these diseases on endobronchial or transbronchial biopsy may be extremely difficult or impossible. Findings on endobronchial or transbronchial biopsy may be suggestive of a hematolymphoid process and lead to an open biopsy such as wedge biopsy to obtain enough tissue for adequate histologic, immunohistochemical, and flow cytometric workup of the lesion.