Chapter 120: Lymphoproliferative and Hematologic Diseases Involving the Lung and Pleura

Introduction

Lymphoproliferative disorders of the lung and pleura comprise a varied but rare group of localized and diffuse processes that span the morphologic gamut from reactive to neoplastic and include several peculiar lesions that do not fit conventional definitions of either hyperplasia or neoplasia. Although most diagnoses are based on light microscopy, immunohistochemical and molecular investigations have assumed a vital role. Nomenclature and classification schemes have undergone drastic changes over the past quarter century and current definitions appear reasonable. Malignant lesions are best classified according to the current World Health Organization (WHO) scheme.¹ This chapter presents the clinicopathologic features of primary and secondary pulmonary and pleural hematolymphoid lesions.

Anatomy and Histology of the Pulmonary Lymphoid System

Pulmonary lymphatics are divided into two interconnecting channels that drain to peribronchial, hilar, and/or mediastinal lymph nodes and eventually into the thoracic duct, right lymphatic duct, and subclavian veins.² One system drains through the visceral pleura around the lung into mediastinal lymph nodes and the other drains from central lung parenchyma to peribronchial and hilar lymph nodes. The lymphatics communicate at lobar, lobular, and pleural boundaries and thus serve each other as potential collaterals.^3,4 Although not usually obvious in histologic sections of normal lung, lymphatics are prominent in disease states ranging from pulmonary edema to lymphangitic carcinoma. In the latter, lymphatic channels distended with malignant cells are apparent within the visceral pleura, interlobular septa, and adventitia of arteries, veins, and bronchioles. Of note, alveolar septa do not contain lymphatic channels. All lymphatics contain valves and flat endothelial cells line the discontinuous basal lamina. Larger lymphatics contain smooth muscle and collagen.

Small submucosal aggregates of lymphoid cells are often prominent at bronchial bifurcations and near distal respiratory bronchioles (pulmonary microtonsils) and represent bronchus-associated lymphoid tissue (BALT) (Fig. 120-1).^5–7 Whether humans are born with this specialized secondary lymphoid system, or whether the aggregates of B lymphocytes, T lymphocytes, HLA-DR+ interdigitating cells, follicular dendritic cells, and lymphoid follicles with overlying flattened and attenuated specialized epithelium develop in response to antigenic stimulation is controversial.^8,9 Viruses, connective tissue disorders, tobacco use, and obstructive pneumonia are just a few pathologic processes known to induce BALT (Table 120-1). Unlike typical lymph nodes that rely on afferent lymphatics for antigen retrieval, BALT is integrated into lung tissue and antigen is sampled directly from the bronchial and bronchiolar lumens through specialized “lymphoepithelium.” Immunoglobulins, most notably IgA, are synthesized and secreted by lymphocytes directly into airway lumens. Amazingly, this system appears capable of mounting a competent adaptive immune response. In addition, BALT B-lymphocytes circulate and “home” to other mucosal sites such as the conjunctiva, salivary glands, stomach, and intestines to create a common mucosal immune system, the mucosa-associated lymphoid system (MALT).⁶ Thus, responses induced in one location can be replicated at other sites.¹⁰ Malignant lymphoma arising in one ...