Atypical Lymphoid Proliferations

The Pathologist's Viewpoint

Mahmoud Rezk Abdelwahed Hussein


Expert Rev Hematol. 2013;6(2):139-153. 

In This Article

Histology of the Lymph Node

Lymph nodes develop in the first trimester by the aggregation of small lymphoblasts around the lymphatic plexuses arising from lymphatic sacs. The differentiation into cortex and medulla occurs in the second trimester.[1] The lymph node is enclosed in a thin fibrous capsule that is continuous with fibrous trabeculae that extend into the parenchyma. The latter consists of four compartments including the cortex with its follicles (B-cell lymphoid follicles), the paracortex (T-cell zone), the medullary zone (histiocytes and plasma cells) and the nodal sinuses.[2] In the cortex, primary lymphoid follicles are composed of small collections of small lymphocytes within a supporting network of dendritic-reticulum cell processes.[2,3] The histology of the normal lymph node is shown in Figure 1.

Figure 1.

Normal and reactive lymph nodes. (A) Normal lymph node composed of cortex with its follicles (F), paracortex (P) and medullary zones (M). (B & C) Sinus histiocytosis in which dilated sinuses are seen distended by proliferating histiocytes. These cells have vesicular nuclei, inconspicuous nucleoli and ample pale cytoplasm. (D–F) Follicular hyperplasia is characterized by variability in the size of the follicles, prominence of the germinal centers, presence of multiple tingible body macrophages and the preservation of the mantle zones. (G–I) Eosinophilia (abundant number of eosinophils) is seen in several conditions such as drug hypersensitivity reaction.

When a primary lymphoid follicle is stimulated by an antigen, a secondary lymphoid follicle is formed. The latter is composed of a central pale-staining germinal center, surrounded by a mantle of lymphocytes – that is, mantle zone. The germinal center can be divided into pale and dark zones. The dark zone lies near the paracortical T zone and is rich in proliferating large lymphoid cells (centroblasts), which are also associated with tingible body macrophages. The pale zone is rich in small-cleaved cells (centrocytes), follicular dendritic cells (dendritic reticulum cells) and CD4-positive (helper/inducer) T cells. At the outer layer of the mantle zone, a layer of densely packed cells, called the marginal zone is seen.[2,3] This zone contains postfollicular memory B cells derived after stimulation of recirculating cells by T-cell-dependent antigen.[4] The marginal zone may not be visualized in many nodes. The cells of the germinal centers are called follicular center cells. They are B cells, which react with monoclonal antibodies against B cells (CD20, CD22 and CD24). They express immunoglobulins such as IgM and IgD on their surfaces.[5,6] Follicular center cells include: small and large cleaved cells (centrocytes), small and large noncleaved cells (centroblasts), dendritic cells and tingible body macrophages.[5–7] The histological structure of the normal lymph node is depicted in Figure 1.

The paracortex is the portion of the node just beneath and inbetween the lymphoid follicles. It is composed of T cells whose nuclei have condensed chromatin and a slightly irregular nuclear membrane. In this region, there are postcapillary or high endothelial venules lined by cuboidal endothelium.[8,9] Also, there are interdigitating dendritic cells (also known as interdigitating reticulum cells). The medulla represents the deepest portion of the lymph node. The medullary zone lies deep in the paracortex and is divided into cords by the medullary sinuses. The medullary cords are aggregations of lymphoid tissue and are made up of small lymphocytes, macrophages and plasma cells.[10] The sinuses are structures that carry the lymph from the afferent lymphatics through the lymph node to the efferent lymph vessels. They are lined by endothelial cells, which are replaced by histiocytes near the hilum.[2] The histology of a normal lymph node is shown in Figure 1.