Benign White Cell Disorders: Reactive Lymphadenopathy REACTIVE LYMPHOID HYPERPLASIA is the benign and reversible enlargement of lymphoid

tissue secondary to antigen stimulus. The lymph node response to stimuli varies. Follicles can increase in size and number; sinuses can enlarge and fill with histiocytes, or the architecture can be diffusely effaced by sheets of lymphocytes, a few immunoblasts and macrophages. In some cases there is a mixture of follicular, sinus and diffuse patterns. Each of these morphologically recognizable patterns is associated with certain antigenic stimuli, thus the morphologic type of lymphadenopathy may offer clues as to the etiology of the lymphadenopathy. FOLLICULAR HYPERPLASIA is characterized by enlargement of lymph nodes by hyperplasia of follicular (germinal) centers. At right, note the variablilty in the size of the follicles and the presence of mantle zones in the reactive node.

In FOLLICULAR HYPERPLASIA, the hyperplastic germinal center contains a normal mixture of varibly sized lymphocytes, plasma cells, and macrophages, as well as a few dendritic reticular cells. No one lymphocyte type predominates as in lymphoma.

In SINUS HYPERPLASIA the sinuses become distended and filled with histiocyte/macrophages and some plasma cells.

In DIFFUSE HYPERPLASIA the lymph node architecture is diffusely effaced by sheets of small lymphocytes, and a few scattered immunoblasts and macrophages.

MIXED HYPERPLASIA is a combination of follicular, sinus and diffuse patterns of hyperplasia.

Morphologic patterns of reactive lymphoid hyperplasia and their associated disorders. FOLLICULAR

rheumatoid arthritis giant lymph node hyperplasia (Castleman's disease) AIDS (persistent generalized lymphadenopathy)* idiopathic (most common)

SINUS

sinus histiocytosis with massive lymphadenopathy lymphangiogram effect

* increasingly frequent, 1 differential malignant lymphoma, especially ML,large cell

Morphologic patterns of reactive lymphoid hyperplasia and their associated disorders. DIFFUSE

post-vaccinial lymphadenitis anticonvulsant therapy viral lymphadenitis dermatopathic lymphadenopathy

MIXED

infectious mononucleosis toxoplasmosis cat scratch disease tuberculosis

In addition to the aforementioned hyperplasias other diseases, i.e., histiocytosis X and metastatic carcinoma can involve lymph nodes causing a reactive hyperplasia or mimic a hyperplasia (Histiocytosis X in the sinuses of a lymph node) and thus need to be carefully ruled out on microscopic exam. Reactive follicular hyperplasia may closely resemble some follicular lymphomas and some diffuse interfollicular viral infections mimic diffuse lymphoma. Whenever a malignant diagnosis is being considered benign reactive disorders must be ruled out by an experienced pathologist.

Lymphoid hyperplasia is the swelling of lymph tissue due to an accelerated increase of lymphocytes when the immune system perceives a threat to the body. Lymphoid hyperplasia, or lymphoid hypertrophy, can occur in the presence of bacteria, a virus, or anomalous tissue growth. The increase in thenumber of lymphocytes, commonly associated with the body's immune response, can be initiated by a local or systemic infection. Physicians refer to lymphoid hyperplasia as benign, reactive, or a combination of the two. Lymphocytes, or B cells, are white blood cells that originate in the bone marrow and travel through the blood and lymphatic systems. An immune response is triggered when the body senses an invasion and lymphocytes attempt to prevent the foreign invader from traveling throughout the circulatory system. Part of the immune system, also known as the reticuloendothelial system, consists of the lymph glands. As blood passes through the lymph system, it is constantly monitored by lymphocytes. Depending on the type of pathogen, the lymphocytes either develop antibodies against that substance or devour the threat in a process known as phagocytosis. Lymphocyte populations in the locality, or throughout the system, begin increasing as part of the normal defense response. The new lymphocytes are generally not released to travel throughout the system until they have reached maturity. When proliferation occurs in a particular area, lymph glands begin swelling. Localized infections in the upper respiratory system, for example, commonly produce parotid gland swelling in the neck. The proliferation and swelling continue until the infection resolves naturally or is treated with medication. Appendicitis is another example of localized lymphoid hyperplasia. The condition usually begins when a blockage occurs between the appendix and the part of the intestine known as the cecum. The blockage might be caused by trapped stool, excess mucus, or lymphatic swelling. Following the blockage, bacteria circulating normally through the intestine may invade the appendix wall, triggering the immune system. Swelling, inflammation and discomfort are signs that the immune system has initiated a response. Castleman's disease is a rare disorder that usually produces benign growths in one location or throughout the body. These growths might appear in the neck, chest, stomach, or intestinal regions. Lymphoid hyperplasia generally occurs as lymphocytes attempt to combat the invasion of foreign tissue. Patients having this malady typically experience fever, weight loss, and skin rashes along with anemia caused by red blood cell destruction. A chemical response generally includes an increase in gamma globulin as well as liver and spleen enlargement from increased populations of lymphocytes.