Pathology of Lymph Nodes DR.Hameed N.Mousa F.I.C.M.S PATHOLOGY

As with other organs, lymph nodes, and more globally, the immune system, can be the site of infectious, immune and neoplastic disease, the latter either primary or metastatic The clinical manifestations of diseases of the lymph nodes are: Local enlargement, tender on nontender, +/_ Compression of adjacent structures +/_ Release of cytokines producing "systemic" symptoms of fever, weight loss and night sweats Infectious organisms can stimulate the same acute, chronic or granulomatous reactions in the draining lymph nodes as they characteristically stimulate at other sites

Several types of immune stimuli can cause "reactive" enlargement of the entire lymph node, or selective expansion of cortical, paracortical or medullary regions Metastatic tumors spread to the lymph nodes primarily via lymphatic drainage from adjacent solid organs Primary neoplasms of the lymph nodes are all malignant They are divided into malignant non-Hodgkin's lymphomas (NHL), and Hodgkin lymphoma

NHL's are more common, and can be simply divided into indolent, or slow growing types, and aggressive types Malignant lymphomas represent clonal malignancies in which mutational events have caused the majority of progeny cells to freeze at a single stage of normal lymphocyte differentiation Lymphomas frozen at a stage associated with high replication --> aggressive lymphomas; Lymphomas frozen at stages associated with recirculation or final function --> indolent lymphomas

The diagnosis of malignant lymphomas is based on the microscopic recognition of the dominant cytologic cell type, supplemented by immunologic and molecular techniques The treatment and prognosis of lymphomas are based on The dominant cell type (and it's inherent biologic behavior), The extent of spread (Stage) The underlying health of the patient All of the previous statements are complicated by the fact that indolent lymphomas can further mutate and transform to aggressive types

Hodgkin lymphoma is a less common nodal disease whose diagnosis is based on the detection of a characteristic cell, the Reed Sternberg cell, in the appropriate histologic setting There are several (five) histologic subtypes, but prognosis is based primarily on extent of disease Hodgkin lymphoma is a more curable disease than non-Hodgkin lymphomas Now watch me confuse this relatively straightforward information with the details.

Lymph node evaluation Biopsy Selection of the lymph node to be biopsied is of great importance. Inguinal nodes are to be avoided whenever possible because of the high frequency of chronic inflammatory and fibrotic changes present in them . Axillary or cervical nodes are more likely to be informative in cases of generalized lymphadenopathy . Whenever possible, the largest lymph node in the region should be biopsied. Small superficial nodes may show only nonspecific hyperplasia, whereas a deeper node of the same group may show diagnostic features.

Bacteriologic examination If there is a possibility that the node contains an infectious process, an adequate sample of the biopsied lymph node must be sent directly for bacteriologic study or at least be placed in a sterile Petri dish in the refrigerator Needle biopsy Core needle biopsy is adequate for the diagnosis of metastatic carcinoma but is rarely used for the evaluation of primary lymphoid disorders.

DNA ploidy studies Examination of DNA ploidy by flow cytometry of cell suspensions from fluids or material from fine needle aspiration or from tissue sections has shown a good correlation with the microscopic grades of malignant lymphoma ,

Overview of the lymphoid immune system Lymphocytes evolve from pluripotent stem cells --> two major functional cell types: B lymphocytes, comprising the humoral immune --> production of antibodies T lymphocytes, comprising the cellular immune system, --> Direct killing of foreign or intracellularly infected cells, cytotoxic T cells Fine control of the immune response through the secretion of cytokines, helper and suppressor T cells.

Both cortex and medulla represent B zones and are therefore associated with humoral types of immune response The paracortex is the zone situated between the cortex and the medulla, which contains the mobile pool of T lymphocytes responsible for cell-mediated. immune response

Lymph node anatomy To recognize lymph node pathology, one has to be familiar with normal lymph node anatomy and cytology

Lymph node histology

Lymph node variation Lymph node histology is dynamic: follicles In the absence of immune stimulation, primary follicles In the presence of immune stimulation, secondary follicles or germinal centers

Reactive germinal center MZ LZ DZ

Pathology of lymph nodes Infections Reactive hyperplasias Sarcoidosis Metastatic tumors Malignant lymphomas Non-Hodgkin’s lymphoma-NHL Hodgkin’s lymphoma

Pathology of lymph nodes Infections Bacterial Acute inflammation, abscess formation Granulomatous, caseous and noncaseous Diagnosis by culture, serologies, and/or special stains

Large adherent tuberculous lymph nodes containing extensive foci of caseation necrosis.

Numerous confluent non-necrotizing granulomas mainly composed of epithelioid cells in a lymph node affected by sarcoidosis

Asteroid body in the cytoplasm of a multinucleated giant cell in sarcoidosis

Reactive hyperplasias Exaggerations of normal histology. Expansion of all regions or selective expansion Some types characteristic of certain diseases, but most not Follicular hyperplasia- increase in number and size of germinal centers, spread into paracortex, medullary areas Collagen vascular diseases Systemic toxoplasmosis Syphillis Interfollicular hyperplasia- paracortex Skin diseases Viral infections Drug reactions Sinus histiocytosis- expansion of the medullary sinus histiocytes- Adjacent cancer Infections

Sinus hyperplasia. The cells present in the sinus represent an admixture of histiocytes and sinus lining cells.