Overview on some causes of lymphadenopathy

General causes of lymphadenopathyGeneral causes of lymphadenopathy

Lymph nodes, act as defensive barriers ,so any immune response against foreign antigens is oftenimmune response against foreign antigens is often associated with lymph node enlargement (lymphadenopathy).Lymph node enlargement may be localized or generalized.The presence of lymphadenopathy may raise theThe presence of lymphadenopathy may raise the possibility of lymphoma, or metastatic carcinoma.Biopsy specimens of unexplained enlarged lymph node p y p p g y pwill be mandatory.

General causes of lymphadenopathyGeneral causes of lymphadenopathyGeneral causes of lymphadenopathyGeneral causes of lymphadenopathy

CAUSES:CAUSES:1- Reactive hyperplasia:

Infection by bacteria or virusesInfection by bacteria or viruses.Immune stimulation, as in rheumatoid arthritis.Draining degradation products from cancerDraining degradation products from cancer.Particulate material.

2 N l ti diti2- Neoplastic conditions:Secondary of deposits of carcinomas.P i l h id tPrimary lymphoid tumors.

Reactive LymphadenitisReactive Lymphadenitis

Reactive Lymphadenitis is often associated with i f ti d i bi l i fl t ti liinfections and nonmicrobial inflammatory stimuli .Reactive lymphadenitis is further subdivided to:

AcuteChronic non-specific & chronic specific lymphadenitis.

In most instances, the histologic appearance of the nodes is entirely non-specific. the nodes is entirely non specific.

Acute Non specificAcute Non-specific Lymphadenitisy p

This form of lymphadenitis may be:y p yLocalized: confined to a local group of nodes draining a focal infection, as in case of suppurative tonsillitis, or breast abscess.abscess.Generalized: in case of systemic bacterial or viral infections ,as in infectious mononucleosis disease.

M h lMorphology:Macroscopically, inflamed nodes in acute non-specific lymphadenitis are swollen, grey-red, and engorged. y p , g y , g gHistologically, there are large germinal centres containing numerous mitotic figures. When the cause is a pyogenic organism a neutrophilic infiltrateWhen the cause is a pyogenic organism, a neutrophilic infiltrate is seen about the follicles and within the lymphoid sinuses.

Reactive lymph node B th th l i th ti lReactive lymph node. Beneath the capsule is the paracortical zone with lymphoid follicles having a pale germinal center in which the immune responses are often generated. Beneath this are sinusoids

t di t th t f th dextending to the center of the node.

Acute Non specificAcute Non-specific Lymphadenitisy p

With severe infections, the centres of follicles can undergo necrosis, resulting in the formation of an abscess.Clinically the affected nodes are tender and whenClinically, the affected nodes are tender and, when abscess formation is extensive, become fluctuant.The overlying skin is frequently red, and penetration ofThe overlying skin is frequently red, and penetration of the infection to the skin can produce draining sinuses.With control of the infection, the lymph nodes can revert

fto their normal appearance or, if damaged by the immune response, undergo scarring.

Chronic Non specificChronic Non-specific Lymphadenitisy p

This condition can assume one of three patterns, depending on the causative agent:

Follicular HyperplasiaFollicular Hyperplasia.Paracortical Hyperplasia.Si Hi ti t iSinus Histiocytosis.

Follicular Hyperplasia.

This pattern is associated with infections or i fl t th t ti t B llB llinflammatory processes that activate B cellsB cells.Morphology; follicular hyperplasia with reactive germinal centers.CausesRheumatoid arthritis, ToxoplasmosisToxoplasmosis,the early stages of HIV infection.

This is a more pronounced reactive change in a lymph node, with a larger p g y p gfollicle and germinal centre containing macrophages. In general, lymph nodes in a benign reactive process are more likely to enlarge quickly and be tender.

Paracortical Hyperplasia

This pattern is characterized by reactive h ithi th TT ll ill i f th l hchanges within the TT--cell regionscell regions of the lymph

node. Causes:viral infections (such as EBV), ( ),following certain vaccinations (e.g., smallpox), in immune reactions induced by certain drugsin immune reactions induced by certain drugs

Sinus Histiocytosis

This reactive pattern is characterized by di t i d i f th l h tidistension and prominence of the lymphatic sinusoids, owing to a marked hypertrophy of li i d th li l ll d i filt t flining endothelial cells and an infiltrate of macrophages (histiocytes). Sinus histiocytosis is often encountered in lymph nodes draining cancers and may represent an immune response to the tumour or its products.

Neoplastic Proliferations Of WhiteNeoplastic Proliferations Of White Cells

Tumours represent the most important of the white cell disorders They can be divided intowhite cell disorders. They can be divided into three broad categories based on the origin of the tumour cells: 1-Lymphoid neoplasms, which include lymphomas, lymphocytic leukaemia, and plasma cell dyscrasiacell dyscrasia. 2-Myeloid neoplasms arise from stem cells that normally give rise to the formed elements of thenormally give rise to the formed elements of the blood: granulocytes, red cells, and platelets. 3-Histiocytic neoplasms represent proliferative y p p plesions of histiocytes

Lymphoid NeoplasmsThe lymphoid neoplasms encompass a group of entities that vary widely in their clinical presentation and y y pbehaviour. A-Lymphocytic leukaemia, tumours that primarily involve the bone marrow with spillage of neoplastic cells into thethe bone marrow with spillage of neoplastic cells into the peripheral blood. B- Lymphomas, tumours that produce masses in in ol ed l mph nodes or other tiss esinvolved lymph nodes or other tissues. C-Plasma cell tumours (the plasma cell dyscrasia),usually present within the bones as discrete masses and y pcause systemic symptoms related to the production of a complete or partial monoclonal immunoglobulin.

Lymphoid NeoplasmsClinical presentation:All lymphoid neoplasms have the potential to spread to lymphAll lymphoid neoplasms have the potential to spread to lymph nodes and various tissues throughout the body, especially the liver, spleen, and bone marrow. In some cases lymphomas or plasma cell tumours spill over into the peripheral blood, creating a leukaemia-like picture. Conversely leukaemia of lymphoid cells originating in the boneConversely, leukaemia of lymphoid cells, originating in the bone marrow, can infiltrate lymph nodes and other tissues, creating the histologic picture of lymphoma.Because of the overlap in clinical presentations, the various Because of the overlap in clinical presentations, the various lymphoid neoplasms can only be distinguished based on the lymphoid neoplasms can only be distinguished based on the appearance and molecular characteristics of the tumour cells.appearance and molecular characteristics of the tumour cells.appearance and molecular characteristics of the tumour cells.appearance and molecular characteristics of the tumour cells.

Infiltration of liver by lymphoma

Lymphoid Neoplasms

Two groups of lymphomas are recognized: A -Hodgkin lymphoma and B- Non-Hodgkin lymphomas

Although both arise most commonly in lymphoid tissues ,the biologic behaviour and clinical treatment of Hodgkin lymphoma are different from those of most NHLs, making the distinction of practical importance.

Non Hodgkin lymphomasNon-Hodgkin lymphomasClassification

World Health Organization (WHO) has formulated a widely accepted classificationformulated a widely accepted classification scheme that relies on a combination of 1-morphologic,2-phenotypic2 phenotypic,3-genotypic, and 4-clinical features.

Non-Hodgkin lymphomasNon Hodgkin lymphomas1-Classification

Non-Hodgkin lymphoma is further subclassified into;B d T ll t th t d i d f ifiB- and T-cell tumors that are derived from specific stages of their normal differentiation pathways. The diagnosis and classification of these tumors reliesThe diagnosis and classification of these tumors relies heavily on tests that detect lineage-specific antigens(B-cell, T-cell, and NK-cell markers) ; ( )

Immunohistochemistry Flow cytometry

Analysis of antigen receptor genes and their protein products is frequently used to differentiate monoclonal neoplasms from polyclonal reactive processesneoplasms from polyclonal, reactive processes

Non-Hodgkin lymphomasNon Hodgkin lymphomas2-Classification

Indolent types (low grade):long natural history but not curable, (e g follicular lymphoma)(e.g., follicular lymphoma)Aggressive types (high grade):

id li i l i b t b d brapid clinical progression but may be cured by chemotherapy,(e.g., diffuse large B-cell lymphoma)

Follicular Lymphoma:

Tumor cells recapitulate the growth pattern of normal germinal center B cells;of normal germinal center B cells; More than 80% of cases are associated

ith h l t l ti th twith chromosomal translocation that results in the over-expression of the anti-apoptotic protein BCL2.

Diffuse Large B-Cell Lymphoma:

The most common type of lymphoma.Heterogeneous group of mature B cell tumors,AggressiveAggressive clinical behavior.ggggHighly associated with genetic rearrangements or mutationsor mutations. ONE-THIRD arise from follicular lymphomas .O i l h d thOccur in lymph nodes or other organs as stomach, small intestine, bones.

Hodgkin Lymphoma:Hodgkin Lymphoma:

Unusual tumor mostly comprised of reactive lymphocytes, macrophages, and stromal cells; the malignant cell, the Reed-; g ,Sternberg cell (which is derived from B cells) typically makes up a minor fractioncells), typically makes up a minor fraction of the tumor mass.

Hodgkin’s Lymphoma

Malignant disorder of lymph nodesthought to be of B cell originthought to be of B cell originspreads sequentially along lymph node chain

Bimodal age distributionBimodal age distributionadolescents and young adults (ages 15-40)

ld d lt ( 55 74)older adults (ages 55-74)

H d ki ’ L hHodgkin’s Lymphoma

Molecular studies have shown that it is a tumor of B-cell origin.

Arises almost in a single lymph node or chain of lymph nodesnodes.

Spreads characteristically in a stepwise fashion to the anatomically contiguous nodes.

It is characterized morphologically by the presence of p g y y pdistinctive neoplastic giant cells called Reed-Sternberg (RS) cells which are admixed with reactive(RS) cells, which are admixed with reactive, nonmalignant inflammatory cells.

Typical Reed-Sternberg cell

Particularly characteristic are cellscharacteristic are cells with two mirror-image nuclei or nuclear lobes,

h t i i leach containing a large (inclusion-like) acidophilic nucleolus psurrounded by a distinctive clear zone; together they impart antogether they impart an owl-eye appearance. The nuclear membrane is distinct.

Lacunar cells HL

Hodgkin’s Lymphoma

It is often associated with somewhat distinctive clinical features, including systemic manifestations such as yfever. It is treated differently than most otherIt is treated differently than most other lymphoid neoplasms. Despite these distinguishing features,

Hodgkin’s Lymphoma

Five subtypes of Hodgkin lymphoma are recognized: lymphocyte predominancelymphocyte predominance nodular sclerosis,mixed cellularity, lymphocyte depletionlymphocyte depletion.

Nodular sclerosis HL

Mixed cellularity HL