HAEMATOLOGY 16

THE LYMPHOID SYSTEM

NON NEOPLASTIC DISEASES OF

LYMPH NODES
Dr Deepti Mahajan, Professor Pathology
 Competencies addressed: PA 19.1, 19.2, 19.3

• Learning Objectives:
 To enumerate the organs of the lymphoid system and briefly
describe their anatomy, histology and physiology.
 To enumerate the causes of lymphadenopathy.
 To list the distinguishing features of benign and malignant
lymphadenopathy.
 To describe the morphology of non specific reactive
lymphadenitis.
 To enumerate the causes of granulomatous lymphadenitis.
 To discuss the pathogenesis of tuberculous lymphadenitis.
 To describe the gross and microscopic features of tuberculous
lymphadenitis.
 THE LYMPHOID TISSUE: ANATOMY

• Lymphoid Tissues can be divided into 2 major categories :

1) CENTRAL or PRIMARY LYMPHOID TISSUES :
• These are tissues in which the lymphoid precursor cells
mature to a stage at which they are capable of performing
their function in response to an antigen.
• Includes Bone Marrow and Thymus.
2) PERIPHERAL or SECONDARY LYMPHOID TISSUE:
• These are tissues in which antigen specific reactions occur.
• Includes Lymph Nodes, Spleen and Mucosa Associated
Lymphoid Tissue.
 THE LYMPHOID CELLS

• The precursor B and T cells in the bone marrow and thymus give rise to
the mature B and T cells bearing membrane bound B cell and T cell
receptors respectively, capable of binding specific antigen. Encounter with
antigen and its binding to B or T cells takes place in the peripheral
lymphoid organs notably lymph nodes and spleen. Prior to antigen
exposure the mature B or T cells are called naïve B and T cells
respectively. In a lymph node naïve B cells occupy the primary or the
resting lymphoid follicle. Following antigenic stimulation B cells undergo
morphological changes to form centroblasts, centrocytes and
immunoblasts (called the follicular centre cells) that occupy the germinal
centre which is a lighter staining area within the lymphoid follicle. Such a
follicle with a germinal centre is called a secondary follicle. These cells
ultimately give rise to plasma cells (capable of producing and secreting
soluble high-affinity antibodies against the antigen) and memory B cells
capable of producing specific antibody on subsequent exposure to the
antigen i.e. the secondary immune response.
 THE LYMPHOID CELLS
• So a secondary lymphoid follicle has a lighter staining germinal centre
comprising of follicular centre cells. A darkly staining outer rim of mantle
cells is present that comprises of naïve B cells. Sometimes a peripheral
marginal zone is also evident. The cells in the marginal zone are post-
germinal centre memory B cells. The plasma cells produced by the
follicular centre cells occupy the medullary cords and sinuses where they
secrete the soluble antibodies that enter the blood via lymph. The T cells
occupy the paracortical areas in between adjacent follicles. They, too,
undergo similar activation following antigen exposure but the
morphological stages in this process are not so well defined.
• Besides the lymphoid cells, the antigen presenting follicular dendritic cells
and interdigitating cells are also present in the lymph node, the former
occupying the lymphoid follicle. Macrophages or histiocytes occupy the
follicles (tingible body macrophages) and the medullary sinuses.
THE LYMPHOID FOLLICLE: STRUCTURE
Enlargement of lymph nodes is called lymphadenopathy.
Causes:

Drugs
Clinical features to differentiate benign
from malignant lymphadenopathy
 THE REACTIVE LYMPH NODE

• Lymph nodes undergo reactive changes whenever they are challenged by

microbiologic agents, cell debris or foreign matter introduced into wounds
or infections in the drainage areas or into the circulation. Reactive
lymphadenitis (reactive hyperplasia) may present as:
• Acute non specific lymphadenitis
• Chronic non specific lymphadenitis:
 Follicular hyperplasia
 Paracortical lymphoid hyperplasia
 Sinus histiocytosis (Reticular hyperplasia)
• Granulomatous lymphadenitis
 ACUTE NON SPECIFIC LYMPHADENITIS

• Acute lymphadenitis is most often seen in cervical region due to microbial

drainage from tooth or tonsillar infections. Inguinal or axillary
lymphadenitis is due to infections of extremeties and acute mesenteric
lymphadenitis usually accompanies acute appendicitis. Clinically nodes are
enlarged and tender.
• Morphology:
• Grossly the nodes are swollen, grey-red.
• M/E – prominent lymphoid follicles with large germinal centres containing
numerous mitotic figures. Macrophages containing ingested bacterial or necrotic
cell debris seen. If causative organisms are pyogenic bacteria, follicular centres
may undergo necrosis. Sometimes the entire node undergoes suppuration.
Sometimes neutrophils may be seen around the follicles and within the sinuses.
 CHRONIC NON SPECIFIC LYMPHADENITIS
• Generally involves inguinal and axillary nodes that drain relatively large
areas of the body. The lymph nodes are non tender. Depending on the
underlying stimulus, chronic immunologic reactions can produce different
morphological alterations:
• Follicular hyperplasia
• Caused by stimuli that activate humoral immune responses. Specific
causes of follicular hyperplasia include rheumatoid arthritis,
toxoplasmosis, early stages of HIV infection.
• Morphology: appearance of pale staining, large round B cell rich germinal centres
in the cortex resulting in formation of secondary follicles, surrounded by a collar of
resting naïve B cells (the mantle zone). The germinal centre has a dark zone
comprising of proliferating centroblasts (large non cleaved cells) and a light zone
of centrocytes with cleaved nuclei (small cleaved cells). Phagocytic macrophages
containing nuclear debris (tingible body macrophages) are present throughout the
follicle.
Follicular hyperplasia lymph node with germinal centres (Left). A germinal
centre showing a mantle zone (top), dark and light zones and scattered
tingible body macrophages (Right).
• Paracortical lymphoid hyperplasia
• This is caused by stimuli that trigger a cellular immune response e.g.
immunologic reactions induced by drugs (especially Dilantin), acute viral
infections (especially Infectious mononucleosis) and following vaccination
against certain viral diseases.
• Morphology:
• Reactive changes in the paracortical T cell zones. The paracortical areas are
enlarged and they encroach on and sometimes appear to efface the B cell follicles.
Activated T cells (immunoblasts) are seen in the interfollicular regions. These cells
are 3-4 times the size of resting lymphocytes and have round nuclei, open
chromatin, several prominent nucleoli and moderate amount of pale cytoplasm.
Florid immunoblastic reaction may mimic a lymphoma. In addition, there is
hypertrophy of sinusoidal and vascular endothelial cells and a mixed cellular
infiltrate principally of macrophages and sometimes of eosinophils.
Paracortical hyperplasia showing enlargement of paracortical areas with
effacement of follicles.
• Sinus histiocytosis (Reticular hyperplasia)
• This form of reactive hyperplasia is prominent in lymph nodes draining
cancers such as carcinoma breast (host immune response against the
tumour antigens) and in certain specific conditions like Rosai Dorfman
Disease.
• Morphology:
• There is distension and prominence of lymphatic sinusoids. The lining
endothelial cells are markedly hypertrophied and macrophages are
markedly increased in numbers resulting in expansion and distension of
the sinuses.
Reactive sinus histiocytosis in a lymph node draining carcinoma breast.
 GRANULOMATOUS LYMPHADENITIS
• Chronic granulomatous lymphadenitis is a distinctive type of
inflammatory immune response in which organized collection of
epithelioid macrophages form granulomas. Granulomatous
inflammation ensues when a foreign agent cannot be eliminated by
the immune system and is, instead, walled off by macrophages.
Various infectious and non infectious etiologies have been
associated with chronic granulomatous inflammation in lymph
nodes. Tuberculosis is the most common cause of granulomatous
lymphadenitis in our set up.
GRANULOMATOUS LYMPHADENITIS: CAUSES
 Tuberculosis: Pathogenesis

M.Tuberculosis enters macrophages and multiplies in the

phagososme. It is not easily digested and induces bacteremia.
TH-1 response is mounted in three weeks. Helper T cells secrete
interferon–γ that activates macrophages and stimulates them to
kill the mycobacteria. Macrophages activated by IFN-γ
differentiate into epithelioid histiocytes that aggregate to form
granulomas. Some epithelioid cells may fuse to form Langhans
giant cells. In many people this response halts the infection
before significant tissue destruction occurs. In others, infection
progresses due to advanced age or immunosuppression resulting
in caseous necrosis.
Gross Features
Tuberculous
Lymphadenitis:
Microscopic features
The characteristic feature is
the tuberculous granuloma
(caseating or soft tubercle)
comprising of multinucleated
giant cells (Lang Hans cells)
surrounded by epithelioid cell
aggregates, T lymphocytes
and fibroblasts.
Granulomatous tubercles
eventually develop central
caseous necrosis and become
confluent, replacing the
lymphoid tissue.
Tuberculous granulomas in a lymph node
Tuberculous Cervical Lymphadenopathy (Scrofula)
Non-neoplastic disorders of lymph node concluded