Transcript Slide 1

Overview on some
causes of
lymphadenopathy
General causes of lymphadenopathy
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Lymph nodes, act as defensive barriers ,so any
immune 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 the
possibility of lymphoma, or metastatic carcinoma.
Biopsy specimens of unexplained enlarged lymph node
will be mandatory.
General causes of lymphadenopathy
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CAUSES:
1- Reactive hyperplasia:
 Infection by bacteria or viruses.
 Immune stimulation, as in rheumatoid arthritis.
 Draining degradation products from cancer.
 Particulate material.
2- Neoplastic conditions:
 Secondary of deposits of carcinomas.
 Primary lymphoid tumors.
Reactive Lymphadenitis
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Reactive Lymphadenitis is often associated with
infections and nonmicrobial inflammatory stimuli .
Reactive lymphadenitis is further subdivided to:
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Acute
 Chronic non-specific & chronic specific lymphadenitis.
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In most instances, the histologic appearance of
the nodes is entirely non-specific.
Acute Non-specific
Lymphadenitis
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This form of lymphadenitis may be:
Localized: confined to a local group of nodes draining a focal
infection, as in case of suppurative tonsillitis, or breast
abscess.
Generalized: in case of systemic bacterial or viral infections ,as
in infectious mononucleosis disease.
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Morphology:
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Macroscopically, inflamed nodes in acute non-specific
lymphadenitis are swollen, grey-red, and engorged.
Histologically, there are large germinal centres containing
numerous mitotic figures.
When the cause is a pyogenic organism, a neutrophilic infiltrate
is seen about the follicles and within the lymphoid sinuses.
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Acute Non-specific
Lymphadenitis
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With severe infections, the centres of follicles can
undergo necrosis, resulting in the formation of an
abscess.
Clinically, the affected nodes are tender and, when
abscess formation is extensive, become fluctuant.
The 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
to their normal appearance or, if damaged by the
immune response, undergo scarring.
Chronic Non-specific
Lymphadenitis
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This condition can assume one of three patterns,
depending on the causative agent:
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Follicular Hyperplasia.
Paracortical Hyperplasia.
Sinus Histiocytosis.
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Follicular Hyperplasia.
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This pattern is associated with infections or
inflammatory processes that activate B cells.
Morphology; follicular hyperplasia with
reactive germinal centers.
Causes
Rheumatoid arthritis,
Toxoplasmosis,
the early stages of HIV infection.
Paracortical Hyperplasia
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This pattern is characterized by reactive
changes within the T-cell regions of the lymph
node.
Causes:
viral infections (such as EBV),
following certain vaccinations (e.g., smallpox),
in immune reactions induced by certain drugs
Sinus Histiocytosis
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This reactive pattern is characterized by
distension and prominence of the lymphatic
sinusoids, owing to a marked hypertrophy of
lining 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 White
Cells
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Tumours represent the most important of the
white 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 dyscrasia.
2-Myeloid neoplasms arise from stem cells that
normally give rise to the formed elements of the
blood: granulocytes, red cells, and platelets.
3-Histiocytic neoplasms represent proliferative
lesions of histiocytes
Lymphoid Neoplasms
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The lymphoid neoplasms encompass a group of entities
that vary widely in their clinical presentation and
behaviour.
A-Lymphocytic leukaemia, tumours that primarily involve
the bone marrow with spillage of neoplastic cells into the
peripheral blood.
B- Lymphomas, tumours that produce masses in
involved lymph nodes or other tissues.
C-Plasma cell tumours (the plasma cell dyscrasia),
usually present within the bones as discrete masses and
cause systemic symptoms related to the production of a
complete or partial monoclonal immunoglobulin.
Lymphoid Neoplasms
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Clinical presentation:
All 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 bone
marrow, can infiltrate lymph nodes and other tissues, creating
the histologic picture of lymphoma.
Because of the overlap in clinical presentations, the various
lymphoid neoplasms can only be distinguished based on the
appearance and molecular characteristics of the tumour cells.
Lymphoid Neoplasms
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Two groups of lymphomas are recognized:
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-Hodgkin lymphoma and
 B- Non-Hodgkin lymphomas
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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 lymphomas
Classification
World Health Organization (WHO) has
formulated a widely accepted classification
scheme that relies on a combination of
 1-morphologic,
 2-phenotypic,
 3-genotypic, and
 4-clinical features.
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Non-Hodgkin lymphomas
1-Classification
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Non-Hodgkin lymphoma is further subclassified into;
B- and T-cell tumors that are derived from specific
stages of their normal differentiation pathways.
The 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 processes
Non-Hodgkin lymphomas
2-Classification
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Indolent types (low grade):
long natural history but not curable,
(e.g., follicular lymphoma)
Aggressive types (high grade):
rapid 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;
 More than 80% of cases are associated
with chromosomal translocation that
results in the over-expression of the antiapoptotic protein BCL2.
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Diffuse Large B-Cell Lymphoma:
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The most common type of lymphoma.
Heterogeneous group of mature B cell tumors,
Aggressive clinical behavior.
Highly associated with genetic rearrangements
or mutations.
ONE-THIRD arise from follicular lymphomas .
Occur in lymph nodes or other organs as
stomach, small intestine, bones.
Hodgkin Lymphoma:
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Unusual tumor mostly comprised of
reactive lymphocytes, macrophages, and
stromal cells; the malignant cell, the ReedSternberg cell (which is derived from B
cells), typically makes up a minor fraction
of the tumor mass.
Hodgkin’s Lymphoma
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Malignant disorder of lymph nodes
 thought to be of B cell origin
 spreads sequentially along lymph node chain
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Bimodal age distribution
 adolescents and young adults (ages 15-40)
older
adults (ages 55-74)
Hodgkin’s Lymphoma
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Molecular studies have shown that it is a tumor of B-cell
origin.
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Arises almost in a single lymph node or chain of lymph
nodes.
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Spreads characteristically in a stepwise fashion to the
anatomically contiguous nodes.
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It is characterized morphologically by the presence of
distinctive neoplastic giant cells called Reed-Sternberg
(RS) cells, which are admixed with reactive,
nonmalignant inflammatory cells.
Hodgkin’s Lymphoma
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is often associated with somewhat
distinctive clinical features, including
systemic manifestations such as
fever.
 It is treated differently than most other
lymphoid neoplasms.
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Hodgkin’s Lymphoma
Five subtypes of Hodgkin lymphoma are
recognized:
 lymphocyte predominance
 nodular sclerosis,
 mixed cellularity,
 lymphocyte depletion.
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