Lymph Nodes: non-neoplastic

Question 1

What are the different levels of lymphoid organs?

Answer 1

-Primary lymphoid organs are bone marrow and thymus
- Secondary lymphoid organ, where B and T cells proliferate in response to exogenous antigens
- Other secondary lymphoid organs are spleen, tonsils, adenoids and Peyer patches
- Tertiary lymphoid organs are tissues with few lymphocytes that recruit more when inflammation is present eg Graft organs

Question 2

Function of lymph nodes

Answer 2

Lymph nodes are organized to detect and inactivate foreign antigens present in lymph fluid that drains skin, GI tract, respiratory tract and other the major organs.

Question 3

What are lymph nodes? (2)

Answer 3

-Discrete encapsulated structures, usually ovoid, ranging in diameter from a few millimetres to several centimetres
-Situated along the course of lymphatic vessels

Question 4

Microarchitecture and functional anatomy (2)

Answer 4

-surrounded by a connective tissue capsule with trabeculae which extend into the substance of the node – provides a framework for contained cellular elements
-subcapsular sinus in which afferent lymphatics drain after penetrating the capsule
lymph passes from the subcapsular sinus  medullary cords  hilum  efferent lymphatic drains

Question 5

What are the three distinct regions?

Answer 5

-cortex – contains nodules of B-lymphocytes either as primary follicles or as germinal centres
-paracortex / deep cortex – T-cell dependant region of the lymph node
-medulla – contains the medullary cords and sinuses which drain into the hilum

Question 6

What are tangible body macrophages? (3)

Answer 6

-Atingible body macrophage isa type ofmacrophagepredominantly found in germinal centers, containing many phagocytized, apoptotic cells in various states of degradation, referred to astingible bodies(tingible meaningstainable).
-Tingible body macrophagescontain condensed chromatin fragments.
These macrophages are processing antigen to pass to lymphocytes to stimulate specific immune responses.
Antigen can be brought to the node via lymphatics or via bloodstream.

Question 7

What is benign lymphadenopathy? (3)

Answer 7

-Localised or widespread
-Common clinical problem
-Frequently requires a biopsy/excision to establish a diagnosis

Question 8

What are the causes of benign lymphadenopathy? (3)

Answer 8

-infection (local and systemic)
-autoimmune disorders
-neoplasms (primary or metastatic)

Question 9

What is the approach to lymphadenopathy?

Answer 9

Clinical history
Blood work
Serology test
Fine needle aspiration(FNA) of lymph nodeCore - incisional biopsy, or excision ( gold standard) of lymph node
Imaging studies

Question 10

examples of chronic non-specific lymphadenitis

Answer 10

Follicular Hyperplasia
Paracortical Lymphoid Hyperplasia
Sinus Histiocytosis
Granulomatous lymphadenitis

Question 11

examples of specific disorders

Answer 11

Infectious Mononucleosis
Cat Scratch Disease
Toxoplasmosis
Kikuchi’s disease
Lymphadenopathy in HIV

Question 12

What is acute non-specific lymphadenitis? (4)

Answer 12

-This form of lymphadenitis can be confined to a local group of nodes draining a focal infection
-Can be generalized in systemic bacterial or viral infections.
-When the cause is a pyogenic organism, a neutrophilic infiltrate is seen with severe infections, abscess is formed.
-Affected nodes are tender and, when abscess formation is extensive, become fluctuant.

Question 13

What is chronic non-specific lymphadenitis?

Answer 13

Follicular Hyperplasia a predominantly B-cell response with germinal centre hyperplasia which may be associated with marginal zone hyperplasia

Paracortical Lymphoid Hyperplasia a predominantly T-cell response with paracortical expansion

Sinus Histiocytosis a macrophage response which is associated with sinus hyperplasia

Question 14

How can granulomatous lymphadenitis occur?

Answer 14

Due to infection (commonest cause), foreign bodies, secondary response to malignancy

Question 15

What are common aetiologies of granulomatous lymphadenitis?

Answer 15

TB and atypical mycobacteria is common
Toxoplasmosis
Cat-scratch fever
Actinomycosis
Sarcoidosis

Question 16

What are the diagnostic features of granulomatous lymphadenitis?

Answer 16

presence and type of necrosis
presence and type of giant cells
size, shape and distribution of granulomas
other associated changes

Question 17

What is non-neoplastic lymphadenopathy?

Answer 17

Lymph nodes respond to a variety of inflammatory stimuli by cellular proliferation  lymph node enlargement

Predominantly B-cell response with germinal centre hyperplasia

Predominantly T-cell response with paracortical expansion

Macrophage response which is associated with sinus and pulp histiocyte hyperplasia

Mixed response (common) – all cellular elements are activated and proliferate

Question 18

What are the specific infective disorders of granulomatous lymphadenitis?

Answer 18

Mycobacterial infection, including Tuberculosis – see Tuberculosis chapter
-Toxoplasmosis
-caused by the protozoal organism Toxoplasma gondii
-in the immunocompetent host, produces a flu-like illness of short duration and localised lymphadenopathy
-usually occipital or high cervical nodes
-histological triad of
follicular hyperplasia
-adjacent granulomas
-marginal zone B-cell hyperplasia

Question 19

What are the specific non-infective disorders of granulomatous lymphadenitis?

Answer 19

-Sarcoidosis
-Crohn’s disease
reaction to tumour antigen
-foreign body reaction - often occurs as a response to silicone compounds used in -plastic surgery and joint replacement

Question 20

What are the features of TB lymphadenitis?

Answer 20

-caseous necrosis, which is amorphous granular eosinophilic debritic material.
-Epitheloid cells which are modified macrophages with abundant cytoplasm and pale staining “slipper” shaped nuclei
-Langhans giant cells, which is a multinucleated giant cell and a
-Collar of lymphocytes surrounding epitheloid cell aggregates

Question 21

What is toxoplasmosis characterised by?

Answer 21

Toxolplasmosis is characterized by poorly formed granulomas in germinal centers.
There is monocytoid B cell hyperplasia.
And follicular hyperplasia.

Question 22

What are specific infective disorders?

Answer 22

Variety of diseases caused by infectious agents may lead to necrosis within lymph nodes
Mycobacterial infections

Lymphogranuloma venereum
sexually transmitted chlamydial disease
most commonly affects groin nodes
stellate abscesses within lymph nodes surrounded by palisaded histiocytes

Cat scratch disease
follows a bite or scratch from an infected cat
days to weeks later – tender lymphadenopathy
cervical, axillary and less commonly groin regions
caused by Bartonella henselae
stellate abscesses within lymph nodes surrounded by palisaded histiocytes

Question 23

TB vs sarcoidosis

Answer 23

caseating and non-caseating granulomas of TB and sarcoidosis respectively.

Question 24

What is necrotising lymphadenitis associated with?

Answer 24

Viral infections
Usually part of disseminated infection
- Herpes lymphadenitis – multinucleated cells with viral inclusions at the edge of the necrotic area(arrows.
CMV lymphadenitis – scattered cytomegalic cells with typical ‘owl’s eye’ inclusions sometimes within areas of necrosis(arrow).

May see other changes attributed to a viral infection

Question 25

Explain syphilis lymphadenitis

Answer 25

occurs in any stage of acquired or congenital syphilis
primary – in nodes draining chancre (therefore often inguinal)
secondary – generalised lymphadenopathy
histology - marked follicular hyperplasia
many plasma cells in interfollicular areas

Question 26

What is paracortical hyperplasia a symptom of?

Answer 26

Paracortical hyperplasia is one of the main symptoms of infectious mononucleosis, caused by Epstein-Barr virus (EBV)

Question 27

What is infectious mononucleosis due to and causes?

Answer 27

due to Epstein Barr virus causes
widespread lymphadenopathy

Question 28

What is infectious mononucleosis characterised by?

Answer 28

It is characterized by paracortical hyperplasia with numerous large transformed T-cells

Question 29

What is sinus histiocytosis caused by?

Answer 29

specific non-infective(inflammatory) disorders

Question 30

Sinus histiocytosis with massive lymphadenopathy (SHML or Rosai-Dorfman syndrome)

Answer 30

rare
unknown aetiology
more common in Black populations
presents typically with bulky cervical lymphadenopathy
first and second decades of life
may affect any age or organ

Question 31

Describe lymph node sinuses histologically

Answer 31

lymph node sinuses are greatly distended by large histiocytic cells containing intact lymphocytes (emperipolesis or lymphocytophagocytosis ) – distinctive feature(arrows)It usually follows a benign course

Question 32

Describe Langerhans cell histiocytosis

Answer 32

may affect lymph nodes and characteristically involves the sinuses initially

clusters of typical pale Langerhans cells(blue arrow) with folded nuclei may be seen among giant cells and eosinophils( yellow arrow)

may present as a variety of clinical syndromes with uni- or multi-focal disease

Question 33

Dermatopathic lymphadenopathy

Answer 33

-patients with exfoliative skin conditions such as severe eczema or psoriasis and patients with cutaneous T-cell lymphoma
-commonly develop enlarged groin and axillary lymph nodes
-lymph nodes – yellow or brown cut surface
microscopically – paracortex is expanded by -pale histiocytes, some containing melanin pigment(red arrows)

Question 34

HIV lymphadenopathy may be observed in association with systemic symptoms in:

Answer 34

-AIDS-related complex – unexplained lymphadenopathy, diarrhoea, night sweats, oral candidiasis and weight loss
-persistent generalised lymphadenopathy (PGL) syndrome – persistent extra-inguinal lymphadenopathy
=in two or more contiguous sites
=of greater than three months duration
=and of no known aetiology other than HIV infection

Question 35

What can lymphadenopathy in HIV be due to?

Answer 35

Infective
mycobacterial infections
fungal infections
Chronic lymphadenopathy syndrome/ persistant generalized lymphadenopathy unexplained enlargement of nodes
Micro: florid reactive hyperplasia
Nodes may also show eventual profound lymphocyte depletion
Neoplastic
lymphoma
Kaposi’s sarcoma

Question 36

HIV lymphadenopathy histological spectrum correlates with the stage of the disease:

Answer 36

Early : Florid reactive hyperplasia (may be serrated,serpentine or dumb-bell shaped) containing macrophages, plasma cells and Warthin-Finkeldey like giant cells
in some follicles, there is focal destruction of the dendritic reticulum cell meshwork which is associated with an invagination/implosion of mantle zone lymphocytes into germinal centres (‘follicular-lysis’)
imparts a moth eaten appearance also called explosive follicular hyperplasia

Late : lymphocyte depletion, fibrosis and vascular proliferation

Question 37

HIV lymphadenopathy histological spectrum correlates with the stage of the disease:

Answer 37

Early : Florid reactive hyperplasia (may be serrated,serpentine or dumb-bell shaped) containing macrophages, plasma cells and Warthin-Finkeldey like giant cells
in some follicles, there is focal destruction of the dendritic reticulum cell meshwork which is associated with an invagination/implosion of mantle zone lymphocytes into germinal centres (‘follicular-lysis’)
imparts a moth eaten appearance also called explosive follicular hyperplasia

Late : lymphocyte depletion, fibrosis and vascular proliferation