4. The Lymph Nodes
Anatomy
oval, bean shaped
structures scattered
throughout body along
lymph vessels
may be deep or superficial
concentrated along the
respiratory tree and GI
tract, in the mammary
glands, axillae, and groin
filter lymph fluid to trap
foreign organisms, cell
debris, and tumor cells
5. Lymphatic Organs – Lymph Nodes
Covered by a fibrous connective tissue capsule
Trabeculae extend from cortex to medulla
Stroma – the internal supportive connective tissue network of
reticular fibers
6. Structure of a Lymph Node
outer cortex - filled
with lymph follicles
outer edge of follicle
contains more T cells
inner germinal center
is the site of B-cell
proliferation
inner medulla - Cortex
medullary cords of
lymphocytes, macrop
hages, plasma cells Medulla
(activated B cells)
8. Circulation in the Lymph Nodes
Lymph enters via a number of
afferent lymphatic vessels
It then enters a large
subcapsular sinus and travels
into a number of smaller
sinuses
It meanders through these
sinuses and exits the node at
the hilus via efferent vessels
The node acts as a “settling
tank,” because there are fewer
efferent vessels, lymph
stagnates somewhat in the
node Only lymph nodes filter lymph!
This allows lymphocytes and
macrophages time to carry out
their protective functions
9. Lymph Flow Through Lymph Nodes
fluid enters cortex
through afferent vessels
filter and trap damaged
cells, microorganisms, forei
gn substances, tumor cells
by reticular fibers
macrophages phagocytize
some, lymphocytes destroy
some by immune defenses
exits medulla by efferent
vessels at hilus
10. Patterns Of Inflammatory Diseases
In ABUTH,2006-2010
Total no of cases= 41
3%
19%
TB
CGI
NSA
78%
19. TB ADENITIS
TB adenitis refers to involvement of lymph
nodes by members of the M.tuberculosis
complex which include
M.tuberculosis, M.bovis, M.africanum, M.canet
ti and M.caprae .
It may be associated with pulmonary TB or
other organ involvement but is usually an
isolated finding - 20% of all TB cases are
extrapulmonary TB
20.
21. Most common EPTB
In the US, non - tuberculous mycobacteria are the
most common cause of mycobacterial
lymphadenitis in children
extrapulmonary TB ( EPTB) rates have not
declined in the US
HIV positive patients with MTB are more likely to
have EPTB than HIV negative patients 45 - 70%
Vs 15%
22. In HIV positive patients TBLN is associated
with CD4 < 300 ( usually <100)
A US based study in Houston revealed the
following characteristics in HIV negative
patients –
1. Predictive factors: Female ,birth in Africa/SE
Asia
2. Protective factors: White Race and Diabetes
Mellitus
23. Pathogenesis
3 suspected routes:
1) Reactivation of PTB or hilar extension is
most common
2)Deep cervical involvement from laryngeal
infection
3) hematogenous
24. Histo-pathology
4 distinct cytological patterns noted on
aspirate, ranging from
- Pattern 1: occasional granulomas with early
epitheloid cells, extensive necrosis and foam
cells, numerous AFB - seen in HIV positive
patients with TBLN
- Pattern 4: Numerous granulomata with most
epitheloid cells and minimal necrosis + absence of
AFB mostly - seen in HIV negative patients with
TBLN
25. Clinical features
Pediatric TBLN is mostly an isolated infection
in the anterior cervical chain
Adult infection is similar with 70% anterior
cervical chain - 58% of which is in the
jugulodigastric region
HIV co - infection is associated with a more
severe/disseminated disease
26. Clinical Features
Abnormal CXR did not correlate with sputum
positivity but wt loss did
Disease associations: Chronic granulomatous
disease, lymphoma, HIV
diabetes,Renal Insufficiency and Alcoholism
and low iron and Vitamin D levels are also
associated with MTB
27. Pathological types:
(1) Caseous type: low immunity, common in
child
(2) Fibrous type: marked fibrosis with minimal
caseation or lymphoid hyperplasia.
(3) Lymphadenoid type: Marked lymphoid
hyperplasia with no caseation or fibrosis
Fate of T.B. Lymphadenitis:
1- Resolution.
2- Calcification
3- Caseation - cold abscess or sinus formation.
28. Diagnosis
About 20% have positive sputum cultures but
only 9 - 15% had positive AFB sputum smears.
Biopsy is the gold standard for diagnosis
FNA biopsy lead to TB diagnosis in 79% of
cases compared to surgical biopsy in 83%
Histology more sensitive than culture
29.
30. Diagnosis
Nucleic acid amplification tests(PCR) for TB
lymphadenitis are rapid but yield variable and
inconsistent results
Immune based blood tests include:
- T cell based cellular response ( IGRA -
Interferon Gamma Release Assay) and
- humoral antibody response
31. Treatment
Drug resistance in 13% of 147 cases of TBLN in
Manitoba only in foreign born
Standard per British Thoracic Society for
uncomplicated TBLN Rifampin+ Isoniazid+
Ethambutol for 2 months followed by Isonizid and
Ethambutol for 6 months
Standard abbreviations include: S =
streptomycin, H or INH= isoniazid, R or RFM=
Rifampin, Z or PZA= Pyrazinamide, E=
Ethambutol
32. Treatment
Extend to 6 - 12 months if LN persists,
rebiopsy and place on a CAT II regimen: 2
months of SHRZE then 1 month of RHZE
followed by 5 months of RHE
Alternate regimen is 4RHZE +2 RH: 5 year
remission rate was 89%
Steroids not recommended by IDSA currently (
Evidence DIII) however has had anecdotal
benefit
33. Treatment
Steroids decrease pain and discomfort
anecdotally though these outcomes have not
been studied in larger trials.
Surgery has no role for MTB unlike non TB
mycobacteria ( Evidence BIII per IDSA)
Interferon gamma and GCSF are under
investigation
34. Paradoxical Response (PR)
Defined as development of enlarging nodes or
new nodes during treatment seen in 23 30%
Among HIV negative patients: Baseline
peripheral monocytosis is a significant
predictor for PR but NOT age, sex, node
size, low Vitamin D, AFB smear/culture
positive, ANC or ALC.
35. Paradoxical Response
Among HIV positive patients: PRs noted in 7%
not on HAART Vs 36% on HAART.
Steroid use did not change duration of PRs
Aspiration, I&D and excision were associated
with a shorter duration of PR but not
significantly so ( p=0.1)
36. Outcomes
Cure rates vary from 81% - 95% with surgery
+ Anti TB regimen for 12 - 18 months
Relapse rates noted to be 8.1 per 1000 person
yrs of follow up
Residual palpable adenopathy in 5 - 30% of
cases Spontaneous drainage in 17%
37. Chronic granulomatous disease
Results from enzymatic defect of granulocytes
and monocytes
These cells ingest microorganisms but are unable
to destroy them
Due to defects in NADPH oxidases
Pattern of inheritance is Y- linked in majority of
patients
Autosomal recessive
Nitro blue tetrazolium test is the technique for its
detection
39. Microscopic features
Granulomas with necrotic purulent centres
Histiocytes are common
40. Acute non-specific
lymphadenitis
Typical case is rarely biopsied
Microscopically:
-sinus dilatation
-accumulation of neutrophils
-Vascular dilatation
-capsular edema
two forms:1.suppurative
2.necrotizing lymphadenitis
41. Chronic non-specific
lymphadenitis
General features:
-follicular hyperplasia
-pominence of postcapillary venules
-increase in immunoblast,plasma cells and
histiocytes
-fibrosis
other features:
-capsular inflammation and or fibrosis
-presence of eosinophils and mast cells
42. Histoplasmosis
Presents as:
1.chronic suppurative lesions
2.granulomatous lesions
May results in widespread nodal necrosis and
diffuse hyperplasia of sinus histiocytes
Histologic diagnosis:1.Gomori methanamine
silver stain
2.PAS stain
43. Other diagnostic modalities:
-culture
-molecular testing
-immunohistochemistry
44. Toxoplasmosis
One of the commonest parasitic diseases of
man
Caused by T.gondii
Posterior cervical nodes in young women
Nodes are firm and moderately enlarged
Microscopically:
-marked follicular hyperplasia
-small granulomas of composed of entirely
epithelioid cells
45. Distension of marginal and cortical sinuses
There may be immunoblast and plasma cells
in the medullary cords
Other techniques:
-PCR
- IgM immunoflorescent antibody test
46. HIV /AIDS –related
lymphadenitis
There four types:
1.Florid reactive hyperplasia
2.Mycobacteria
3.Opportunistic infection
4.Malignacy
Microscopically:
-collection of monocytoid B cells in the
sinusoids
47. Reactive germinal centres show follicle lysis
Evagination of mantle zone B-cells into
germinal centres
HIV may be found in follicular dendritic cells by
immunohistochemistry{fascin stain}
HIV protein p24 may be found in germinal
cetres
Other features:
-lymphocyte depletion
-Prominent interfollicular vascular
proliferation
48. Recommendations
Detailed clinical information by clinicians
Procurement and utilization of modern diagnostic
methods by the pathologist
Proper record keeping of histopathological results
Political will to improve the efficiency of our
Laboratories
Clinico-pathological collaboration
A careful approach at sample
collection, processing, and utilization of ancillary
techniques optimizes diagnostic yield
49. Conclusion
TB is the commonest cause of lymphadenitis in
our environment
Expansion of DOTS TB treatment progammes
Not every lymphadenitis is tuberculous
Need for exploration of modern diagnostic
technique
Increasing need for utilization of commonly used
staining methods
Lymph nodes provide invaluable information in the
diagnostic evaluation of several diseases
50. References
Surgical pathology(ninth edition) by Juan
Rosai pages 1893-1917
Robins Pathological basis of diseases , sixth
edition page 645-650
E-medicine
2012 NPMCN update course ,faculty of
pathology