ABUTH ZARIA,NIGERIA

1. PATTERNS OF
INFLAMMATORY
DISEASES IN LYMPH
NODE BIOPSIES IN
ABUTH ,ZARIA .
A FIVE YEAR
REVIEW(2006-2010)
BY DR.MUSA EZEKIEL
DEPT.OF MEDICINE

2. SYNOPSIS
 Lymph node Anatomy.
 Patterns of inflammatory diseases affecting
lymph nodes.
 Discussion.
 Recommendation
 Conclusion
 References.

3. ANATOMY
OF THE LYMPH NODE
.

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)

7. Histology of Lymph Nodes
follicles with
germinal centers

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%

11. Prevalence of Age-related TB
Adenitis
16
14
12
10
8
No of cases
6
4
2
0
0-18 19-45 46-64 >65

12. Prevalence of Sex-related
Inflammatory Diseases in ABUTH
16
14
12
10
TB
8
CGI
6 NSA
4
2
0
MALE FEMALE

13. PAEDIATRIC VS ADULT TB
25%
ADULT
PAED.
75%

14. TB

15. Toxoplasmosis

16. HIV

17. HIV

18. DISCUSSION

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

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

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

38. Clinical features
 lymphadenitis,
 hepatosplenomegaly,
 Skin
rash, anaemia,leucocytosis,hypergammaglobu
linemia
 pulmonary infiltrates

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

51. THANK YOU