PATTERNS OF INFLAMMATORY DISEASES IN LYMPH NODE BIOPSIES IN ABUTH ,ZARIA . A FIVE YEAR REVIEW(2006-2010)
BY DR.MUSA EZEKIEL
DEPT.OF MEDICINE
SYNOPSIS
Lymph node Anatomy. Patterns of inflammatory diseases
affecting lymph nodes. Discussion. Recommendation Conclusion References.
ANATOMY OF THE LYMPH NODE
.
The Lymph NodesAnatomy
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
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
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 - medullary cords of lymphocytes, macrophages, plasma cells (activated B cells)
Cortex
Medulla
follicles withgerminal centers
Histology of Lymph Nodes
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
This allows lymphocytes and macrophages time to carry out their protective functions
Only lymph nodes filter lymph!
Lymph Flow Through Lymph Nodes fluid enters cortex
through afferent vessels filter and trap damaged
cells, microorganisms, foreign substances, tumor cells by reticular fibers
macrophages phagocytize some, lymphocytes destroy some by immune defenses
exits medulla by efferent vessels at hilus
Patterns Of Inflammatory Diseases In ABUTH,2006-2010
77%
19%
3%
Total no of cases= 41
TBCGINSA
Prevalence of Age-related TB Adenitis
0-18 19-45 46-64 >650
2
4
6
8
10
12
14
16
No of cases
Prevalence of Sex-related Inflammatory Diseases in ABUTH
MALE FEMALE0
2
4
6
8
10
12
14
16
TBCGINSA
PAEDIATRIC VS ADULT TB
75%
25%
ADULTPAED.
TB
Toxoplasmosis
HIV
HIV
DISCUSSION
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.canetti 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
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%
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
Pathogenesis
3 suspected routes: 1) Reactivation of PTB or hilar extension is most common 2)Deep cervical involvement from laryngeal infection 3) hematogenous
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
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
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
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.
4- General dissemination
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
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
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
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
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
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.
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)
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%
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
Clinical features
lymphadenitis, hepatosplenomegaly, Skin rash,
anaemia,leucocytosis,hypergammaglobulinemia
pulmonary infiltrates
Microscopic features
Granulomas with necrotic purulent centres
Histiocytes are common
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
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
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
Other diagnostic modalities: -culture -molecular testing -immunohistochemistry
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
Distension of marginal and cortical sinuses
There may be immunoblast and plasma cells in the medullary cords
Other techniques: -PCR - IgM immunoflorescent antibody test
HIV /AIDS –related lymphadenitis
There four types:1.Florid reactive hyperplasia2.Mycobacteria3.Opportunistic infection4.MalignacyMicroscopically: -collection of monocytoid B cells in the
sinusoids
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
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
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
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
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