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

THANK YOU