Lecture Outline

Lymphoreticular system

1. Functions of the lymphoid system

2. Lymphadenopathy

3. Splenomegaly

4. Thymic hyperplasia / tumours & Myasthenia Gravis

5. Non-hodgkin’s & Hodgkins lymphoma

6. Plasma cell tumours

7. Leukaemias

1. Functions of the lymphoid system

·  production and maturation of lymphocytes

·  antigen presentation and the immune response

·  filtration & phagocytosis of micro-organisms & particulate material

2. Lymphadenopathy

·  Acute bacterial infection

§  neutrophils in peripheral sinuses

§  resolution

§  abcsess formation

§  patchy scarring

·  LGV (lymphogranuloma venereum)

§  Chlamydia trachomatis

§  Enlarged inguinal lymphnodes

§  Stellate abcsess

§  Dx confirmed with Frei test / complement fixation

·  Tuberculosis

§  Granulomatous response

§  Caseation

·  Viral Infection

§  NB: paracortical hyperplasia

·  Glandular Fever

§  Infectious mononucleosis

§  EBV

§  Young adults

§  Cervical lymph nodes

·  Measles

§  NB: multinucleate giant cells = Warthin-Finkeldey

·  Toxoplasmosis

§  Toxoplasma gondii

§  Congenital disease

§  Adults = enlarged LN

·  Follicular hyperplas.

·  Small epithelioid granul.

·  ↑ B cells in sub capsular sinus

·  Foreign material

§  Macrophage accumulation

§  E.g. carbon / silica

§  Silicone in axilary LN

·  Chronic skin disease

§  A.k.a dermatopathic lymphadenopathy

§  E.g. sporiasis , eczema

3. Splenomegaly

·  Important & common clinical sign

·  Mainly due to ↑ phagocytes & blood cells

·  Aetiology:

§  Infection

o  In systemic bacterial infections

o  200 – 400g

o  E.g. Subacute bacterial endocarditis

§  Circulatory disturbances

o  Systemic venous congestion due to heart failure (500g)

o  Portal hypertension due to liver cirrhosis (1000+g)

§  Storage diseases & degenerations

o  Amyloidosis

o  Are rare

§  Neoplasia

o  Secondary from Hodgkin’s disease & chronic leukaemia

§  Disorders of the blood

o  NB: hypersplenism = splenic anaemia i.e. the spleen has removed excess blood cells

o  Often the case in splenomegaly of portal hypertension

o  Blood disorders causing splenic enlargement

§  Haemolytic anaemia

§  Leukaemia & lymphoma

§  Chronic marrow failure

4. Thymic hyperplasia / tumours & Myasthenia Gravis

·  Thymic hyperplasia

§  >35 g

§  More NB is lymphoid follicles with germinal centres

·  Thymic tumours

§  Thymoma is rare

§  Low-grade ca. + lymphocytes

§  Other prim. Tumours

§  T cell lymphoblastic lymphoma

§  Hodgkin’s disease

§  Teratoma

§  Carcinoids

·  Myasthaemia Gravis

§  80% have thymic hyperplasia (young females)

§  20% thymoma in middle aged males

5. Non-Hodgkin’s & Hodgkin’s lymphoma

Introduction

·  malignant tumours of lymphoid cells

·  Can arise in LN or other sites (extra-nodal lymphomas)

·  Divided into 2 groups

§  (1) Hodgkin’s disease 20-25%

§  LN origin

§  Reed-Sternberg cells

§  (2) Non-hodgkin’s disease 75-80%

§  ¾ arise in LN

Non-hodgkin’s lymphoma

·  Spread

§  Usually arises in cervical LNs

§  Spreads via lymphatics to

§  Mediastinal & para-aortic nodes

§  Also to spleen & BM

§  Extra-nodal sites include

§  Thyroid

§  Stomach

§  Intestines

§  Brain

§  Ultimately a generalized spread including liver, lungs & heart

·  NB: Complications

§  Physical bulk = local compression

§  BM infiltration = anaemia ± pancytopenia

§  Splenic infiltration = hypersplenism = anaemia ± pancytopenia

§  Immunological disturbances = autoimmune haemolysis = anaemia ± pancytopenia + opportunistic infections

·  Classification

§  REAL (Revised European American Lymphoma) classification includes immunohistochemistry & genetic data

§  B Cell > 90%

§  Follicle centre lymphoma

§  Burkitt’s lymphoma

§  Waldenstrom’s macroglobulinaemia (lymphoplasmcytoid lymphoma)

§  Multiple myeloma (myelomatosis)

§  T Cell < 10%

§  Mycosis fungoides

§  Anaplastic large cell lymphoma

·  Follicle centre lymphoma

§  Commonest form of B cell lymphoma

§  Malignant follicles throughout LN

§  Tumor cells express anti-apoptosis gene bcl-2

§  T(14;18) translocation

§  Slowly progressive – eventually fatal

·  Burkitt’s lymphoma

§  High grade lymphoma of equatorial Africa, New Guinea, malaria endemic areas

§  Lesions typically in jaw or abdomen

§  Diffuse proliferation of B type cells with macrophages interspersed give “starry sky” appearance

·  Waldenstrom’s macroglobulinaemia (lymphoplasmcytoid lymphoma)

§  In males in late middle age & elderly

§  Low grade proliferation of plasma cells in LN, BM & spleen

§  Produce large amounts of IgM

§  Red cell agglutination & haemolysis

§  Increased viscosity = capillary stasis = visual and CNS disturbances

§  Coats platelets & interferes with fibrin polymerization = haemorrhages

·  Multiple myeloma

§  Wide spread BM deposits

§  X-ray app. Is classical – punched out defects in bones (skull)

§  Peak in 5th & 6th decades

§  Rapid progress with death in 2 – 4 years

§  Pathological effects

·  (A) Tumour growth

·  Q. Discuss the pathological effects (16)

·  (B) Excess Ig synthesis

·  A single Ig is produced & varies from one case to the next

·  IgGΚ is the most common

·  Plasma electrophoresis shows:

§  Normal Igs are ↓

§  High ESR

§  Marked rouleaux formation

§  Depending on type of Ig - ↑ blood viscosity

§  Incomplete light chains are often formed

·  Theses have serious complications

Pass through glom. filtrate

§  Appear in urine as Bence-Jones protein (precip. During heating redissolves @ 90º - 100º)

§  Precipitates in tubules as casts – damage tubular epithelium = myeloma kidney

Also cross capill. Wall

§  Incorporated in amyloid

§  Damage many organs including kidney

Hodgkin’s Disease

§  Incidence

§  20% of lymphomas

§  peak in adolescence & 6th decade

§  avg = 30 cases/million

§  Presentation

§  PAINLESS enlargement of LN groups – usually cervical

§  25% have systemic symptoms e.g. fever, night sweats, weight loss, itch

§  Increased infections

§  Spread & Staging

§  Direct spread via lymphatics from one LN group to the next.

§  Summarise Ann Arbor system of staging (8 marks)

§  Histology & RYE classification

§  NB: Dx pos. if RS cell present

o  30-60μm diam. Amphophilic cytoplasm

o  mirror image nuclei

o  large eosinophilic nucleoli

o  peripheral clumping of nuclear chromatin

§  NB: know names & %’s of RYE classification (8 marks)