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
o 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
o 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)