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The leukaemias are caused by an acquired malignant transformation in the stem cell in the haemopoietic system. Acute leukaemia has a rapidly fatal course if untreated, while chronic leukaemia has a variable chronic course with an inevitable fatal outcome. See FIGURE 26.1. The main features of each type are as follows.
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The usual age range for acute lymphatic leukaemia (ALL) is 2–10 years with a second peak at about 40 years. The median age of presentation of acute myeloid leukaemia (AML) is 55–60 years.
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General constitutional (e.g. malaise)
Symptoms of anaemia
Susceptibility to infection (e.g. sore throat, mouth ulceration, chest infection)
Easy bruising and bleeding (e.g. epistaxis, gingival bleeding)
Bone pain (notably in children with ALL) and joint pain
Symptoms due to infiltration of tissues with blast cells (e.g. gingival hypertrophy in AML)
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DxT malaise + pallor + bone pain ➜ ALL
DxT malaise + pallor + oral problems ➜ AML
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Pallor of anaemia
Petechiae, bruising
Gum hypertrophy/gingivitis/stomatitis
Signs of infection
Variable enlargement of liver, spleen and lymph nodes
Bone tenderness, especially sternum
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Treatment: chemotherapy, immunotherapy, stem cell therapy.
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Note: As a rule, relapse of acute leukaemia means imminent death unless bone marrow transplantation is successful. The mean 5-year survival rate for childhood ALL is about 75–80%, for adult ALL 30%; for AML it varies with age with poorer survival, about 20%, over 55 years of age.
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Chronic myeloid leukaemia (CML)
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A disorder of middle age, typically 40–60 years
Insidious onset
Constitutional symptoms: malaise, weight loss, fever, night sweats
Symptoms of anaemia
Splenomegaly (very large); abdominal discomfort
Priapism
Gout
Markedly elevated white cell count (granulocytes)
Marked left shift in myeloid series
Presence of Philadelphia chromosome
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DxT fatigue + fever/night sweats + abdominal fullness (splenomegaly) ➜ CML
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Chronic lymphocytic leukaemia (CLL)
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A disorder of late middle age and elderly
Insidious onset
Constitutional symptoms: malaise, weight loss, fever, night sweats
Lymphadenopathy (large rubbery nodes)—neck, axilla, groin (80%)
Moderately enlarged spleen and liver (about 50%)
Mild anaemia
Lymphocytosis >15 × 109/L
‘Mature’ appearance of lymphocytes
Consider cytogenetics
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Note: Most cases, especially early indolent CLL, require no specific therapy but observation.
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DxT fatigue + weight loss + fever/night sweats + lymphadenopathy ➜ CLL
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Lymphomas, which are malignant tumours of lymphoid tissue, are classified as Hodgkin lymphoma and non-Hodgkin lymphoma on the basis of histological appearance of the involved lymph tissue.
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Painless (rubbery) lymphadenopathy, especially cervical nodes
Constitutional symptoms (e.g. malaise, weakness, weight loss)
Fever and drenching night sweats—undulant (Pel–Ebstein) fever
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Pruritus
Alcohol-induced pain in any enlarged lymph nodes
Possible enlarged spleen and liver
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Diagnosis is by lymph node biopsy with histological confirmation. Other tests: FBE, CXR, CT/MRI (to stage), bone marrow biopsy, functional isotopic scanning. Staging is by using Ann Arbor nomenclature (IA to IVB). Treatment includes chemotherapy, immunotherapy and radiotherapy.
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DxT malaise + fever/night sweats + pruritus ➜ Hodgkin lymphoma
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Non-Hodgkin lymphomas
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Non-Hodgkin lymphomas are a heterogeneous group of cancers of lymphocytes derived from the malignant clones of B or T cells.
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Painless lymphadenopathy—localised or widespread
Constitutional symptoms possible, especially sweating
Pruritus is uncommon
Extra nodal sites of disease (e.g. CNS, bone, skin, GIT)
Possible enlarged liver and spleen
Possible nodular infiltration of skin (e.g. mycosis fungoides)
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Diagnosis is by lymph node biopsy.
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CXR and CT abdomen to stage.
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DxT malaise + fever/night sweats + lymphadenopathy ➜ non-Hodgkin lymphoma
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Multiple myeloma is a clonal malignancy of the differentiated β lymphocyte—the plasma cell. It is regarded as a disease of the elderly, the mean age of presentation being 65 years.8 It is asymptomatic in 20% of patients. The classic presenting triad in an older person is anaemia, back pain and elevated ESR which helps to differentiate it from monoclonal gammopathy of uncertain significance (MGUS).
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Other investigations include serum protein electrophoresis and immunofixation, Sestamibi scan.
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Bone pain (e.g. backache)—in more than 80% of patients (possible pathological fracture)
Bone tenderness, e.g. femur, ribs, spine
Weakness, tiredness, increased thirst
Anorexia and weight loss
Recurrent infections, e.g. chest infection
Symptoms of anaemia
Bleeding tendency
Replacement of bone marrow by malignant plasma cells
Impaired renal failure → kidney failure
Associated with amyloidosis and hypercalcaemia
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DxT weakness + unexplained back pain + susceptibility to infection ➜ multiple myeloma
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Diagnostic criteria comprise the presence of:6
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paraprotein in serum (on electrophoresis)
Bence–Jones protein in urine
bony lytic lesions on skeletal survey
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Treatment is with chemotherapy including thalidomide or lenalidomide: 5-year median survival. The younger patient may be given a stem cell transplant.9
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Monoclonal gammopathy of undetermined significance (MGUS) involves the production of paraprotein (M protein) by non-cancerous cells in the absence of other clinical manifestations of multiple myeloma. It is associated with various disorders. MGUS is usually asymptomatic but peripheral neuropathy can occur. No chemotherapy treatment is recommended.
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This uncommon but difficult-to-diagnose disorder caused by the deposition of amyloid protein is classified as primary, familial or secondary (from chronic infection, e.g. TB, inflammation, RA, some cancers, others). It may be localised or generalised. Clinical features depend on the organ targeted such as the heart (CCF), kidney (nephrotic syndrome), GIT (malabsorption), brain (dementia) and peripheral nerves (e.g. CTS). Diagnosis is by tissue biopsy. Treatment, which varies with the type, is basically symptomatic and specialised. In primary amyloid it resembles the treatment for myeloma.
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Hormone secretion by carcinoid cells causes the characteristic carcinoid syndrome long before local growth or metastatic spread of the tumour is apparent (80% metastasise). Most carcinoid tumours are asymptomatic.
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Classic triad: skin flushing (especially face), diarrhoea (with abdominal cramps), valvular heart disease
Other possible features: wheezing, telangiectasia, hypotension, cyanosis
Sites of tumours: appendix/ileum, stomach, bronchi
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This is a malignant proliferation of RBCs and also WBCs and platelets.
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Older person
Fatigue
Headache, dizziness, tinnitus
Pruritus after hot bath, shower
Epistaxis
Facial plethora
Splenomegaly
Thrombosis
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