Lymphoid proliferations can be benign or malignant. Benign causes include infections while malignant causes include lymphomas. Lymphomas are divided into Hodgkin's lymphoma and non-Hodgkin's lymphoma. Hodgkin's lymphoma is characterized by Reed-Sternberg cells while non-Hodgkin's lymphoma can be of B-cell or T-cell origin. Investigation of lymph node enlargement includes history, examination, blood tests, imaging and biopsy to determine if the cause is benign reactive hyperplasia, infection, or malignancy such as lymphoma or metastatic carcinoma.

1. Lymphoid Proliferations
Characteristics of Lymphocytes
They originate in the bone marrow & differentiate in
primary lymphoid tissues:
They circulate in the peripheral blood & migrate into
secondary organs (ex: lymph nodes).
Differentiating the Types of Lymphocytes
Flow cytometry and immunohistochemistry: use markers –
antibodies which will react with their specific type:
• All lymphocytes: CD45
• B lymphocytes: CD20, CD79(a)
• T lymphocytes: CD2, CD3 (predominant), CD4, CD5, CD8.
B cells express different antigens throughout their
development:
Phagocytic Cells
• Monocytes: WBC that differentiate into macrophages,
involved in immunity.
• Histiocytes: phagocytic tissue monocytes that produce
cytokines.
• Macrophages: histiocytes w/ more phagocytic function.
• Multinucleated cell: fused histiocytes.
• Dendritic cell: APC to T cell.
• Langerhan cell: APC.
Causes of Enlarged Nodes
Can be benign or malignant:
Lymphoid Tissue Proliferation
Clinical Signs:
1. Lymphadenopathy, splenomegaly, hepatomegaly
2. Thymic enlargement, marrow expansion
3. Masses in nasopharynx, GIT, etc.
4. Night sweats: very important (if patients comes in
with night sweats worry if they have a lymphoma).
5. Recurrent infection: marrow produces immature cells
that can’t function; marrow failure  reduced bone
products  anaemia, infection, bleeding.
T cells Thymus; cell mediated immunity; 70% in blood;
paracortex of nodal tissue.
B cells Bone Marrow; humoral immunity; 10% in blood;
cortex of nodal tissue.
Null cells Not B/T cell marker responsive; 20% in blood;
NK cells May react with T cells.
Lymphopenia
(Low lymphocyte count)
Lymphocytosis
(High lymphocyte count)
• Advanced HIV infection
• Congenital immune
deficiency syndromes
• Steroids
• Chemotherapeutic drugs
• Autoimmune diseases
• Viral infection (infectious
mononucleosis)
• Rare bacterial infections
(Whooping cough,
Tuberculosis, Brucellosis)
Benign Reactive Hyperplasia
Patterns:
1. Cortex follicular hyperplasia – B cells in germinal
centre of cortex mainly
• Non-specific reaction
• Infection/immune stimulation
Macrophages may be present in follicle centre.
2. Paracortical hyperplasia – T cells mainly
3. Sinus histiocytosis
• Dilated sinuses
• Histiocytes
• Lymphocytes
• Antigen presenting cells
Journey through sinuses: afferent lymphatics  sub-
capsular sinuses  cortical sinuses  medullary
sinuses  efferent lymphatics (metastasis initially
spreads to this part of the node).
Most reactive nodes have a combination of these.
Causes:
1. Infections (always discuss the types)
• Bacterial (syphilis, brucellosis, cat scratch disease)
• Viral (infectious mononucleosis)
• Protozoal
2. Granulomas (TB, Sarcoid, Crohn’s, Fungi)
3. Deposits (Amyloid)
4. Immune Reactions (Rheumatoid arthritis, SLE)
5. Storage Disorders (Gaucher’s disease - histiocytes/
macrophages contain undigested material)
Classification
Acute Reactive Lymphadenitis
Lymphadenopathy secondary to bacterial or viral infection
in the area drained by the lymph node. Lymph node is
enlarged and tender ex: cervical nodes in acute
streptococcal tonsillitis.
Histology:
• Preserved architecture
• Follicular hyperplasia
• Neutrophilic infiltrate and abscess formation
Chronic Reactive Lymphadenitis
A response to chronic antigen exposure
• Immune-mediated/Collagen vascular disease:
1. Rheumatoid arthritis  Generalised
lymphadenopathy & follicular hyperplasia
2. Sjögren’s syndrome  Increased risk of
lymphoma & follicular hyperplasia
3. Systemic lupus erythematosus (SLE) --> Cervical
lymphadenopathy & follicular hyperplasia
Different markers are used
for different stages of B cell
proliferates; CD20 doesn’t
stain plasma cells
⑲-㉒

2. Investigation of an Enlarged Lymph Node
Diagnostic Questions:
 Is the node benign or malignant?
 If benign is there an identifiable cause for node
enlargement?
 If malignant is it a carcinoma, lymphoma (most
likely), melanoma or sarcoma?
 If it is a metastatic carcinoma, where is the primary
site?
1. Proper history and clinical examination. Ask:
 Evidence of recent infection?
 Evidence of malignancy in adjacent lymphatic
draining site?
 Any localising symptoms?
 Any weight loss?
 Any night sweats?
 Duration of lymphadenopathy?
 Are nodes sore/tender?
3. Investigations:
• FBC
• CRP (C-reactive Protein)  indicates inflammation
• LDH  indicates RBC lysis
• Viral screen
• Chest X-ray
• CT chest and abdomen
• Biopsy (to investigate histology)
1. Fine needle aspiration/biopsy
2. Incisional biopsy
3. Excision of whole node  ensures that
malignant portion is not missed & is thus the best
sample.
4. Bone marrow trephine
NB: enlarged retroperitoneal nodes present because
they’re in the abdomen and need to be very large to be
felt.
Malignant (Lymph Node Enlargement)
Causes:
Primary:
• Lymphoma
• Leukaemia
Secondary:
• Metastatic carcinoma – commonest
• Metastatic melanoma
• Metastatic sarcoma – rare
• Others i.e. Germ cell – rare
To investigate likely primary site of a metastasis in a node:
• Suspect the area which drains that node:
Examples:
1. Metastasis in inguinal node  due to melanoma of skin
of lower limb (not squamous cell carcinoma because it
rarely metastasises)
2. Metastasis in supraclavicular node  upper GIT
carcinoma, bronchogenic carcinoma, breast
3. Metastasis in cervical node  nasopharyngeal
carcinoma, oropharyngeal carcinoma, head and neck
carcinoma, salivary glands, thyroid.
4. Metastasis in axillary node  breast carcinoma
5. Melanoma  check anal skin and retina for primary site.
Histological features that identify type of malignancy:
Morphological features that suggest a carcinoma:
• Keratin –Squamous cell carcinoma
• Mucin –Adenocarcinoma
• Tubules –Adenocarcinoma
If morphological features are not evident, we use tumour
markers:
• Cytokeratin –CK – Epithelial –Metastatic Carcinoma
• Vimentin – Mesenchymal
• CD45 – Common Leucocyte Antigen – Lymphoma
• S100P and HMB45 – Melanoma
o If an undifferentiated malignancy in a lymph node is
CD45 (Common Leucocyte antigen) positive, then
diagnosis is of a LYMPHOMA.
o If an undifferentiated neoplasm is Cytokeratin (CK)
positive it is a metastatic carcinoma.

3. Lymphoma
Definition
Malignant neoplasm of lymphoid cells that may be nodal or
extra-nodal. Divided into Hodgkin & non-Hodgkin
lymphoma.
Hodgkin Lymphoma (HL) – 20%
Characteristics
Malignancy of Reed-Sternberg (RS) cells and Hodgkin cells.
They secrete cytokines that attract benign reactive cells
including lymphocytes, plasma cells, macrophages and
eosinophils and may lead to fibrosis.
• RS cells: bi-nucleated B cells with large vesicular
nuclei and prominent eosinophilic (pink) nucleoli.
• Hodgkin cells: larger mononuclear RS cells.
Bimodal Age Distribution: Peaks: 20s-30s (60-70%) & >60s.
Usually presents as an enlarged, firm node – usually cervical.
Immunohistochemistry Markers
CD15+, CD30+ and no CD20, CD45.
Clinical Presentation
• Commonest: persistent lymphadenopathy (usually in
neck or mediastinum). Mediastinal  superior vena cava
syndrome.
• B Symptoms (FAWN): fever, night sweats, weight loss,
anaemia.
• Pruritis (itchy skin) & pain located at the site of nodal
enlargement & which is exacerbated by drinking alcohol.
• Hepatosplenomegaly.
• Extra nodal swelling.
Grading/Rye Classification
Based on microscopic grounds: amount of lymphocytes,
types of RS cells & degree of fibrosis:
1. Nodular Lymphocyte Predominant Hodgkin
Lymphoma
• A controversial entity in that the RS cells stain positively
for B cell markers (and so may actually be a B cell NHL).
• The popcorn RS cell is characteristic.
• Lymphocytes make up the reactive cell population and
may be so numerous as to obscure the often scanty RS
cells.
2. Classical Hodgkin
Staging (Ann Arbor Staging) & Diagnosis
Done radiologically using: chest x-ray, CT, MRI, PET (after
some treatment to monitor lymph node size), bone
aspirate, bone trephine, presence/absence of B symptoms,
LDH level (dead lymphocytes), performance index
(determines how well patient will withstand treatment)
• Stage 1: 1 lymph node region/1 lymphoid organ.
• Stage 2: 2 or more lymph node regions on the same side
(LHS or RHS) of the diaphragm.
• Stage 3: nodes both sides of diaphragm.
• Stage 4: involvement of extra-nodal sites: liver, bone,
lung, and nodes.
Prognosis
• 80% excellent response to treatment and many cured.
• Prognosis worsens with presence of B symptoms, age >
60, stage III or IV and increased LDH level of activity.
• Many associated with EBV infection.
Lookalikes: need to be separated from Hodgkin disease
using Immunomarkers:
• Ki1 Lymphoma (anaplastic large cell lymphoma)
• T cell lymphoma
• T cell rich B cell lymphoma
Non Hodgkin Lymphoma (NHL) – 70-
80%
Characteristics/Classification
• Commonly extra-nodal: 70-80%
• The REAL classification system and divides diseases into
T cell, B cell and null cell lymphomas.
• Can be B cell or T cell, low grade (small cell size) or high
grade (large cell size).
Immunohistochemistry Markers Used
• CD20 and CD79 – B Cell Lymphomas
• CD3 – T Cell lymphomas
• BCL2 and CD10 – Follicular lymphoma
• CD5 and CD23 – Small cell lymphocytic Lymphoma
• Cyclin D1 – Mantle cell lymphoma
Diagnostic Steps
• Immunohistochemistry is not sensitive enough for Dx.
• Molecular studies are required to show monoclonality
e.g. gene rearrangements.
• Clonality to diagnose malignancy – Monoclonal
(important)
• B Cell Lymphomas – Ig gene rearrangements.
• T Cell lymphomas – T cell receptor rearrangements.
• IHC to diagnose type of lymphoma.
• Ann Arbor Staging is also used here.
Comparison Table
Most common HL.
Thick bands of sclerotic
collagen divide the lymph
node into nodules.
RS or Hodgkin cells.
Eosinophils are prominent.
Granulomas and necrosis are
frequent and may lead to
confusion with tuberculosis.
The rarest & most aggressive
form of HL.
Pleomorphic RS cells.
Sclerosis may be prominent.
HL NHL
Incidence Less than NHL More than HL
Cell of origin B-cells B or T cells
Type of Cell RSC No characteristic cells
Age Commonly young adults Older adults
L.N spread Contiguously (orderly) Sporadic
B-symptoms Common Less common (>20% of
patients)
Extra-nodal Less common More common
Cure Most Some

4. Non-Hodgkin Lymphoma (NHL) cont’d
B cell NH-Lymphomas:
B Cell
Lymphoma
Cell of Origin &
Markers
Pathogenesis & Presentation Epidemiology & Prognostics
Follicular B Cell
Lymphoma
Centrocyte/
Centroblast
BCL2 & CD10.
Definition: Small neoplastic B cells form follicle-like nodules.
Cause: t(14;18) BCL2.
Pathogenesis: Antiapoptotic BCL2 gene on chromosome 18 translocated to chromosome 14
 overexpression of anti-apoptotic proteins  B cell proliferation.
NB: Follicular Lymphoma is BCL2 positive, monoclonal, destroys lymph node architecture
and doesn’t have tingible body macrophages where as reactive follicular hyperplasia is the
opposite.
One of the commonest lymphomas:
• Affects >50 years
• 60% stage III or IV at presentation.
• Rarely get cured but indolent (not
aggressive) and progressive disease.
• 70% - 5 year survival.
• 20% - transform to high grade.
Small Cell
Lymphocytic
Lymphoma
Lymphocyte
CD5 & CD23
Definition: Chronic lymphocytic leukaemia that has spread to/manifested in the tissues.
Presentation: Widespread adenopathy, Splenomegaly, decreased Ig  increased infection
• 5-10% Richter’s Syndrome – high grade
transformation (cells become big)
• Commonly stage III or IV because
asymptomatic at presentation.
Mantle Cell
Lymphoma
Mantle cells
Cyclin D1
Definition: diffuse replacement of node by malignant/neoplastic mantle B-cells.
Cause: t(11;14) Cyclin D1.
Pathogenesis: Cyclin D1 gene on chromosome 11 translocated to chromosome 14  inc.
cyclin D1  more cells enter G1/S phase  increased proliferation.
<5% of all lymphomas (rarer):
• Age distribution: peak 60-70 years.
• Often high stage at presentation .
• 20-40% - 5 year survival.
Marginal Zone
Lymphoma (ex:
Maltoma – GIT)
Marginal zone
cells
Definition: Extra-nodal lymphomas that are usually low grade.
Predisposing Factors: Antigen Challenge.
Pathogenesis: associated with and found in chronic inflammatory conditions:
GIT –HLO in stomach, Thyroid –Hashimoto’s, Salivary gland –Sjogren’s, Lungs
Due to increased cell turnover precipitated by the underlying condition
Diffuse Large Cell
B Cell
Lymphoma
Centroblasts Definition: Large mononuclear neoplastic B cells proliferate and can spread to extra-nodal
sites.
Commonest high grade B cell lymphoma:
• Aggressive but curable.
Lymphoblastic B
Cell Lymphoma
Lymphoblast Rare (Majority are T cell LBLs); Bone lytic lesions. • Many children and young adults
Burkitt’s
Lymphoma
Lymphoblast,
EBV + & activated
c-Myc
Definition: Type of lymphoblastic lymphoma. Intermediate B cell proliferation.
Cause: t(8;14) c-Myc.
Pathogenesis: EBV associated, c-Myc translocation from chromosome 8 to 14 present
deregulation of oncogenic function  increased cell growth.
Clinical Presentation: extra-nodal mass in jaw, GIT, gonads in young adults/kids. IHC  starry
sky appearance on microscopy.
• African form  jaw.
• Sporadic form  abdomen.
• Rare in Europe.
• Occurs in children and adolescents.
Lymphocyte, Mantle cell, Marginal cell, Lymphoblast, Immunoblast,
Centrocyte/Cleaved FCC – follicle centre cell
Centroblast/Non cleaved FCC
Plasma cell – large B cells
F.C.C.
Cleaved &
non-cleaved
Aka  centrocytes/
centroblasts Histiocytes Mantle cells
Marginal Cells
Plasma
cell
Lymphocytes
L
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5. T cell NH-Lymphomas
Low Grade
1. Mycosis Fungoides – T cell lymphoma producing scaly,
pruritic, well-demarcated skin plaques and patches. In
the later stages of the disease, mushroom-shaped
tumours develop within the plaque lesions, and
ultimately lymphadenopathy and hepatosplenomegaly
can develop.
• Occurs in adults
• 12 year survival
2. Sezary syndrome – Cutaneous (skin) T-cell lymphoma
with leukaemic dissemination of mutated T cells (which
distinguishes it from mycosis fungoides). It thus
becomes a T cell leukaemia and is considered an
advanced stage of mycosis fungoides.
3. T cell Chronic Lymphocytic leukaemia (CLL)
High Grade
1. Peripheral T CellLymphoma (most high grade are
classified as this)
2. Enteropathy associated T CellLymphoma (EATL) – It is a
complication of celiac disease, occurs in the small bowel
and is commoner in those with poor dietary control.
3. T Lymphoblastic Lymphoma
• Young adults but very rare
• Rapid enlargement of nodes
• On histology, large lymphoid cells that react with T
lymphocyte markers
4. T Adult T cell leukaemia/lymphoma
• Rare
• Japan/Caribbean
• HTLV1 Virus
• Hypercalcaemia (PTH)
Other Lymphomas
1. Extra-Nodal Lymphoma
• Lymphomas of mucosa and non-nodal tissue
2. Nasal Lymphoma
• High grade lymphoma of nose
• Null of NK cells
• Common in Asia but uncommon in Europe
• EBV associated
Causes of Lymphoma
1. Antigen challenge: the first encounter between an
immunocompetent lymphocyte and an invading
antigen.
2. Viruses
• EBV associated with: Burkitt’s, Nasal lymphomas,
Hodgkin’s (BNH)
3. Immunodeficiency
4. Radiation
5. Previous chemotherapy
Leukaemia vs Lymphoma
Summary of Management (for ALL NHLs)
Diagnosis –
• Radiologist takes the trucut
• Painless persistent enlargement of node ± B symptoms
• Loss of normal architecture (not reactive follicular
hyperplasia)
• Monoclonality  malignancy (determined by molecular
studies of gene rearrangements)
• Hodgkin or Non Hodgkin
• Reed Sternberg cell  Dx Hodgkins
• No RS cells Dx  Non Hodgkins
• Small cells (Low Grade) or large cells High Grade)
replace node
• Lymphoid markers are essential to type lymphoma
correctly
• Molecular markers now being increasingly used
Grade – Rye Grading
Stage – Ann Arbor Staging – CT, PET, BMT
Treatment –
• Rituximab –B cell (CD20 monoclonal antibody)
• Chemotherapy
• Radiotherapy
• Bone marrow transplant
Lymphoma Leukaemia
High WCC >20,000 Normal WCC
Patchy marrow involvement Extensive marrow
replacement
Little lymphadenopathy Prominent
lymphadenopathy

6. Thymus
The thymus arises from the endoderm of 3rd and 4th
branchial pouch. It migrates down from the neck to the
mediastinum where it houses T cells and produces
hormones that allow them to mature further.
Thymus gets smaller after birth and is almost completely
atrophied in adults.
Functions of Thymus
• Responsible for differentiation and direction of T cells
• Central role in cell mediated immunity
Enlargement of Thymus
1. Myasthenia gravis
• 80% thymic hyperplasia – autoimmune thymitis
• 80% AChr antibody – against myeloid cells
• 15% get thymoma
• Treatment – Thymectomy
2. Thymomas (epithelial neoplasm of thymus; ‘oma’
doesn’t indicate benign or malignant - can be either)
• May present with associated diseases:
⁃ 30% myasthenia gravis
⁃ Rheumatoid arthritis
⁃ Sjogren’s syndrome
⁃ Anterior mediastinal mass
⁃ NB: Prognosis behaviour correlates with grade
3. Lymphomas
• T cell – most are T cell
• B cell
4. Germ cell tumours
5. Carcinoid tumours
Spleen
• White pulp: lymphoid follicles (Malpighian bodies).
• Red pulp: venous sinuses & cords (lymphocytes).
• Weight: 120-150g.
Functions of Spleen
Splenic Atrophy
• Physiological – old age.
• Sickle cell disease – sickle cells get trapped in blood
vessels that supply the spleen  spleen becomes
infarcted in areas  heals by fibrosis  small spleen.
• Coeliac disease – idiopathic.
Splenomegaly
Splenomegaly causes: hypersplenism which is the
enlargement of spleen for any reason –causing destruction
of blood cells and consequently a reduction in these cells in
the peripheral blood  anaemia, thrombocytopenia &
leukopenia.
Causes of splenomegaly include:
1. Congestive
• Cirrhosis of liver  portal vein thrombus  inc.
pressure on the splenic vein.
2. Collagen Vascular Diseases (Autoimmune Disorders)
• Rheumatoid arthritis
• Systematic Lupus Erythematosus (SLE)
• Polyarteritis Nodosa (PAN)
3. Storage Disorders
• Hyperlipidaemias
• Lipid storage disorders
• Gaucher’s disease
• Neiman Pick’s Disease
4. Infections
• Malaria
• Leishmaniasis (protozoal)
• Infectious mononucleosis  spontaneous rupture
• Brucellosis
• S.B.E – subacute bacterial endocarditis
• Endocarditis – septic emboli from endocarditis go to
the spleen  abscess.
NB: Splenomegaly due to infection is more seen in
children and when seen in adults more due to viral than
bacterial infection (esp. infectious mono).
5. Amyloidosis
6. Disorders of blood & marrow
• Leukaemias and Lymphomas
• Haemolytic anaemia  red cells broken down by
histiocytes & macrophages in spleen  gets bigger.
• Myelofibrosis  myelo = fibrosis; spleen can’t
produce red cells & blood components so function
taken over by the liver.
• Myeloproliferative disorders
Myeloproliferative Cell
Neoplasms/Disorders
Clonal neoplastic proliferation of stem cells, affecting all cell
lines of the bone marrow with variable clinical presentation
and variable prognosis (excluding acute leukaemia).
• Diagnosis
• Clinical presentation – (3 conditions)
• FBC
• BMT and BM aspirate
• Pathogenesis – activating mutation in gene coding for
tyrosine kinases.
Characteristics
1. Arise from common stem cell cases with intermediate
features
2. Frequent evolution of 1 type to another
3. Invariable involvement of more than 1 cell line – due to
an abnormal clone with increased sensitivity to growth
factors.
4. Occur in people > 50 years
5. Splenomegaly
6. Mutation of the tyrosine kinase JAK2 (Janus kinase – 2
gene). Causes increased sensitivity to intercellular
signalling from growth factors.
Presentation
Concepts
• Excess of one cell type may cause a decrease of other
cell types
High content of one cell type may cause symptoms
• Anaemia and infection
• Bleeding/thrombosis
• Hyperviscosity syndrome
Tumour Markers in Nodes & Spleen, Thymus and
Bone Marrow
1. Haemopoiesis
2. Antibody formation
3. Cell sequestration
4. Cell destruction
5. Iron metabolism
6. Phagocytosis

7. 1. Chronic granulocytic/myeloid leukaemia
(commonest)
2. Myelofibrosis – 60% JAK2
3. Polycythaemia rubra vera (RBC) – 90% JAK2
4. Essential thrombocythaemia/ Thrombocytosis
(Platelets) – 60% JAK2
1) Chronic Myeloid/Granulocytic
Leukaemia
(CML/CGL)
• Neoplastic proliferation of stem cells that differentiate
into mature myeloid cells, especially granulocytes
(characteristically basophils).
• Characterised by Philadelphia fusion chromosome –
t(9;22) which results in a BCR-ABL fusion protein with
increased tyrosine kinase activity.
• This is also an MPD (Myeloproliferative Disorder).
Presentation
• Marrow replacement with/without failure  anaemia,
bleeding, bruising, infection.
• Marked leucocytosis – 50,000 abnormal.
• Marked hepatosplenomegaly.
• Weight loss.
Epidemiology
• Middle age 40-60 years.
Diagnosis
1. WCC above 100,000 instead of 7,000
2. Increased blasts in the peripheral blood  too many
being released (shouldn’t normally be there)  can
become a crisis.
3. PHI chromosome 22.9 (used to)
4. BCR-ABL rearrangement diagnostic of CML.
2) Myelofibrosis - 60% JAK2
Neoplastic proliferation of mature myeloid cells especially
megakaryocytes.
Primary Myelofibrosis:
Megakaryocytes produce excess platelet-derived growth
factor (PDGF)  marrow fibrosis.
Secondary Myelofibrosis:
• Metastases to marrow
• Radiotherapy to marrow
• Cytotoxic drugs
Presentation
• Fibrosis reduces marrow’s haematopoietic capability 
migration of erythroid precursors to spleen & liver 
extramedullary haematopoiesis  hepato-
splenomegaly & poikilocytosis (abnormal RBCs).
• Loss of marrow cells
• Terminal blast crisis
• Life expectancy - 7 years
Treatment
• Supportive
• Marrow stimulation
• +/- Splenectomy (cells being produced are being
destroyed in the spleen remove it to salvage the
few being produced)
3) Essential
thrombocythemia/thrombocytosis
(platelets) - 60% JAK2
Neoplastic proliferation of mature myeloid cells especially
platelets.
Presentation:
• Increased platelet count: 1 million; (normal: 350,000)
• Bleeding/thrombotic abnormalities
• Enlarged spleen
• Enlarged liver
Treatment
• Hydroxyurea
4) Polycythaemia Rubra Vera – 90%
JAK2
Neoplastic proliferation of mature myeloid cells especially
RBCs  increased red cell volume.
Primary Polycythaemia:
• Malignancy of red blood cells
• High Hb and Haematocrit
Secondary Polycythaemia:
• High altitudes
• Congenital Heart Disease
• Tumours (e.g. renal cell carcinoma )
• Erythropoietin production (e.g. renal carcinoma)
Presentation
• Red face (jumping jacks  JAK  red face)
• Thrombotic and haemorrhagic events
• Increased Hb
• Enlarged spleen
• Marrow erythropoiesis
Treatment
1. 1st line: Phlebotomies (older patients): remove excess
cells by removing blood.
2. 2nd line: Hydroxyurea (myelosuppressive treatment)
3. Exclude secondary causes
4. Radiotherapy with 32P isotope.
Prognosis: 50%= 12 year survival (usually terminal with blast
crisis).

8. Investigations
• FBC
• Leukocyte ALK phosphatase (LAP) differentiates CML from other
causes of leucocytosis
• BCR-Abl gene rearrangement
• Uric acid
• JAK2
• BMT – bone marrow trephine (always have to do this)
Myelodysplastic Syndrome
Smouldering neoplastic proliferation of stem cells of bone marrow,
majority terminate after 1-3 years in leukaemia (more aggressive)
occurs in younger ppl
• A pre-leukaemic disorder
• Usually low peripheral cell count with hypercellular marrow
• Often in Myeloproliferative cell neoplasms/disorders you have a
high peripheral cell count and hypercellular marrow 
• Associated with a variety of chromosomal abnormalities
• Diagnosis based on clinical haematological and bone trephine
• May follow previous chemotherapy treatment or may occur de
novo
• Classification of myelodysplasia depends on which cell line shows
the dominant abnormality.
• There are 8 different types
• These are difficult to diagnose and require cytogenetic
studies and correlation between the marrow aspirate and
the FBC etc
• Some will progress into Leukaemia within 2 years