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HEMATOLOGICAL
MALIGNANCIES
CREATED BY -
HEMATOLOGICAL
MALIGNANCIES
Abnormal monoclonal replication of WBC precursors
Leukemias are neoplastic cells in blood while lymphomas are solid tumors in lymph
nodes. You can imagine it being water (leukemia) and ice (lymphoma)
Leukemia can have a lymphoma component (eg CLL has SLL) while lymphomas can
have a leukemic component.
CD markers
CD34(+) = Blast
CD3(+) = T-cell
CD19(+) = B-cell
CD33(+) = Myeloid
CD34(+) = Acute leukemia
CD34(+) CD19(+) = B-ALL
CD34(+) CD3(+) = T-ALL
CD34(+) CD33(+) = AML
CD34(-) CD33(+) = APL (promyelocyte differentiated one step above blast)
MNEMONIC:
T cell markers are all < 10.
B cell markers hang around 20 (19,20,22).
Myeloid/monos are in the teens (13,14,15,16).
13 and 33 are myeloid (Both have 3's)
123456 for Blastic Plasmacytoid Dendritic Cell Neoplasm BPDCN (CD123, CD4, CD56)
Medicine
HEMATOLOGICAL
MALIGNANCIES
ACUTE LEUKEMIA
Neoplastic proliferation of blasts.
Defined as the accumulation of >20% blast cells in bone marrow
Blast cells usually enter the blood stream, resulting in a high WBC count.
(Blasts are large, immature cells often with punched out nucleus)
Acute leukemia is classified into:
(a) Acute Lymphoblastic leukemia (ALL)
(b) Acute myelogenous Leukemia (AML)
ALL AML
Acute lymphoblastic leukemia are Acute myeloblastic leukemia are
neoplasms composed of neoplasms composed of immature
immature B or T lymphocytes myeloid cells known as myeloblasts
(lymphoblasts have marker TdT+) (myeloblasts stain positive with MPO -
This presents earlier in life myeloperoxidase)
(childhood) This presents later in life : 50-60yrs
Associated with Down's Syndrome Most often happens due to mutations
Further classified into in genes.
Further classified into
Clinical features
ALL and AML are aggressive diseases and most patients present within a few
weeks of onset of symptoms.
Symptoms due to bone marrow depression include - Bleeding due to
thrombocytopenia, fatigue due to anaemia and infections due to leucopenia.
Due to neoplastic infiltration there can be lymphadenopathy, bone pain and
hepatosplenomegaly.
If CNS is involved it can cause headache, vomiting and nerve palsies.
Treatment
Induction phase - High dose chemotherapy (Supresses all cell lines - leads to
Pancytopenia and infections) - supportive therapy with RBC, platelets and
myeloid growth factors
On remission : Consolidation therapy
Medicine
HEMATOLOGICAL
MALIGNANCIES
CHRONIC LEUKEMIA
Monoclonal disorder of "late" haematopoetic cells.
The neoplastic cells are smaller (morphologically mature) but not
functionally mature.
Blast cells in bone marrow are less <10%
Onset is insidious and has subacute presentation.
Chronic leukemia is classified into:
(a) Chronic Lymphoblastic leukemia (CLL)
(b) Chronic myelogenous Leukemia (CML)
CLL CML
Clinical features
CML often presents with non-specific symptoms like fatigue, weight loss and
night sweats.
The hallmark feature of CLL is lymphadenopathy due to the infiltration of
malignant B lymphocytes.
Treatment
Tyrosine kinase inhibitors (TKI's) are central to the treatment of CML. (Imatinib,
dasatinib, nilotinib)
In CML along with TKIs, chemotherapy and allogeneic stem cell transplantation
can be considered
CLL has various treatment modalities which are decided based on patient's
individual status. Treatment options include Chemotherapy, pharmacotherapy,
HSCT.
Medicine
HEMATOLOGICAL
MALIGNANCIES
LYMPHOMA
Lymphoma is a haematological malignancy with solid tumors arising from
lymphoid tissue (Cervical lymph nodes are most common)
They are commonly categorised as Hodgkin or Non-Hodgkin lymphoma
*General Features :
Nodal + Extra-nodal involvement
GIT is the m/c extra-nodal site followed by skin.
CNS is the m/c extra nodal site in HIV patients.
Constitutional B Cell symptoms (Fever, Night sweats, Weight loss)
Some lymphomas lead to "compression syndromes" - obstruction of airway, major
vessels, GIT, Spinal cord
Some lymphomas produce too much IgM - leads to hyperviscosity of blood and
autoimmune hemolytic anemias.
Some lymphomas lead to agammaglobulinemia (No IgM production) leading to
infections.
NHL is the 2nd most common cancer in HIV patients (one of the AIDS defining
malignancies)
Has an overt leukemic phase (cancer cells found in blood)
*Risk factors :
Age > 60
Viruses
EBV - Burkitt's, DLBCL, Primary CNS Lymphoma
Hepatitis - C Virus : B cell lymphoma
HTLV-1 - T cell lymphoma
HIV
HHV 8 - Primary Effusion Lymphoma (causes pulmonary effusions)
Autoimmune
Sjogrens syndrome - Salivatory and GI lymphomas
Hashimotos thyroiditis - Thyroid lymphoma
Immunodeficiency (Post transplant and congenital immunodeficiency)
Radiation exposure (used to treat HODGKIN'S lymhoma) - Causes NHL
H-Pylori -Maltoma
Medicine
HEMATOLOGICAL
MALIGNANCIES
Diagnosis.
Excisional biopsy - Cell appearance and lymph node architecture viewed
Immunotyping : CD-20 positive
Serum LDH levels
CBC - Do a bone marrow biopsy if cytopenia present
Uric acid levels
For staging: PET CT
Treatment.
Chemo regime - "R CHOP"
Localised DLBCL - 3 chemo cycles + radiation
Advanced DLBCL - 6 to 8 chemo cycles
For CNS Lymphomas - Chemo / Methotrexate + Cortico-Steroids ( non surgical)
Almost all patients respond to treatment
In refractory cases or recurrence - Chemo again (HSCT in young patients)
Pathogenesis. t(8:14)
In chromosome 8 there's a gene known as MYC gene which promotes cell
proliferation and inhibits differentiation.
This gene when breaks from chromosome 8 and is translocated to chromosome 14
leads to very strong expression of this gene which leads to cancerous pathology.
The gene coding for heavy chain of IgG from chromosome 14 is translocated to
chromosome 8 making it "reciprocal translocation".
Such genes which lead to
cancer when triggered are
called proto oncogenes.
Hence, MYC gene is a proto
oncogene.
Diagnosis.
Excisional biopsy - "Starry sky appearance"
Immunotyping : IgM, HLA-DR, CD-43, B cell
antigens (CD 19, CD 20, CD 22)
Serum LDH levels high Stars - Macrophages (histiocytes
CBC - Do a bone marrow biopsy if cytopenia clearing dead cells)
Sky - Background of neoplastic cells
present with 3-4 nucleoli. The cells are tightly
Uric acid levels high packed giving a blue sky like
appearance
High mitotic index (to differentiate from DLBCL)
For staging: PET CT
Treatment.
Treatment has to start within first 48 hours of diagnosis
Any intensive Chemotherapy regime that includes Cyclophosphamide
Management of tumor lysis syndrome - Fluids + Allopurinol
For CNS prophylaxis - Intrathecal chemo
Medicine
&CHARTS
X-RAYS
Paracortex
(has T cells)
Mantle zone (betwen germinal center and margin)
Margin zone
(has B cells)
Mantle is in the cortex which has B cells, hence Mantle cell lymphomas are B cell
lymphomas.
Rare form of NHL
Aggressive but less than DLBCL.
Median age 60 and male > female
Palpable painless lymphadenopathy + B cell constitutional symptoms
GIT involvement is common
Leukemic phase can be present.
Pathogenesis t(11:14)
In chromosome 11 there's a gene known as BCL-1 gene which codes for the
protein "Cyclin D1" which is a crucial protein for cell cycle regulation
This gene when breaks from chromosome 11 and is translocated to chromosome
14 leads to very strong expression of this gene which leads to cancerous
pathology.
There is over expression of cyclin-D1
Diagnosis.
Core needle biopsy/excisional biopsy - Malignant cells in the mantle region
Immunotyping : CD-5 (+), CD-23 (-), B cell antigens (CD 19, CD 20, CD 22)
CBC - Do a bone marrow biopsy if cytopenia present
For staging: PET CT
Treatment.
Chemo regime - "Hyper CVAD" + Rituxemab
Localised disease - Combination chemo + radiation
Advanced disease - aggressive combination chemo + HSCT
For CNS Lymphomas - Chemo / Methotrexate + Cortico-Steroids ( non surgical)
Almost all patients respond to treatment
In refractory cases or recurrence - Chemo again (HSCT in young patients)
Medicine
&CHARTS
X-RAYS
Paracortex
(has T cells)
Mantle zone (betwen germinal center and margin)
Margin zone
(has B cells)
Marginal zone is in the cortex which has B cells, hence marginal cell lymphomas are
B cell lymphomas.
Indolent NHL ( non aggressive )
Could be nodal or MALT associated (maltoma) or splenic
Median age 60 years
Nodal Lymphomas will have painless palpable lymphadenopathy while extra-nodal
→
organs involved will have respective symptoms. (Lungs Cough, Glands →mass)
B cell constitutional symptoms
Leukemic phase can be present
Can transform into DLBCL
Risk factors
Sjogrens syndrome - Salivary gland MALToma
Hashimotos thyroiditis - Thyroid MALToma
H Pylori - Gastric MALToma
Borrelia burgdorferi (Lyme disease spirochete) : Cutaneous MALToma
Hepatitis C virus - Splenic MALToma
Chlamydia Psittaci - Conjunctivitis - Ocular MALToma
Diagnosis.
Biopsy of lymph node/respective organ tissue - Malignant cells in the marginal
region of lymph nodes
Immunotyping : B cell antigens (CD 19, CD 20, CD 22) +
Associated with BCL-2 gene mutation
↑LDH
↑β² microglobulin
CBC - bone marrow biopsy if neutropenia is present
For staging: PET CT
Gastric MALToma - Stool sample for H pylori testing
Treatment.
Prognosis is very good
No symptoms - no treatment (wait and watch)
Treat the infections (Hep c , H Pylori)
For Splenic MALToma splenectomy can be done
Medicine
&CHARTS
X-RAYS
Follicle
Paracortex
(has T cells)
Mantle zone (betwen germinal center and margin)
Margin zone
(has B cells)
Diagnosis.
Excisional biopsy - Malignant cells lined in follicular pattern
Immunotyping : B cell antigens (CD 19, CD 20, CD 22) +
Associated with BCL-2 gene mutation
CBC - bone marrow biopsy if neutropenia is present
For staging: PET CT
Treatment.
Prognosis is very good
No symptoms - no treatment (wait and watch)
Rituxemab can be used- monoclonal antibody against CD-20
Medicine
&CHARTS
X-RAYS
Pathogenesis.
BRAF V600E mutation : This results in uncontrolled cell division and growth, which
can lead to cancer.
"Reticulin fibres" deposited inside bone marrow leads to cytopenia.
There is splenic sequestration as well which highlights the cytopenia
Features.
Lethargy and pale appearance - Anaemia
Infections - Leukopenia
Bleeding -Thrombocytopenia
Hepatospleenomegaly
Lymphadenopathy (there can be no lymphadenopathy in 10% cases)
Diagnosis.
Peripheral smear : Lymphocytes with hairy projections (TRAP stain positive)
Immunotyping: CD-103, CD-11c, CD-25, B cell markers (CD-19,20,22)
"Dry tap" on bone marrow aspiration
Treatment.
Prognosis is very good
Cladribine (Purine analogue) shows dramatic response.
VRAF inhibitor - Vemurafinib
Spleenectomy
Medicine
&CHARTS
X-RAYS
Pathogenesis.
13q deletion : Good prognosis
11q or 17q deletion - Bad prognosis
Diagnosis.
Peripheral smear : "Smudge cells"
Lymphadenopathy
Hepatosplenomegaly
↑
CBC: Lymphocytosis, Reticulocytes
Immunotyping : CD-5, CD-23, B cell markers (CD 19,20,22)
Treatment.
Early stage : No treatment (follow up)
Symptomatic disease : Combination chemotherapy
Steroids for autoimmune hemolytic anemia
For local lymphadenopathy - Radiation
HSCT is last resort
Splenectomy for spleenomegaly
Diagnosis.
*Serology
Antibodies against HTLV-1
*CBC
WBC count - 10,000 to 50,000
RBC - Normocytic anaemia
Platelets - Thrombocytopenia
*Immunotyping
Lymphoblasts: CD-4(+) and TdT (-)
*Peripheral smear
Flower cells " Cells with indenting nucleus"
Treatment.
Zidovudine
Arsenic Trioxide
Chemotherapy regime : CHOP
An exceedingly rare
*General Features : condition accounting for
Nodal + Extra-nodal involvement around 5% of HL.
GIT is the m/c extra-nodal site followed by skin. It is characterised by the
CNS is the m/c extra nodal site in HIV patients. lymphohistiocytic Reed-
Constitutional B Cell symptoms (Fever, Night sweats, Weight
Sternberg loss)
variant.
Some lymphomas lead to "compression syndromes" - obstruction of airway, major
vessels, GIT, Spinal cord
Some lymphomas produce too much IgM - leads to hyperviscosity of blood and
autoimmune hemolytic anemias.
CLASSICAL
Some lymphomas lead to agammaglobulinemia (No IgM production) leading to
The four ‘classical’ forms of HL (cHL) account for around 95% of cases of HL. There
infections.
are
NHLfour subtypes:
is the 2nd most common cancer in HIV patients (one of the AIDS defining
Nodular sclerosis: Most common subtype, accounts for around 70% of cHL.
malignancies)
HasMixed cellularity:
an overt leukemic Accounts for around
phase (cancer cells20% of in
found cHL.
blood)
Lymphocyte-rich: Accounts for around 5% of cHL. Has the best prognosis.
Lymphocyte-depleted:
*Risk factors : Rare, accounting for <1% of cHL. Has the the worst
prognosis.
Medicine
HEMATOLOGICAL
MALIGNANCIES
LYMPHOMA
CLINICAL FEATURES
Lymphoma is a haematological
Lymphadenopathy: malignancy
Typically painless, with solidlymph
firm, enlarged tumorsnodes,
arising most
from
lymphoid found
commonly tissue (Cervical lymph nodes are most common)
in the neck.
‘B’ They are commonly
symptoms: categorised
‘B’ symptoms referas
toHodgkin or Non-Hodgkin
fever, night sweats and lymphoma
weight loss
(unexplained, >10% in 6 months).
HODGKIN'S
Mediastinal mass:LYMPHOMA
May be incidental finding NON HODGKIN'S
on chest imagingLYMPHOMA
or present with
shortness of breath,
Nodal tumors (onlycough,
in lymphpain or superior vena
More cava obstruction.
common
nodes)
Pruritis Nodal + Extra-nodal
Local spread (contagious spread
Hepatosplenomegaly Because of extra nodal nature it has
from one cell to next)
Malaise constitutional B cell symptoms (fever,
Presence of "Reed Sternberg cell"
Fatigue weight loss, night sweats) and
(large, abnormal lymphocytes that hepatosplenomegaly
DIAGNOSIS
may contain more than one B cell lymphomas (70%) and T cell
nucleus) lymphomas (30%)
Excision biopsy of affected lymph nodes is normally required in patients with
B cell lymphomas are further graded
suspected cHL.
cHL is diagnosed following biopsy and immunophenotyping of HRS cells.
PET/CT is the preferred imaging modality for staging disease.
Low grade Intermediate grade High grade
The Lugano staging system is used to classify HL.
Follicular lymphoma Mantle zone Diffuse large B cell
MANAGEMENT
Small lymphocytic lymphoma lymphoma (DLBCL)
leukemia (SLL) / CLL Marginalare
zone Burkitt's lymphoma
Chemotherapy and radiotherapy the mainstay of management in patients
lymphoma (maltomas)
with cHL.
The management of cHL is complex and depends on the Lugano staging and
other prognostic markers
PROGNOSIS
Overall cHL has a reasonably good prognosis.
Limited disease: Of those with stage I and II disease, 90% survive 5 years.
Advanced disease: Of those with stage III and IV disease, 75-90% survive 5 years.
*General Features :
Medicine
HEMATOLOGICAL
MALIGNANCIES
MULTIPLE MYELOMA
Multiple myeloma (MM) is the second most common haematological malignancy.
It is characterised by excess secretion of a monoclonal antibody.
We term it a monoclonal antibody, because it is derived from a single clone of
plasma cells that have undergone malignant proliferation.
CLINICAL PRESENTATION
The clinical presentation of MM is generally related to the infiltration of plasma cells
and secretion of monoclonal antibodies.
Patients with MM may have constitutional features of malignancy including weight
loss, fatigue, loss of appetite and/or generalised weakness.
There are a number of typical clinical presentations that relate to the excess
proliferation and infiltration of plasma cells (usually in bone marrow) and the excess
secretion of monoclonal antibodies.
These key clinical features of MM can be remembered using the mnemonic ‘CRAB’.
C - calcium levels high
R - renal impairment
A - anaemia
B - bone disease
Bone disease: widespread due to clonal proliferation in bone marrow. Seen as
lytic lesions on imaging. Can lead to fractures.
Impaired renal function: >50% have raised creatinine at diagnosis. Kidneys
affected in multiple ways. Commonly due to light chain nephropathy (tubules
blocked by light chain casts).
Anaemia: seen in >90% at some point during disease course. Normal bone
marrow destroyed by proliferation of malignant plasma cells. Renal disease may
contribute (EPO deficiency).
Hypercalcaemia: MM-induced bone demineralisation. More common in active
disease. At high levels (≥ 2.9 mmol/L) should be treated as a medical emergency
Other syndromes
Hyperviscosity syndrome: may develop with high paraprotein levels (i.e. high IgA
or IgG). Typical symptoms include blurred vision, headaches, mucosal bleeding
and dyspnoea due to heart failure. Requires urgent plasma exchange.
Spinal cord compression: can occur in 5% of patients during course of disease.
Highly variable depending on lesion causing compression, location, and rate of
development.
Diagnosis
Diagnosis of MM involves identifying a monoclonal antibody, bone marrow
analysis and assessing organ damage.
Management
MM is an incurable condition, treatments aim to increase periods of disease
remission.
Myeloma is associated with a number of complications, which require further
management.
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