Malignancy Flashcards
Haematological malignancy can be classed based on:
lineage
developmental stage within lineage
anatomical site involved
Lineage of malignancy can be
myeloid or lymphoid
Developmental stage of malignancy can be
acute myeloblastic/ lymphoblastic (EARLY DEVELOPMENTAL STAGE)
chronic myeloid/ lymphocytic (LATE DEVELOPMENTAL STAGE)
Anatomical site of malignancy can be
blood involvement- LEUKAEMIA
lymph node involvement with lymphoid malignancy - LYMPHOMA
____________ and ____________ are histologically and usually clinically more aggressive than chronic leukaemia and low grade lymphomas
acute leukaemia and high grade lymphomas
Features of histological aggression?
large cells with high nuclear-cytoplasmic ratio
prominent nucleoli
rapid proliferation
Feature of clinical aggression?
rapid progression of symptoms
Acute leukaemia present with ________
failure of normal marrow function
Explain what leukaemia is?
primary malignant tumours of haemopoietic cells
neoplastic haemopoietic cells fill the marrow including long bones and there is spill over of abnormal cells into the blood
What is the marrow cellularity like in leukaemia?
high marrow cellularity
Explain the clinical presentation of leukaemia?
blast cells are taking over marrow so get ineffective haemopoiesis and deficiency in other parts of the blood
deficiency of red cells > anaemia
deficiency of platelets > thrombocytopenia
deficiency of white cells > infection
Describe the spread of leukaemia?
leukaemia cells circulate in the blood and/ or lymph and can therefore spread anywhere in the body
nodular deposits are however uncommon
after initially successful treatment, leukaemia infiltration may recur especially in the CNS (meninges) and the testis
What are the four main leukaemias?
acute myeloblastic leukaemia
acute lymphoblastic leukaemia
chronic myeloid leukaemia
chronic lymphocytic leukaemia
What is the aetiology of leukaemia?
in most cases the cause is unknown but risk factors include:
radiation
chemicals e.g. chemo, benzene
genetics
virus e.g. human T cell leukaemia virus 1
Describe the features of acute leukaemia?
rapidly progressive clonal malignancy of the marrow/ blood with maturation defects
defined as an excess of blasts ( > 20%) in either peripheral blood or bone marrow
decrease/ loss of haemopoietic reserve
What is the most common childhood cancer?
acute lymphoblastic leukaemia
Which acute leukaemia is mainly adults and which is mainly children?
children: acute lymphoblastic leukaemia
adults: acute myeloid leukaemia
What is ALL?
malignant disease of primitive lymphoid cells (lymphoblasts)
Clinical presentation of ALL?
symptoms of marrow failure:
anaemia - pallor, fatigue, breathlessness, faintness
infections
bleeding- failure of primary haemostasis due to thrombocytopenia, mucosal bleeding, easy bruising
bone pain
more common in ALL than other leukaemia to get CNS and testis involvement
Marrow is packed with blast cells and blood shows presence of blast cells?
acute leukaemia
What is required for definitive diagnosis of leukaemia?
immunophenotyping
What may FBC show in acute leukaemia?
low Hb, neutrophils and platelets
WCC may be raised because there are lots of blast cells
What is AML?
malignant disease of primitive myeloid cells (myeloblasts)
Who is AML more common in?
elderly (> 60 yo)
AML can occur de novo or?
secondary due to treatment of other cancer
Presentation of AML?
similar to ALL
there are certain subgroups though with characteristic presentations
Auer rods?
AML
What is chronic lymphocytic leukaemia?
cancer with monoclonal proliferation of small lymphocytes (the leukaemia form of lymphocytic lymphoma)
most cases are B cell type
Presentation of chronic lymphocytic leukaemia?
presents more slowly
anaemia, recurrent infections and can also get swollen lymph nodes
Treatment of chronic vs acute leukaemia?
acute tends to be more treatable
but chronic is less treatable but people live for years with it and people can die with the cancer not of the cancer
Curative treatment of acute leukaemia involves?
multi-agent chemotherapy
If someone getting chemo for leukaemia has neutropenic fever ______
they need empirical treatment with broad spectrum antibiotics
When should you suspect fungal infection in someone on chemo for leukaemia?
prolonged neutropenia and persisting fever unresponsive to anti-bacterial agents
Prognosis of acute leukaemia?
many patients will go into remission (< 5% blasts with recovery of normal haemopoiesis)
unfortunately remissions may not be durable depending on the type of acute leukaemia and many patients will relapse
some patient will die of treatment related toxicity
childhood leukaemia has higher cure rates (ALL)
2 main categories of lymphadenopathy?
reactive hyperplasia (should cease when stimulus stops) neoplastic (no stimulus)
What are the causes of reactive hyperplasia lymphadenopathy?
infection by bacteria or virus
immune stimulation e.g. RA
drugs
particulate material e.g. carbon breathed into the lungs causing a reaction
What are the two causes of neoplastic lymphadenopathy?
primary lymphoid tumours
secondary metastatic cancer spread
What types of lymphadenopathy would cause tender lymph nodes?
viral and bacterial
What types of lymphadenopathy would cause non-tender lymph nodes?
lymphoma and metastatic cancer
What will the consistency of lymph nodes in bacterial or viral infection be like?
firm
What will the consistency of lymph nodes in lymphoma be like?
rubbery/ soft
What will the consistency of lymph nodes in metastatic cancer be like?
hard
What types of lymphadenopathy will have smooth lymph nodes?
bacterial and viral infection
lymphoma
What types of lymphadenopathy will have irregular lymph nodes?
metastatic cancer
What type of lymphadenopathy will have skin inflammation?
bacterial
Are lymph nodes tethered in viral infection?
no
Are lymph nodes tethered in bacterial infection?
sometimes
Are lymph nodes tethered in lymphoma?
no
Are lymph nodes tethered in metastatic cancer?
yes
What is lymphoma?
malignant tumours derived from lymphoid cells, may arise within the lymph nodes or at other sites (extra nodal)
Describe what 2 groups are lymphomas classically divided into?
Hodgkin 20-25%
- almost always lymph node origin
- characterised by presence of Reed-Sternberg cells
Non-Hodgkins 75-80%
- 3/4 arise in lymph nodes
- 90% are B cell and B cell is usually low grade and T cell high grade
Risk factors for lymphoma?
none may be present
immunosuppression e.g. HIV, inherited immunodeficiency states
auto-immune disorders e.g. Sjrogens, coeliacs
infections e.g. EBV, H. pylori, HHV-8, HTLV-1
genetic predisposition
environmental factors
Reed Sternberg cell?
hodgkin lymphoma
Peak incidence in hodgkin lymphoma is in?
3rd decade
Spread to lymph nodes in hodgkin lymphoma is____
orderly
Treatment of hodgkin lymphoma is?
multi agent chemo +/- radio
Bleomycin used in treatment of hodgkin lymphoma can cause
pneumonitis
What is the cure rate of hodgkin lymphoma like?
good cure rates, particularly in younger patients
What are the risks of intensive treatment in hodgkin lymphoma?
long term toxicity, including secondary cancers, CVS disease, infertility
What is an option for patients with hodgkin lymphoma not responding to chemo?
immunotherapy/ stem cell transplantation
What is a common high grade non hodgkin lymphoma?
diffuse large B cell lymphoma
Is extra nodal disease common in non hodgkin lymphoma?
yes more so that hodgkins
particularly in T cell NHL, Burkitt lymphoma
Treatment of non-hodgkin lymphoma?
multi agent chemo +/- radio
can also do monoclonal Ab therapy + chemo
e.g. ritixumab for B cell and brentuximab for T cell
Is non hodgkin lymphoma curable?
high grade NHL is potentially curable
low grade is incurable but many patients may not need treatment
What is an option for non hodgkin lymphoma patients failing chemo?
high dose therapy with autologous stem cell rescue or CART therapy
What is the fastest growing human tumour?
Burkitt lymphoma (a type of non hodgkin lymphoma)
What does Burkitt lymphoma have a relationship with?
EBV
Where is Burkitt lymphoma more common?
equatorial africa, new guinea and other malaria endemic areas
Chromosomal translocations involving c-myc gene?
Burkitt lymphoma
Cure rate of Burkitt lymphoma?
has a high cure rate in high income countries
What is meant by B symptoms?
Used in Ann Arbor staging
if someone has lymphadenopathy and absence of symptoms write A
if someone has some of the systemic symptoms listed it is denoted with a B
List the B symptoms of lymphoma?
fever or
night sweats or
weight loss (unintentional 10% over 6 month period)
What are some other symptoms of lymphoma that are not B symptoms?
itch without rash
alcohol induced pain of lymph nodes
symptoms relevant to compression > renal failure, SVC obstruction, effusions, marrow failure
What is often increased in lymphoma?
LDH
What type of biopsy is best for lymphoma?
FNA and core biopsy are often insufficient
excision biopsy is best
What is the role of steroids in treatment of lymphoma?
lymphocytes are normally sensitive to steroid therapy and some lymphomas are exquisitely sensitive
steroids are an integral part of multi-agent chemo regimens for routine treatment of lymphoma
steroids can be used in emergency management of suspected lymphoma but starting steroid before biopsy can cause cell necrosis and distort cellular and tissue architecture confusing the diagnosis
What do smudge cells suggest?
chronic lymphocytic leukaemia
the lymphocytes are fragile so break more easily when being prepared for the blood film
What can cause atypical lymphocytes?
generally viral infections
EBV is the main one
(COVID can cause it too)
Offer an urgent FBC (within 48 hours) for? (7)
Anyone presenting with unexplained:
- pallor
-fatigue
- generalised lympahdenopathy
- persistent infections
-bone pain
-bruising
-bleeding
Children with what should be sent for immediate specialist referral due to chance of leukaemia?
unexplained petechiae or hepatosplenomegaly
