CQAS Meeting 6 November Morphology Session

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CQAS Meeting 6 NovemberMorphology Session

• Jim Murray
• University Hospital Birmingham

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• Whats the difference between a BMS in
  haematology and a BMS in clinical chemistry?
• Whats the difference between Jesus Christ and
  Peter Mandelson?

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• Morphology takes time, is subjective and has less
  impact on diagnosis and management than it used
  to.
• Books have not been replaced by the internet.
• The cinema has not been replaced by videos and
  DVDs.
• Digital morphology will not substitute looking
  down the microscope.

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• A number of clinical scenarios illustrating
  myelodysplasia, chronic myeloproliferative
  disorders and unexplained anaemia will be
  presented to show how morphology complements
  other diagnostic assessments.

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• Unexplained anaemia
• At the age of 14 years a young girl develops
  inflammatory bowel disease and hepatitis. At the
  age of 23 she requires a liver transplant. Seems
  to be doing well but is admitted to hospital with
  a Hb of 4.1g/dl after particularly troublesome
  menorrhagia. Transfused up. Commenced on
  Tranexamic acid, sent home.

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• A month later in the absence of menorrhagia,
  again admitted to hospital with a Hb of 5.3g/dl.
• Normocytic anaemia
• Low reticulocyte count
• Bone marrow performed

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MCQ 1

• A 16-year-old girl with sickle cell disease
  presents to hospital with malaise and rapidly
  increasing dyspnoea. An FBC shows
• Hb 5.1 g/dL
• Reticulocyte count 5.5 x 109/L (25-85)
• What is the most likely cause?
• Epstein-Barr virus
• Hepatitis E virus
• Human immunodeficiency virus
• Human papillomavirus-16 (HPV 16)
• Parvovirus B19

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MCQ 1

• Parvovirus B19 infects RC progenitors in the bone
  marrow, resulting in cessation of haematopoiesis
  and a very rapid drop in Hb
• The condition is usually self-limiting in most
  cases

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MCQ 2

• A 44-year-old woman with type 1 DM has not
  attended the diabetic clinic for 5 years. Her
  HbA1c is 10.1. Examination shows no
  abnormalities.
• Her Hb is 9 g/dL, Hct is 0.28, MCV is 94.
• Blood film normochromic, normocytic anaemia
• Which of the following is the most likely cause?
• acute blood loss
• chronic lymphocytic leukemia
• erythropoietin deficiency
• microangiopathic hemolysis
• sideroblastic anemia

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MCQ 2

• The most likely cause is progressive renal
  failure leading to reduced production of
  erythropoietin by the kidneys
• Sideroblastic anaemia is a form of myelodysplasia
  and usually seen in older patients
• CLL and MAHA are unlikely given the clinical
  scenario

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SLIDE SEMINARCHRONIC MYELOPROLIFERATIVE DISORDERS
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• When youre under pressure and everyones waiting
  for your answer
• The Weakest Link (BBC2)
• Anne Robinson Oscar Wilde, Adolf Hitler and
  Jeffrey Archer have all written books about their
  experience in what prison or the Conservative
  party?
• Contestant The Conservative Party

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• 2.Steve Wright in the afternoon
• (BBC Radio 2)
• Wright Johnny Weismuller died on this day.
  Which jungle-swinging character clad only in a
  loin cloth did he play?
• Contestant Jesus

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• 3. GWR FM (Bristol)
• Presenter What happened in Dallas on November
  22, 1963?
• Contestant I dont know, I wasnt watching it
  then.

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• 4. University Challenge
• Bamber Gascoigne What was Gandhis first name?
• Contestant Goosey?
• 5. Rock FM (Preston)
• Presenter Name a film starring Bob Hoskins that
  is also the name of a famous painting by Leonardo
  da Vinci?
• Contestant Who Framed Roger Rabbit?

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• 6. BBC Norfolk
• Stewart White Who had a worldwide hit with What
  a Wonderful World?
• Contestant I dont know
• White Ill give you some clues. What was Lord
  Mountbattens first name?
• Contestant Louis
• White Correct. And what do you call the part
  between your hand and your elbow?
• Contestant Arm?
• White Correct. If youre not weak, youre?
• Contestant Strong?
• White Well, there we are then. So who had a
  worldwide hit with What a Wonderful World?
• Contestant Frank Sinatra?

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• Case 1
• A 45 year old woman presents with pallor and mild
  jaundice. Following splenectomy her general
  health is much improved. 6 years later she
  becomes transfusion dependent.
• Hb 8.8g/dl, WCC 42 x 109/l, Platelets 55 x 109/l
• You are provided with views of blood film.
• How has her myeloproliferative disease evolved?

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• Discussion
• Original presentation with splenomegaly and
  significant marrow fibrosis. Transfusion
  dependency in 2001 abolished by splenectomy.
  Relatively few tear drop poikilocytes.
• Remains well for 6 years but then redevelops
  transfusion dependency. No change in white cell
  or platelet counts. No real change in blood film
  appearances.
• Trephine biopsy shows dense fibrosis, no evidence
  of leukaemia.

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• Case 2
• A 48 year old man failed his blood donor screen
  and was referred for investigation of a
  normocytic anaemia of 10g/dl. His 14 year old
  daughter had been successfully treated for ALL
  but his elder brother had not survived treatment
  for AML. The patient admitted to weight loss and
  night sweats and had 4cm splenomegaly on
  examination. LDH elevated at 1140u/l (230-460).
• His marrow is essentially a dry tap but karyotype
  proves normal. After several years monitoring he
  becomes transfusion dependent so splenectomy was
  performed. Following splenectomy he develops
  recurrent L pleural effusions and his blood film
  appearances change.

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• Discussion
• Original myelofibrosis. Dense fibrosis in
  marrow, relatively few tear drop poikilocytes in
  blood film.
• Following splenectomy blood film appearances
  change with marked thrombocytosis and circulating
  megakaryoblasts. Patient thought to have
  pulmonary infarction from platelet chunks causing
  pulmonary hypertension.
• Myelofibrosis transformed to megakaryoblastic
  leukaemia.

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• Case 3
• Many patients with chronic myeloproliferative
  disease will have increased numbers of
  megakaryocytes in the marrow. On a trephine
  biopsy they may be associated together in
  clusters. Recently there has been debate on the
  morphological differences in trephine histology
  between cases of primary thrombocythaemia and
  pre-fibrotic myelofibrosis.
• You are provided with 4 views of trephine
  histology 2 show loose clusters and staghorn
  nuclei from a patient with classical PT. The
  other 2 show dysplastic megakaryocytes from a
  pre-fibrotic myelofibrosis.

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SLIDE SEMINARMYELODYSPLASTIC SYNDROMES
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• Case 1
• A 67 year old retired solicitor reports a 6 week
  history of lethargy and dizziness. Routine blood
  count shows a pancytopenia
• Hb 10.5g/dl, WCC 2.4 x 109/l, Platelets 88 x
  109/l
• B12 and folate proves normal.
• The blood film shows striking abnormalities.
• What might you expect the bone marrow to show?

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• Discussion
• Blood film shows striking dimorphic change.
• Bone marrow shows erythroid hyperplasia and
  ringed sideroblasts. Diagnosis of RARS.
• Modest improvement in Hb with EPO and GCSF.

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• Case 2
• A 42 year old rock musician reports dyspnoea on
  exertion, easy bruising and a skin rash.
• Hb 6.0g/dl, WCC 1.4 x 109/l, Platelets 163 x
  109/l
• Cytogenetic analysis of the marrow shows a 3q
  abnormality.
• Does this carry any prognostic significance?

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• Discussion
• Blood film shows hypogranular neutrophils and
  occasional myeloblasts. History consistent with
  a smouldering course before transformation to
  acute myeloid leukaemia.

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• Case 3
• A 5 month old boy has been anaemic from birth and
  has failed to thrive. 2 months after transfusion
  blood tests show
• Hb 8.9g/dl, WCC 12.2 x 109/l, Platelets 617 x
  109/l
• Reticulocytes 86 x 109/l (normal 25-75)
• Hb F 8.6
• Hb A2 2.4
• Ferritin 55µ/l

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Basophilic Stippling Alpha and beta
thalassaemia Lead poisoning Pyrimidine 5
nucleotidase deficiency Congenital
dyserythropoietic anaemias Megaloblastic
anaemia Sideroblastic anaemia Myelodysplasia
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• Macrocytic anaemia
• Haematinic (B12 or folate) deficiency
• Myelodysplasia
• Liver disease
• Hypothyroidism (macrocytosis rather than anaemia)

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• A 34 year old lady with a short history of
  lethargy and bruising.
• WCC 40x 109/l
• Hb 71g/l
• Platelets 24 x 109/l
• Comment on the blood film and give a diagnosis
  and three further tests to confirm your diagnosis.

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• Answers
• B-ALL (L3, Burkitts)
• Further tests
• Bone marrow
• Surface marker studies
• Cytogenetics (814)

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• A 67 year old retired solicitor reported that he
  was unable to play golf and squash to his usual
  level. His GP checked a blood count
• Hb 94g/l
• WCC 2.4 x 109/l
• Comment on the blood film.
• Give 3 useful investigations.

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• Answers
• The blood film shows striking dimorphic
  change
• Occasional red cell fragments and targets
• Occasional Howell-Jolly bodies and tear
  drops.
• Occasional NRBCs. Platelets reduced
• Useful investigations
• 1. Serum ferritin
• 2. Bone marrow examination (iron stain)
• 3. Cytogenetics

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• A 77 year old lady with a previous history of
  hypothyroidism (current TSH normal) complains of
  dyspnoea and lethargy. GP checks FBC and is
  phoned by haematology laboratory with
• Hb 59g/l
• WCC 2.4 x 109/l
• Platelets 49 x 109/l
• Patient refuses hospital referral.
• Examine the blood film and describe the changes.
  
• The GP asks for advice on further investigations.
  Suggest 2.

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• Answer
• Blood film shows Oval macrocytes
• Basophilic stippling
• NRBCs (with stippling)
• Red cell fragments
• Howell-Jolly bodies
• Occasional neutrophil hypersegmentation
• Investigations Serum B12 / folate level
• Intrinsic factor / parietal cell antibody
• or bone marrow

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• A 38 year old West African lady develops a fever
  and arthralgia. FBC shows
• Hb 60g/l
• WCC 6.0 x 109/l
• Platelets 356 x 109/l
• Describe the major changes in the blood film
  
• Give 2 further investigations that would be
  helpful.

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• Answer
• Patient has chronic iron deficiency (MCV 51) and
  Hb C trait
• Any 6 of these
• Numerous target cells
• Microcytosis
• Hypochromasia
• Pencil cells
• Dimorphic change
• Basophilic lymphoid cells
• Giant platelet forms
• Contracted cells/spherocytes
• Investigations Any 2 of these
• Hb electrophoresis
• Serum ferritin
• Or viral/EBV (1)

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• A 29 year old male university lecturer develops
  headaches and cervical lymphadenopathy. FBC
  shows
• Hb 125g/l
• WCC 9.6 x 109/l
• Examine the blood film and describe 3 major
  changes.
• Suggest a diagnosis and a relevant investigation

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• Answer
• Basophilic reactive lymphoid cells
• Smear cells
• Marked thrombocytopenia
• Glandular fever
• Monospot or
• EBV serology

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• A 42 year old male with a short history of
  tiredness and bruising.
• WCC 21.6 x 109/l
• Hb 90g/l
• 1. Comment on the blood film
• 2. What is the likely diagnosis?
• 3. Give 4 investigations you would like to carry
  out

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• Answer
• 1. Hypergranular promyelocytes, with
  cleaved/reniform and binucleate forms
• Thrombocytopenia
• 2. APML with variant features
• APML only
• 3. Bone marrow examination
• Cytogenetics
• PML/RARA screen
• Coagulation screen

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• A 24 year old Caucasian male who has a life
  history of anaemia
• WCC 12.1 x 109/l
• Hb 95g/l
• Plts 658 x 109/l
• 1. Describe the blood film changes
• 2. How would you interpret your findings?

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• Answers
• 1. Macrocytosis/or spherocytes
• Polychromasia
• Echinocytes
• Target cells
• Howell-Jolly bodies
• 2. PK deficiency
• Post splenectomy changes
• Congenital haemolytic anaemia or enzymopathy
  

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Case 1 PB film of a newborn baby girl, LB,
Caucasian, born to non-consanguineous parents,
who presented at 10 days of age with epistaxis.
Peripheral blood cytogenetic analysis was normal.
Bone marrow cytogenetic analysis was not normal.
FBC was WBC 36 x 10?/1, Hb 13.3 g/dl, platelet
count 74x 10?/1
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Case 1
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Case 1
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Case 1
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Case 1 Clear evidence of megakaryocytic
differentiation Is this transient
myeloproliferative disorder or AML M7 in Downs
syndrome? (GATA-1) Is this AML M7 in a neonate
without Downs?
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Case 4 PB film on Mr M.T. A 25-year-old man from
Pakistan who had last visited Pakistan for 3
weeks in December 2003. He presented in late 2004
with intermittent cough associated with shortness
of breath of several months duration. This was
relieved by a steroid inhaler. A CT of chest and
echo cardiography were normal. IgE was normal and
a RAST test for Aspergillus fumigatus was
negative . ANCA had previously been weakly
positive but was negative on referral. FBC was
WBC 36.8 x 10?/ 1, Hb 12.9 g/dl, platelet count
194 x 10?/ 1
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Case 4
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Case 4
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Case 4
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Case 4
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Chronic Eosinophilic Leukaemia Identification of
FIP1L1 PDGFRA fusion gene has led to
reclassification of cases previously diagnosed as
idiopathic HES and indicates responsiveness to
imatinib. 8p11 Syndrome FGFR1 Fusion gene t (5
12) CML PDGFRB Fusion Gene Monocytes usually
prominent in film
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Marked Eosinophilia Reactive, Leukaemic or
idiopathic? The eosinophilia is reactive in
Hodgkins disease, T-cell lymphoma, parasitic
infections and drug allergies. Some myeloid
neoplasms may have an eosinophil population that
is reactive rather than clonal. Previously any
patients with striking eosinophilia have
incorrectly been diagnosed as idiopathic
hypereosinophilic syndrome (HES). Idiopathic HES
is a diagnosis of exclusion whereas eosinophilic
leukaemia requires positive identification of
leukaemic features, such as increased blast cells
or evidence of clonality.
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Case Report 80-year-old lady with eosinophil
count of 50 x 10?/1 found to have t (5 12).
Responded to 100mg imatinib, but negative for TEL
PDGFRB. Professor Nick Cross We find this
with about half of t (5 12) samples and the
pathogenic event in these cases is believed to be
via over expression of IL 3 rather than
anything involving PDGFRB. Cools et al Blood
2002 99 1776 84 So why did she respond to
imatinib? And why does PDGFRA negative HES
respond?
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Case 5

• An 18 year old female presenting with vulva
  ulcers
• Hb 55 g/L
• WCC 9.1 x 109/L
• Pts 10 x 109/L

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Case 5 features

• Vacuolation
• Neutrophils, lymphocytes, monocytes
• Partial degranulation
• Eosinophils, neutrophils
• Howell-Jolly Body-like inclusions
• neutrophils
• Thrombocytopenia, occ giant platelets
• Anaemia, rouleaux, anisopoikilocytosis, occ HJB

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Case 5 diagnosis

• Myelodysplasia of HIV infection

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Friedreich NietzscheSleeping is no mean
art.For its sake one must stay awake all
day.Jewish proverbSleep faster. We need the
pillows
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Cymbeline

• Weariness
• Can snore upon the flint, when resty sloth
• Finds the down pillow hard

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A Midsummer Nights Dream

• If we shadows have offended
• Think but this, and all is mended
• That you have but slumbered here,
• While these visions did appear.