Primary myelofibrosis

1. Dr. B.V.Vydehi M.D
PROFESSOR OF PATHOLOGY
NARAYANA MEDICAL COLLEGE,NELLORE
Primary Myelofibrosis

2. PMF - Synonyms
• Idiopathic myelofibrosis
• Osteomyelofibrosis
• Agnogenic myeloid metaplasia
• Myelofibrosis with myeloid metaplasia
(MMM)

3. Primary Myelofibrosis
• Characterized by rapid development of
obliterative marrow fibrosis
• M.F suppresses BM hematopoiesis → PB
cytopenias & extensive neoplasitc
extramedullary hematopoieis in spleen,
liver & lymphnodes

4. Primary Myelofibrosis - Pathophysiology
• Marrow fibrosis is due to
inappropriate release of
fibrogenic factors (PDGF &
TGF-β) from neoplastic
megakaryocytes

5. Reticulin content of marrow is graded as follows
(Banner meister 1971)
Grade ‘0’ Normal-around blood vessels only
Grade ‘I’ Mild increase – Occasional few individual
fibres & foci of fine fibre network between the
Sinusoids
Grade ‘II’ Moderate increase – Fine fibres thr out most
of the section; no coarse fibres
Grade ‘III’ Marked increase –Diffuse fine network with
some coarse fibres; no collagen
Grade ‘IV’ Diffuse coarse fibres with areas of
collagenization (Masson – Positive)
Bone Marrow Reticulin & Fibrosis

6. Grade – 0 Grade – 1

7. Grade – 4
Grade – 3
Grade – 2

8. Myelofibrosis : Increased marrow fibrosis tissue
Fibrosis is of 2 types 1.Reticulin fibrosis
2.Collagenous fibrosis
Collagenous fibrosis represents a later stage of
fibrosis in which collagen fibres appear as a
confluent, eosinophilic matrix seen on H & E &
Trichrome staining

9. PMF – Bone marrow
Cellular phase :
• Initially hyper cellular with  in maturing cells of
all lineages
• Megakaryocytes are large, dysplastic &
abnormally clustered
•  Micromegakaryocytes & bare M.K.nuclei
• Fibrosis – Minimal
Fibrotic :  Hemopoietic precursors
- Diffuse fibrosis
- Clusters of megakaryocytes +
Very late in disease coarse, fibrotic marrow space
converts to bone → Osteosclerosis

10. PMP– Peripheral Blood
• N/N anemia
• Cellular phase – marked leucocytosis
(80000 to 1 lakh /cumm) with
leucoerythroblastosis
• Teardrop erythrocytes (Dacrocytes) –
characterstic
• Basophilia
• Early stages – Platelets may be normal or
elevated with large sized platelets
progressive disease - Thrombocytopenia

11. PMF – Clinical Features
• Median age at diagnosis : 60 yrs
• Familial form has been reported
• Wt loss, Bleeding, Splenic Pain, Jaundice
etc.,
• Hepatosplenomegaly (> 50% of cases)

12. Diagnostic Criteria for PMF –WHO-2008
Major criterion 1:
Megakaryocyte proliferation and atypia (small to
large megakaryocytes with dense clustering, an
aberrant N/C ratio and hyperchromatic and
irregularly folded nuclei, often described as ‘cloud-
like’ or ‘balloon-shaped’) accompanied by either
reticulum or collagen fibrosis OR
In the absence of reticulin fibrosis, the
megakaryocyte changes must be accompanied by
increased marrow cellularity, granulocytic
proliferation and often decreased erythropoiesis (i.e.
pre-fibrotic PMF)

13. Major criterion 2:
Not meeting WHO criteria for CML, PV, MDS or other myeloid
neoplasm
Major criterion 3:
Demonstrationof JAK2 V617F or other clonal marker (MPL W515K/L)
or no evidence of reactive marrow fibrosis

14. Minor criterion 1: leukoerythroblastosis
Minor criterion 2: increased serum LDH
Minor criterion 3: anemia
Minor criterion 4: palpable splenomegaly
Criteria essential for diagnosis :
•All 3 major criteria + any two minor criteria
Diagnostic Criteria for PMF

15. Hyper cellular Phase
ExcessMegakaryocytes

17. Fibrotic Phase - Intrasinusoidal
Hematopoiesis

20. Symptoms Thrombotic Mass ABD * Plethora/HTN
Cytopenia Negative Maybe ± Negative
Cytosis Yes Yes * Yes
Leucoerythroblasts Negative Positive * Negative
Splenomegaly Mild ± Mod-Severe Mild – Mod
Marrow aspirate Possible Dry tap * Possible
Marrow cellularity   / * 
Megakaryocytes in number
Morph:N
/Dysmorphic *
Mostly in clusters
 ii/Dysmorphic
Fibrosis Minimal /
Absent
Diffuse / Mod*-
Severe
Minimal / absent
Terminal Fibrosis/AML AML Hyperuricemia
/Gout/AML
ET IMF PRV