Chronic Myeloid Neoplasms
Myeloproliferative neoplasms (MPN)
Polycythemia vera

Author: Nikhil Sangle, M.D. (see Authors page)

Revised: 8 March 2017, last major update August 2011

Copyright: (c) 2002-2017, PathologyOutlines.com, Inc.

PubMed Search: Polycythemia vera [title]

Cite this page: Polycythemia vera. PathologyOutlines.com website. http://pathologyoutlines.com/topic/myeloproliferativePV.html. Accessed June 25th, 2017.
Clinical features
  • Also called polycythemia rubra vera
  • Clonal, neoplastic proliferation of multipotent myeloid stem cells (panmyelosis)
  • RBC production increases independent of the mechanisms that normally regulate erythropoiesis
  • Prevalence of 2 - 3 per million (Am J Hematol 2008;83:359)
  • Median age 60 years, uncommon in children
  • Etiology unknown
  • Genetic predisposition reported by some
  • 3 clinical phases:
    1. pre-polycythemic (previously called latent PV) with borderline increase in RBC mass
    2. overt polycythemic with significant RBC increase; and
    3. "spent" or post-polycythemic with ineffective hematopoiesis, marrow fibrosis, extramedullary hematopoiesis causing splenomegaly, and peripheral cytopenia
  • Most symptoms are due to polycythemia (increased hematocrit) with associated increased total blood volume, vascular distention and stasis; mild hepatosplenomegaly due to extramedullary hematopoiesis
  • Patients are plethoric, cyanotic and hypertensive with headache, dizziness, gastrointestinal symptoms, pruritis or ulcers, possibly from basophilic histamine
  • May have hyperuricemia or gout due to increased cell turnover
  • 25% have thrombotic episodes (stroke, deep venous thrombosis, myocardial infarction) due to abnormal blood flow and possibly abnormal platelet function; also Budd-Chiari syndrome (hepatic vein thrombosis), bowel infarction, hemorrhagic strokes due to thrombosis of venous sinuses of brain, life threatening hemorrhage in 10%
  • May have iron deficiency due to bleeding, which corrects the hematocrit to normal
Diagnosis
WHO 2008
  • Requires major criteria #1 and #2 plus one minor criterion OR major criterion #1 plus 2 minor criteria:
  • Major criterion #1: Hgb > 18.5 g/dl for men or 16.5 g/dl for women OR Hgb or Hct > 99th percentile of reference range for age, sex or altitude of residence OR Hgb > 17 g/dl men or 15 g/dl women if associated with a sustained increase of 2 g/dl or more from baseline that cannot be attributed to correction of iron deficiency OR elevated red cell mass > 25% above mean normal predicted value
  • Major criterion #2: Presence of JAK2 V617F or functionally similar mutation like JAK2 exon 12 mutation
  • Minor criterion #1: bone marrow trilineage myeloproliferation (panmyelosis)
  • Minor criterion #2: subnormal serum erythropoietin level (EPO) below the reference range for normal
  • Minor criterion #3: endogenous erythroid colony (EEC) growth in vitro (Table, WHO 2008 diagnostic algorithm)

Criteria for diagnosis of post-PV myelofibrosis ("spent" phase):
  • Required criteria: established diagnosis of PV, and marrow fibrosis 2 - 3 (European consensus system on a 0 - 3 scale)
  • Additional criteria (at least 2 required) - anemia or peripheral cytopenia, leukoerythroblastic peripheral blood picture, progressive splenomegaly or constitutional symptoms like fever, night sweats
  • Diagnosis (WHO 2001): polycythemia (increased red blood cell mass) with nonelevated erythropoietin levels; Table - not used anymore
Laboratory
  • Elevated red cell mass, white blood cell count and platelet count
  • Marked increase in hemoglobin and hematocrit
  • Abnormal aggregation of platelets, normal or increased LAP score, no CML translocation, decreased erythropoietin (EPO), EPO-independent erythroid colony (EEC) growth formation in vitro
Prognostic factors
  • Spent phase with marrow fibrosis and marked cytopenias in 15% after 10 years, death in months if no treatment
  • Acute myeloid leukemia in 2% with phlebotomy but 15% with alkylating agents or radioactive phosphorus (no longer used)
  • Acute lymphocytic lymphoma is rare
Case reports
Treatment
Microscopic (histologic) description
  • Peripheral blood: increased erythrocytes, leukocytes, platelets, basophils; large platelets
  • Bone marrow: Mean 80% cellularity (range 37 - 100%), panmyelosis (helps distinguish from ET)
  • Usually marked erythroid hyperplasia although may be subtle
  • Increased megakaryocytes (PAS stain can help identify), megakaryocytes are often larger and more polymorphic than normal, some may have bulbous nuclei, they form loose clusters or lie close to the bone trabeculae; increased vascularity, modestly increased reticulin (particularly near megakaryocytes), reduced storage iron
  • Late changes are fibrotic marrow observed with reticulin stain, megakaryocytes then start to cluster and have hyperchromatic and dysmorphic nuclei
Microscopic (histologic) images

Images hosted on PathOut server:

Peripheral blood:

Hb of 19 g/dL, WBC of 12.8

Spent phase



Bone marrow biopsy:

Markedly hypercellular marrow with prominent megakaryocytes

Posttreatment with myelofibrosis due to metastatic prostate carcinom


Left two images: predominance of immature cells, some erythroid precursors have dysplastic features; right: marked increase in coarse reticulin fibers (reticulin stain)



Images hosted on other servers:

Bone marrow biopsy:

Various images

Positive stains
Negative stains
  • c-Mpl (thrombopoietin receptor) on megakaryocytes (usually moderate / strong) but this is not used for diagnosis
Molecular / cytogenetics description
Differential diagnosis
  • Secondary polycythemia due to dehydration, smoking, high altitude (these have increased erythropoietin levels)
  • Gaisbock syndrome: associated with hypertension, obesity, anxiety or other causes; normal megakaryocytes, less cellular marrow, no increase in reticulin, more normal iron stores, normal or high erythropoietin levels
  • CML: no erythroid hyperplasia