Polycythemia Vera (PV)

Major Criteria

One of the following
- Hgb. > 16.5 g/dL or Hct. > 49% in men
- Hgb. > 16.0 g/dL or Hct. >48% in women
- Elevated RBC mass (at least 25% above the mean predicted value)
BM with trilineage hyerpcellularity (panmyelosis) including pleomorphic megakaryocytes (variability in size)
JAK2 V617F or JAK2 exon 12 mutation

Minor Criteria

Low serum EPO level

All major criteria are required to make the diagnosis of PV. However, in the absence of a JAK2 mutation, PV can still be diagnosed with evidence of a low EPO level. Additionally, BM marrow changes described in the major criteria may not be necessary if all other major and minor criteria are met.

PV has a long survival time (>10 years), but approximately 20% transform to MDS or AML.

JAK2 Mutations

JAK2 V617F present in ~95% of cases
JAK2 exon 12 mutation present in ~80% of the remaining cases

Molecular Testing

JAK2, CALR, & MPL Testing in Myeloproliferative Neoplasms (MPN)

Treatment

Hydroxyurea has been a mainstay of treatment.
JAK 1/2 inhibitor ruxolitinib/Jakafi® is now available when hydroxyurea is ineffective or not tolerated.

Immunohistochemistry

The use of immunohistochemistry (IHC) in many of the myeloproliferative neoplasms is limited. Identifying an increased blast population is one of the most useful, and may indicate a more aggressive course or transformation to acute leukemia. Helpful IHC markers may include:

Stain	Comment
CD34	CD34 marks immature cells including myeloblasts. In the setting of AML, it is ~70% sensitive. A subset of lymphoblasts may express CD34.
CD117	CD117 is a specific myeloid marker, and marks a subset of myeloblasts. The expression is dim, and one often must look at 20-40X to clearly see expression. Mast cells (fried egg looking cell) will have very strong expression.
CD71	CD71 marks nucleated erythroid cells. This may be helpful in quantitating and differentiating erythroid cells from myeloid cells. This marker may be set-up as a double stain with CD34.
E_Cadherin	In the setting of hematopoietic cells, E-Cadherin marks immature erythroid cells. Like CD71, E-Cadherin may be useful to differentiate immature erythroid cells from immature myeloid cells.
TdT	TdT is a sensitive lymphoblast (~95%) marker. It is not entirely specific for lymphoblasts, but other markers can help clarify diagnostic difficulties (B and T-cell markers).

References

Swerdlow SH, Campo E, Harris, NL, Jaffe ES, Pileri SA, Stein H, Thiele J (Eds): WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues (Revised 4th edition). IARC: Lyon 2017

Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127: 2391–2405. doi:10.1182/blood-2016-03-643544

Klco JM, Vij R, Kreisel FH, Hassan A, Frater JL. Molecular pathology of myeloproliferative neoplasms. Am J Clin Pathol. 2010;133: 602–615. doi:10.1309/AJCPPPZ1WFVGNE4A

Cao M, Olsen RJ, Zu Y. Polycythemia vera: new clinicopathologic perspectives. Arch Pathol Lab Med. 2006;130: 1126–1132.