L2a

Polycythemia vera	Stem cell defect resulting in autonomous erythrocytic cell line, with some overproduction of other hematopoietic cells as well;	JAK2 100%	• LABORATORY FEATURES: - Increased total body RBC mass → increased H - ↓ EPO - Pancellular hematopoietic increase  SYMPTOMS - Hyperviscosity syndrome • SIGNS – -          “Ruddy cyanosis” -          Hepatosplenomegaly -            • COURSE – -          Thromboembolism -           hemorrhage, -          myelofibrosis (“burnt out”), -          acute leukemia (almost always AML) in 5-15% of cases
	Secondary polycythemia Non-neoplastic erythrocytosis secondary to physiologic or abnormal overproduction of erythropoietin		High EPO CAUSES:  -          High altitude -          Cardiopulmonary disease -           Alveolar hypoventilation (“Pickwickian” syndrome) Neoplasms (e.g. renal cell or hepatocellular carcinoma)

 

Chronic Myeloproliferative neoplasms: 

CML, P.Vera, Primary myelofibrosis, Essential Thrombocytopenia

-          Myelogenous or pluripotent stem cell defects  à overproduction of mostly mature cells

-           Three major non-lymphocytic lineages affected; one predominates

-          Some clinical and morphologic overlap among subtypes, especially in early stages

-          • Some subtypes share a common gene abnormality (JAK2 mutation, affecting tyrosine kinase activity); CML associated with BCR-ABL1, also affecting  tyrosine kinase activity

-           Transformation to acute leukemia

·         Why might the patient have a history of DVTs?

o   Hyperviscosity syndrome due to excess RBCs à stasis/ increased risk for clots (see image above)

·         What does this patient likely have? 

                   P. Vera; a stem cell defect resulting in autonomous erythrocytic cell line

·         What mutation is associated with this disease? JAK2 (~100%)

·        

         What is the cause of splenomegaly?  

•       The spleen filters old/damaged RBC -- excess RBC --> splenic congestion
•       Later in course spleen maybe involved in extramedullay hematopoiesis 

·         What is the difference between P.Vera and secondary polycythemia?

o   Secondary polycythemia is in response to increase EPO and is not a neoplastic process (see chart)

·         An elevated EPO would be seen in which kind of cancer?

§  HCC/RCC