European vs 2015-World Health Organization clinical molecular and pathological classification of myeloproliferative neoplasms

Table 2 Polycythemia vera study group criteria for polycythemia vera[10] and diagnostic differentiation of polycythemia vera from all variants of primary and secondary erythrocytoses by bone marrow histology[17]

Major criteria PV	Minor criteria PV
A1 RCM, males > 36 mL/kg females > 32 mL/kg. Hemoglobin	B1 Thrombocytosis Platelet count > 400 × 109/L
18.5 g/dL male and > 16.5 g/dL females (PVSG, WHO)	B2 Leukocytosis > 12 × 109/L
A2 Normal arterial oxygen saturation > 92%	B3 Raised neutrophil alkaline phosphatase score > 100 or raised B12
A3 Splenomegaly on palpation	(> 900 ng/L) or raised unsaturated B12 binding capacity (> 2200 ng/L)
	B3 is replaced by spontaneous EEC as a specific clue to PV
Benign erythrocytosis: 1980 RCP criteria	Myeloproliferative PV: 1980 RCP criteria
RCM, males > 36 mL/kg females > 32 mL/kg or increased erythrocytes above 6 × 1012/L	Increased red cell counts > 6 × 1012/L or increased RCM and increase of clustered large megakaryocytes with hyperlobulated nuclei is a pathognomonic diagnostic clue to PV
Normal platelet and leukocyte counts	Normal RCM = inapparent erythrocytosis is not associated with splenomegaly
Normal bone marrow histopathology: normal cellularity and erythropoiesis, and normal size, morphology and	and shows normal bone histology, whereas IPV is associated with splenomegaly and show typical features of PV bone marrow histology
distribution of megakaryocytes
Classification of erythrocytoses[74]	Notes anno 1980-1999[74]
Congenital or primary erythrocytosis including mutation	Increased RCM does not distinguish between PV and primary erythrocytosis
truncated EPO recepotor, disrupted oxygen homeostasis in	Increased RCM does not distinguish between PV and IPV. IPV is featured by
Chuvash erythrocytosis, high oxygen affinity	advanced PV with normal hb, Ht and erythrocyte count due to splenomegaly and
hemoglobinopathy, and congenital autonomous EPO	hypersplenism and with increase of reticulin fibrosis with typical PV bone
production	marrow features
Secondary erythrocytosis due to autonomous EPO production in renal diseases or by tumour cels or due to hypoxia	In IPV the values of hemoglobin hematocrit and erythrocytes are normal but RCM is increased due to splenomegaly with absence of hypervolemic symptoms
Idiopathic erythrocytoses

Diagnostic criteria for polycythemia vera (PV) proposed in 1975 by the polycythemia vera study group (PVSG)[10] and used in the 2001 and 2008 World Health Organization Classifications of MPD and MPN[75,76]. Diagnosis of PV is acceptable if the following combinations are present: A1 + A2 + A3 or A1 + A2 + any two from category B. Diagnostic differentiation of benign erthrocytosis from myeloproliferative polycythemia vera by histopathology from bone marrow sections according to the Rotterdam clinical and pathological (1980 RCP criteria for PV) (Table 1)[73,74]. RCM does not distinguish between PV and primary or secondary erythrocytosis. RCM does not distinguish between PV and inapparent PV with splenomegaly in splanchnic vein thrombosis (IPV, Table 3). In IPV RCM is increased due to splenomegaly with absence of hypervolumemic symptoms. Bone marrow histology distinguishes PV from all variants of erythrocytosis with a sensitivity and specificity of 100%. RCM: Raised red cell mass; EEC: Erythroid colony formation; IPV: Inapparent PV.