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

Table 1 The 1980 Rotterdam clinical and pathological criteria for essential thrombocythemia and polycythemia vera

1A The 1980 RCP major (A) and confirmative (B) criteria for prefibrotic ET
A1 Persistent platelet count in excess of 400 × 109/L
A2 Increase and clustering of enlarged megakaryocytes in bone marrow biopsy
A3 No or slight increase of reticulin fibers (RF 0 or RF 1)
B1 Presence of large platelets in a peripheral blood smear
B2 Absence of any underlying disease for reactive thrombocytosis and normal ESR
B3 No splenomegaly (< 12 cm) or slight splenomegaly on palpation or scan (< 15 cm)
B4 Increase of LAP-score and no signs of fever or inflammation
Exclusion criterion
Ph+ chromosome and any other cytogenetic abnormality in blood or bone marrow cells
1B The 1980 RCP major (A) and minor (B) criteria for prefibrotic PV
A1 Raised red cell mass. Male > 36 mL/kg, female > 32 mL/kg consistent with erythrocyte count of > 6 × 1012/L (Dameshek[1,2])
A2 Absence of primary or secondary erythrocytosis by clinical and laboratory tests
A3 Slight, moderate or marked increase in bone marrow biopsy of clustered, enlarged pleomorphic megakaryocytes with hyperlobulated nuclei and moderate to marked increase cellularity of megakaryopoiesis/erythropoiesis or typically trilinear mega-erythro-granulopoiesis. A typical PV bone marrow excludes erythrocytosis. No or presence of reticuline fibers and no collagen fibers (no dry tap)
B1 Thrombocythemia, persistant increase of platelet > 400 × 109/L
B2 Leukocytosis, leucocyte count > 109/L and low erythrocyte sedimentation rate
B3 Raised leukocyte alkaline phosphatase score > 100, absence of fever or infection
B4 Splenomegaly on palpation or on isotope/ultrasound scanning
A1 + A3 plus one of B establishes PV and excludes any variant of erythrocytosis
1C Grading of bone marrow biopsy content of RF according to Ellis et al[41], Georgii et al[35,36] and Wilkins et al[171] and WHO grading of MF[98-101]
Grading RF[41]	Grading MF 2008 WHO91	Description of RF and reticulin/collagen fibers in MF as a secondary event in MPN
Normal RF 0	N MF 0	No reticulin fibers, occasional individual fibers or focal areas with tiny amount of reticulin fiber network
Slight increase RF 1	+ MF 0	Fine reticulin fiber network throughout much of section and no course reticulin fibers
Moderate increase RF 2	++ MF 1	Diffuse fine reticuline network with focal collections of thick course reticulin fibers and no collagenisation
Marked increase RF 3	+++ RCF = MF 2	Diffuse and dense increase in reticulin with extensive intersections, and presence of collagen fibers and no or minor O
OS Dry tap RF 4	Sclerotic RCF and O = MF 3	Diffuse and dense reticulin with with coarse bundles of collagen associated with significant O

MF: Myelofibrosis; MPN: Myeloproliferative neoplasms; O: Osteosclerosis; RCP: Rotterdam clinical and pathological; ET: Essential thrombocythemia; RF: Reticulin fibrosis; PV: Polycythemia vera.