ISSN: 1300-7777 E-ISSN: 1308-5263
The European Clinical, Molecular, and Pathological (ECMP) Criteria and the 2007/2008 Revisions of the World Health Organization for the Diagnosis, Classification, and Staging of Prefibrotic Myeloproliferative Neoplasms Carrying the JAK2V617F Mutation [Turk J Hematol]
Turk J Hematol. 2014; 31(3): 239-254 | DOI: 10.4274/Tjh.2013.0131  

The European Clinical, Molecular, and Pathological (ECMP) Criteria and the 2007/2008 Revisions of the World Health Organization for the Diagnosis, Classification, and Staging of Prefibrotic Myeloproliferative Neoplasms Carrying the JAK2V617F Mutation

Jan Jacques Michiels1, Fibo Ten Kate3, King H. Lam3, Wilfried Schroyens2, Zwi Berneman2, Hendrik De Raeve4
1Antwerp University Hospital, Department Of Hematology, Antwerp, Belgium; Goodheart Institute, European Working Group On Myeloproliferative Neoplasms (ewg-mpn), Rotterdam, Netherlands
2Antwerp University Hospital, Department Of Hematology, Antwerp, Belgium
3Erasmus University Medical Center, Department Of Pathology, Rotterdam, Netherlands
4Olv Hospital Aalst And University Hospital, Departments Of Pathology, Brussels, Belgium

OBJECTIVE: The prefibrotic stages of JAK2V617F essential thrombocythemia (ET) and JAK2V617F polycythemia vera (PV) can easily be diagnosed clinically without use of bone marrow biopsy histology. We assessed the 2008 WHO and European Clinical, Molecular, and Pathological (ECMP) criteria for the diagnosis of myeloproliferative neoplasms (MPNs).
METHODS: Studied patients included 6 JAK2V617F-mutated ET and 4 PV patients during long-term follow-up in view of critical analysis of the literature. The bone marrow biopsy histology diagnosis without use of clinical data was PV in 7 (of which 3 were cases of ET with features of early prodromal PV) and classical PV in 4.
RESULTS: The ECMP criteria distinguish 3 sequential phenotypes (1, 2, or 3) of JAK2V617F-mutated ET: normocellular ET-1; ET-2, with clinical and bone marrow features of PV (prodromal PV), and ET-3, with hypercellular dysmorphic megakaryocytic and granulocytic myeloproliferation (ET.MGM). The 3 patients with ET-2 or prodromal PV developed slow-onset PV after a follow-up of about 10 years. Bone marrow biopsy histology differentiates MPNs of various molecular etiologies from all variants of primary or secondary erythrocytoses and thrombocytoses with sensitivity and specificity of near 100%.
CONCLUSION: Normocellular ET (WHO-ET), prodromal PV, and classical PV show overlapping bone marrow biopsy histology features with similar pleomorphic clustered megakaryocytes in the prefibrotic stages of JAK2V617F mutated MPN. Erythrocytes are below 6x1012/L in normocellular ET and prodromal PV, and are consistently above 6x1012/L in classical PV and at the time of transition from prodromal PV into classical PV. Red cell count at a cut-off level of 6x1012/L separates ET from PV and obviates the need for red cell mass measurement when bone marrow histology and JAK2V617F mutation screening are included in the diagnostic work-up of MPNs.

Keywords: Myeloproliferative disorders, Myeloproliferative neoplasm, Essential thrombocythemia, Polycythemia vera, Primary myelofibrosis, JAK2V617F mutation, Bone marrow histopathology, Red cell mass, Erythrocyte count


JAK2V617F Mutasyonu Bulunan Prefibrotik Myeloproliferatif Neoplazmların Tanı, Sınıflandırma ve Evrelendirmesinde Dünya Sağlık Örgütü Kriterlerinin 2007/2008 Gözden Geçirilmesi ve Avrupa Klinik, Moleküler ve Patolojik (ECMP) Kriterleri

Jan Jacques Michiels1, Fibo Ten Kate3, King H. Lam3, Wilfried Schroyens2, Zwi Berneman2, Hendrik De Raeve4
1Antwerp University Hospital, Department Of Hematology, Antwerp, Belgium; Goodheart Institute, European Working Group On Myeloproliferative Neoplasms (ewg-mpn), Rotterdam, Netherlands
2Antwerp University Hospital, Department Of Hematology, Antwerp, Belgium
3Erasmus University Medical Center, Department Of Pathology, Rotterdam, Netherlands
4Olv Hospital Aalst And University Hospital, Departments Of Pathology, Brussels, Belgium

AMAÇ: JAK2V617F esansiyel trombositemi (ET) ve JAK2V617F polisitemia veranın (PV) prefibrotik evrelerinin tanısı, kemik iliği biyopsi histolojisine gerek kalmadan kolaylıkla klinik olarak konulabilir. Biz, myeloproliferatif neoplazmlarının (MPNs) tanısı için 2008 Dünya Sağlık Örgütü (DSÖ) ve Avrupa Klinik, Moleküler ve Patolojik (ECMP) kriterlerini değerlendirdik.
YÖNTEMLER: Çalışmaya, literatür değerlendirmesi gözönünde bulundurularak uzun sureli gözlemde tutulan 6 JAK2V617F mutasyon pozitif ET ve 4 PV hastası dahil edildi. Dört klasik PV ve 7 PV olgusuna klinik veriler kullanılmadan, kemik iliği biyopsi histolojisine dayanarak tanı konuldu (bunların 3’ü erken prodromal PV özellikleri taşıyan ET idi).
BULGULAR: ECMP kriterleri JAK2V617F mutasyonu olan ET’yi 3 ardışık fenotipe ayırmaktadır. Normosellüler ET-1; PV’nin klinik ve kemik iliği özelliklerini taşıyan ET-2 (prodromal PV) ve hipersellüler dismorfik megakaryositik ve granülositik myeloproliferasyon ile birlikte olan, ET-3 (ET.MGM). ET-2 ya da prodromal PV’li 3 hasta, yaklaşık 10 yıllık bir izlemin ardından yavaş başlangıçlı PV’ye dönüşmüşlerdir. Kemik iliği biyopsi histolojisi, çok çeşitli moleküler etiyolojik etkenlere sahip olan myeloproliferatif neoplazmları neredeyse %100’e varan bir duyarlık ve özgüllükle, birincil ve ikincil trombositoz ve eritrositozun hemen her tipinden ayırt etmektedir.
SONUÇ: Normosellüer ET (DSÖ-ET), prodromal PV ve klasik PV’nin üçü de prefibrotik evrede benzer pleomorfik megakaryosit kümeleşmesi özelliği barındıran birbirleriyle örtüşen kemik iliği biyopsi histolojisine sahiptirler. Eritrosit sayısı, normosellüler ET ve prodromal PV’de 6x1012/L’nin altındayken, klasik PV’de ve prodromal PV’den klasik PV’ye dönüşümde ise kalıcı olarak 6x1012/L’nin üstünde seyretmektedir. 6x1012/L düzeyindeki kırmızı hücre cut-off değeri ET’yi PV’den ayırmakta ve ek olarak kemik iliği histolojisi ve JAK2V617F mutasyon taramasının uygulanan prosedürler içinde olmasıyla myeloproliferatif neoplazmların tanısında kırmızı hücre kitle tayini ihtiyacını da ortadan kaldırmaktadır.

Anahtar Kelimeler: Myeloproliferatif hastalıklar, Myeloproliferatif neoplasm, Esansiyel trombositemi, Polisitemia vera, Primer myelofibrozis, JAK2V617F mutasyonu, Kemik iliği histolojisi, Kırmızı kan hücresi kitlesi, Kırmızı kan hücresi sayısı


Jan Jacques Michiels, Fibo Ten Kate, King H. Lam, Wilfried Schroyens, Zwi Berneman, Hendrik De Raeve. The European Clinical, Molecular, and Pathological (ECMP) Criteria and the 2007/2008 Revisions of the World Health Organization for the Diagnosis, Classification, and Staging of Prefibrotic Myeloproliferative Neoplasms Carrying the JAK2V617F Mutation. Turk J Hematol. 2014; 31(3): 239-254

Corresponding Author: Jan Jacques Michiels, Netherlands


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