title: The myeloproliferative neoplasms, unclassifiable: clinical and pathological considerations.
abstract: In this study, we investigate in detail the morphological, clinical and molecular features of 71 consecutive patients with a diagnosis of myeloproliferative neoplasms, unclassifiable. We performed a meticulous morphological analysis and found that most of the cases displayed a hypercellular bone marrow (70%) with normal erythropoiesis without left-shifting (59%), increased granulopoiesis with left-shifting (73%) and increased megakaryocytes with loose clustering (96%). Megakaryocytes displayed frequent giant forms with hyperlobulated or bulbous nuclei and/or other maturation defects. Interestingly, more than half of the cases displayed severe bone marrow fibrosis (59%). Median values of hemoglobin level and white blood cells count were all within the normal range; in contrast, median platelets count and lactate dehydrogenase were increased. Little less than half of the patients (44%) showed splenomegaly. JAK2V617F mutation was detected in 72% of all patients. Among the JAK2-negative cases, MPLW515L mutation was found in 17% and CALR mutations in 67% of the investigated cases, respectively. Finally, by multiple correspondence analysis of the morphological profiles, we found that all but four of the cases could be grouped in three morphological clusters with some features similar to those of the classic BCR-ABL1-negative myeloproliferative neoplasms. Analysis of the clinical parameters in these three clusters revealed discrepancies with the morphological profile in about 55% of the patients. In conclusion, we found that the category of myeloproliferative neoplasm, unclassifiable is heterogeneous but identification of different subgroups is possible and should be recommended for a better management of these patients.
authors.affiliation: Hematopathology Service, Division of Pathology, Department of Pathophysiology and Transplantation, University of Milan, and IRCCS Ca' Granda-Maggiore Policlinico Hospital Foundation, Milan, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: Gianelli
authors.affiliation: Oncohematology Division, IRCCS Ca' Granda-Maggiore Policlinico Hospital Foundation, and Department of Oncology and Oncohematology, University of Milan, Milan, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Cattaneo
authors.affiliation: Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Bossi
authors.affiliation: Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
authors.forename: Ivan
authors.initials: I
authors.lastname: Cortinovis
authors.affiliation: Hematopathology Service, Division of Pathology, Department of Pathophysiology and Transplantation, University of Milan, and IRCCS Ca' Granda-Maggiore Policlinico Hospital Foundation, Milan, Italy.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Boiocchi
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Cornell Medical College/New York Presbyterian Hospital, New York, NY, USA.
authors.forename: Yen-Chun
authors.initials: YC
authors.lastname: Liu
authors.affiliation: Hematopathology Service, Division of Pathology, Department of Pathophysiology and Transplantation, University of Milan, and IRCCS Ca' Granda-Maggiore Policlinico Hospital Foundation, Milan, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Augello
authors.affiliation: Hematopathology Service, Division of Pathology, Department of Pathophysiology and Transplantation, University of Milan, and IRCCS Ca' Granda-Maggiore Policlinico Hospital Foundation, Milan, Italy.
authors.forename: Arturo
authors.initials: A
authors.lastname: Bonometti
authors.affiliation: Hematopathology Service, Division of Pathology, Department of Pathophysiology and Transplantation, University of Milan, and IRCCS Ca' Granda-Maggiore Policlinico Hospital Foundation, Milan, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Fiori
authors.affiliation: Oncohematology Division, IRCCS Ca' Granda-Maggiore Policlinico Hospital Foundation, and Department of Oncology and Oncohematology, University of Milan, Milan, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Orofino
authors.affiliation: Oncohematology Division, IRCCS Ca' Granda-Maggiore Policlinico Hospital Foundation, and Department of Oncology and Oncohematology, University of Milan, Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Guidotti
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Cornell Medical College/New York Presbyterian Hospital, New York, NY, USA.
authors.forename: Attilio
authors.initials: A
authors.lastname: Orazi
authors.affiliation: Oncohematology Division, IRCCS Ca' Granda-Maggiore Policlinico Hospital Foundation, and Department of Oncology and Oncohematology, University of Milan, Milan, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Iurlo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology*; D064032:Calbindin 2 / Q000235:genetics; D005260:Female; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009196:Myeloproliferative Disorders / Q000145:classification* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D055728:Primary Myelofibrosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D053628:Receptors, Thrombopoietin / Q000235:genetics; D055815:Young Adult
chemical_list: D064032:Calbindin 2; D053628:Receptors, Thrombopoietin; C082218:MPL protein, human; C507924:JAK2 protein, human; D053614:Janus Kinase 2