Essential thrombocythaemia with mutation in MPL: clinicopathological correlation and comparison with JAK 2V617F-mutated and CALR- mutated genotypes

J Clin Pathol. 2018 Nov;71(11):975-980. doi: 10.1136/jclinpath-2018-205227. Epub 2018 Jun 22.

Abstract

Aim: To characterise the clinical and histological features of MPL-mutated essential thrombocythaemia (ET).

Patients and methods: Bone marrow biopsies of 175 patients with ET were centrally reviewed according to the 2016 WHO classification, including 42 cases with MPL mutation, 98 JAK2V617F-mutated and 35 CALR-mutated. Clinical and histological features were compared among the three genotypes included in the current 2016 WHO classification and among the different types of MPL mutations.

Results: Patients with MPL-mutated ET were significantly older than those with the other genotypes. Haematological values at diagnosis were similar among MPL-mutated and CALR-mutated ET, with both genotypes showing higher platelet counts and lower haemoglobin values than ET with JAK2V617F genotype. In the bone marrow, the median number of megakaryocytes was higher in MPL and CALR than in JAK2V617F genotype (16, 19 and 14 megakaryocytes per ×20 power field, respectively, p=0.004). Histological features of prefibrotic myelofibrosis were rarely observed in MPL genotype, whereas sinusoidal hyperplasia, dense clusters of megakaryocytes and reticulin fibrosis were more frequent in CALR-mutated ET, with 11% of such cases fulfilling WHO 2016 histological criteria of prefibrotic myelofibrosis. With a median follow-up of 3.5 years, no significant differences were seen among genotypes regarding survival, vascular complications or myelofibrotic transformation. There were no significant differences in the clinical data or in the histological characteristics depending on the type of MPL mutation.

Conclusion: MPL and CALR ET genotypes share clinical and histological characteristics. In contrast to CALR genotype, features of prefibrotic myelofibrosis are uncommon in MPL-mutated ET.

Keywords: diagnostic hematology; essential thrombocythemia; genetics; histopathology; myeloproliferative neoplasms.

Publication types

  • Comparative Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biopsy
  • Bone Marrow Examination
  • Calreticulin / genetics*
  • Cell Proliferation
  • Child
  • DNA Mutational Analysis
  • Female
  • Genetic Markers
  • Genetic Predisposition to Disease
  • Hemoglobins / analysis
  • Humans
  • Janus Kinase 2 / genetics*
  • Male
  • Megakaryocytes / pathology
  • Middle Aged
  • Mutation*
  • Phenotype
  • Platelet Count
  • Primary Myelofibrosis / blood
  • Primary Myelofibrosis / genetics*
  • Primary Myelofibrosis / pathology
  • Prognosis
  • Receptors, Thrombopoietin / genetics*
  • Thrombocythemia, Essential / blood
  • Thrombocythemia, Essential / genetics*
  • Thrombocythemia, Essential / pathology
  • Young Adult

Substances

  • CALR protein, human
  • Calreticulin
  • Genetic Markers
  • Hemoglobins
  • Receptors, Thrombopoietin
  • MPL protein, human
  • JAK2 protein, human
  • Janus Kinase 2