Myeloproliferative Neoplasms With Calreticulin Mutations Exhibit Distinctive Morphologic Features

Am J Clin Pathol. 2016 Mar;145(3):418-27. doi: 10.1093/ajcp/aqw005.

Abstract

Objectives: Calreticulin (CALR) mutations are present in 50% to 85% of JAK2/MPL wild-type (wt) myeloproliferative neoplasms (MPNs). The histopathologic features of CALR-mutated MPNs are unknown.

Methods: We identified 71 patients with essential thrombocythemia (ET), primary myelofibrosis (PMF), and post-essential thrombocythemia myelofibrosis (post-ET MF) with available CALR status. CALR was assessed using capillary electrophoresis followed by Sanger sequencing confirmation. CALR status was correlated with histopathologic features.

Results: The megakaryocytes of CALR-mutated PMF more often were hyperchromatic (20/21) compared with CALR-wt cases (10/14) (P = .05). CALR-mutated ET showed more megakaryocytic clustering (7/7) compared with CALR-wt cases (5/9) (P = 03). Megakaryocytes of CALR-mutated post-ET MF (8/8) had a predominance of convoluted nuclei compared with CALR-wt cases (2/4) (P = .03). CALR mutations were more frequent in post-ET MF compared with ET (P = .04).

Conclusions: CALR-mutated MPNs have a higher frequency of megakaryocytic aberrancies compared with CALR-wt cases. Patients with CALR-mutated ET appear to be more likely to develop myelofibrosis compared with patients with wt CALRUpon completion of this activity you will be able to: describe morphologic features that are associated with CALR-mutated myeloproliferative neoplasms.examine cases of essential thrombocythemia and primary myelofibrosis and predict which cases are more likely to be CALR-mutated based on histopathologic features.initiate CALR mutation testing for cases likely to have mutations. The ASCP is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The ASCP designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 Credit™ per article. Physicians should claim only the credit commensurate with the extent of their participation in the activity. This activity qualifies as an American Board of Pathology Maintenance of Certification Part II Self-Assessment Module. The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose. Exam is located at www.ascp.org/ajcpcme.

Keywords: CALR; Calreticulin; Essential thrombocythemia; Myelofibrosis; Myeloproliferative.

MeSH terms

  • Adult
  • Aged
  • Calreticulin / genetics*
  • Education, Medical, Continuing
  • Exons
  • Female
  • Genotype
  • Humans
  • Male
  • Megakaryocytes / pathology*
  • Middle Aged
  • Mutation
  • Myeloproliferative Disorders / diagnosis
  • Myeloproliferative Disorders / genetics*
  • Myeloproliferative Disorders / pathology
  • Neoplasms / diagnosis
  • Neoplasms / genetics*
  • Neoplasms / pathology
  • Primary Myelofibrosis / diagnosis
  • Primary Myelofibrosis / genetics*
  • Primary Myelofibrosis / pathology
  • Thrombocythemia, Essential / diagnosis
  • Thrombocythemia, Essential / genetics
  • Thrombocythemia, Essential / pathology
  • Young Adult

Substances

  • CALR protein, human
  • Calreticulin