Myeloproliferative Neoplasms With Calreticulin Mutations Exhibit Distinctive Morphologic Features

Area of Science:

• Hematology
• Oncology
• Pathology

Background:

• Calreticulin (CALR) mutations are prevalent in JAK2/MPL wild-type myeloproliferative neoplasms (MPNs), affecting 50% to 85% of cases.
• The specific histopathologic characteristics of CALR-mutated MPNs remain largely uncharacterized.

Purpose of the Study:

• To investigate and define the histopathologic features associated with CALR mutations in MPNs.
• To correlate CALR mutation status with specific megakaryocyte morphologies in essential thrombocythemia (ET), primary myelofibrosis (PMF), and post-ET myelofibrosis (post-ET MF).

Main Methods:

• Seventy-one patients with ET, PMF, and post-ET MF were analyzed for CALR mutation status using capillary electrophoresis and Sanger sequencing.
• Histopathologic features, particularly megakaryocyte morphology, were assessed and correlated with CALR status.

Main Results:

• CALR-mutated PMF cases exhibited more hyperchromatic megakaryocytes compared to CALR-wild-type (wt) cases (P = .05).
• CALR-mutated ET showed increased megakaryocytic clustering versus CALR-wt cases (P = .03).
• Megakaryocytes in CALR-mutated post-ET MF displayed a predominance of convoluted nuclei compared to CALR-wt cases (P = .03), with CALR mutations being more frequent in post-ET MF than ET (P = .04).

Conclusions:

• CALR-mutated MPNs demonstrate a higher incidence of megakaryocytic aberrancies compared to CALR-wt cases.
• Patients with CALR-mutated ET may have an increased likelihood of progressing to myelofibrosis compared to those with wt CALR.
• Identifying these morphologic features can aid in predicting CALR mutation status and guide diagnostic testing.