Unique morphologic and genetic characteristics of acute myeloid leukemia with chromothripsis: a clinicopathologic study from a single institution

Hum Pathol. 2020 Apr:98:22-31. doi: 10.1016/j.humpath.2020.02.003. Epub 2020 Feb 21.

Abstract

Chromothripsis is a unique type of genomic instability and is recognized in various cancers. In myeloid neoplasms (MNs), chromothripsis was linked to poor prognosis and specific genetic alterations (complex karyotype, 5q deletions, and loss of TP53). However, the clinicopathologic features of MNs with chromothripsis have not been thoroughly characterized. We identified chromothripsis in 11 cases of MNs (9 acute myeloid leukemia [AML] and 2 myelodysplastic syndrome [MDS] cases) and noted that all chromothripsis-positive AML cases were AML with myelodysplasia-related changes (AML-MRC). We performed a comparative clinicopathologic and genetic characterization of AML-MRC cases with and without chromothripsis. AML-MRC with chromothripsis is associated with lower white blood cell and platelet counts and higher degree of karyotypic complexity. Chromothripsis in AML-MRC most frequently involves chromosomes 8 and 11 with consequent amplification of either MYC or KMT2A. Comparative morphologic assessment of blast morphology revealed unique features characteristic of AML-MRC with chromothripsis: a variable degree of cytoplasmic vacuolization, granulation, and blebbing. These morphologic markers in the context of AML-MRC may prompt additional studies to identify cases with chromothripsis.

Keywords: AML-MRC; Blasts morphology; Chromothripsis.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics*
  • Chromothripsis*
  • Female
  • Genetic Predisposition to Disease
  • Genomic Instability*
  • Humans
  • Karyotype
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / pathology*
  • Lymphocytes / pathology*
  • Male
  • Middle Aged
  • Phenotype
  • Prognosis
  • Retrospective Studies

Substances

  • Biomarkers, Tumor