Analyzing Morphologic Features of ALK-Negative Anaplastic Large Cell Lymphomas with DUSP22 Rearrangements
Anaplastic large cell lymphomas (ALCLs) represent a group of CD30-positive T-cell non-Hodgkin lymphomas that vary in genetics, clinical presentation, and biological behavior. According to the World Health Organization, there are three distinct types of ALCL:
- Systemic ALK-positive ALCL
- Systemic ALK-negative ALCL
- Primary cutaneous ALCL
Systemic ALK-positive ALCLs often feature rearrangements of the ALK gene and have favorable outcomes in most cases after standard combination chemotherapy, while systemic ALK-negative ALCLs lack ALK rearrangements and have inferior outcomes than ALK-positive ALCLs.
However, in a recent study, Mayo Clinic researchers reported that ALK-negative ALCLs are genetically heterogenous. In the study, published in the journal Blood, the largest subset, representing 30% of cases, had rearrangements of the DUSP22 locus. These cases had favorable outcomes similar to ALK-positive ALCL and superior to other ALK-negative ALCLs. To explore this research further, Mayo Clinic researchers conducted another study to examine the morphologic features of these cases in more detail. The study was published in The American Journal of Surgical Pathology.
According to Rebecca King, M.D., Senior Associate Consultant of Hematopathology at Mayo Clinic and first author on this study, because ALK-negative ALCL was recently shown to be a genetically and clinically heterogeneous entity, the researchers were interested in evaluating these cases for pathologic features that might correlate with the genetic features.
“Specifically, we were interested in the morphologic features of DUSP22-rearranged cases, which account for approximately one-third of ALK-negative ALCLs and have a more favorable clinical outcome than other ALK-negative cases,” said Dr. King.
The research team wanted to establish whether there was a reproducible set of morphologic findings that distinguished DUSP22-rearranged cases from other ALK-negative ALCLs. To do so, they determined they needed to evaluate the morphologic features in a blinded fashion (i.e., without knowledge of the genetics).
“In our study, we had two groups of cases: one to establish a set of morphologic features associated with DUSP22-rearranged cases, and a second to test whether these features could be utilized to establish a ‘histologic score’ reflecting the likelihood of a DUSP22 rearrangement in a given case,” added Dr. King.
Based on the results, researchers discovered that DUSP22-rearranged ALCLs have a reproducible constellation of morphologic features.
“Our study is the first to dissect the morphologic features of systemic ALK-negative ALCLs with DUSP22 rearrangements. Next to ALK rearrangements, DUSP22 rearrangements are the second most common chromosomal rearrangements in ALCL. Here, we have demonstrated that DUSP22-rearranged ALCLs have a unique and reproducible constellation of morphologic features recognizable on haematoxylin and eosin stains,” said Dr. King.
These results provide further support that DUSP22-rearranged ALCLs are a clinicopathologically distinct subset of cases.
“This may aid pathologists in recognizing these cases and support the need to perform FISH studies to evaluate for DUSP22 rearrangements in ALK-negative ALCL,” added Dr. King.