JAK2 Rearrangements Are a Recurrent Alteration in CD30+ Systemic T-Cell Lymphomas With Anaplastic Morphology

Abstract

Peripheral T-cell lymphoma (PTCL) comprises a heterogenous group of rare mature T-cell neoplasms. While some PTCL subtypes are well-characterized by histology, immunophenotype, and recurrent molecular alterations, others remain incompletely defined. In particular, the distinction between CD30+ PTCL, not otherwise specified and anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma can be subject to disagreement. We describe a series of 6 JAK2 rearrangements occurring in a cohort of 97 CD30+ ALK− PTCL (6%), assembled after identifying an index case of a novel PABPC1-JAK2 fusion in a case of ALK− anaplastic large cell lymphoma with unusual classic Hodgkin lymphoma (CHL)-like features. Fusions were identified using a comprehensive next-generation sequencing based assay performed between 2013 and 2020. Five of 6 cases (83%) showed JAK2 rearrangements with 4 novel partners: TFG, PABPC1, ILF3, and MAP7, and 1 case demonstrated a previously described PCM1-JAK2 fusion. By morphology, all cases showed anaplastic large cells and multinucleated Reed-Sternberg–like cells within a polymorphous inflammatory background with frequent eosinophilia reminiscent of CHL. By immunohistochemistry, atypical large cells expressed CD30 with coexpression of at least 1 T-cell marker, aberrant loss of at least 1 T-cell marker and, in 4 of 5 cases stained (80%), unusual CD15 coexpression. These findings suggest that a subset of CD30+ ALK− systemic PTCL with anaplastic morphology carry JAK2 rearrangements, some of which appear to show CHL-like morphologic features. The presence of JAK2 rearrangements in cases of CD30+ PTCL augments current classification and may provide a therapeutic target via JAK2 inhibition.

The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms

“…ALCLs with DUSP22 rearrangement are characterized by neoplastic cells with a “doughnut cell” appearance [ 250 ] and sheet-like growth pattern with less pleomorphic cells; LEF1 expression may serve as a surrogate marker for this molecular alteration [ 251 ]. A subset of cases with Hodgkin-like morphology shows aberrant ERBB4 protein expression [ 252 ], while more anaplastic cells are seen in cases with JAK2 rearrangement [ 253 ]. Breast implant-associated ALCL (BIA-ALCL) is an entity distinct from other ALK- ALCL; notably it is a usually non-invasive neoplasm arising in association with textured-surface breast implants and is associated with an excellent outcome [ 254 ].…”

World Health Organization‐defined eosinophilic disorders: 2022 update on diagnosis, risk stratification, and management

“…T-cell lymphoma and myocosis fungoides). 61,62 JAK2 fusion partners other than PCM1 have been detected, but are best categorized under the provisional entity BCR-ABL1-like ALL (e.g, involving ETV6 or BCR), or T cell lymphoma (e.g. involving the fusion partner TFG) if they present with these phenotypes.…”

PCM1-JAK2Fusion Tyrosine Kinase Gene-Related Neoplasia: A Systematic Review of the Clinical Literature

“…Six patients with MPN transformed into acute leukemia. Two developed ALL (one B cell 54 and one T cell 37 ) and 4 AML 26 , 34 , 35 (including one erythroleukemia 36 ). Both patients with ALL received HSCT and are alive at 68+ and 63+ months (41+ and 53+ months after transplant).…”