### Patient Information
This retrospective case series encompasses 43 adult patients diagnosed with cutaneous T-cell lymphoma (CTCL) found to harbor JAK2 gene fusions. The cohort consisted of 31 male (72.1%) and 12 female (27.9%) patients, with a median age of 45 years (range: 16-65 years). The patients were identified between 2000 and 2025 at a single US referral cancer center. The patients primarily presented with lesions consistent with mycosis fungoides (MF), CD30-positive lymphoproliferative disorders (LPD), or overlapping disease phenotypes, reflective of a spectrum from indolent to aggressive CTCL.
### Diagnosis
The diagnosis was established through molecular profiling employing a custom RNA sequencing panel and a targeted hybrid-capture-based next-generation DNA sequencing panel. These assays identified JAK2 gene fusions involving ten different partner genes, notably ATXN2L, CAPRIN1, and PCM1. Among the 43 patients, 38 (88.4%) presented with MF, CD30-positive LPD, or overlap syndromes, while 4 were classified as primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma (pcAETCL), and 1 case was peripheral T-cell lymphoma not otherwise specified (PTCL NOS).
Secondary genetic alterations included mutations affecting epigenetic regulators and transcriptional machinery, but neither mutational burden nor the specific fusion partner correlated significantly with clinical stage or disease aggressiveness.
