Track

Abstract

Primary cutaneous CD30+ lymphoproliferative disorders (pcCD30+LPDs) include primary cutaneous anaplastic large cell lymphoma (pcALCL), lymphomatoid papulosis (LyP) or borderline disorders. PcCD30+LPDs may overlap histopathologically and immunophenotypically with systemic anaplastic large cell lymphoma (sALCL), but show more indolent clinical behavior. Molecular studies have revealed shared alterations with sALCL including DUSP22/IRF4 rearrangements, and less frequently, ALK or TP63 rearrangements, like sALCL. “Triple negative” pcCD30+LPDs are negative for these rearrangements and unidentified driver rearrangements have been suspected. To identify such drivers, we retrospectively reviewed all cases of pcCD30+LPD at our institution from 2014-2025 that had RNA-based next generation sequencing results, or available material for fluorescence in situ hybridization. We identified 11 patients with JAK2 fusions, including 6 different fusion partners. Patients were predominantly male (7:4 M:F), and young; average age at diagnosis was 39 (range = 23-56). All patients presented with waxing and waning papules/plaques; 5 with concurrent progressing patches/plaques/non-specific rash. Histologically, 9 cases showed epidermotropic T-cell infiltrates, 6/9 overlapped significantly with mycosis fungoides. Immunophenotype showed CD4+ predominance in 7 cases; many cases had numerous CD30+ cells. Seven cases were TIA1 and/or GZB positive. Three patients had nodal involvement requiring systemic treatment while eight patients required observation only or topical steroid treatment, all with good response. JAK2 rearrangements in pcCD30LPDs appear to be common, occurring in young-mid age with overlapping presentations of CD30+LPD/mycosis fungoides and with cytotoxic marker expression. While cases appear clinically indolent, the presence of this oncologic driver may be diagnostically helpful and allow for therapeutic targeting in time.