<scp>CD30</scp> ‐Positive Lymphoproliferative Disorder With <i>DUSP22‐IRF4</i> Rearrangement and Gamma‐Delta T‐Cell Phenotype: A Novel Indolent Presentation

We present a case of an 84-year-old female with an isolated and asymptomatic 1.0 cm red papule on the left medial knee. A shave biopsy revealed a diffuse atypical lymphoid infiltrate in the dermis with epidermotropism, diffuse expression of CD30 and positive T-cell receptor (TCR) gamma-delta immunophenotype. Fluorescence in situ hybridization (FISH) identified a chromosomal rearrangement involving dual-specificity phosphatase-22 (DUSP22) and interferon regulatory factor-4 (IRF4). Next generation sequencing (NGS) indicated a low tumor mutational burden with no gene variants. Upon follow-up, there was no evidence of residuum or recurrence. The findings provided the best support for an unusual presentation of lymphomatoid papulosis (LyP) with DUSP22-IRF4 gene rearrangement and TCR gamma-delta phenotype. LyP was favored over anaplastic large-cell lymphoma due to spontaneous resolution and lack of systemic involvement. The clinical history and immunohistochemistry excluded mycosis fungoides or other lymphomas. LyP associated with DUSP22-IRF4 gene rearrangement is rarely documented in the literature. This is a unique presentation of LyP with concurrent DUSP22-IRF4 gene rearrangement and TCR gamma-delta phenotype along with an indolent clinical course. Diagnosing LyP can be particularly challenging due to its histologic similarities with other cutaneous lymphomas, underscoring the importance of distinguishing this relatively benign condition from more aggressive malignancies.