Abstract

An 84-year-old woman with no significant past medical history presented with an isolated 1 cm pink plaque on the left medial knee. The clinical differential diagnosis was seborrheic keratosis versus atypical nevus. A shave biopsy revealed a dense atypical lymphoid infiltrate in the dermis with epidermotropism. The intradermal lymphocytes were composed of medium to large cells, while the intraepidermal component showed small cell morphology. Immunohistochemical analysis showed partial and weak expression of CD3 and CD4, along with diffuse expression of CD30 and TCR gamma-delta in both the dermal and epidermal components. The infiltrate was negative for TCR alpha-beta, CD2, CD5, CD8, CD20, EBV-ISH, TIA, granzyme, CD15 and ALK1. These findings led to a differential diagnosis of gamma-delta T cell lymphoma versus a CD30+ lymphoproliferative disorder. The clinical history and morphology effectively excluded mycosis fungoides. Imaging studies confirmed the disease was skin-limited, with no evidence of hemophagocytic syndrome, and the lesion resolved spontaneously without treatment.

FISH analysis demonstrated a DUSP22/IRF4 (dual-specificity phosphatase-22, interferon regulatory factor-4) gene rearrangement in 82% of nuclei. Next-generation sequencing analysis detected no variants in select cancer-associated genes.  DUSP22/IRF4 gene rearrangement has been identified in several lymphoproliferative disorders, including lymphomatoid papulosis (LyP) and anaplastic large cell lymphoma. The constellation of findings, including the spontaneous resolution of the lesion and the absence of extracutaneous involvement, provided the strongest support for LyP with DUSP22/IRF4 rearrangement and an unusual gamma-delta T cell phenotype. TCR gamma-delta expression is another pertinent example of how LyP can mimic rare and aggressive cutaneous T-cell lymphomas.