T-cell lymphoproliferative disorder with a STAT3 mutation causing a lymphocytic variant of hypereosinophilic-like syndrome without eosinophilia.

Lymphocytic variant of hypereosinophilic syndrome (LV-HES) is a rare T-cell lymphoproliferative disorder characterized by an immunophenotypically abnormal Th2 T-cell clone which produces eosinophilopoietic cytokines, resulting in eosinophilia and end-organ damage. A 38-year-old woman presented to an outside institution with a 10-year history of a pruritic, recurrent, steroid-responsive skin eruption and a 3-year history of mild lymphadenopathy. Excisional lymph node biopsy demonstrated a clonal, surface CD3-CD4+ T-cell infiltrate, prompting a diagnosis of peripheral T-cell lymphoma, not otherwise specified. Further workup revealed bone marrow and peripheral blood involvement. She received multiagent chemotherapy with temporary resolution of her skin eruption and lymphadenopathy, but persistent bone marrow disease. Presenting to our institution 3 years later, she exhibited numerous flesh-colored papules involving the extremities, without patches or plaques of mycosis fungoides. Skin biopsies demonstrated a dermal perivascular and interstitial proliferation of monotonous small T-cells without significant epidermotropism. T-cell receptor gene rearrangement studies of skin and peripheral blood specimens revealed identical clonal peaks, and peripheral blood flow cytometry showed persistence of the previously identified T-cell clone. Laboratory workup demonstrated a markedly elevated IgE level (66,580 kU/L) with a normal eosinophil count and IL-5 level. Next-generation sequencing of a peripheral blood sample revealed a pathogenic STAT3 S614R variant, previously documented in LV-HES. Although lacking eosinophilia, the patient's indolent course, characteristic skin lesions, steroid responsiveness, and pathologic features are typical of LV-HES, and the elevated IgE and STAT3 activation underscore a similar biology. We thus propose that this case expands the spectrum of indolent Th2-T cell lymphoproliferative disorders that need to be distinguished from peripheral T-cell lymphoma clinically.