Abstract

Lymphocytic variant of hypereosinophilic syndrome (LV-HES) is a rare T-cell lymphoproliferative disorder characterized by immunophenotypically abnormal Th2 T-cell clones which produce eosinophilopoietic cytokines, resulting in eosinophilia and end-organ damage. A 38-year-old female presented 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-negative/CD4-positive T-cell infiltrate, prompting a diagnosis of peripheral T-cell lymphoma, not otherwise specified, by an outside institution. Further workup revealed bone marrow and peripheral blood involvement. She received multiagent chemotherapy with temporary resolution of her skin eruption, but persistent bone marrow disease detected by flow cytometry. Three 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 that expressed cytoplasmic CD3 and CD4. Focal epitheliotropism was evident. T-cell receptor gene rearrangement studies of skin, bone marrow, 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 SH2 domain variant in the clonal T-cell population. Although lacking eosinophilia, the indolent course, steroid responsiveness, and immunophenotype are typical of LV-HES, as supported by an elevated IgE and STAT3 activation. Close monitoring is required due to the known risk of its progression to lymphoma.