A Case of Hydroa Vacciniforme Lymphoproliferative Disorder with Progression into T-Cell Lymphoma

Hydroa vacciniforme lymphoproliferative disorder (HV-LPD) is a rare cutaneous disorder characterized by hemorrhagic vesicle formation due to infiltrative Epstein-Barr virus (EBV)-infected T-cells. The disorder is most often observed in children and young adults from Asia and South America, typically following sun exposure, and generally follows an indolent clinical course with the potential for spontaneous regression. In rare cases, patients can develop systemic manifestations that may progress to aggressive T-cell or natural killer (NK)-cell leukemia/lymphoma. Here, we present, to our knowledge, the first reported case of systemic HV-LPD progressing into a T-cell lymphoma in an elderly adult in the United States, resulting in a fatal outcome.

The patient was a 63-year-old Asian woman who presented with an approximately 10-month history of progressive hemorrhagic bullae and vesicles involving the face, fingers, and toes, as well as small erythematous monomorphic papules on the lower extremities. Skin biopsies of the fingertips demonstrated ischemic necrosis with vascular thrombi and small-vessel vasculitic changes with concomitant biopsies of the lower extremity lesions revealing a non-necrotizing granulomatous infiltrate.  

She was initially treated with mycophenolate mofetil and hydroxychloroquine for vasculitis. She subsequently developed a 4 cm subareolar breast mass, numerous cutaneous papules, and diffuse subcutaneous nodules. Repeat skin biopsies demonstrated an atypical lymphoid infiltrate with CD3 and EBER-ISH positivity as well as variable CD7 concerning for T-cell LPD. A PET/CT demonstrated extensive FDG-avid lymphadenopathies above and below the diaphragm, increased metabolic activity of the spleen and liver, and multiple FDG-avid soft tissue nodules involving all four extremities. Core needle biopsy of a right inguinal lymph node revealed atypical lymphocytes positive for CD3, CD4, and EBER-ISH. CD30 was negative. T-cell receptor (TCR) gene rearrangement analysis confirmed clonality. Based on these findings, together with the patient's clinical presentation, a diagnosis of systemic HV-LPD progressing into a T-cell lymphoma was established.

After completing one cycle of CHEOP, the patient presented with fever, new cutaneous lesions, and an increase in plasma EBV DNA to 4,650 IU/mL. Biopsy of the new skin lesions confirmed progression of lymphoma. She was subsequently treated with nivolumab as salvage therapy. Despite completing four cycles, she experienced continued progression of her cutaneous lesions involving the face and hands as well as persistent fever. Repeat PET/CT demonstrated persistent and diffuse avid lymphadenopathy consistent with refractory disease. Given this progressive disease and the absence of additional effective therapeutic options, the patient elected to enroll in hospice care and died several weeks later.

To our knowledge, this represents the first reported case of systemic EBV-associated HV-LPD progressing into a T-cell lymphoma in an elderly adult in the United States. Although similar cases have been reported previously, they have been observed predominantly in children and young adults in Asia and South America. Given the rarity of HV-LPD and its potential for aggressive disease progression, increased awareness and further research are needed to improve recognition, optimize treatment strategies, and improve patient outcomes.