Adult-onset non-langerhans histiocytosis with multisystem involvement and sustained remission on immunochemotherapy

Abstract Histiocytosis refers to a group of rare disorders characterized by the proliferation and accumulation of cells derived from the monocyte-macrophage or dendritic cell lineages. These conditions present with a broad spectrum of manifestations, ranging from isolated cutaneous or osseous lesions to multisystem involvement with significant morbidity. The most recognized subtypes include Langerhans cell histiocytosis (LCH), Rosai-Dorfman disease (RDD), and Erdheim-Chester disease (ECD), each with distinct histopathologic and clinical features. Given their rarity and frequent overlap with infectious, inflammatory, or neoplastic processes, histiocytic disorders often pose diagnostic and therapeutic challenges. We report the case of a 71-year-old Hispanic woman with a history of hypertension, mental disability, and generalized anxiety disorder, referred to hematology-oncology following the incidental discovery of a hepatic lesion during evaluation for an aortic aneurysm. Contrast-enhanced chest CTA demonstrated a hyperenhancing lesion in the left hepatic lobe measuring 2.2 × 2.5 × 2.7 cm, as well as an enlarged left paratracheal lymph node. PET-CT revealed hypermetabolic lymphadenopathy involving the pretracheal, left paratracheal, carinal, and right hilar regions. Dedicated chest CT showed bibasilar atelectasis and subcentimeter mediastinal lymph nodes, with no pulmonary masses or pericardial effusion. The patient reported unintentional weight loss of approximately 15–20 pounds over six months and persistent fatigue. Family history was notable for endometrial cancer in her mother and esophageal cancer in her father. She had not undergone prior age-appropriate cancer screening. An ultrasound-guided biopsy of a para-aortic lymph node demonstrated florid histiocytosis composed predominantly of pigment-laden histiocytes, with scant peripheral B lymphocytes and pericapsular soft tissue involvement. Immunohistochemistry revealed CD68-positive histiocytes, scattered S100-positive dendritic cells, and negative staining for CD1a and CD30, consistent with non-Langerhans histiocytosis. The patient was treated with oral etoposide 200 mg for 3 days every 21 days, in combination with oral prednisone, over the course of one year. She has now sustained clinical remission for the past six months and remains asymptomatic, with no evidence of disease-related complications. This case highlights the diagnostic complexity and therapeutic considerations in adult-onset histiocytosis. Recognition of characteristic histopathologic and immunohistochemical profiles, in combination with imaging to exclude alternative diagnoses, is essential for accurate classification. Early recognition and initiation of immunochemotherapy can lead to durable remission, even in cases with multisystem involvement.