Malignancies Presenting With ANCA Positivity: Two Case Reports and Diagnostic Considerations

ANCA-associated vasculitides (AAV) are small-vessel inflammatory disorders characterized by the presence of anti-neutrophil cytoplasmic antibodies (ANCA), including those against proteinase 3 (PR3) and myeloperoxidase (MPO). ANCA positivity is not exclusive to vasculitis and may also occur in the context of malignancies or infections, leading to diagnostic confusion. In this report, we present two cases of malignancy with ANCA positivity.

The first case involved a 42-year-old male with nasopharyngeal symptoms, hearing loss, and proteinuria. Laboratory findings revealed elevated PR3-ANCA and MPO-ANCA levels, and a diagnosis of AAV was initially made. Despite immunosuppressive treatment, the patient developed persistent fever and rapid clinical deterioration. A subsequent bone marrow biopsy confirmed lymphoma with bone marrow infiltration. The second case presented with abdominal pain and retroperitoneal fibrosis. PET-CT imaging identified multifocal soft tissue masses in the lacrimal glands, nasopharynx, retroperitoneum, thoracic-lumbar vertebrae, and rib region. Histopathological analysis confirmed an inflammatory myofibroblastic tumor.

These cases highlight the potential for tumors to mimic AAV both clinically and serologically. They emphasize the importance of a careful differential diagnosis in patients with ANCA positivity, particularly when clinical progression is atypical or treatment response is suboptimal. The pathophysiological relationship between tumors and AAV remains unclear, but may involve common mechanisms such as neutrophil extracellular trap formation and autoantigen presentation of PR3 and MPO. Further studies are needed to elucidate these links and improve diagnostic accuracy in such complex presentations.