Splenic and Systemic Lymphoma in an FIV‑Positive Cat: A Case Report Highlighting Diagnostic Discordance in Cytology Interpretation

Feline immunodeficiency virus (FIV) causes chronic immune dysregulation that provokes lymphoid hyperplasia, often complicating the cytologic diagnosis of neoplasia. We present a 3-year-old female domestic shorthair cat from Iran evaluated for chronic pyrexia, approximately 12% weight loss, and generalized lymphadenopathy. Ultrasonography revealed marked splenomegaly with a “Swiss-cheese” or mottled parenchymal pattern, hepatomegaly, and bilateral renal medullary rim signs. Hematological analysis demonstrated persistent hyperglobulinemia, hypoalbuminemia, and a markedly decreased albumin-to-globulin (A/G) ratio (~0.24), indicative of sustained antigenic stimulation. Virologic testing confirmed persistent FIV infection via PCR. Notably, a single initial FeLV ELISA was positive, but subsequent PCRs were negative, suggesting transient antigenemia or false-positive detection. Cytologic evaluations of different lymph nodes yielded highly discordant results: mandibular aspirates indicated reactive lymphoid hyperplasia, whereas mesenteric aspirates 16 days later revealed high-grade lymphoblastic lymphoma. This striking disparity illustrates profound lesion heterogeneity and spatial sampling bias under retroviral immunosuppression. Despite partial initial responsiveness to a vincristine-prednisolone-based chemotherapy protocol and supportive care, the patient’s condition deteriorated, culminating in death 15 months post-diagnosis. This case emphasizes the diagnostic challenges of differentiating FIV-induced reactivity from lymphoma. It highlights the necessity of serial, multisite cytologic sampling integrated with advanced imaging and precise virologic testing for the accurate diagnosis of feline hematopoietic malignancies.