From juvenile idiopathic arthritis to blastic plasmacytoid dendritic cell neoplasm: A diagnostic odyssey in a 14-year-old patient

Abstract Musculoskeletal symptoms can often present within a wide differential diagnosis in pediatrics, with juvenile idiopathic arthritis (JIA) often considered early in the differential at times. However, in cases of seronegative polyarthritis, a high index of suspicion should be maintained, as rare hematologic malignancies like blastic plasmacytoid dendritic cell neoplasm (BPDCN) can closely mimic JIA and lead to misdiagnosis. Early recognition of atypical features—such as unexplained cytopenias or organomegaly—is important to avoid delays in diagnosis and inappropriate immunosuppressive therapy. Case presentation: We present a rare case of a 14-year-old patient , who initially diagnosed with seronegative polyarticular JIA after an 8-week history of migratory joint pain without systemic symptoms. The patient was treated with standard therapy including methotrexate and adalimumab. Three months into therapy, the patient developed persistent fever, mucositis with black-blue gingival discoloration, cervical lymphadenopathy, and pancytopenia. With these atypical features, further evaluation was prompted and ultimately led to a diagnosis of blastic plasmacytoid dendritic cell neoplasm (BPDCN ) . Bone marrow biopsy revealed 60% blasts with a distinct immunophenotype (CD4⁺, CD56⁺, CD123⁺, TCL1⁺, CD303⁺). The patient was started on the Children's Oncology Group (COG) AALL1732 protocol, a high-risk ALL-directed chemotherapy regimen. The patient achieved remission and continue to be in remission till this date. Discussion: This case highlights the diagnostic complexity and clinical overlap between JIA and other malignant hematological conditions, underscoring the importance of maintaining a broad differential in pediatric patients with persistent cytopenias and B-symptoms. Although patients with JIA and other autoimmune conditions have a modestly increased risk of therapy related to myeloid neoplasms and Non-Hodgkin Lymphoma (NHL), there is less than a handful number of cases with an incidental diagnosis of BPDCN following a diagnosis of an autoimmune disease, and none reported JIA, making this presentation exceedingly rare. Novel therapeutics targeting CD123, such as tagraxofusp (SL-401), a CD123-directed cytotoxin, have shown high response rates in adult populations, yet pediatric efficacy and safety data remain limited. Other investigational agents includes, venetoclax and CD123-directed CAR-T cells. Pediatric treatment remains challenging, with ongoing studies needed to establish safety and efficacy in this population. Conclusion: This case emphasizes the urgent need for increased awareness of BPDCN in pediatric practices, given it is bimodal distribution. Earlier diagnostic consideration in atypical autoimmune presentations and expanded access to pediatric-specific treatment protocols and clinical trials are critical keys for improving outcomes in such vulnerable population.