Abstracts
PO95
Persistent Diagnostic Uncertainty in Suspected Castleman Disease: A Case of Recurrent Non-Diagnostic Biopsies Across an Anterior Mediastinal Mass and Cervical Lymphadenopathy
Introduction/Background/Significance: Castleman disease is a lymphoproliferative disorder marked by benign overgrowth of lymphoid tissue, split into unicentric (UCD) and multicentric (MCD) forms. Castleman disease presents with non-specific features: lymphadenopathy, fevers, cytopenias, hypoalbuminemia, and elevated inflammatory markers, which overlap with a myriad of other conditions making it a diagnosis of exclusion. The internationally accepted approach requires both major histopathologic criteria plus at least 2 of 11 minor criteria, and critically, ruling out infectious, autoimmune, and malignant mimics (1). Likewise, the diagnosis depends on intact nodal architecture fine-needle and core-needle biopsies are frequently inadequate, requiring full excisional sampling and expert hematopathology evaluation.
Materials and Methods/Case Presentation/Objective: This case presentation features a 36-year-old female who has been under evaluation for recurrent lymphadenopathy. She was initially evaluated for cervical lymphadenopathy after a PET scan demonstrated two metabolically active cervical lymph nodes. Excisional biopsy of these nodes showed reactive lymphoid hyperplasia without immunophenotypic abnormalities. The workup subsequently expanded after a repeat PET scan identified FDG-avid soft tissue in the right anterior mediastinum, measuring 2.0 x 5.1 cm with an SUV max of 6.6. Given her history of previous lymphadenopathy; there was strong suspicion for Castleman disease. The patient had presented to the hospital with chief complaints of chest discomfort. With a reassuring EKG and negative troponin, the patient was concerned that etiology of symptoms was secondary to her mediastinal mass. Subsequently she underwent VATS biopsy of the mediastinal mass and pericardial sac; pathology returned two lymph nodes and pericardial tissue, both negative for neoplasm. She was medically clear for discharge with instruction to follow up with her primary care team.
Results/Description/Main Outcome Measure(s): Pathology report on revealed that biopsy of pericardial sac was "negative for malignancy" and that excised lymph nodes excised from the mediastinum were also "negative for malignancy."
Conclusion(s).: This case illustrates a gap between how the pathology results were reported and what a Castleman diagnosis actually requires. Each biopsy across this patient's two-year course, two cervical lymph node excisions and now the mediastinal/pericardial VATS specimens, was reported simply as "negative for neoplasm" or "reactive," a binary malignancy screen that answers whether cancer is present but says nothing about the specific architectural features that establish or exclude Castleman disease. True diagnosis of Castleman disease based on biopsy requires characteristic lymph node histopathology; regressed germinal centers often with expanded mantle zones containing concentric rings of lymphocytes classically characterized as "onion-skinning" (2). This patient has neither been ruled in nor ruled out for Castleman disease. The teaching point is less about any single missed finding than about the importance of explicitly matching the diagnostic test requested, and the pathology read requested in return, to the actual criteria for the disease under consideration.
Trademarked Items:
References: 1. Fajgenbaum, David C., et al. "International, evidence-based consensus diagnostic criteria for HHV-8-negative/idiopathic multicentric castleman disease." Blood, vol. 129, no. 12, 23 Mar. 2017, pp. 1646-1657, https://doi.org/10.1182/blood-2016-10-746933.
2. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Castleman Disease. Version 2.2026. Published April 28, 2026. Accessed July 31, 2026. https://www.nccn.org/guidelines
Materials and Methods/Case Presentation/Objective: This case presentation features a 36-year-old female who has been under evaluation for recurrent lymphadenopathy. She was initially evaluated for cervical lymphadenopathy after a PET scan demonstrated two metabolically active cervical lymph nodes. Excisional biopsy of these nodes showed reactive lymphoid hyperplasia without immunophenotypic abnormalities. The workup subsequently expanded after a repeat PET scan identified FDG-avid soft tissue in the right anterior mediastinum, measuring 2.0 x 5.1 cm with an SUV max of 6.6. Given her history of previous lymphadenopathy; there was strong suspicion for Castleman disease. The patient had presented to the hospital with chief complaints of chest discomfort. With a reassuring EKG and negative troponin, the patient was concerned that etiology of symptoms was secondary to her mediastinal mass. Subsequently she underwent VATS biopsy of the mediastinal mass and pericardial sac; pathology returned two lymph nodes and pericardial tissue, both negative for neoplasm. She was medically clear for discharge with instruction to follow up with her primary care team.
Results/Description/Main Outcome Measure(s): Pathology report on revealed that biopsy of pericardial sac was "negative for malignancy" and that excised lymph nodes excised from the mediastinum were also "negative for malignancy."
Conclusion(s).: This case illustrates a gap between how the pathology results were reported and what a Castleman diagnosis actually requires. Each biopsy across this patient's two-year course, two cervical lymph node excisions and now the mediastinal/pericardial VATS specimens, was reported simply as "negative for neoplasm" or "reactive," a binary malignancy screen that answers whether cancer is present but says nothing about the specific architectural features that establish or exclude Castleman disease. True diagnosis of Castleman disease based on biopsy requires characteristic lymph node histopathology; regressed germinal centers often with expanded mantle zones containing concentric rings of lymphocytes classically characterized as "onion-skinning" (2). This patient has neither been ruled in nor ruled out for Castleman disease. The teaching point is less about any single missed finding than about the importance of explicitly matching the diagnostic test requested, and the pathology read requested in return, to the actual criteria for the disease under consideration.
Trademarked Items:
References: 1. Fajgenbaum, David C., et al. "International, evidence-based consensus diagnostic criteria for HHV-8-negative/idiopathic multicentric castleman disease." Blood, vol. 129, no. 12, 23 Mar. 2017, pp. 1646-1657, https://doi.org/10.1182/blood-2016-10-746933.
2. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Castleman Disease. Version 2.2026. Published April 28, 2026. Accessed July 31, 2026. https://www.nccn.org/guidelines
