Journal of Pathology and Translational Medicine

Original Article

Multicenter evaluation of the PASS score as a negative predictive tool and the impact of inter-observer variability in pheochromocytoma and paraganglioma risk stratification: Sungyeon Jung, Hye-Ri Shin, Su-Jin Shin, Hee Young Na, Soon-Won Hong, So Yeon Park, Chan Kwon Jung, Kyeong Cheon Jung, Young Lyun Oh, Jae-Kyung Won; J Pathol Transl Med. 2026;60(2):202-213. Published online February 23, 2026; DOI: https://doi.org/10.4132/jptm.2025.11.05

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Abstract PDF: Background
The Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) is widely used for risk stratification in pheochromocytoma and paraganglioma (PPGL), but its clinical utility is limited by inter-observer variability of its parameters and inconsistent predictive performance. Methods: We conducted a multicenter retrospective study of 1,518 patients with PPGL from five tertiary referral centers in Korea. Prognostic utility of PASS system was assessed using logistic regression, Kaplan-Meier analysis, and receiver operating characteristic (ROC) curve analysis. Inter-observer variability was inferred by comparing area under the ROC curve (AUCs) across institutions. Simplified PASS systems were developed based on multivariable analysis of key histopathological parameters. Results: The PASS system was a significant predictor of adverse events and recurrence-free survival. Although the PASS system demonstrated only modest discriminative ability (AUC, 0.673), it showed a high negative predictive value (NPV, 0.885), supporting its usefulness as a screening tool for benign behavior. However, there was significant inter-institutional variability in PASS performance (AUC; range, 0.513 to 0.727; p < .05). The 3-factor Simple PASS, which incorporates necrosis, spindling, and mitotic figures, exhibited less inter-observer variation. The 4-factor Simple PASS, which adds vascular invasion to the 3-factor model, also showed reduced inter-observer variability and improved AUC and NPV compared to the original PASS system. Conclusions: In this multicenter cohort, the PASS system demonstrated high NPV and screening potential, but significant inter-observer variability remains a challenge. Simplification of the PASS system and enhanced pathologist training may improve reproducibility and clinical utility in PPGL risk stratification.

Case Report

Composite Pheochromocytoma or Paraganglioma of Adrenal Gland: A Case Report with Immunohistochemical Studies and Electron Microscopic Examination.: Hyeyoon Chang, Hoiseon Jeong, Younghye Kim, Sung Hye Park, Aeree Kim; Korean J Pathol. 2011;45(3):306-310.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.3.306

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1 Crossref

Composite pheochromocytoma or paraganglioma of the adrenal gland is a well-recognized, yet extremely rare tumor with only one case reported in Korea. We report a case of incidentally found composite pheochromocytoma and ganglioneuroma of the adrenal gland in a 44-year-old female composed of intermingled components of pheochromocytom, ganglioneuroma, and cells with intermediate features. On immunohistochemical staining, the pheochromocytoma component was positive for synaptophysin and chromogranin, but negative for S-100 protein. Staining for the S-100 protein revealed sustentacular cells which formed a peripheral coat around the "Zellballen" and Schwann cells. The Fontana-Masson stain defined neuromelanin granules of ganglion cells and the ganglion cells expressed neural markers such as neurofilament proteins. Ultrastructural findings revealed pheochromocytes with a round or ovoid nucleus and occasionally prominent nucleolus containing numerous adrenaline and noradrenaline granules.

Citations

Citations to this article as recorded by

Bilateral pheochromocytoma with ganglioneuroma component associated with multiple neuroendocrine neoplasia type 2A: a case report
Boubacar Efared, Gabrielle Atsame-Ebang, Soufiane Tahirou, Khalid Mazaz, Nawal Hammas, Hinde El Fatemi, Laila Chbani
Journal of Medical Case Reports.2017;[Epub] CrossRef

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