Comparison of the Pheochromocytoma of the Adrenal Gland Scaled Score (PASS), Grading of Adrenal Pheochromocytoma and Paraganglioma (GAPP) and Modified GAPP: A Cross-sectional Study

Introduction: Pheochromocytoma (PCC) is a rare adrenal tumour with variable biological behaviour. Several histopathological scoring systems have been proposed to predict metastatic potential, including the Pheochromocytoma of the Adrenal Gland Scaled Score (PASS), the Grading of Adrenal Pheochromocytoma and Paraganglioma (GAPP), and the Modified GAPP (M-GAPP) incorporating Succinate Dehydrogenase Subunit B (SDHB) Immunohistochemistry (IHC). The present study focused to compare the performance of these scoring systems in an Indian single-centre series of adrenal PCC. Aim: To evaluate and compare the prognostic performance of PASS, GAPP, and M-GAPP scoring systems in predicting the malignant potential of adrenal PCC. Materials and Methods: This retrospective cross-sectional study was conducted at tertiary care centre,India, and included 111 histopathologically confirmed adrenal PCC cases diagnosed between 2000 and 2020 at a tertiary care centre in India. Clinical, biochemical, histopathological, and follow-up data were analysed. Sensitivity, specificity, Positive Predictive Value (PPV), Negative Predictive Value (NPV), and Receiver Operating Characteristic (ROC) curve analysis, with the Area Under the Curve (AUC), was used to calculate at predefined cut-offs (PASS ≥4; GAPP ≥3; M-GAPP high-risk). Chi-square test, Fisher’s exact test, Student’s t-test, or Mann-Whitney U test was used where appropriate, with significance set at p-value <0.05. Results: The mean age at diagnosis was 36.8±14.8 years. Tumours were right-sided in 45.05%, left-sided in 39.64%, and bilateral in 15.31%. Metastasis occurred in 8.11% of cases, while recurrence was seen in 3.60%. Among syndromic cases, Von Hippel–Lindau (VHL) mutation was associated with metastasis in 11.76% of patients. Comedo-type necrosis showed a significant correlation with metastasis (p-value = 0.008). PASS (≥4) showed a sensitivity of 55.56% and specificity of 67.60%. GAPP (≥3) showed a sensitivity of 66.67% and specificity of 59.80%. M-GAPP incorporating SDHB loss showed higher specificity (71.40%) and NPV (98.00%), though sensitivity was 21.30%. ROC curve analysis demonstrated M-GAPP had the highest AUC compared to PASS and GAPP. Conclusion: In this Indian Institutional series, M-GAPP outperformed PASS and GAPP by demonstrating better specificity and NPV, making it more reliable in excluding aggressive tumours. Incorporating SDHB IHC into histopathological assessment may improve risk stratification. Limitations include the retrospective, single-centre design and small number of metastatic events.