[Abstract]Objective: To screen specimens with high qPCR positive rates based on HE histopathological characteristics for the rapid, accurate, and economical diagnosis of pulmonary tuberculosis. Methods: A retrospective analysis was conducted on the clinical data and CT findings of 189 patients with pulmonary granulomatous diseases. Formalin-fixed paraffin-embedded(FFPE) specimens were initially screened by Hematoxylin and Eosin (H&E) staining, followed by Ziehl-Neelsen (Z-N) staining and qPCR assay for further verification. Results: 1) Based on CT Findings, 189 specimens were divided into two groups: the peripheral nodular group predominantly showed hilar and mediastinal lymphadenopathy(87/149, 58.4%), lobulation sign (66/149, 44.3%), and spiculation sign (63/149, 42.3%); the central mass group mainly exhibited bronchial obstruction (31/40, 77.5%) and atelectasis (29/40, 72.5%). These findings were often indistinguishable from neoplastic lesions, leading to diagnostic delays.2) HE staining results from 95 confirmed pulmonary tuberculosis specimens revealed that the percentage of necrotic area≥25% (χ2 = 41.649, P = 0.000) and granuloma diameter≥8 mm (χ2 = 8.071, P = 0.004) were correlated with qPCR positivity. 3) Binary logistic regression analysis showed that the percentage of necrotic area and granuloma diameter in pulmonary tuberculosis were independent predictors of qPCR positivity(OR =1.324, 95%CI:1.202-1.460, P＜0.001; OR =0.265, 95%CI:0.164-0.429, P＜0.001). For FFPE specimens of pulmonary tuberculosis, the area under the curve (AUC), sensitivity, and specificity for measuring necrotic area percentage and granuloma diameter were 0.794/0.600, 78.2%/88.5%, and 78.9%/43.7%, respectively. Conclusion: When CT findings of peripheral nodules show hilar and mediastinal lymphadenopathy, lobulation sign, spiculation sign, they are more likely to delay diagnosis of granulomatous diseases such as pulmonary tuberculosis. The measurement of necrotic area and granuloma diameter can improve the sensitivity of qPCR detection. Preliminary screening with HE staining to select high-quality specimens for testing can enhance the accuracy of tuberculosis diagnosis.