pCLE will be introduced to detect suspected areas of the parietal pleura. The pCLE inspection will follow a standardized protocol with two main steps. First, any visible abnormalities under white light, such as nodules or thickening, will be examined with pCLE to evaluate intralesional heterogeneity and determine the best biopsy site. Second, the basal pleura will be systematically swept, covering at least two intercostal spaces above the costophrenic recess, including the diaphragmatic pleura and lower posterior chest wall, which are common sites for malignant involvement. After confirming the targeted area of the parietal pleura for pleural biopsy, the pCLE probe will be withdrawn, and a flexible forceps biopsy will be performed. This process will be repeated eight times, and eight samples will be obtained. All specimens will be transported in separate formalin containers with biopsy sequences for histopathological analysis.

For patients assigned to receive pleural biopsy via semi-rigid thoracoscopy alone, the parietal, visceral, and diaphragmatic pleura will be inspected, and eight biopsies will be obtained under direct vision in all suspected areas of the parietal pleura.

After the completion of the routine thoracoscopic examination, the biopsy location was determined based on the results of chest CT/ ultrasound. The benign and malignant states of pleural lesions were explored by nCLE and image records were collected. Then, the biopsy tissues were collected under the guidance of nCLE.

The proportion of participants in whom a specific diagnosis is established following pleural biopsy via semirigid thoracoscopy, based on histopathological analysis and final reference diagnosis (including 12-month follow-up for initially benign or nonspecific results).

The negative likelihood ratio is defined as the probability of a negative biopsy result (i.e., no specific malignant or tuberculous diagnosis) in a patient who truly has the target disease (malignant pleural mesothelioma, metastatic cancer, or tuberculous pleurisy), divided by the probability of a negative biopsy result in a patient who does not have the disease.

Because pleural biopsy results have no false positives in this study (specificity = 1, false-positive rate = 0), the NLR simplifies to 1 - sensitivity.

It will be calculated using the final reference diagnosis at 12 months as the gold standard.