1. Patients characteristics
A total of 122 patients were finally enrolled into the study, median age was 34 (22 ~ 59) years old, males were 66.4% (81/122), 76 patients (76/122, 62.3%) had accompanied with pulmonary TB, 54 cases (54/122, 44.3%) showed pleural thickness with average diameter at 3.1 (2.0 ~ 4.3) cm. During the follow up of treatment, 42 patients were observed to develop pleural based mass with occurrence rate of 34.4% (42/122). In patients with pleural based mass, 64.3% (27/42) had single nodule, 26.2% (11/42) had two nodules, 9.5% (4/42) had more than 3 nodules. For occurrence time during the anti-TB treatment, 47.6% (20/42) occurred at 4 to 6 months of course (Table 1). Clinical characteristics and flow diagram of included cases were shown in figure 2.
Patients with occurring pleural based mass were younger (29 years old vs. 42 years old, p=0.001) and had higher rate of pleural thickness (78.6% vs. 26.3%, p=0.001) and pleural adhesion (47.6% vs. 18.8%, p=0.001) and higher proportion of packaged pleural effusion (47.6% vs. 18.8%, p=0.001) compared with those without occurring pleural based mass (P=0.001), however, MTB culture positive rates from any specimens were similar in both groups, P>0.05(Table 2).
2. Biochemical and cytokines expression in pleural effusion
To further explore characteristics of patients with occurring pleural based mass, we tested biochemical and cytokines in pleural fluid at the initiation of anti-TB treatment, LDH and ADA were significantly higher and glucose was lower in patients with pleural based mass patients than those without pleural based mass, p value was 0.001, 0.001, 0.008, respectively. TGF-β and PAI-1 were statistically higher and t-PA was significantly lower in patients with pleural based mass than those in patients without pleural based mass (20.021 μg/L vs. 16.386 μg/L, P=0.044, 241.014 μg/L vs 187.152 μg/ L, P=0.048, 1.733 μg/L vs 3.025 μg/L, P=0.024), Detailed data were showed in Table 3.
3. Surgical findings
Among 42 patients occurred pleural based mass, 12 of them (12/42, 28.6%) were received surgical resection. 41.7% (5/12) of pleural based masses were actually located in parenchyma closed to the pleura and only 58.3% of them were located on pleura through the surgical findings (see in Figure 3A, B and C). Only 2 pleural based masses (2/12, 16.7%) showed encapsulated empyema exhibited as abundant pus wrapped in fibrous tissue. Others (10/12, 83.3%) were shaped as tuberculoma.
4. Pathological observations
Pathological diagnosis was made on 12 surgical and 30 biopsy specimens. According to pathological findings, pleural based masses had three pathological types: (1) granulomatous inflammation type, in which lesions mainly included inflammatory cells, epithelioid histiocytes, Langhans giant cells with or without necrosis. Most pleural based mass lesions (34/42, 81.0%) presented this type; (2) fibrous hyperplasia type, in which lesions mainly consisted of fibroblasts and fibrous proliferation without any granulomatous changes, few cases (3/42, 7.1%) presented this type; (3) necrosis type, in which lesions showed large area of caseous necrosis with or without infiltration of inflammatory cells, fibrous hyperplasia and granuloma were not obviously observed. Necrosis seemed as dominant morphology including 2 cases of encapsulated empyema, 5 cases (5/42, 11.9%) presented type 3(See in figure 4).
AFB stain was positive in 52.4% of cases (22/42,). IHC expression of PAI-1 (50 vs. 20, p<0.05) was higher and t-PA (100 vs. 160, p<0.05) was lower in patients with pleural based mass compared to patients without pleural based mass, which were in accordance with the cytokines change trend in pleural effusions tested by ELISA.
5. Anti-TB drug-resistance genes mutation detections
Specimens were extracted DNA and tested by rpoB, katG, inhA, embB and rpsL genes mutation. 57.1% (24 /42) of cases were found positive of MTB DNA, only 9.5% (4/42) of them were detected mutation of drug resistance gene, including 1 case (2.4%) with resistance to isoniazid, rifampicin and streptomycin, 2 cases (4.8%) with isoniazid resistance and 1 case (2.4%) with resistance to rifampicin (see in table 4).
6. Treatment and outcome:
We following all patients with pleural TB, all patients without pleural based mass had cured after full course of chemotherapy. Among 42 cases with pleural based mass, 12 cases received surgical resection got cure, 73.3% of cases (22/30) without received surgical resection had their pleural based mass no change after finished one year of chemotherapy, only 4 cases (4/30, 13.3%) got partly absorption and 4 cases (4/30, 13.3%) got obviously absorption, and no patient found their lesions deteriorated. All patients remained the anti-TB regimen no matter pleural based mass occurred or not.
Most pleural based mass (90.9%, 20/22) larger than 3 cm had no change after finished anti-TB treatment course, however, lesions with smaller than 1cm in diameter had absorbed, including 75% (3/4) of lesions obviously absorbed and 25% (1/4) of lesions partially absorbed after finished the treatment (see in table 5).
7. Analysis of predictive risk factors of pleural based mass
We found nearly 30% of patients with pleural TB occurred pleural based mass during the treatment. To explore the risk factors of occurring pleural based mass on patients with pleural TB, ROC curve was used to choose the best appropriate clinical characteristics, biochemical and cytokines indexes for association of occurrence of pleural based mass. After screening and calculating the value of AUC, age, glucose, ADA, LDH, protein, TGF-β, PAI-1 and t-PA were associated with the occurrence of pleural based mass, data were shown in table 6.
We further used Fagan's nomogram to evaluate the prognostic possibility of pleural based mass occurrence. We found the probability of pleural TB to develop pleural based mass can reach 99.7% when patients have pleural thickness, packaged pleural effusion, LDH>461.5IU/L, ADA>62.9IU/L, GLU<4.75mmol/L, TGF-β>15.235μg/L, PAI-1>180.720μg/L, t-PA<2.875μg/L and age<32.5 years old. There was no probability (0.0%) to develop pleural based mass when patients do not have above nine characteristics (see in table 6 and figure 5).