The combination of maximum standardized uptake value and clinical parameters for improving the accuracy in distinguishing primary mediastinal lymphomas from thymic epithelial tumors
Introduction
Mediastinal tumors are relatively uncommon, and more than half (about 59%) of masses in the anterior compartment are pathologically diagnosed as malignant tumors (1). The pathological types of primary anterior mediastinal masses include cyst, thymic hyperplasia, thymoma, thymic carcinoma, thymic neuroendocrine neoplasm, germ cell tumor, and lymphoma, among which thymic epithelial tumors (TETs; including thymoma, thymic carcinoma, and thymic neuroendocrine neoplasm) and lymphoma are the two most common types (2). The treatment strategies of TETs and lymphomas are almost completely different: surgery is suggested for most TETs, whereas immunochemotherapy and/or radiotherapy is more appropriate for the treatment of lymphomas (3,4). Traditional imaging modalities [e.g., computed tomography (CT) and magnetic resonance imaging (MRI)] have been widely used in clinical practice to evaluate mediastinal tumors; however, the similarity of TETs and lymphomas in morphologic assessment performed by traditional imaging technics consistently leads to misdiagnosis, thereby resulting in ineffective or inaccurate management and therapy (e.g., Ackman et al. reported a high rate of 59.4% of lymphomas with nontherapeutic thymectomy) (5). Therefore, the discrimination of lymphomas with TETs before treatment is essential for developing appropriately varied treatment strategies for anterior mediastinal masses.
Invasive biopsy is the only means to histologically diagnosing isolated anterior mediastinal masses; unfortunately, some patients are unable to obtain a pathological diagnosis due to certain reasons, such as an aversion to undergoing invasive examination, a physical debilitation preventing mediastinal lesion biopsy, or an insufficient sample volume in mediastinal lesion biopsy. However, as the most widely used molecular imaging modality for tumor diagnosis, 18fluorine-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET-CT) can provide information on glucose metabolism from different tumors and enable the noninvasive diagnosis of tumors. The maximum standardized uptake value (SUVmax) is the most commonly used 18F-FDG PET-CT parameter for tumor diagnosis and is able to reflect the glycolytic activity of tumors (6). Recently, the SUVmax of lymphomas was found to be significantly higher than that of TETs [except in several non-PET-avid subtypes such as mucosa-associated lymphoid tissue (MALT) lymphoma] (7,8); however, the accuracy, sensitivity, and specificity of SUVmax to predict anterior mediastinal lymphomas are all only about 70.0% and need to be improved (9). Since certain clinical parameters [e.g., gender, age, lactate dehydrogenase (LDH) level] were also demonstrated to be potential biomarkers of lymphomas or TETs (10), we speculate that the combination of clinical parameters may improve the accuracy of SUVmax for diagnosing anterior mediastinal lymphomas.
To investigate whether the combination of 18F-FDG PET-CT findings and clinical parameters can help differentiate anterior mediastinal lymphomas from TETs, this study analyzed the correlation between 18F-FDG SUVmax and clinical parameters [including gender, age, serum leukocytes, hemoglobin (Hb), LDH, and tumor size] and histology subtypes of TETs and lymphomas in anterior mediastinal masses. We present this article in accordance with the STARD reporting checklist (available at https://qims.amegroups.com/article/view/10.21037/qims-23-496/rc).
Methods
Study population
There were a total of 476 patients with anterior mediastinal masses who underwent 18F-FDG PET-CT 1 to 2 weeks before tumor resection or biopsy between August 2016 to March 2022 at Shanghai Chest Hospital. Ultimately, 304 patients histologically diagnosed with TETs and lymphomas were enrolled in this retrospective study (Figure 1). The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013) and was approved by the Institutional Review Board of Shanghai Chest Hospital (No. KS1753). Individual consent for this retrospective analysis was waived.
The inclusion criteria for patients were as follows: (I) presence of anterior mediastinal mass, (II) confirmation via histologic examination, (III) no history of any mediastinal mass-associated treatment before PET-CT, and (IV) availability of pathologic findings. Meanwhile, the exclusion criteria were as follows: (I) no detailed histologic results (n=97), (II) a history of radiotherapy or chemotherapy before PET-CT (n=35), (III) a histologic subtype other than TETs and PET-avid lymphomas [germ cell tumor (n=18), MALT lymphoma (n=3), thymic benign tumor (n=11), and other rare tumors (n=8)]. Records of included patients were reviewed to retrieve information on gender, age, serum leukocytes, Hb, and LDH levels (normal value 120–250 U/L at our institution).
According to a stratified analysis, patients were randomly assigned in a 7:3 ratio to cohorts for the modeling (n=230) and validation (n=74) of lymphoma predictors.
PET-CT imaging
18F-FDG PET-CT was performed after patients fasted for at least 6 hours and 60 min after an intravenous administration of 18F-FDG (3.7 MBq per kilogram of body weight, radiochemical purity 95%) provided by Shanghai Kexin Pharmaceutical (Shanghai, China). The blood glucose levels were measured just prior to tracer administration, and a maximal blood glucose level of 140 mg/dL was required for optimal 18F-FDG uptake.
Imaging was performed with a combined PET-CT device (Biograph mCT 64; Siemens Healthineers, Erlangen, Germany). CT scanning (120 keV, 30–100 mA in auto mA mode, 5.00-mm slice thickness) was first performed without contrast material administration. Immediately after CT scanning, PET imaging was performed with an acquisition time of 3 minutes per bed position. The regions of interest (ROIs) of primary lesions were manually defined, and SUVmax and diameters were independently recorded by two experienced nuclear medicine physicians (W.X. and C.C., with approximately 20 and 15 years of experience in the interpretation of PET-CT images, respectively) blinded to the study design. The differences between physicians’ assessments were resolved by consensus through discussion, and they reached an almost perfect agreement.
Histologic classification
Based on the 2021 World Health Organization (WHO) classification system (11), thymomas were classified into the five following subtypes depending on the morphology of epithelial cells and the lymphocyte-to-epithelial cell ratio: type A, AB, B1, B2, and B3. If a thymoma was composed of diverse (two or more) histologic subtypes (n=12), we selected the higher grade tumor subtype, irrespective of the extent of each subtype. According to previous reports (12,13), we classified thymoma into two groups: low-risk thymoma (type A, AB, and B1) and high-risk thymoma (type B2 and B3). Thymic carcinomas, which include thymic squamous cell carcinoma, adenocarcinoma, and sarcoma, exhibit a similar morphology to that of malignant neoplasms arising from other organs besides thymomas. Thymic neuroendocrine neoplasms include carcinoid tumor, small cell carcinoma, and large-cell neuroendocrine carcinoma. Regarding mediastinal lymphoma, we chose the three most common types: primary mediastinal large B-cell lymphoma, Hodgkin lymphoma, and T-lymphoblastic lymphoma (1).
Statistical analysis
Data were analyzed with SPSS software version 24.0 (IBM Corp., Armonk, NY, USA), GraphPad Prism 6 (GraphPad Software, San Diego, CA, USA), and MedCalc version 20.211 (MedCalc Software Ltd., Ostend, Belgium). Quantitative data conforming to a normal distribution are presented as the mean ± standard deviation (SD) values. The unpaired two-tailed t-test or one-way analysis of variance (ANOVA) test was used to determine the association of age, gender, leukocytes, Hb, LDH, tumor size, and SUVmax between different histologic types in independent samples. The area under the receiver operating characteristic (ROC) curve (AUC) was calculated, and the DeLong test was used to compare AUCs and the cutoff values, with the highest Youden index being used as the optimal cutoff threshold for lymphoma diagnosis. Logistic regression analysis was used to assay the prediction rate of lymphoma among the three risk groups. A two-tailed P value <0.05 indicated a significant difference.
Results
Study population
A total of 304 patients (169 males and 135 females; age range, 12–79 years) who had anterior mediastinal masses and received 18F-FDG PET-CT scans were included in this retrospective study. Histologic confirmation of mediastinal masses was obtained via surgery or biopsy. As listed in Table 1, 108 of 304 patients (35.5%) were found with thymoma (type A: n=10; type AB: n=33; type B1: n=20; type B2: n=32; type B3: n=13), 109 of 304 patients (35.9%) were found with thymic carcinoma (squamous cell carcinoma: n=102; adenocarcinoma/sarcoma: n=7), 27 of 304 patients (8.9%) were identified with thymic neuroendocrine neoplasms (carcinoid tumor: n=10; small-cell carcinoma: n=14; large-cell neuroendocrine carcinoma: n=3), and 60 of 304 patients (19.7%) were identified with lymphoma. Among 60 patients with lymphoma, more than half (36/60, 60.0%) had primary mediastinal large B-cell lymphoma, with other types of lymphoma including Hodgkin lymphoma (13/60, 21.7%) and T-lymphoblastic lymphoma (11/60, 18.3%).
Table 1
Factors | All patients (n=304) | Modeling cohort (n=230) | Validation cohort (n=74) | P value |
---|---|---|---|---|
Age (years), median [interquartile range] | 53 [12–79] | 53 [12–79] | 54 [19–75] | 0.97 |
Gender | 0.19 | |||
Male | 169 | 123 | 46 | |
Female | 135 | 107 | 28 | |
Histologic type | ||||
Thymoma | 108 | 82 | 26 | 0.79 |
A | 10 | 7 | 3 | |
AB | 33 | 24 | 9 | |
B1 | 20 | 17 | 3 | |
B2 | 32 | 25 | 7 | |
B3 | 13 | 9 | 4 | |
Thymic carcinoma | 109 | 84 | 25 | 0.57 |
Squamous cell carcinoma | 102 | 78 | 24 | |
Adenocarcinoma/sarcoma | 7 | 6 | 1 | |
Thymic neuroendocrine neoplasm | 27 | 20 | 7 | 0.38 |
Carcinoid | 10 | 8 | 2 | |
Small-cell carcinoma | 14 | 9 | 5 | |
Large-cell neuroendocrine carcinoma | 3 | 3 | 0 | |
Lymphoma | 60 | 44 | 16 | 0.68 |
PMBL | 36 | 25 | 11 | |
Hodgkin lymphoma | 13 | 10 | 3 | |
TLL | 11 | 9 | 2 | |
Pathologic procedure | 0.21 | |||
Surgery | 159 | 125 | 34 | |
Needle biopsy | 145 | 105 | 40 |
PMBL, primary mediastinal large B-cell lymphoma; TLL, T-lymphoblastic lymphoma.
The characteristics of patients in the modeling and validation cohorts are also listed in Table 1; there was no significant difference in patient characteristics (age, gender, and pathological type) between the modeling and validation cohorts (P=0.19–0.97). Moreover, 159 patients underwent surgery, and 145 patients underwent needle biopsy. The differences of ways to obtain pathology between modeling and validation cohorts were not statistically significant (P=0.21).
Age, serum LDH, tumor size, and SUVmax differed across the five groups in the modeling cohort
To investigate the correlation of clinical and 18F-FDG metabolic features with different histological subtypes of anterior mediastinal masses, we analyzed the differences in gender, age, serum leukocytes, Hb, LDH, tumor size, and SUVmax of tumor in five anterior mediastinal mass groups (Table 2). This analysis indicated that the age of patients with lymphoma was significantly lower than that of those with low-risk thymoma, high-risk thymoma, thymic carcinoma, or thymic neuroendocrine neoplasms (P<0.001) (Figure 2A). Serum LDH level, tumor size, and SUVmax in those with lymphoma were all significantly higher than those in patients in the other four groups (all P values <0.001) (Figure 2B-2D), whereas gender, leukocytes, and Hb were not significantly different among the different types of anterior mediastinal masses (P=0.22–0.75).
Table 2
Factors | All patients (n=230) | Low-risk thymoma (n=48) | High-risk thymoma (n=34) | Thymic carcinoma (n=84) |
Thymic neuroendocrine neoplasm (n=20) | Lymphoma (n=44) | P value |
---|---|---|---|---|---|---|---|
Gender (M/F) | 123/107 | 23/25 | 14/20 | 49/35 | 14/6 | 23/21 | 0.22 |
Age (years) | 50.40±15.64 | 52.73±13.04 | 50.09±14.79 | 56.58±12.07 | 59.85±9.37 | 32.00±12.72 | <0.001 |
Leukocytes (109/L) | 7.25±2.72 | 6.95±1.75 | 6.51±2.59 | 7.36±2.57 | 7.37±2.44 | 7.90±3.83 | 0.22 |
Hb (g/L) | 137.03±17.99 | 137.48±20.58 | 140.12±15.32 | 137.08±16.79 | 135.80±18.80 | 134.58±19.15 | 0.75 |
LDH (U/L) | 249.49±163.25 | 188.17±46.74 | 185.32±33.74 | 225.58±92.33 | 242.25±109.71 | 414.89±283.40 | <0.001 |
Tumor size (cm) | 7.83±3.00 | 6.83±2.57 | 7.50±1.91 | 6.79±2.60 | 8.97±2.64 | 10.63±3.14 | <0.001 |
SUVmax | 12.00±7.82 | 5.64±2.26 | 7.18±2.68 | 12.36±5.51 | 12.82±7.42 | 21.63±8.55 | <0.001 |
Data are presented as n or mean ± standard deviation. SUVmax, maximum standardized uptake value; M, male; F, female; Hb, hemoglobin; LDH, lactate dehydrogenase.
Age, serum LDH, tumor size, and SUVmax were independent predictors of lymphoma
ROC analysis was next performed to obtain the optimal cutoff values of age, LDH, tumor size, and SUVmax to predict lymphoma in anterior mediastinal masses. In the results (Table 3, Figure 3), the optimal cutoff values for age, LDH, tumor size, and SUVmax to predict lymphoma were 40.5 years (accuracy 84.8%), 197 U/L (accuracy 67.8%), 10.72 cm (accuracy 85.2%), and 11.95 (accuracy 78.3%), respectively (AUC =0.802–0.890).
Table 3
Factors | Cutoff value | AUC (95% CI) | Accuracy | Univariate analysis | Multivariate analysis | |||
---|---|---|---|---|---|---|---|---|
OR (95% CI) | P value | OR (95% CI) | P value | |||||
Age (years) | 40.5 | 0.886 (0.826–0.947) | 84.8% | 29.83 (12.10–73.53) | <0.001 | 20.14 (6.02–67.40) | <0.001 | |
LDH (U/L) | 197 | 0.817 (0.748–0.886) | 67.8% | 16.57 (5.69–48.30) | <0.001 | 4.89 (1.27–18.89) | 0.021 | |
Tumor size (cm) | 10.72 | 0.802 (0.727–0.876) | 85.2% | 16.47 (7.40–36.64) | <0.001 | 8.82 (2.31–33.69) | 0.001 | |
SUVmax | 11.95 | 0.890 (0.838–0.942) | 78.3% | 30.44 (10.33–89.66) | <0.001 | 30.01 (6.59–136.72) | <0.001 |
AUC, area under the curve; CI, confidence interval; OR, odds ratio; LDH, lactate dehydrogenase; SUVmax, maximum standardized uptake value.
Univariate and multivariate logistic regression analyses were subsequently performed to identify the potential predictive factors for lymphoma in anterior mediastinal masses (Table 3). In the univariate analysis, young age, high serum LDH, large tumor size, and high SUVmax were significantly associated with anterior mediastinal lymphoma (all P values <0.001). Subsequent multivariate logistic regression analysis further revealed that age, LDH, tumor size, and SUVmax were independent predictors for lymphoma (P<0.001 to P=0.021). Young age was strongly associated with lymphoma, with an odds ratio (OR) value of 20.14 [95% confidence interval (CI): 6.02–67.40; P<0.001]. High LDH, tumor size, and SUVmax values were associated with an increased risk for lymphoma, with an OR value of 4.89 (95% CI: 1.27–18.89; P=0.021), 8.82 (95% CI: 2.31–33.69; P=0.001), and 30.01 (95% CI: 6.59–136.72; P<0.001), respectively.
To investigate that whether the combination of age, LDH, tumor size, and SUVmax could improve the predictive accuracy for lymphoma in anterior mediastinal masses, we next compared the probability of lymphomas being present in a high-risk group (age ≤40.5 years, LDH ≥197 U/L, tumor size ≥10.72 cm, and SUVmax ≥11.95), moderate-risk group (other than age ≤40.5 years, LDH ≥197 U/L, tumor size ≥10.72 cm, and SUVmax ≥11.95 or age >40.5 years, LDH <197 U/L, tumor size <10.72 cm, and SUVmax <11.95), and a low-risk group (age >40.5 years, LDH <197 U/L, tumor size <10.72 cm, and SUVmax <11.95) in the modeling cohort. The probability of lymphoma presence in the low-, moderate-, and high-risk groups were 0.0% (0/77), 18.2% (24/132), and 95.2% (20/21), respectively, while the probability TET presence in the low-, moderate-, and high-risk groups were 100.0% (77/77), 81.8% (108/132), and 4.8% (1/21), respectively (P<0.001; Table 4). We also calculated the accuracy of the high-risk group for predicting lymphoma and observed that the accuracy of the combined parameters to predict lymphoma was 89.1% (205/230). Furthermore, when age, LDH, tumor size, and SUVmax were combined in ROC analysis, the AUC (0.963; 95% CI: 0.935–0.991) was significantly higher than that of any of these parameters used alone (all P values <0.05) (Figure 3).
Table 4
Group | All patients, N | Probability of TET, % (n/N) | Probability of lymphoma, % (n/N) | P value |
---|---|---|---|---|
Modeling cohort | <0.001 | |||
Low risk | 77 | 100.0 (77/77) | 0.0 (0/77) | |
Moderate risk | 132 | 81.8 (108/132) | 18.2 (24/132) | |
High risk | 21 | 4.8 (1/21) | 95.2 (20/21) | |
Validation cohort | <0.001 | |||
Low risk | 19 | 100.0 (19/19) | 0.0 (0/19) | |
Moderate risk | 48 | 81.2 (39/48) | 18.8 (9/48) | |
High risk | 7 | 0.0 (0/7) | 100.0 (7/7) |
TET, thymic epithelial tumor.
Age, LDH, tumor size, and SUVmax were proven to be independent predictors for anterior mediastinal lymphoma, and their combination could improve the predictive accuracy for lymphoma. Representative examples are shown in Figure 4.
Validation of the effectiveness of age, LDH, tumor size, and SUVmax to predict lymphoma
To validate the effectiveness of the above mentioned cutoff values to predict lymphoma, we next analyzed the probabilities of lymphoma presence in young and old age, low and high LDH level, small and large tumor size, and low and high SUVmax in the validation cohort and confirmed that the probability of lymphoma was 59.1% (13/22), 34.9% (15/43), 56.2% (9/16), and 53.6% (15/28), respectively. The accuracy of predicting lymphoma using age, LDH, tumor size, and SUVmax based on the abovementioned cutoff values was 83.8% (62/74), 60.8% (45/74), 81.1% (60/74), and 81.1% (60/74), respectively (all P values ≤0.05; Table 5).
Table 5
Group | All patients, N | Probability of TET, % (n/N) | Probability of lymphoma, % (n/N) | Accuracy, % (n/N) | P value |
---|---|---|---|---|---|
Age | 83.8 (62/74) | <0.001 | |||
Low risk | 52 | 94.2 (49/52) | 5.8 (3/52) | ||
High risk | 22 | 40.9 (9/22) | 59.1 (13/22) | ||
LDH | 60.8 (45/74) | 0.001 | |||
Low risk | 31 | 96.8 (30/31) | 3.2 (1/31) | ||
High risk | 43 | 65.1 (28/43) | 34.9 (15/43) | ||
Tumor size | 81.1 (60/74) | <0.001 | |||
Low risk | 58 | 87.9 (51/58) | 12.1 (7/58) | ||
High risk | 16 | 43.8 (7/16) | 56.2 (9/16) | ||
SUVmax | 81.1 (60/74) | <0.001 | |||
Low risk | 46 | 97.8 (45/46) | 2.2 (1/46) | ||
High risk | 28 | 46.4 (13/28) | 53.6 (15/28) |
LDH, lactate dehydrogenase; SUVmax, maximum standardized uptake value; TET, thymic epithelial tumor.
To validate the effectiveness of the combination of age, LDH, tumor size, and SUVmax as a predictor of lymphoma in anterior mediastinal masses, we performed the same procedure as that described above in the validation cohort. The analysis revealed that the probabilities of lymphoma presence in the low-, moderate-, and high-risk groups were 0.0% (0/19), 18.8% (9/48), and 100.0% (7/7), respectively, while the probabilities of TET presence in the low-, moderate-, and high-risk groups were 100.0% (19/19), 81.2% (39/48), and 0.0% (0/7), respectively (P<0.001; Table 4). The accuracy of the high-risk group for predicting lymphoma was 87.8% (65/74). These data validated the superiority of the combined use of age, LDH, tumor size, and SUVmax for predicting lymphoma over the use of any these parameters used alone.
This study not only demonstrated the potential of age, LDH, tumor size, and SUVmax used alone to predict lymphoma in anterior mediastinal masses but also proved the superiority of their combination for prediction in this scenario.
Discussion
This study’s principal aim was to investigate whether the combination of SUVmax with clinical parameters could improve diagnostic accuracy in differentiating lymphoma and TETs in anterior mediastinal masses. The major findings were as follows: First, younger patient age, higher LDH level, larger tumor size, and higher SUVmax were associated with lymphoma in patients with anterior mediastinum masses. Second, age (≤40.5 years), LDH (≥197 U/L), tumor size (≥10.72 cm), and SUVmax (≥11.95) were each independent predictors for lymphoma. Third, the combination of age, LDH, tumor size, and SUVmax could increase the accuracy of each parameter alone to predict lymphoma, with a high predictive accuracy in the modeling (from 67.8–84.8% to 89.1%) and validation (from 81.1–83.8% to 87.8%) cohorts and a significantly high AUC in the ROC analysis (0.802–0.890 vs. 0.963). Indeed, previous studies have reported that lymphoma tends to occur in young adults, LDH is elevated in lymphomas (14), and the mean maximal diameter and SUVmax of lymphomas are significantly higher than those of TETs (15,16), which is consistent with our results. However, to our knowledge, our study is the first to combine SUVmax with clinical parameters and includes the largest sample used to investigate the differentiation of primary mediastinal lymphomas from TETs in anterior mediastinal masses.
Primary mediastinal lymphoma usually occurs in the anterior mediastinum, and lymphoma accounts for nearly 20% of all mediastinum neoplasms in adults and 50% in children (17). The discrimination of lymphoma and TETs is difficult due their associated low CT and MRI diagnostic efficiency and a lack of specific tumor markers (18,19). As the most well-known of the metabolic functional imaging techniques, 18F-FDG PET-CT can provide the metabolic and anatomic information of tumors and therefore has unique advantages in tumor imaging diagnosis. It has been reported that increased 18F-FDG uptake is associated with heightened risk level for TETs (20), which is in line with our research. Moreover, previous studies have reported that the 18F-FDG SUVmax of lymphoma is significantly higher than that of TETs (15,16). Similarly, our study found that SUVmax (≥11.95) was an independent predictor for lymphoma, with a significantly higher OR value (30.01) than that of the other three independent factors, meaning SUVmax was the most important diagnostic factor for predicting lymphoma. The accuracy of SUVmax alone was 78.3% and 81.1% in the modeling and validation cohort, respectively. Cumulatively, the above data highlight the potential of 18F-FDG PET-CT in helping the diagnosis of anterior mediastinal TETs or lymphoma. The 18F-FDG SUVmax of lesions may be a key metabolic biomarker associated with the pathologic types of anterior mediastinal masses.
Treatment strategies of mediastinal lymphoma and TETs are completely disparate: surgical resection is the major treatment strategy for TETs, whereas nonsurgical chemotherapy or radiation is preferred for the treatment of lymphoma (14,21). Certain situations, such as middle-aged patients with a high LDH level, younger patients with a normal LDH level, patients with multiple enlarged lymph nodes or distant metastasis, or patients with neuroendocrine neoplasms with atypical FDG uptake, can make it difficult to distinguish the pathological type. As 18F-FDG PET-CT and blood testing are routinely performed for the pretreatment workup of patients before treatment, our data have the potential to predict lymphoma in anterior mediastinal masses and may be helpful for developing suitable antitumor therapeutic strategies when clinical pathological and imaging findings failed to discriminate between lymphoma and TETs. For those with a high probability of lymphoma and an age ≤40.5 years, an LDH level ≥197 U/L, a tumor size ≥10.72 cm, and an SUVmax ≥11.95, partial resection or needle biopsy is recommended for suspected lymphoma to avoid unnecessary surgery. For those that with high probability of TETs and an age >40.5 years, an LDH level <197 U/L, a tumor size <10.72 cm, and an SUVmax <11.95, tumor resection can be considered first.
Our findings can be explained in terms of the relevant mechanisms. Lymphomas are clonal neoplasms that arise from B-cell, T-cell, and natural killer (NK)-cell subsets at various stages of maturation (22), whereas TETs are rare tumors arising from thymic epithelial cells. The difference in origin cells of lymphomas and TETs may explain the relatively young age of those with lymphoma compared to those with TETs (14) since young people tend to have more active immune cells which can increase the risk of lymphomas emergence; meanwhile, the physiological involution of the thymus progresses with age (23). LDH is a tumor marker associated with the proliferation, metastasis, and prognosis of many cancer types (24-26). The higher serum LDH levels in lymphoma compared to those in TETs suggests that lymphoma has a more aggressive phenotype than do TETs, which may be explained by lymphoma-induced high tumor burden and activation of oncogenic factors [e.g., hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF)] (27). From the viewpoint of tumor metabolism, high 18F-FDG uptake in lymphomas may be explained by the contribution of cellular energetics to the pathogenesis of lymphoma, for example the B-cell receptor (BCR)-independent diffuse large B-cell lymphoma (DLBCL)-designated oxidative phosphorylation (OxPhos) marked by increased expression of mitochondrial electron transport chain (ETC) components and BCR-dependent DLBCLs with high glycolytic flux typical of the Warburg phenotype (28). Meanwhile, the biologic mechanism of 18F-FDG uptake in TETs is related to the abnormal expression of glucose transporters (Glut1) and HIF-1α (20). Our data showed that lymphoma had relatively high glucose metabolic activity compared to TETs, and thus the mechanisms underlying the metabolic differences between lymphomas and TETs merit additional research.
Lymphomas and TETs are the two most common types of anterior mediastinal masses and can be easily confused with each other; hence, in this study, we focused on distinguishing TETs from lymphomas, and those relatively easy to diagnose types (e.g., germ cell tumors with elevated serum α-fetoprotein and β-human chorionic gonadotropin levels in patients) (29) or those that rarely occur (e.g., thymolipoma, thymic cyst, parathyroid adenoma) were excluded. In selecting lymphoma types to examine, we excluded MALT lymphoma due to its low average FDG uptake value (it is not as FDG-avid as other lymphomas) as well as other rare lymphoma subtypes (e.g., anaplastic large cell lymphoma and mature T-cell and NK-cell lymphoma) (30). We believe our data for noninvasively distinguishing lymphomas from TETs may be helpful for both the diagnosis and the treatment of anterior mediastinal masses that are difficult to diagnose.
There were a few limitations in this study that should be mentioned. First, this study focused on distinguishing between only two groups of neoplasm potentially involving the anterior mediastinum. Second, we employed a retrospective study design that inevitably involved some selective bias, and a prospectively designed study will be conducted in the future to further improve the accuracy of 18F-FDG PET-CT in predicting anterior mediastinal lymphoma. Third, this study was performed in a single-center and included only one hospital in the Shanghai Province of China, with most of the patients being from East China. Moreover, factors affecting the SUV of 18F-FDG PET-CT (such as blood glucose level, length of uptake period, image acquisition, and reconstruction) were controlled for and standardized at a single institution. Hence, it is necessary to enroll more patients from other hospitals within and outside of Shanghai to obtain a more accurate, predictive model for mediastinal lymphoma in our subsequent study. Considering these limitations cumulatively, we intend to conduct a multicenter, prospective study to optimize the data collection for predicting anterior mediastinal lymphoma via 18F-FDG PET-CT.
Conclusions
SUVmax on 18F-FDG PET-CT has the potential to discriminate lymphoma from TETs for the diagnosis of anterior mediastinal masses, and the combination of clinical parameters can improve the diagnostic accuracy of SUVmax for anterior lymphoma and therefore may be helpful in preventing unnecessary operation for anterior mediastinal lymphomas.
Acknowledgments
Funding: This study was supported by
Footnote
Reporting Checklist: The authors have completed the STARD reporting checklist. Available at https://qims.amegroups.com/article/view/10.21037/qims-23-496/rc
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-23-496/coif). The authors have no conflicts of interest to declare.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013) and was approved by the Institutional Review Board of Shanghai Chest Hospital (No. KS1753). Individual consent for this retrospective analysis was waived.
Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
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