PH is frequently discovered on chest radiographic examination and requires further evaluation because it is usually asymptomatic, presenting as small, single, well-circumscribed round nodules(19). The radiological diagnosis of PH is usually based on CT findings, particularly the detection of popcorn-like calcifications(1) and fat(11). However, typical lesions may be absent, which makes CT insufficient for a benign versus malignant diagnosis(16, 17, 20). At this point, PET-CT can be used for further evaluation. Like other lung benign lesion, PH usually shows a lower glucose uptake than malignant tumor, which makes PET-CT a useful noninvasive tool to diagnose PH.
PET-CT is an established noninvasive procedure for lung tumor characterization and staging. The standardized uptake value (SUV) together with visual assessment improved the diagnostic accuracy, making PET-CT more accurate and reliable than CT and resulting in far fewer indeterminate test results(21). As we know, there are few studies related to assessing the value of PET-CT in the diagnosis and treatment of PH have been reported. Herein, the study retrospectively analyzed the publications and patients who had undergone PET-CT, and try to delineate the PET/CT characteristics of hamartomas and figure out more accurate cut-off value to obtain a profile that may serve to distinguish these lesions from malignant lesions.
First, a total of 165 cases were included in this analysis from 4 literatures, and the results are shown in Table 1. The SUVmax value of pulmonary hamartoma is low, even lower than the internationally recognized cut-off value (SUVmax=2.5)(10), indicating low uptake or no uptake. Which were in line with previous experience(22, 23).
We analyzed and compared the diagnostic differences between PET-CT and CT, and the results shows in Table 2. PET-CT was usually taken to further define and evaluate the SPN and was more accurate and reliable than CT(21), but a recent meta-analysis showed no significant difference in their diagnostic parameters (24). In our study, the difference between the two diagnoses was statistically significant and the diagnostic sensitivity of PET-CT is superior to CT, which showed that PET-CT could be a valuable tool to evaluate PH with a better result due to less misdiagnosed rate.
CT diagnosis of SPNs is based on the lesion's imaging characteristics such as size, morphology and whether there is an associated lymph node enlargement. Based on the CT characteristics of the lesion, PET-CT further evaluate by combining the glucose uptake of the lesion and surrounding lymph nodes(25). The atypical imaging characteristics and malignant CT diagnosis led to false positive results relatively frequently (26). To explore the association between the two diagnostic modalities, we included 87 patients with concurrent CT and PET-CT diagnosis for analysis. In our study, as shown in Table 3, the diagnostic sensitivity of PET-CT was also lower for PH lesions diagnosed as malignant by CT (67.4%, 29/43), indicating a certain consistency of diagnostic efficiency between CT diagnosis and PET-CT diagnosis. It has been reputed that the malignant tumors with low metabolic activity or tumors smaller than 1.0 cm in diameter often show low glucose uptake(27), therefore, PETCT is more inclined to make malignant diagnosis when lesions have malignant CT characteristics, causing false positive.
Next, we analyzed 28 patients who had received PET-CT examination with detailed clinical data, and the results were shown in Table 4 and 5. PET-CT images of PH are shown in Figure 2.
First, we analyzed the CT characteristics of PH lesions. Among the 28 patients with PH, most of the patients lacked calcification(23/28), fat density(22/28), which are characteristic changes of PH; and no patients showed popcorn calcification. Atypical CT imaging findings lead to unclear CT diagnosis; Only 2 cases were diagnosed as PH by CT. 9 patients underwent contrast-enhanced CT, and 4 of which showed enhanced images. Christensen et al showed that PET-CT is preferable to enhanced CT in evaluating indeterminate pulmonary nodules(28).
PET-CT examination was performed in all cases because a malignant diagnosis could not be ruled out. According to the results of PET-CT examination, 2 showed increased glucose uptake and were diagnosed malignant, but most PH lesions (26/28) and lymph node showed no significant increase in glucose uptake. Some cases were diagnosed as malignant due to the suspicious combination of malignant tumor and metastasis could not be excluded. Care must be taken because PET-CT had its limitation for the identifying metastasis lesion from benign SPN when complicated with malignant tumor. PET-CT couldn’t make definite diagnosis due to the suspected metastasis of lung lesions, which were not mentioned in the previous experience.
Based on the above results, we analyzed the factors influencing the accuracy of PET-CT diagnosis of PH. The factors contributed to diagnosis of PH by means of PET-CT including a single lesion, low SUVmax of lesion (lower than the internationally recognized cut-off value of 2.5) and no other malignant tumor. On the contrary, some PH lesions have increased glucose uptake(which may be caused by the large size of the lesions, combined with inflammation, etc.) could cause false positive, which was consistent with the literature(29). Meantime, according to our results, some patients complicated with other malignant tumors, PH lesions were diagnosed as malignant due to the inability to exclude malignant tumor metastasis, indicating the limitations of PET-CT in the diagnosis of PH.
So, the ability of PET-CT to differentiate benign lesions from malignant is significant for the following clinical decisions. In addition to visual assessment of pulmonary tumors, malignant lesions demonstrated higher 18F-FDG uptake than the normal mediastinal blood pool (30). 18F-FDG PET-CT using cut-off SUVmax of 2.5 has an established role for diagnosing pulmonary malignancies for an extended period time(31). Studies have been performed to examine the accuracy, as some new cut-off values put forward. Yaichiro et al (32) showed a SUV cut-off value of 1.59 and proposed that lower uptake suggests lower probability of malignancy (0%~15%), they also showed that the median SUVs were 1.69 (range, 0.97–2.29) for malignant lesions and 1.31 (range, 0.65–2.31) for benign lesion. Nevertheless, Aleksandar et al (33)hold the view that an SUV below 1.25 was always combined with benign lesions. In our study, we obtained one SUVmax cut-off value of 2.65 according to the ROC curve, which was higher than the previous experiences(31-33). Several possible reasons should be taken into consideration. First, the SUV is affected by a large number of factors. Second, the cases included to plot the ROC curve were not sufficient enough to be convictive, causing selection bias. Meanwhile, Giant PH(17) , multiple PH(16) and PH combined with pneumonia(27) can demonstrated a higher uptake could make the cut-off value increasing. However, Sim et al even thought that using threshold SUVmax values to differentiate malignant from benign lesions is unrealistic(25).
There are some limitations to our study. First, cases were collected from our hospital and the literature, CT and PET–CT analysis criteria adopted might be diverse. Second, lack of case data limited the analysis of the results. Third, our research was a retrospective study and could cause selection bias. Last, the collection was not big enough to be convictive, so further work needs to be done on providing a more extensive statistical database.