Imaging algorithm and multimodality evaluation of spinal osteoblastoma

This study was approved by the institutional review board. Using a picture archiving and communication system (PACS) developed by our hospital, from 2008 to 2019, 21 patients were identified to have a histologically-confirmed diagnosis of spinal OB. The group consisted of 15 males and 6 females, with a median age of 25.2 years and age range of 10–53 years.

All 21 patients underwent CT scans (GE Light Speed 16 CT; Siemens Somatom Definition 64 CT) with the following parameters: 120KV, 240–320 mAs, pitch 1–1.5 mm, matrix 380*380. Nineteen patients had MRI scans (Philips Achieva 3.0 T; GE Excite HD 3.0 T), comprised of axial and sagittal T1-weighted imaging (T1WI) (TE 14–23.7 ms, TR 400–754 ms) and T2-weighted imaging (T2WI) (TE 76–138 ms, TR 3000–5100 ms), sagittal fat-suppressed T2WI (TE 80–127 ms, TR 3200–5100 ms), and axial, sagittal and coronal contrast-enhanced T1WI (TE4.6–23.4 ms, TR 189–750 ms). For all patients, contrast agent (Omniscan TM, GE Healthcare, Ireland; Magnevist, Schering, Berlin, Germany; gadopentetate dimeglumine, Consun, Guangzhou, China) was administered at a dose of 0.2 mmol/kg and a rate of 2.0–2.5 ml/s, using a power injector (Spectris Solarisl EP, Medrad, USA; TennesseeXD003, Ulrich Medical, Germany) through the antecubital vein, followed by a 20 ml sterile saline flush. Eight patients underwent 18F-FDG PET/CT examinations (Siemens, Germany), and semi-quantitative analysis was used to calculate the maximum standard uptake value (SUVmax) of tumors relative to the surrounding tissue.

The MR examinations were evaluated visually from the hard copy images. The radiological features, including size, location, shape, density, signal intensity, contrast enhancement, sclerotic rim, flare phenomenon, uptake of 18F-FDG, and tumor staging were evaluated by three radiologists (X.X., X.X. and X.X. with 15, 9 and 4 years of experience, respectively) in concert. The assessment of the tumor staging was performed according to the Enneking staging system [12]. Discrepancies in interpretation were aligned by consensus.

Based on CT, 3 of 21 cases were considered Enneking stage 1, 12 cases as stage 2, and 6 cases as stage 3. Based on MRI, 1 of 19 cases was considered Enneking stage 2 and the remaining 18 cases as stage 3. Consistency between CT and MRI was reached in 6 of 19 cases (31.6%), but the staging based on MRI was otherwise higher than that on CT in the other cases, as shown in Table 1.

a) Size: Size is an important differentiator between osteoblastomas (OB) and osteoid osteomas, with the former typically measuring greater than 2 cm in size [13]. All of the OB tumors in this study were larger than 2 cm. b) Density/signal intensity: Due to the large amount of loose fibrous connective tissue and abundant vascular matrix, most OBs demonstrate hypo- to iso-attenuation on non-contrast CT images, slight hypo- to iso-intensity on T1WI, and hyper-intensity on T2WI, with variable enhancement patterns on contrast-enhanced T1WI [14]. c) Calcification: Intratumoral calcification is a common sign of OB and was noted in all cases in our cohort. d) The sclerotic rim: As shown in the present study, 20/21 cases had marked sclerotic rims. Of note, completeness of the rim could not differentiate between conventional and aggressive OB. e) Location: Spinal OB mostly involves the posterior elements of the spine. In the report by Anne et al, 49/102 cases of OB were confined to the posterior elements [1]. However, extension from the posterior elements into the vertebral body might be more common [2, 15]. In the present study, the majority of OBs not only involved the posterior element but also the vertebral body. According to the literature and our present study, it is apparent that intratumoral calcification, presence of a sclerotic rim, and predominant involvement of the posterior elements are important features to consider in the diagnosis of spinal OB.

The flare phenomenon is one of the most interesting features of spinal OB, and is characterized by diffuse swelling of the marrow of adjacent vertebrae and ribs, as well as soft tissues in paravertebral regions and/or within the spinal canal [14]. Pathologically, the “flare phenomenon” reflects nonspecific inflammatory edema mixed with loose fibrous tissue, hypervascularity, mature lymphocytes, and plasma cells [10]. This inflammatory response is thought to be caused by tumor-derived prostaglandins [16]. The abnormal signals in the “flare area” can completely resolve after the tumor is surgically resected [11, 17]. In general, non-contrast CT is not a useful way to confidently detect flares. In contrast, MRI T2WI or fat-suppressed T2WI can clearly visualize them, and usually shows obvious enhancement following administration of contrast agents [2] (Figs. 1 and 2). Notably, flares can lead to an overestimation of the extent or Enneking staging of the tumor, especially on MRI. As exemplified in this study, the staging based on MRI was higher than on CT in ~ 70% of the cases examined. Furthermore, flares can result in the overestimation of the degree of malignancy of the tumor, leading to a misdiagnosis of osteosarcoma, Ewing’s sarcoma, or lymphoma [11, 18‐20]. In fact, the current Enneking staging system involves only CT or MRI and is challenged as a clinical treatment guide for spinal OBs [21]. Chan et al. reported only a moderate level of agreement (Fleiss k coefficient = 0.47) between independent observers who recommended surgical resection of primary spinal tumors according to the Enneking staging system [21]. In addition, not all adjacent soft tissue masses in the setting of OB are afflicted by inflammation. Shaikh et al. [11] reported 2/12 cases of osteoblastomas where tumor tissue was found in the regions surrounding the diseased bone, as in Case 16 of the present study (Fig. 4). In short, owing to the flare phenomenon, it is difficult to accurately diagnose spinal OB based only on CT and/or MRI.

PET reflects the metabolic level of tissues and is very helpful for the qualitative diagnosis of tumors. Generally speaking, SUV_max > 2.5 mostly indicates a malignant tumor, SUVmax of 2.0–2.5 indicates a borderline lesion, and SUVmax < 2.0 is suggestive of a benign lesion. However, all reported cases of OB with ¹⁸F-FDG PET data uniformly showed hypermetabolic foci, with an average SUVmax of 7.0 [3, 4, 6‐9]. In line with the literature, the average SUVmax of 8 cases in this present study was up to 14.6. As reported by Kusai et al., the metabolic rate of glucose does not necessarily correlate with biologic aggressiveness of bone tumors [6]. Generally, osteoblastoma has high osteogenic activity, which consequently leads to high uptake of ¹⁸F-FDG by tumors [14]. Thus, it might be concluded that PET cannot be used to distinguish between conventional and aggressive OB. With regard to the flare phenomenon, we could not find any published data on their detection using PET scans. In our study, among 8 cases with flares on CT and/or MRI, 7 showed no uptake of ¹⁸F-FDG in the region of “flare”, and the other showed coexistence of high and low metabolism (Fig. 4). This indicated that PET could be very helpful in the accurate characterization of a flare phenomenon, and thus can make up for the shortcomings of MRI.

It is clear that CT, MRI and PET have their own advantages and disadvantages in diagnosing and staging OB. Although CT can clearly show any sclerotic rim and calcifications of tumor matrix, it is subject to underestimation of the extent of the lesion. MRI can depict the flare phenomenon very clearly and help to provide a more complete vision of the lesions. At the same time, MRI is prone to overestimating the degree of malignancy and Enneking tumor stage, and thus the preoperative evaluation based on MRI alone may lead to unnecessary resection of bone [22] and other therapeutic interventions. ¹⁸F-FDG PET has the advantage of determining metabolic characteristics of the tumor and its true boundaries, but it is subject to overestimation of malignancy of the lesion and can fail to properly characterize inflammation in tissues surrounding the tumor. Therefore, combining the full potential of these three imaging techniques is critical to improving the accurate diagnosis and treatment options for patients with spinal OB. A proposed flow chart for patient care is provided in Fig. 5. For patients with suspected bone tumor of the spine, non-contrast CT would initially be recommended to identify any sclerotic rim, intratumoral calcifications and location of the lesion, followed by an MRI to look for the flare phenomenon, and then an ¹⁸F-FDG PET to determine the metabolic level of the flare tissues. When the flare tissues show low metabolism (uptake) on PET, the diagnosis of conventional spinal OB is strongly suggested, and the extent of surgical resection can be designed based on the sclerotic rim shown on CT. Meanwhile, when the clinical situation permits (e.g., no obvious spinal cord compression by inflammation in the surrounding tissues), the adjacent tissues in the spinal canal might be preserved. On the other hand, tissues surrounding the tumor that give a “flare signal” (or high metabolism) suggests OB with extraosseous extension or other malignant tumors, such as osteosarcoma or Ewing sarcoma, and the exact area(s) of surgical resection should be determined by MRI, where a more obvious flare signal can guide complete resection of the afflicted tissue.

While the sample size of the current study is relatively small, especially for PET, our report is the largest cohort of spinal OB with PET data reported in the literature so far. In addition, due to the retrospective nature of this study, the work-up we proposed had not been integrated into clinical practice. Not all patients underwent total en bloc resection, which may affect the accuracy of the results. Therefore, a large-scale, multi-center and prospective study is needed to confirm the efficacy and applicability of our current findings.