Due to the contributions of previous studies [3, 5, 12], OBLOS were increasingly recognized. The patient from our center was the first case involving the occipital bone. Briefly, we found that AOS could affect PFS while metastasis could impact OS. A worse PFS was observed in the subgroup of patients treated with surgery + CMT, NGTR + RT and NGTR + CMT, while a worse OS was observed in the subgroup of patients treated with surgery + RT or NGTR + RT, finally the use of NGTR + RT could result in poor PFS and OS.
It was reported that OBLOS affected more male than female patients [3, 7]. A study that mainly included OBLOS reported a male to female ratio of 1.125:1 (9/8) . One patient from our center and the pooled 56 patients also showed a minor male predominance (56.1% and 42.1%, respectively) for OBLOS, which corresponded with the findings reported by Gambarotti et al . This neoplasm often developed in the 2nd half of the 2nd decade of life . Similar results were also observed in other studies [3, 7, 13, 14]. However, 1 patient from our center and the pooled 56 patients showed this lesion often developed in the 1st the 2nd decade of life (Fig. 2a). The median symptom duration of 2 months indicated a relatively aggressive disease course. The tumor occurred in various sites of the skeleton. The most common location was the tibia in fifteen cases, followed by the vertebra, ten cases. Small bones of the skull, face and foot were also involved, that were relatively uncommon locations of conventional osteosarcoma (Supplemental table 1).
Kathrin et al. believed that OBLOS was a low-grade lesion, similar results were reported by Luigia et al. and Bertoni et al [5, 11, 15]. However, we agreed with the report that OBLOS was a kind of high-grade neoplasm [5, 8]. The report that recurrence was common, and metastases occurred in some patients [3, 5] while our study verified that OBLOS had a high risk of recurrence (n = 17, 29.8%) and metastasis( n = 14, 24.6%) (Table 1). OBLOS was a kind of malignant lesion because of the high risk of recurrence and distant metastasis.
It was usually easy to differentiate from conventional osteosarcoma, which usually had a short clinical presentation, more aggressive radiographic findings, and high-grade histologic features . However, there are unusual variants of osteosarcoma that are so histologically similar to osteoblastomas that there may be some diagnostic confusions. The symptoms at presentation may not raise suspicion about such a specific disease. However, progressive symptoms and new-onset clinical findings after an initial diagnosis of osteoblastoma must be alarming for the clinicians in favor of OBLOS.
OBLOS could resemble osteoblastoma histologically[1, 7]. The pathological findings included areas resembling classic osteoblastoma, sheets of cells without bone production, variable quantities of lace-like osteoid, rounded and ovoid nuclei with or without nuclear atypia, with or without prominent nucleoli and admixed spindled stromal cells, the proliferation of osteoblasts forming osteoid or bone and fibrovascular tissue between its bony trabeculae. OBLOS had a low mitotic rate. OBLOS characterized histologically by the presence of neoplastic cells cytologically identical to osteoblasts set in a trabecular osteoid matrix mimicking that of osteoblastoma . All these histological features overlapped with those expected in osteoblastomas. Tumor permeation of host bone was mentioned as the primary histological feature to differentiate OBLOS from osteoblastoma . Our report was consistent with this (Fig. 1f).
OBLOS shared radiological features with osteoblastoma and osteosarcoma. However, OBLOS lesions usually lack the soft-tissue component when compare to typical osteosarcoma in MRI. Radiologically the lesions were usually lytic with poorly defined borders and cortical destruction. OBLOS can be high uptake on radionuclide bone imaging [1, 2, 8, 11] and radiolucent or radio-dense [2, 5, 11]. Ossifications, a sclerotic nidus, lytic, expansile pattern and periosteal reaction can be present inside the lesion [2, 5, 8]. Mild periosteal new bone formation can be present . MRI can show isointense on T1 images , hyperintense, edema, sclerosis or permeability on T2 images [1, 2, 4, 8] and contrast enhancement [1, 2, 8, 11]. Gambarotti et al. reported that the borders of the tumor can be poorly defined with cortical destruction or well defined and distinct, even featuring a sclerotic rim [7, 8]. This sign was also observed in CT scans on our case ((Fig. 1a, b). The diagnosis was entirely dependent on the demonstration of peripheral permeative growth by the tumor, characterized by marrow permeation between preexisting trabeculae and trabecular appositional growth.
Bertoni et al. reported four tumor recurrence, five metastasis and four deaths over a three-year follow-up (17 cases) while Gambarotti et al. reported six tumor recurrences, five metastasis and four deaths over a mean follow-up was 128 months (range 9-552 months) (15 cases) [3, 7]. By contrast, the median follow-up in our pooled study was 39 months, and the 1-year PFS, 3-year PFS, 5-year PFS, 1-year OS, 3-year OS and 5-year OS were 74.4%, 39.5%, 25.6%, 96.2%, 76.8% and 70.5%, respectively (Table 1). The observation that OBLOS tended to develop with recurrence and metastasis frequently. The lung was the most frequent metastasis region. When Metastasis development occurred, most patients died soon. Our study proved that the metastasis could independently affect the OS (Fig. 4).
Studies on prognostic factors with exclusive emphasis on OBLOS were scattered. Gambarotti et al. reported that the presence of AOS seemed to be the critical parameter to differentiate these tumors and to predict an aggressive outcome . Our study verified this argument that the presence of areas of conventional osteosarcoma independently predicted poor PFS (Fig. 3).
Surgical intervention was essential to make an accurate diagnosis and relieve symptoms by reducing the mass effect. The argument that GTR could yield good outcomes was less persuasive because our study failed to confirm the efficacy of GTR in patient outcomes. Univariate analysis revealed that the GTR could predict better PFS and OS. As the case from our institute, the patient got a GTR surgery, and the patient did not have any sign of recurrence or metastasis. Therefore, if the lesion was easily accessible, e.g. appendage bone, GTR was still advocated; otherwise, NGTR or biopsy rather than GTR should be considered to avoid the potential complications, such as malignant esophageal fistula or even death . Discouragingly, the role of RT in the treatment of OBLOS was questionable. In this pooled analysis, we found that the 5-year OS of patients treated with Regime 2 was significantly shorter than that of patients treated with Regime 1 (27.8% vs 77.8%, p = 0.020), and a trend of poor PFS and OS were also found in the NGTR + RT subgroup (Table 3, Table 4 and Table 5). Although a trend of better PFS and OS was found in the GTR + RT group, the difference was not significant. And, our case had a good outcome after the adjuvant radiotherapy. We may conclude that the radiotherapy may be an optimal treatment modality. However, which radiotherapy and the dose of the radiotherapy were unknown.
A longer 5-year of PFS (34.6%) was reported in our studies consisting of patients with surgery alone than the patients treated with surgery plus CMT (Table 2). When compared to the entire group, a trend of poor PFS was also found in the NGTR + CMT subgroup (Table 4). Similarly, though trends of higher 5-year OS were observed in patients treated with surgery plus CMT and the GTR + CMT, the difference was not significant. We could not conclude that the CMT is useful for this kind of tumor. And, compared to the whole cohort, GTR + CMT predicted a better OS thought the difference is not significant.
We agreed with the recommendation that patients with OBLOS should be considered for wide resection [5, 11]. Unlike the treatment modalities of conventional osteosarcoma is surgical removal of all detectable tumor sites and chemotherapy , we did not have the enough grounds to confirm that the GTR followed by CMT could be recommended. However,if tolerable, RT or CMT could be alternative treatment modalities.
Herein, we presented a rare case and summarized all of the previously published cases which could substantially increase our experience to diagnosis and treat this rare condition. OBLOS is a rare lesion with a high preoperative misdiagnosis rate. Patients with AOS had poor PFS and metastasis predicted a poor OS. The lung was the most frequently involved regions of metastasis. The patients with OBLOS should be considered for gross total resection. If tolerable, gross total resection followed radiotherapy or chemotherapy could be an alternative treatment modality. Our findings need to be verified in the future.