Etiology
Osteofibrous tumors of the craniofacial massif are characterized by the replacement of normal bone by a connective tissue matrix with variable mineralization patterns. Hypothetically, this phenomenon is caused by overproduction of a myxofibrous cell stroma capable of ossification during the development of septa in the paranasal sinuses [13, 15]. Sutures could act as origin zones because they produce ossicles and chondrocytes grouped in spheres [14, 16]. Some authors have even hypothesized about the role of cranial trauma or radiation acting as potential triggering mechanism, but this assertion has not been confirmed over the years [13, 17, 18]. Genetically, juvenile forms of OFs constitute unique entities. The absence of the activated mutation of the GNAS1 gene allows them to be differentiated from fibrous dysplasia [19]. On the other hand, the absence of haploinsufficiency in the HRPT2 gene allows juvenile tumors to be distinguished from the conventional variant of ossifying fibromas [20].
Clinical presentation
Craniofacial JPOFs are usually diagnosed in the second to fourth decades of life. Exceptionally, they might affect very young or elderly patients [15, 21], as observed in our case. Most of these tumors arise in the frontoethmoidal complex and show a locally aggressive behavior, frequently extending into the paranasal sinuses and orbit at diagnosis [8, 21]. The participation of the cranial vault is extremely rare [13, 14, 23, 24]. Liu et al. graphically represented the most frequent origin of these lesions: the tumor originated in the supraorbital ethmoidal cell, an accessory chamber that drains posterolaterally in the frontal recess and extends superolaterally along the frontal orbital plate during its process of pneumatizaton [24].
JPOFs are painless tumors that go initially unnoticed. As they reach larger dimensions, and depending on their location, clinical manifestations become evident except in those rare cases discovered incidentally [14]. Due to their usual epicenter of origin, the most commonly symptom of craniofacial JPOFs is proptosis [21]. Other symptoms include nasal obstruction, recurrent sinusitis, facial pain and painful local swelling [23]. Visual impairment, as observed in our patient, usually reflects an advanced stage of growth of the JPOF towards the orbital apex, with extrinsic mechanical distortion of the optic nerve causing obstruction of the neuronal axonal flow and ischemia from compression of the vasa nervorum [14, 24]. In this setting, visual prognosis may depend to a great extent on both early diagnosis and surgical decompression, even in case of severe deficits, as observed in our patient (Fig. 1).
Differential diagnosis
JPOFs must be distinguished from other osteofibrous neoplastic and non-neoplastic lesions. The most frequent entity involving the craniofacial skeleton, fibrous dysplasia (FD), consists mainly of hypertrophy of the affected bone while maintaining its intact shape [25, 26]. This growth usually stabilizes when skeletal maturity is reached [27, 28]. Radiologically, FD appears as a poorly circumscribed bone expansion covered by a thin cortex with various degrees of opacity, showing a ground glass appearance [26, 28, 29, 30]. Likewise, its mineralization pattern is homogenous [26].
On the other hand, ossifying fibromas (OF) are slow-growing tumors that present a mixture of bone and soft tissue densities with thickened bone walls, well-defined margins and loss of the anatomical shape of the affected bone. Likewise, they present a heterogenous signal intensity in conventional MRI sequences, as well as after contrast uptake [26, 31]. The presence of a fluid level has been reported in association with an aneurysmal bone cyst [26, 32]. Juvenile OFs, unlike the classic variant, present short-term rapid growth. The trabecular variant usually affects the maxila and mandible of younger patients than JPOFs. Radiologically, the former usually presents as an expandable, uni or multiloculated well delimited mass by a thinned cortex [28, 33, 34]. Histologically, it is composed of a densely cellular, fusiform fibrous tissue with little collagen and thin bony bands known as trabeculae within an osteoid matrix [28, 35]. In contrast, the JPOF variant is characterized by a dense fibrous stroma with concentric calcifications containing osteocytes reminiscent of psammoma bodies [26, 35] (Fig. 3). Remarkably, a case of juvenile ossifying fibroma sharing trabecular and psammomatoid features has been reported [28].
Another craniofacial lesion commonly indistinguishable from JPOF is the extracranial psammomatous meningioma, representing 2% of all meningiomas. Histopathologically, they can be difficult to distinguish in an intraoperative biopsy – as occurred in our patient (Video 1) - since both lesions share psammomatoid elements. However, psammomatoid meningioma is additionally composed of meningothelial cells arranged in “whorls” patterns [10]. Likewise, the JPOF psammoma bodies have a heterogenous distribution and are associated with a lining of osteoblastic and osteoclastic cells [30, 36].
Treatment
Given the absence of pathognomonic radiological features, some authors recommend performing a preoperative biopsy in every patient with a suspicion diagnosis of a craniofacial osteofibrous lesion [26]. The treatment of choice of the JPOF is gross total resection (GTR), with free margins of up to 5 millimeters according to some authors [24, 37, 38]. Incomplete resections are associated with high recurrence rates (up to 50%) [2].
Numerous alternative approaches have been proposed for the surgical treatment of theses tumors [39, 40]. Although the endoscopic approach has gained popularity over the years due to its minimally invasive nature and the significant reduction of CSF leak rates achieved with the refinement of the technique, it should not be considered systematically the route of choice [24, 34]. The transcranial approach continues to occupy an important position into the therapeutic arsenal, especially if decompression of neural structures represents the primary objective given the presence of a significant inbound growth of the tumor, as occurred in our patient.
JPOF is a highly vascular tumor which increases surgical risk due to significant bleeding [41]. Some authors found useful preoperative embolization, in those cases where the main blood supply came from the sphenopalatine artery or other less frequent extracranial arteries such as occipital [13]. However, as in most cases, if the main feeding artery is an ethmoidal branch, the risks of embolization outweigh its benefits [22]. In addition, small anastomotic connections between the external and internal carotid circulation, product of embryonic vestiges, could exist and favor the development of ischemic complications, which is why, in agreement with others authors we do not recommend the systematic use of this tool despite the great current advances in endovascular techniques [26]. The most effective method to reduce bleeding is to quickly remove the internal component of the tumor until its margins are identified. Likewise, removing the “external bone shell” and drilling the pathologic bone to healthy limits, guarantees with greater probability a successful resection degree to avoid recurrences [22].
Information about adjuvant treatment is scarce in the literature. To date, radiotherapy is not recommended due to the minimal or null response of ossifying fibromas and to avoid their side effects, mainly because they are young patients [38]. Moreover, in case of recurrences, clinical and radiological surveillance is usually recommended [14, 34]. Chemotherapy is ineffective so a second surgery should be considered although clinical protocols have not yet been standardized [13, 17, 42].
Overall prognosis
Despite their benign nature, the characteristic local aggressive behavior of JPOFs has been associated with a reported recurrence rate that varies between 30–50% in case of incomplete resections [8, 15, 28, 37, 43]. This phenomenon seems to be related to those tumors that produce greater cortical destruction and/or periosteal elevation during their expansion usually between 6 months to 19 years, according to the literature [12, 14]. For this reason, complete excision with tumor-free margins is the treatment of choice. However, to date no cases of malignant transformation or metastatic spread have been documented to date [11, 36].