Clinical pathology correlation case 4: right-sided sinonasal mass associated with ocular proptosis

Abstract

Clinical Presentation

An 11-year-old male patient presented with a right-sided facial asymmetry and proptosis of the right eye with associated vision loss and neuropathy. Review of his health history was otherwise unremarkable. Computed tomography (CT) scan of the head revealed a well-demarcated, expansile, heterogeneous radiodense mass with central lucent zone that obliterated the right nasal cavity and ethmoid sinus spaces (Figure 1). While impinging on the optic nerve, the lesion displaced the globe of the right eye, deviated the nasal septum, and displaced the sphenoid bone posteriorly.

Differential Diagnosis

The differential diagnosis for sinonasal conditions associated with ocular proptosis is broad and includes a range of reactive processes along with benign and malignant neoplastic conditions arising in both soft tissues and hard tissues.¹ Since this lesion demonstrates radiodensity comparable to those of the hard tissues, primary intraosseous pathologic conditions are favored in the differential diagnostic considerations with notable exception of sinonasal meningioma.

Meningioma is a tumor of possible meningiothelial cell origin that represents 24%-30% of all intracranial neoplasms.² It arises across a broad age range with rare occurrence in children and an overall female predilection.³ Primary extracranial meningiomas are relatively rare representing less than 1% of all cases which mostly occur in the orbit, middle ear, soft tissues, skin, and sinonasal tract.^3,4 Clinical manifestations of sinonasal meningiomas are nonspecific including nasal obstruction, epistaxis, nasal discharge, proptosis, facial pain and deformity.^2,3 On CT imaging, sinonasal meningioma presents as a homogenously enhancing mass associated with hyperostosis of the surrounding bone. While it generally demonstrates soft tissue density, speckled opacifications may also be observed especially in the psammomatoid variant of this tumor.^3-5 The present case demonstrates a heterogeneous radiodensity comparable to that of hard tissues and therefore meningioma is not considered a likely diagnostic consideration.

Osteomas are the most common primary bone tumors of the craniofacial skeleton which may arise in paranasal sinuses, maxilla, mandible, mastoid air cells, external auditory canal, and the cranial vault.⁶ While the exact pathogenesis of osteomas remain largely elusive, possible traumatic, infectious, and developmental etiologies have been suggested.^6,7 In the paranasal sinuses, osteomas show a propensity for frontal and ethmoid sinuses.⁶ Arising across a broad age range, most sinonasal osteomas are diagnosed in 5th-6th decades of life.^7,8 While most tumors are asymptomatic and incidentally discovered on imaging studies, depending on their location, sinonasal osteomas may induce symptoms such as headache, nasal congestion, local pain, ocular proptosis, and visual field disturbances.^6-8 On CT imaging sinonasal osteoma is characterized by a well-delineated, homogenous radiodense mass that arises from the cortical surface of bone and occupies the sinus space. However, depending on the proportions of dense and cancellous bones, heterogeneous radiographic variants are also recognized.⁸ The present case is characterized by a heterogeneous well-delineated radiodense mass with a central lucent core that does not originate from cortical bone surface prompting exclusion of sinonasal osteoma from the diagnostic considerations.

Osteoblastomas are rare mesenchymal neoplasms that comprise 1-4% of all primary bone tumors.⁹ Most commonly involving the vertebrae and long skeletal bones, sinonasal osteoblastomas are extremely rare.^9,10 While the paucity of sinonasal osteoblastomas precludes a definitive clinicoradiographic characterization, differentiation of these tumors from the more common fibro-osseous sinonasal lesions is crucial from the therapeutic stand point.¹¹ Most commonly observed in adolescents and young adults, sinonasal osteoblastomas are mostly asymptomatic. However, when impinging on the adjacent structures, sinonasal osteoblastomas may produce symptoms such as ocular proptosis, visual disturbance, and nasal obstruction.¹² On CT imaging studies, sinonasal osteoblastoma is characterized by a well-defined expansile, heterogeneous lytic lesion that often exhibits an eccentric cap of radiodense mature bone.¹¹ The absence of this characteristic feature in this current case disfavors sinonasal osteoblastoma as a likely diagnostic consideration.

Fibrous dysplasia (FD) is a sporadic benign fibro-osseous lesion characterized by progressive replacement of bone with fibrous connective tissue.¹³ Characterized by postzygotic activating missense mutation of the GNAS gene, the timing of mutation impacts the extent of the disease involvement hence the subclassification of FD into monostotic and polyostotic forms. FD demonstrates a predilection for membranous bones of the skeleton such as femur and tibia.^13,14 Polyostotic FD may rarely be accompanied with endocrinopathies and café-au-lait skin pigmentations (McCune-Albright syndrome) or soft tissue myxoma in the setting of Mazabraud syndrome (15). Between 50% and 100% of polyostotic FD and 10%-30% of monostotic cases may involve the craniofacial skeleton.¹⁴ Usually arising before the age of 30 years, craniofacial FD frequently affects the maxilla and mandible followed by frontal, parietal, and occipital bones along with infrequent involvement of the sinonasal tract.¹³ Although most cases are clinically asymptomatic and discovered incidentally, craniofacial FD may be associated with bone deformity, headaches, visual defects, ocular proptosis, hearing loss, nasal obstructions, and anosmia depending on the anatomic location.¹⁴ The most characteristic finding in CT imaging with FD is bone expansion exhibiting a ground-glass appearance with ill-defined borders that blend with the surrounding bone. However, depending on the degree of metaplastic bone formation, radiographic appearance may range from radiolucency to a dense, homogenous radiopacity.¹⁶ Although the absence of a ground glass appearance excludes fibrous dysplasia as a likely diagnostic consideration of the present case, correlation with the clinical, intraoperative, and histopathologic features is required to ultimately rule out this entity.

Ossifying fibromas (OF) are benign fibro-osseous neoplasms characterized by replacement of normal bone with a cellular fibrous stroma exhibiting bone or cementum-like calcifications.¹⁷ Two major variants of this entity are recognized with overlapping clinicopathologic features which include cemento-ossifying fibroma (COF) and juvenile ossifying fibroma (JOF). Furthermore, JOF is subdivided in psammomatoid and trabecular types. Of these, the psammomatoid variant of JOF demonstrates a predilection for ethmoid sinus and orbits.^17,18 Arising primarily in patients younger than the age of 15 years, paranasal JOF often displays steady progressive growth leading to ocular proptosis, impaired vision, facial swelling, nasal obstruction, periorbital pain, and headache.¹⁹ The lesions arising in younger ages or those with concurrent development of an aneurysmal bone cyst may be associated with rapid growth and locally aggressive clinical behavior.²⁰ Radiographically, JOF is well-delineated mixed-dense lesion that characteristically demonstrates peripheral ossification surrounding a radiolucent core.^17,18,21 Although distinction between FD and JOF may be challenging when solely based on imaging studies, the present case exhibits characteristic and distinctive demographic, anatomic, clinical, and radiographic features which are in favor of the diagnosis of JOF. However, ultimately, a correlation with histopathologic and intraoperative findings is warranted for a definitive diagnosis.

Diagnosis and Management

A biopsy of the right sinonasal mass demonstrated a cellular uniform bland fibroblastic stroma composed of spindled to stellate cells (Figure 2). Interspersed between the fibroblastic cells were numerous spherical lamellated ossicles exhibiting varying degrees of calcification. These psammoma body-like ossicles were relatively acellular, with a concentric pattern of lamination, basophilic centers, and peripheral eosinophilic rims (Figure 3). Mitotic figures were not evident. The final diagnosis was juvenile psammomatoid ossifying fibroma. Complete surgical excision was performed (Figure 4) with no recurrence detected at 2 years follow up.

Discussion

Ossifying fibroma (OF) is a benign neoplasm that falls into the broader category of benign fibro-osseous lesions (BFOLs). Despite having distinct clinical features and treatment approaches, all BFOLs are characterized by the replacement of native bone with fibrous and mineralized tissues, and they are grouped together because of their histologic similarities.²² Because an ossifying fibroma may contain bone and/or cementum, the term cemento-ossifying fibroma (COF) can also be used interchangeably.²² OF is subdivided into conventional and juvenile clinicopathologic subtypes.²⁵ By convention the term ossifying fibroma generally refers to the cemento-ossifying type, which is associated with tooth-bearing areas, whereas the term "juvenile" refers to juvenile ossifying fibroma. The juvenile ossifying fibromas are characterized by rapid and destructive growth, occur in younger patients relative to conventional OF, and are seen with considerably less frequency than their conventional counterpart.²⁶ These neoplasms have been further categorized into juvenile trabecular ossifying fibroma (JTOF) and juvenile psammomatoid ossifying fibroma (JPOF) by the World Health Organization (WHO).²³ While the trabecular variant is more prevalent in children under the age of 15 and prefers the maxilla, the psammomatoid variant is typically seen in the paranasal sinuses and in those 20 years and older. Nonetheless, older patients may occasionally be affected by both categories. Radiographically, the lesion presents as a well-delineated, expansile radiolucent lesion with variable focal calcifications.²⁷ The JTOF is characterized histologically by cellular fibrous background comprising variable trabeculae of immature bone with osteoblastic rimming and collagenous rim. The JPOF has a variably cellular background with irregular spherical ossicles exhibiting varying degrees of calcification. These psammoma body-like ossicles are relatively acellular, with a concentric pattern of lamination.²⁸ Furthermore, both variations frequently exhibit multinucleated giant cells and scattered mitotic figures. Without treatment, tumors continue to enlarge requiring complete surgical excision. Recurrence rates reach 58%, necessitating reconstruction surgery that may be potentially disfiguring.