Nasoseptal Cholesterol Granuloma: Title and subTitle BreakA Case Report and Review of Pathogenesis

A 60-year-old Hispanic man was referred to the otolaryngology department with a history of nasal obstruction, intermittent right-sided blurry vision, and frontal/occipital headaches of 2 years' duration. The patient denied any history of trauma, radiation, or nasal surgery. Rigid nasal endoscopy showed a submucosal mass extending on both sides of the nasal septum and abutting the bilateral lateral nasal walls (Figure 1). Noncontrast paranasal and orbital computed tomography showed a 3.1 × 3.1-cm mass centered within the superior nasal septum with cartilage destruction, and adjacent bony remodeling of the right nasal bone and lamina papyracea (Figure 2A-C). Magnetic resonance imaging of the paranasal sinuses and orbits showed a lesion originating from the nasal septum with right orbital extension exhibiting high-signal intensity on both T1- and T2-weighted views, without contrast enhancement or dural involvement (Figure 2D and E). The patient underwent outpatient endoscopic resection of the mass using general intravenous anesthesia with findings of a yellow-brown cystic lesion (Figure 3A). Intraoperative frozen section was reported as a “cluster of granuloma.” The cyst wall was removed entirely (Figure 3B and C) without any complications. The degree of quadrangular cartilage destruction was such that more than 1-cm dorsal strut could be preserved negating the need for further intervention to prevent a saddle-nose deformity. Final histopathologic diagnosis was consistent with a cholesterol granuloma (Figure 3D and E). The patient's postoperative course was uneventful. Nasal endoscopic examination 8 months after surgery showed a well-healed and mucosalized nasal cavity without evidence of recurrence (Figure 4).

The first report of a cholesterol granuloma was in 1894 by Manasse,² located within the middle ear cavity and external auditory canal. Cholesterol granuloma of the petrous apex was first described in 1982 by House and Brackmann.¹ Histologically, cholesterol granulomas are composed of a core of cholesterol crystals, surrounded by foreign body giant cells and chronic inflammation. With an exterior capsule of thick fibrous tissue, cholesterol granulomas form expansile round or ovoid cysts that are locally destructive.³ The pathogenesis of the granulomatous formation is thought to be an inflammatory reaction to hemosiderin, which is produced on macrophage breakdown of extravasated hemoglobin.

Two theories exist to explain the development of cholesterol granulomas of the petrous apex. The first, and older theory, is called the obstruction-vacuum theory. It postulates that mucosal swelling occludes the outflow tracks of the pneumatized air cells, which leads to increased negative pressure and extravasation of intravascular fluid and blood into air cell mucosa; the hemosiderin formed after the breakdown of hemorrhage products eventually forms cholesterol crystals that then trigger an inflammatory macrophage-mediated granulomatous reaction, causing expansion of the mass and bony erosion.³

The obstruction-vacuum theory has been challenged by the exposed marrow hypothesis. Proponents of this hypothesis argue that the source of hemorrhage into pneumatic air cells is generally insufficient to produce aggressive cholesterol granulomas.⁴ Furthermore, if hypoventilation is the trigger, then exposed marrow supporters, such as Jackler and Cho,³ propose that the granulomas should not arise in well-pneumatized areas, such as the petrous apex. Alternatively, this theory purports that as air cells develop they erode vascular marrow-filled cavities causing subacute hemorrhage. The same inflammatory reaction occurs, except in this hypothesis, the expanding cyst causes further hemorrhage from marrow cavities. This provides for a substantial blood supply, and explains the predominance of cholesterol granulomas at the vascular petroclival junction.⁵

The more recent documentation of rarer paranasal sinus cholesterol granulomas points to a multifactorial etiology with no single unifying theory. The exposed marrow hypothesis indicates that direct hemorrhage into air-filled spaces is a nidus for pathogenesis especially when considering the high vascularity of both the septum's elastic submucosal space and the mucosa of aerated paranasal sinuses.⁶ In addition, a history of chronic sinusitis may cause small hemorrhages, further contributing to disease progression.⁷ In keeping with the obstruction-vacuum theory, mucosal edema from infectious or allergic triggers can create ventilation obstruction and air trapping. The negative pressure generated may then cause extravasation of transudative fluid and blood; the former may undergo fatty degeneration—producing cholesterol in addition to that generated from hemosiderin catabolism, ultimately spawning a granulomatous inflammatory response.⁸ It is perhaps this multifactorial etiology that makes paranasal sinus cholesterol granulomas so rare.

In conclusion, to our knowledge, we report the first case of cholesterol granuloma arising from the nasal septum. It is unclear exactly why cholesterol granulomas of the well-pneumatized petrous apex are common, and those of the paranasal sinuses and nasal cavity are rare. In the search for a unified theory explaining the pathogenesis of cholesterol granulomas, it is clear that the 2 locations differ significantly in their susceptibility to trauma and potential for infectious and allergic insults; both of which are known to indirectly result in hemosiderin catabolism that fuels the inflammatory cycle of this complicated disease process.