Imaging Spectrum of Cavernous Sinus Lesions with Histopathologic

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(a) (d) RSNA, 2019 • RSNA, article, the cavernous sinus lesions encountered in our institution the cavernous article, The purpose of the article during period a 10-year are reviewed. is to the multimodality imagingonstrate spectrum of a wide variety of correlating sinus, the cavernous pathologic conditions involving with the histopathologic findings; and clues for differential diagnosis; potential pitfalls in interpretation. this article. for Online supplemental material is available © are connected to the orbit, the pterygopalatine fossa, the infratem the the pterygopalatine fossa, orbit, are connected to the the nasopharynx, and the posterior cranial fossa by poral fossa, A multitude in the skull base. and canals fissures, various foramina, of structures rise give sinus cavernous to the in close relation to a can be broadly classi myriad of possible pathologic conditions that fied into or imaging a cru plays Hence, clinical manifestations. overlapping a providing assessing its extent, cial role in identifying the disease, pertinent and differential diagnosis to guide further management, MRI is the modality of choice suggesting a site or route for biopsy. with CT and digital subtraction an sinuses, to depict the cavernous giography supplementary In this playing roles in certain situations. Cavernous sinuses are paired interconnected venous plexuses situ plexuses venous sinuses are paired interconnected Cavernous either side of thefloor of the middle cranial fossa on in the ated and are lined by dura mater They sinus. sella turcica and sphenoid sinusesThe cavernous channels within. venous consist of multiple to the internal related are intimately carotid artery and its associ the trochlear nerve, the oculomotor nerve, plexus, sympathetic ated sinuses Cavernous nerve. and the ophthalmic the abducens nerve, Cavernous sinuses are paired complex venous spaces situated on spaces situated are paired complex venous sinuses Cavernous the either side of the sphenoid sinus and the sella turcica and are at The internal structures. crucialcrossroads of many neurovascular carotid artery within the cavity (ICA) and the abducens nerve travel and the oculomotor nerve (cranial nerve III), sinus; of the cavernous and the ophthalmic nervethe trochlear nerve (cranial nerve IV), sinus. of the cavernous wall in the lateral V1) travel (cranial nerve V2) courses just inferior to the The maxillary nerve (cranial nerve

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CCF [email protected] Address correspondenceAddress to LEARNING OBJECTIVES Imaging Spectrum Cavernous of with Histopathologic Lesions Sinus Correlation = cerebrospinal fluid, FLAIR = cerebrospinal fluid,

See rsna.org/learning-center-rg. = World Health Organization World =

activity, participants will be able to: Describe the anatomy of the cavernous of the cavernous Describe the anatomy Identify the imaging of a wide features Recognize imaging clues for differential ■ ■ ■ RSNA, 2019 RSNA, SA-CME After completing this journal-based SA-CME relationships. relationships. (e-mail: S.E.M. cal College, Ida Scudder Road, Vellore, Tamil Tamil Vellore, Ida Scudder Road, cal College, and the Department of India; Nadu 632004, New NYU Langone Medical Center, Radiology, as an education Presented NY (G.M.F.). York, Re Meeting. Annual RSNA 2017 the at exhibit requested May revision 2018; March 31, ceived For accepted July 20. July 15; 24 and received the authors, this journal-based SA-CME activity, disclosed no relevant and reviewers have editor, From the Departments of Radiology (H.V.M., From the Departments of Radiology (H.V.M., Neurosurgery G.C.), (B.P., Pathology S.E.M.), Christian Medi and Neurology (M.A.), (K.P.), sinus. sinus lesions. variety of cavernous pitfalls in interpreta- and avoid diagnosis, tion. © RadioGraphics 2019; https://doi.org/10.1148/rg.2019180122 Content Codes: Girish M. Fatterpekar, MD Fatterpekar, Girish M. MD Geeta Chacko, Abbreviations: CSF tula, ICA recovery, inversion attenuated IgG4 carotid artery, WHO Harsha Vardhan Mahalingam, MD Mahalingam, Vardhan Harsha MD Mani, Sunithi E. MD Bimal Patel, MCh Krishna Prabhu, DM Alexander, Mathew ■ ■ ■ 796 May-June 2019 radiographics.rsna.org

TEACHING POINTS Diverse pathologic conditions of this region can, however, have similar clinical features; and ■■ Cavernous sinuses are paired complex venous spaces situated imaging plays a crucial role in confirming the on either side of the sphenoid sinus and the sella turcica and are at the crossroads of many crucial neurovascular structures. presence of disease, assessing its extent, guid- The internal carotid artery (ICA) and the abducens nerve trav- ing further investigations, and planning therapy el within the cavity of the cavernous sinus; and the oculomo- (medical management, microsurgery, endovascular tor nerve (cranial nerve III), the trochlear nerve (cranial nerve surgery, or radiation therapy). MRI is the imaging IV), and the ophthalmic nerve (cranial nerve V1) travel in the modality of choice for assessment of the cavernous lateral wall of the cavernous sinus. sinus, owing to the superior contrast resolution of ■■ The cavernous sinus can be affected by neoplasms (benign or malignant), infection or inflammation, vascular pathologic MRI. CT and digital subtraction angiography are conditions, and congenital lesions, among others. Diverse useful in certain cases. A thorough knowledge of pathologic conditions of this region can, however, have simi- anatomy, awareness of the imaging appearance of lar clinical features; and imaging plays a crucial role in con- the wide variety of lesions that can possibly involve firming the presence of disease, assessing its extent, guiding this region, and correlation with clinical and further investigations, and planning therapy (medical management, microsurgery, endovascular surgery, or radiation histopathologic features are essential for providing therapy). MRI is the imaging modality of choice for assess- appropriate patient care. We review the anatomy ment of the cavernous sinus, owing to the superior contrast of the cavernous sinus, along with the imaging resolution of MRI. CT and digital subtraction angiography are technique, the multimodality imaging features of useful in certain cases. individual pathologic conditions of the cavernous ■■ Common neoplasms that involve the cavernous sinus include sinus correlating with histopathologic findings, pituitary adenoma, meningioma, nerve sheath tumors, head an algorithmic imaging approach to differential and neck malignancies such as nasopharyngeal carcinoma, and metastases. These neoplasms can be classified on the ba- diagnosis, and imaging pitfalls. sis of the origin or epicenter of the lesion as (a) lesions that arise primarily within the cavernous sinus, (b) lesions that Anatomy invade the cavernous sinus from adjacent structures, and Each of the paired cavernous sinuses is a ve- (c) metastatic or hematologic disease. nous lake situated lateral to the sella turcica, ■ ■ Vascular lesions of the cavernous sinus—namely, cavernous the pituitary gland, and the sphenoid sinus and sinus thrombosis, ICA aneurysm, and CCF—are great clinical mimics, with a wide variety of clinical manifestations varying medial to the medial aspect of the temporal lobe from trivial to life threatening. Among this category of cavern- of the brain. The term cavernous sinus was first ous sinus lesions, septic thrombosis is the most common and used by Winslow in 1734 owing to the multiple is managed primarily by controlling the source of sepsis with filaments, or septa, within, which gave it a cavern- medical and surgical means. Digital subtraction angiography ous or plexiform appearance. However, this term plays an important role in the management of CCF and ICA aneurysm. has courted controversy because the cavernous sinus has certain anatomic differences from other ■■ Considerable overlap exists in the radiologic findings of cavernous sinus involvement in infective or inflammatory diseas- dural venous sinuses. It is extradural in location, es; the most common findings encountered are a bulky cav- contains fat, and is continuous with the epidural ernous sinus and increased enhancement, which may extend space (extradural space) of the spine (by way of to the orbit or the adjacent dura. Imaging clues that point to the periosteum of the skull base) and the orbital infection or inflammation as the possible cause, as compared space, in contrast to other dural venous sinuses with neoplasms, are a sheetlike configuration of the abnormal soft tissue and T2 hypointensity. However, certain neoplasms, that are located between the two dural layers. such as lymphoma and en plaque meningioma, can mimic Parkinson (1) has argued that the cavernous si- these findings. Among this spectrum of infective and inflam- nus should be more accurately called “the lateral matory disorders, Tolosa-Hunt syndrome is a diagnosis of sellar compartment.” Because the term cavernous exclusion; other disease processes are diagnosed by specific sinus is well established in the medical literature, serum or histopathologic biomarkers. it continues to be used widely to refer to this anatomic compartment. The cavernous sinus has been described as junction of the lateral and medial walls of the an “anatomic jewel box” owing to its complex- cavernous sinus. Pathologic conditions of the ity. Figure 1 is a diagram of a coronal section cavernous sinus can have various clinical conse- through the cavernous sinuses. The cavernous quences, ranging from subtle to devastating, and sinus extends from the superior orbital fissure including headache, ophthalmoplegia, exophthal- anteriorly to the petrous apex and the dorsum mos (proptosis), chemosis, vision loss, trigeminal sellae posteriorly. The cavernous sinus is said neuralgia, and, rarely, cerebral infarction owing to have a shape resembling a boat and is nar- to ICA involvement. The cavernous sinus can rowest anteriorly and widest posteriorly. It is be affected by neoplasms (benign or malignant), bounded by dura and has five walls: (a) lateral; infection or inflammation, vascular pathologic (b) medial; (c) superior, or roof; (d) anterior; conditions, and congenital lesions, among others. and (e) posterior (2). The medial wall is the RG • Volume 39 Number 3 Mahalingam et al 797

Figure 1. Diagram of a coronal section through the cavernous sinuses and the sella turcica. Note that the medial wall of the cavernous sinus (CS) is constituted by only a single layer of the dura mater. ACA = anterior cerebral artery, ICA = cavernous segment of the ICA, III = oculomotor nerve, IV = trochlear nerve, MCA = middle cerebral artery, OC = optic chiasm, PIT = pituitary gland, SS = sphenoid sinus, VI = abducens nerve, V1 = ophthalmic nerve, V2 = maxillary nerve, black arrowhead = inner periosteal layer of the dura, white arrowhead = outer meningeal layer of the dura, * = subarachnoid space.

Figure 2. Diagram of the segments and major branches of the cavernous segment of the ICA. Light blue structure represents the cavernous sinus (CS). The segments of the cavernous carotid artery from proximal to distal are the posterior vertical (PV), the posterior genu (PG), the horizontal (HORZ), the anterior genu (AG), and the anterior vertical (AV). ACP = anterior clinoid process, DDR = distal dural ring, OA = ophthalmic artery, PDR = proximal dural ring, PLL = petro lingual ligament.

only one that consists of a single dural layer; the and V1 are located within the inner dural layer of other walls consist of two dural layers—an outer the lateral cavernous sinus wall. The lateral and meningeal dural layer and an inner periosteal medial walls merge inferiorly with each other at dural layer (1,3). the superior margin of cranial nerve V2 (2). The medial wall is the weakest one and sepa- The ICA within the cavernous sinus bends rates the cavernous sinus from the lateral wall of to form an S shape, as seen in both coronal and the sphenoid sinus inferiorly and the pituitary sagittal sections. The ICA is divided into five gland superiorly. The part of the medial wall that segments on the basis of its course: posterior separates the cavernous sinus from the pituitary vertical, posterior genu, horizontal, anterior gland is continuous with the diaphragma sel- genu, and anterior vertical (Fig 2). Although the lae (3). Inherent weakness of this wall makes ICA is firmly adherent at its point of entry and the cavernous sinus susceptible to invasion from exit, the intervening segment is unsupported pituitary tumors. Although the two dural layers and can have a variable degree of tortuosity (4). of the lateral cavernous sinus wall may not be The intracavernous ICA commonly gives rise to discernible as separate structures at imaging, they two branches—namely, the meningohypophy- are important for the neurosurgical approach to seal trunk and the inferolateral trunk. The ICA the cavernous sinus. These two layers can be dis- divides the cavernous sinus into four venous sected apart, and cranial nerves can be accessed spaces: (a) the medial (between the ICA and without entering the venous compartment of the the medial wall of the cavernous sinus), (b) the cavernous sinus because cranial nerves III, IV, anteroinferior (relative to the posterior genu), 798 May-June 2019 radiographics.rsna.org

(c) the posterosuperior (between the ICA and the posterior part of the roof of the cavernous sinus), and (d) the lateral (between the ICA and the ophthalmic nerve) (2). The oculomotor nerve and the trochlear nerve pierce the roof of the cavernous sinus in the oculomotor triangle to enter the cavernous sinus, and the abducens nerve enters through the posterior wall. The oculomotor nerve (cranial nerve III), the trochlear nerve (cranial nerve IV), and the ophthalmic division of the trigeminal nerve (or ophthalmic nerve) (cranial nerve V1) lie in the lateral wall of the cavernous sinus in that order from superior to inferior. The maxillary division of the trigeminal nerve (or maxillary nerve) (cranial nerve V2) lies just inferior to the junction of the lateral and medial wall dura of the cavernous sinus. The abducens nerve (cranial nerve VI) and the sympathetic plexus around the carotid artery, on the contrary, lie within the cavity of the cavern- Figure 3. Diagram of the venous connections of the cavernous sinus in close relation to the ICA. The abdu- ous sinus (CS). BasVP = basilar venous plexus, ICC = intercavernous communication, IJV = internal jugular vein, IOV = inferior cens nerve courses in the lateral venous space (2). ophthalmic vein, IPS = inferior petrosal sinus, PteryVP = ptery- The venous connections of the cavernous goid venous plexus, SOV = superior ophthalmic vein, SphPS = sinus are illustrated in Figure 3. Each cavernous sphenoparietal sinus, SPS = superior petrosal sinus, SS = sig- sinus communicates with its counterpart on the moid sinus. opposite side by way of intercavernous communications—these are the anterior, inferior, and posterior intercavernous communications and the sions of the anterior part of the cavernous sinus basilar venous plexus (2). manifest with ophthalmoplegia and ptosis and Apart from the venous blood, the cranial nerves, usually do not involve the lower two trigeminal and the ICA, each cavernous sinus also contains nerve divisions. Blurring of vision or vision loss variable amounts of fat and fibrous tissue. The can occur when the lesion extends anteriorly structures within the cavernous sinus are embed- to involve the orbital apex. The combination of ded in a weblike fibrous skeleton. Adipose tissue is lateral rectus muscle palsy and Horner syndrome predominantly located adjacent to the lateral wall is highly specific for cavernous sinus pathologic of the cavernous sinus medial to the cranial nerves conditions and usually indicates a lesion located (5). Multiple foramina and fissures act as a con- within the cavernous sinus, as opposed to a lateral duit of structures from the cavernous sinus to the wall lesion. Pain is usually unilateral, localized to surrounding spaces, including the orbits, the face, the orbitofrontal region, and dull aching or boring the pterygopalatine fossa, the nasopharynx, the in character. The presence or absence of pain, infratemporal fossa, and the middle and posterior however, does not provide any clue with regard to cranial fossae. These fissures and foramina and the the nature of the underlying lesion (6,7). Other veins and nerves passing through the cavernous less common manifestations include hypotha- sinus also act as pathways for the spread of disease lamic-pituitary axis impairment, seizures caused to and from the cavernous sinus. Figure 4 illustrates by irritation of the adjacent cortex, and stroke these anatomic relationships and pathways. owing to ICA involvement. Onset can be insidious (usually with neoplastic and chronic inflamma- Clinical Manifestations of Cavernous tory causes) or sudden (with acute inflammatory Sinus Lesions (Cavernous Sinus and vascular causes), but considerable overlap in Syndrome) symptoms exists among the various causes. Clini- The classic manifestations described are ophthal- cal manifestations specific to a particular lesion are moplegia, ptosis, exophthalmos, chemosis, Horner highlighted in the respective sections. A practical syndrome (characterized by partial ptosis and classification of different causes of cavernous sinus miosis, with or without anhidrosis), facial pain or lesions is presented in Figure 5. loss of sensation in the trigeminal nerve distribution, and headache. These symptoms may occur Imaging Protocol individually or in combination, depending on the MRI is the mainstay of imaging the cavernous location of the lesion in the cavernous sinus. Le- sinus because of the superior soft-tissue contrast RG • Volume 39 Number 3 Mahalingam et al 799

Figure 4. Anatomic pathways related to the cavernous sinuses and the regional bone anatomy. Blue areas represent the position of the cavernous sinuses in the floor of the middle cranial fossa. Yellow lines outline the anatomic region set in boldface in each label. ACP = anterior clinoid process, OC = optic canal, PCP = posterior clinoid process, PPF = pterygopalatine fossa (outlined in orange on image at far left).

Figure 5. Etiologic classification of cavernous sinus lesions. IgG4 = immunoglobulin G4. resolution of MRI and its multiplanar capa- based contrast material are the mainstay for bilities. In our institution, a typical basic MRI interpretation. The coronal thin-section MR im- protocol is followed for suspected cavernous ages should cover from the orbits anteriorly to sinus lesions (Table 1). The coronal thin-section the brainstem posteriorly. Additional sequences high-spatial-resolution T2-weighted sequence that can be useful in certain situations are the and the thin-section fat-suppressed T1-weighted three-dimensional heavily T2-weighted sequence sequence in the axial and coronal planes before and time-of-flight angiography. Contrast-en- and after injection of intravenous gadolinium- hanced constructive interference in steady-state 800 May-June 2019 radiographics.rsna.org

Table 1: Basic 3-T MRI Protocol for Suspected Cavernous Sinus Lesions

Section TE TR Thickness Flip Fat Sequence (msec) (msec) (mm) Field of View Matrix Angle (°) Suppression Axial T2 weighted 80 3000 6 230 × 184 512 90/180 SPIR Coronal thin-section T2 weighted 80 3000 3 150 × 150 512 90/180 NA FLAIR (TI = 2800 msec) 125 11 000 6 230 × 184 512 90/180 NA T1 weighted 3.9 8.4 0.8 230 × 230 512 8 NA Susceptibility weighted 21 15 1 230 × 230 512 15–20 NA Diffusion weighted 68 2132 5 230 × 230 256 90/180 SPIR Nonenhanced and contrast agent–en- 2.3 4.7 0.9 395 × 278 432 10 SPAIR hanced T1 weighted fat suppressed Driven equilibrium* 185 1500 1 140 × 148 800 90/180 NA Note.—FLAIR = fluid-attenuated inversion recovery, NA = not applicable, SPAIR = spectral attenuated inversion recovery, SPIR = spectral presaturation with inversion recovery, TE = echo time, TI = inversion time, TR = recovery time. *DRIVE (Philips Healthcare, Andover, Mass).

imaging can clearly delineate the intracavernous Tumors Arising within the Cavernous course of the cranial nerves (8). Sinuses CT plays an adjunctive role in imaging of the cavernous sinus. Plain helical CT with a thin- Meningioma.—Meningiomas are one of the most section (<1 mm) axial acquisition and multi- common lesions to involve the cavernous sinus. planar reconstruction is useful for studying the They constituted 41% of all cavernous sinus le- osseous relationship of cavernous sinus masses sions in one large series (10). Advanced age (peak before surgery and for evaluating osseous ero- incidence in the 5th to 7th decade) and female sion or sclerosis. CT angiography performed sex are identified risk factors for development of with a bolus-tracking technique after injecting meningioma (11). Multiple meningiomas may be 60–80 mL of intravenous iodinated contrast encountered in the setting of neurofibromatosis material at a rate of 3–5 mL/sec can be used type 2. Meningiomas arise from the arachnoid to assess the relationship of the ICA to cavern- cap cells of the dura. About 80%–90% of menin- ous sinus mass lesions and in the evaluation of giomas are well-circumscribed benign neoplasms suspected vascular lesions of the cavernous sinus (World Health Organization [WHO] grade I), such as aneurysm, carotid-cavernous fistula with grade II (atypical, clear cell, and chordoid) (CCF), or cavernous sinus thrombosis. CT and grade III (anaplastic, rhabdoid, and papil- scanning in cases of cavernous sinus thrombosis lary) lesions being rare. Brain invasion, necrosis, requires attention to the scan delay, with a mini- prominent nucleoli, sheeting, hypercellularity, mum recommended delay of at least 45 seconds and small cell formation can be seen in atypical after contrast material injection (9). Contrast- meningiomas; and anaplastic meningiomas are enhanced CT is also used in planning for frankly malignant and can have areas resembling stereotactic radiosurgery in certain cavernous carcinoma, sarcoma, or melanoma at histopatho- sinus lesions such as meningioma and cavernous logic examination (12). hemangioma. Cavernous sinus meningiomas arise from the dura of the cavernous sinus (more specifically, Neoplasia the lateral wall dura) or arise from the adjacent Common neoplasms that involve the cavernous dura in the petroclival region, the sphenoid sinus include pituitary adenoma, meningioma, ridge, or the clinoid process with extension to the nerve sheath tumors, head and neck malignancies cavernous sinus. Meningiomas also differ in the such as nasopharyngeal carcinoma, and metasta- extent of their cavernous sinus involvement. They ses. These neoplasms can be classified on the basis can be (a) predominantly exophytic, projecting of the origin or epicenter of the lesion as (a) le- laterally from the lateral dura of the cavernous sions that arise primarily within the cavernous sinus; (b) localized to the lateral wall, growing in sinus, (b) lesions that invade the cavernous sinus between the two dural layers of the lateral wall in from adjacent structures, and (c) metastatic or the “interdural plane”; or (c) invading the cav- hematologic disease. ernous sinus proper. Meningiomas invading the RG • Volume 39 Number 3 Mahalingam et al 801

Figure 6. Cavernous sinus meningioma in a 50-year-old woman who presented with left-sided facial pain and numbness, which had been present for 2 years, and diplopia, which had been present for 2 months. At physical examination, the patient had bilateral papilledema, left ophthalmoparesis, an absent corneal reflex on the left side, and left-sided deviation of the jaw. (a) Axial contrast-enhanced fat-suppressed T1-weighted MR image shows a homogeneously enhancing mass involving the left cavernous sinus. Note the markedly narrowed flow void of the left ICA (arrow).(b) Photomicrograph shows sheets of meningothelial cells with mild nuclear pleomorphism, prominent nucleoli, and eosinophilic cytoplasm, as well as a mitotic figure (arrow). Whorling is inconspicuous. The features are those of an atypical meningioma. (Hematoxylin-eosin [H-E] stain; original magnification,3 400.) cavernous sinus proper can encase the cavernous 6th decades. Patients with neurofibromatosis type segment of the ICA, causing its narrowing, or can 2 develop multiple schwannomas at an earlier even invade the ICA wall (13). age. Histologically, these tumors are composed of Meningiomas are iso- to hypointense to gray spindle cells, which can be arranged in two pat- matter on T1- and T2-weighted MR images and terns: (a) Antoni type A, the compact or neuri- show homogeneous intense enhancement on lemoma pattern; or (b) Antoni type B, the loose gadolinium-enhanced MR images. The cellular pattern (17). Verocay bodies and degenerative nature of these tumors manifests as hyperat- changes are common. This results in a heteroge- tenuation at nonenhanced CT and as restricted neous appearance of schwannomas at imaging, diffusion at MRI. Although generally homoge- especially when they are large. neous in appearance, tumor heterogeneity can On T2-weighted MR images, schwannomas be seen owing to calcification, tumor-associated are heterogeneously hyperintense; and on T1- vascularity, cystic areas, and, rarely, hemorrhage. weighted MR images, the lesions are hypointense. The dural tail sign and hyperostosis of adjacent Schwannomas demonstrate heterogeneous en- bone, if depicted, can provide a clue to diagnosis. hancement on gadolinium-enhanced T1-weighted Luminal narrowing of the ICA (Fig 6a) can be MR images (Fig 7). Cystic areas are common. seen if it is encased by tumor (14). Fluid-fluid levels and hemorrhage can be seen within the lesion. These lesions tend to have an Schwannoma.—Schwannomas are benign nerve ovoid shape when they are restricted to the cav- sheath tumors arising from Schwann cells. Cav- ernous sinus but assume a classic dumbbell shape ernous sinus schwannomas most commonly arise when they extend into the posterior cranial fossa, from the trigeminal nerve. Oculomotor schwan- the orbit, or the infratemporal fossa (18). Heavily nomas are less common. Schwannomas arising T2-weighted thin-section MR images are useful from the abducens nerve and the sympathetic to directly depict the cranial nerves and assess plexus around the ICA are extremely rare, with their relation to the tumor. However, it may be only a few cases reported (15,16). Most lesions difficult to localize the origin to a particular cra- occur sporadically, are solitary, and are encoun- nial nerve, especially when the lesion is restricted tered most commonly in patients in the 5th and to the confines of the cavernous sinus. 802 May-June 2019 radiographics.rsna.org

Figure 7. Cavernous sinus schwannoma in a 55-year- old woman presenting with a holocranial headache, which had been present for 1.5 years, and diplopia, which had been present for 1 year. The patient had bilateral papilledema, right temporalis wasting, an absent right corneal reflex, and right lateral rectus palsy. (a) Axial fat-suppressed T2-weighted MR image shows a hyperintense lesion in the right cavernous sinus, with an anterior cystic component (arrow). (b) Axial contrast- enhanced fat-suppressed T1-weighted MR image shows enhancement in the solid component. (c) Photomicro- graph shows fascicles of spindle-shaped cells arranged compactly (at left) and loosely (at right), with wavy mildly pleomorphic nuclei, inconspicuous nucleoli, and eosinophilic cytoplasm. (H-E stain; original magnification, 3100.)

Plexiform Neurofibroma.—Plexiform neurofi- thought to arise from the pericytes surrounding bromas are seen almost exclusively in the set- the capillaries and precapillary venules. In the ting of neurofibromatosis type 1. These lesions central nervous system, these neoplasms usually most commonly occur in the distribution of the arise from the dura. Previously known as simply ophthalmic or maxillary divisions of the trigemi- hemangiopericytoma, this tumor has been reclassi- nal nerve in young adults. The involved cranial fied into the category of a combined entity termed nerves become diffusely enlarged. Histologically, solitary fibrous tumor/hemangiopericytoma in the there is a multinodular pattern from the involve- 2016 update to the fourth edition of the WHO ment of multiple fascicles, which are expanded classification of central nervous system neoplasms by tumor cells and wisps of collagen. Lesions because of the similarities in the genetic makeup of typically show peripheral T2 hyperintensity and these tumors (21). At histopathologic examination, central hypointensity, a finding that has been la- the tumor exhibits a spectrum of two patterns. beled as the “target sign” (Fig E1). Other features The classic solitary fibrous tumor–like pattern is a of neurofibromatosis type 1, such as sphenoid patternless architecture of hypo- and hypercellular wing dysplasia, can provide additional clues to areas of spindle-shaped to oval cells separated by the diagnosis. The amount of enhancement after thick bands of keloid-like or amianthoid-like col- administration of a gadolinium-based contrast lagen. The other pattern is that of a classic heman- agent can be variable. Pointers to malignant giopericytoma, with high cellularity composed of change in a plexiform neurofibroma are rapid ovoid cells with a haphazard pattern and a charac- growth, an irregular infiltrative outline, loss of teristic branching “staghorn” pattern of vascula- the target sign, disproportionate erosion of bone, ture. In the WHO classification, these tumors are a peripheral enhancement pattern, peritumoral graded in a three-tier system, with grade I tumors edema, and intratumoral cysts (19,20). being considered as benign and with grade II and grade III tumors considered as malignant. Most of Solitary Fibrous Tumor/Hemangiopericytoma.— these neoplasms harbor a genomic inversion at the These are rare mesenchymal neoplasms that are 12q13 locus that fuses the NGFI-A binding pro- RG • Volume 39 Number 3 Mahalingam et al 803

Figure 8. Cavernous hemangioma in a 40-year-old woman with decreased vision in the left eye that had been present for 6 months. No other clinically important cranial nerve deficits were seen.(a) Axial T2-weighted MR image shows a homogeneous hyperintense mass (arrow) in the left cavernous sinus and the left trigeminal cave (Meckel cave). The superior orbital fissure (arrowhead) is not involved.(b) Axial T1-weighted MR image obtained 2 minutes after contrast agent injection shows central enhancement within the lesion. (c) Axial T1-weighted MR image obtained 9 minutes after contrast agent injection shows complete fill-in of contrast agent, with homogeneous enhancement. (Note that the gadolinium-enhanced images in b and c have a different axial orientation, compared with the axial T2-weighted image in a.) (d) Scintigraphic image obtained after administration of technetium 99m (99mTc) pertechnetate–labeled red blood cells shows accumulation of the tracer within the lesion in the left cavernous sinus (arrow).

cavernous sinus or cerebellopontine angles and have clinical behavior and imaging features different from their intra-axial counterparts (24,25). Extra-axial hemangiomas occur more commonly in middle-aged women. Microscopically, these lesions consist of numerous dilated vascular channels lined by endothelial cells. tein 2 gene, NAB2, and the signal transducer and At MRI, cavernous hemangiomas are charac- activator of transcription 6 gene, STAT6, leading terized by high signal intensity on T2-weighted to STAT6 nuclear expression (22). and FLAIR MR images. Dynamic contrast- The imaging features of solitary fibrous tumor/ enhanced T1-weighted MR images show char- hemangiopericytoma closely mimic those of me- acteristic progressive “fill-in” of contrast agent, ningiomas. Some of the clues that are suggestive with intense homogeneous enhancement on of a diagnosis of solitary fibrous tumor/heman- late gadolinium-enhanced MR images (Fig 8). giopericytoma are a narrow base of attachment Hemangiomas encasing the cavernous segment to the dura, erosion of the adjacent bone, and of the ICA usually do not cause luminal nar- the presence of associated flow voids (Fig E2). rowing of the ICA, in contrast to meningiomas, On the other hand, meningiomas usually have a which tend to cause luminal narrowing of the broad base of attachment to the dura, hyperosto- ICA. Scintigraphic imaging after administration sis of adjacent bone, and intratumoral calcifica- of 99mTc pertechnetate–labeled red blood cells tion. Solitary fibrous tumor/hemangiopericytoma demonstrates accumulation of tracer within the also occurs in a younger age group, compared lesion, a finding that is said to be specific for with meningiomas, which occur in patients in the making the diagnosis of cavernous hemangioma 5th to 7th decades (23). (25). Digital subtraction angiography may show hypertrophic branches from the ICA and the ex- Cavernous Hemangioma.—Cavernous heman ternal carotid artery, as well as variable vascular giomas are not true neoplasms and are better blush (26). Establishing the diagnosis of cavern- described as vascular malformations. In the ous hemangioma before surgery is of paramount central nervous system, they are encountered importance, because these tumors are notorious most commonly in the brain parenchyma. Extra- for causing profuse and often uncontrollable axial hemangiomas are rare and can occur in the intraoperative hemorrhage. 804 May-June 2019 radiographics.rsna.org

Figure 9. Cavernous sinus melanoma in a 36-year-old woman who presented with headache, which had been present for 3 years, numbness on the left side of the face, difficulty in chewing on the left side, and diplopia, which had been present for 6 months. The patient had left lateral rectus palsy, mild ptosis, left temporalis and masseter wasting, and an absent left corneal reflex. (a) Axial nonenhanced CT image at the level of the cavernous sinuses shows a heterogeneous mass with peripheral hyperattenuation in the left cavernous sinus. (b) Coronal T1-weighted MR image shows the T1 hyperintensity of the mass (arrow). (c) Photomicrograph shows sheets and nests of spindle-shaped to polygonal cells that are heavily pigmented and show moderate nuclear pleomorphism and some prominent nucleoli. (H-E stain; original magnification,3 400.)

Melanocytoma or Melanoma.—Primary melanocytic tumors are said to arise from melanocytes in the leptomeninges. These tumors can be benign (represented by melanocytoma) or malignant (melanoma). Malignant melanoma of the central nervous system can be primary or metastatic. At histopathologic examination, these tumors are made up of polygonal to spindle-shaped cells. Mitotic activity and nucleoli are inconspicuous in melanocytomas but are prominent in melanomas. Other pigmented neoplasms of the central nervous system, such as melanocytic meningiomas and melanocytic schwannomas, can mimic melanoma at histopathologic examination. Common sites of occurrence for melanocytoma or melanoma in the central nervous melanocytosis of the first and second divisions system are the posterior fossa, the trigeminal of the trigeminal nerve (28). cave (Meckel cave), and the cervical and tho- racic spinal canal. Most patients with primary Tumors That Arise from Adjacent meningeal melanocytoma are in the 5th decade Structures and Secondarily Invade of life (27). Melanoma of the cavernous sinus is the Cavernous Sinus a rare entity. These lesions are hyperattenuating on CT images. At MRI, the lesions demonstrate Pituitary Adenoma.—Pituitary adenomas are characteristic hyperintensity on T1-weighted the most common lesion to involve the cavern- MR images and heterogeneous signal inten- ous sinus. They are primarily tumors of adults. sity on T2-weighted MR images, with areas These tumors can be functional or clinically and of hypointensity ascribed to the paramagnetic biochemically silent. Although prolactinomas effects of melanin (Fig 9). Enhancement of a and corticotroph adenomas are more frequent in melanoma of the cavernous sinus after admin- women, growth hormone–secreting adenomas are istration of a gadolinium-based contrast agent more often found in men. Around a quarter of can be variable, ranging from no enhancement all adenomas are the null-cell type (29). Around to intense enhancement. This tumor can also 6%–10% of all pituitary adenomas invade the be associated with cutaneous nevus of Ota and cavernous sinus. RG • Volume 39 Number 3 Mahalingam et al 805

Figure 10. Juvenile nasopharyngeal angiofibroma in a 15-year-old male patient presenting with recurrent epistaxis and nasal obstruction, which had been present for 3 years. (a) Axial gadolinium-enhanced fat-suppressed T1-weighted MR image shows an intensely enhancing mass lesion centered in the left pterygopalatine fossa, causing its expansion, with anterior bowing of the posterior wall of the left maxillary sinus (white arrow). A normal right pterygopalatine fossa (black arrow) is also depicted. (b) Axial gadolinium-enhanced fat-suppressed T1-weighted MR image obtained at a more cranial level than a shows involvement of the left cavernous sinus and orbit by the lesion.

Invasion of the cavernous sinus is an impor- occur almost exclusively in adolescent male pa- tant prognostic factor with regard to surgery for tients. Recurrent spontaneous epistaxis is the usual pituitary adenomas, with a higher incidence of presenting symptom. Histologically, these tumors both intraoperative ICA injury and postoperative consist of stellate and staghorn-shaped blood ves- leakage of cerebrospinal fluid (CSF) when cav- sels embedded in an irregular fibrous stroma with ernous sinus invasion is present. Hence, preoper- interspersed spindle-shaped fibroblasts. Cavernous ative identification of cavernous sinus invasion is sinus invasion by juvenile nasopharyngeal angio- of paramount importance. The lateral part of the fibroma can occur owing to skull base erosion or dural sac of the pituitary gland forms the medial extension by way of the skull base foramina. wall of the cavernous sinus, and its perforation Juvenile nasopharyngeal angiofibromas are by the tumor indicates cavernous sinus invasion. generally hyperintense to muscle on T2-weighted However, this thin dural layer is not depicted MR images and iso- to hypointense on T1- with routine CT or MRI; and hence, indirect weighted MR images. Flow voids can be observed signs have been proposed to predict cavernous within the lesion, reflecting its highly vascular sinus invasion. Knosp et al (30) used medial, nature. Juvenile nasopharyngeal angiofibromas median, and lateral intercarotid lines to classify exhibit intense enhancement on gadolinium- pituitary adenomas invading the cavernous sinus; enhanced MR images (Fig 10). Expansion of the and Cottier et al (31) used the percentage of pterygopalatine fossa is an important diagnostic ICA circumference contacting the tumor and the clue to a diagnosis of juvenile nasopharyngeal invasion of five venous compartments around the angiofibroma. The lesion characteristically ICA. These two classification systems are repre- causes anterior bowing of the posterior wall of sented in Figure E3 (30,31). Greater than 67% the maxillary sinus. These tumors have a notori- circumferential contact with the ICA indicates ous tendency to bleed profusely when dissected. invasion, and less than 25% contact and the tu- Hence, preoperative endovascular embolization mor not crossing the medial intercarotid line have of the tumor is a part of routine management of high negative predictive values for invasion. these lesions (32,33).

Juvenile Nasopharyngeal Angiofibroma.—These Chondrosarcoma.—Cranial chondrosarcomas lesions are locally aggressive, histologically benign usually arise from the skull base, most com- neoplasms that arise in the nasal cavity or naso- monly at the site of the petro-occipital synchon- pharynx near the sphenopalatine foramen. They drosis, and can extend to involve the cavernous 806 May-June 2019 radiographics.rsna.org

Figure 11. Chondrosarcoma in a 25-year-old man who presented with numbness on the left side of the face, difficulty in chewing, diplopia on looking to the left, and a left-sided headache, which had been present for 2 years. The patient had left lateral rectus palsy, left temporalis wasting, and an absent left corneal reflex.(a) Axial nonenhanced CT image shows a mass causing expansion of the left petrous apex. Note the large calcified component of the mass anteriorly (arrow).(b) Axial fat-suppressed T2-weighted MR image shows a markedly hyperintense mass lesion (arrow) involving the posterior part of the left cavernous sinus. sinus. These lesions are usually slow growing consists of lobules containing highly vacuolated but invasive lesions. Cranial chondrosarcomas physaliferous cells and pools of mucin sepa- can be encountered in any age group, with the rated by fibrous septa. The chondroid variety average age of occurrence being in the 4th and of chordoma may have histopathologic features 5th decades (34). On the basis of the histo- closely resembling those of chondrosarcomas, pathologic findings, cranial chondrosarcomas and analysis of immunohistochemical markers is are subdivided into three types: classic, mesen- often required for accurate distinction between chymal, and dedifferentiated. The classic type these two entities. Chordomas are positive for is the most common and consists of large cells epithelial markers such as cytokeratin and epi- with abundant pale cytoplasm in a chondroid thelial membrane antigen, but chondrosarcomas background matrix. are not (37). Chordomas are typically located in MRI characteristically demonstrates high the midline of the skull base. signal intensity in chondrosarcomas on T2- At imaging of chordomas, CT shows a well-de- weighted MR images because of the chondroid fined soft-tissue mass with lytic destruction of the matrix. Regions of low signal intensity can bone. At MRI, the signal intensity characteristics be depicted owing to calcifications. The le- of chordomas parallel those of chondrosarcoma. sions usually show marked enhancement on The T2 hyperintensity of chordomas is ascribed gadolinium-enhanced MR images (35). CT to the high fluid content of the physaliferous cells. demonstrates matrix calcification in a chondroid The chondroid variant of chondrosarcoma more pattern (“ring and arc” pattern) and helps in the commonly has calcifications within (36). Differ- assessment of bone destruction (Fig 11). entiation of chordomas from chondrosarcomas can be difficult at imaging, especially if the lesion Chordoma.—Chordomas are locally aggressive grows in a position off the midline. neoplasms of the axial skeleton, with around one-third occurring in the clivus. Chordomas Nasopharyngeal Carcinoma.—Nasopharyn- are mostly encountered in patients who are in geal carcinomas are the most common primary the 4th decade of life (36). Chordomas arise malignancy of the nasopharynx and the most from notochordal cell rests. The clival chordo- common extracranial malignancy to invade the mas arise from the spheno-occipital junction. cavernous sinus. Nasopharyngeal carcinomas On the basis of the histopathologic findings, are encountered in patients in the 5th and 6th chordomas can be classified into classic and decades of life. Nasopharyngeal carcinomas can chondroid types. The classic type of chordoma be of two pathologic types: (a) the keratinizing RG • Volume 39 Number 3 Mahalingam et al 807 type, which is similar in behavior to other head 40% of rhabdomyosarcomas occurring in the and neck squamous cell carcinomas; and (b) the head and neck region. Common sites of occur- nonkeratinizing type, which is strongly associ- rence in the head and neck region include the ated with Epstein-Barr virus infection. Cavernous nasopharynx, the parapharyngeal and mastica- sinus involvement occurs by perineural spread or tor spaces, the paranasal sinuses, and the orbits. by direct invasion of the skull base (38). Cavern- Rhabdomyosarcoma often manifests as a solitary ous sinus involvement occurs late in the course of bulky heterogeneous mass (41). Rhabdomyosar- the disease and represents T4 disease in the TNM coma can invade the cavernous sinus by way of staging of nasopharyngeal carcinoma. The signal bone destruction or perineural extension. intensity characteristics of nasopharyngeal carcinomas at MRI are nonspecific—iso- to hypo Suprasellar Neoplasms.—A wide spectrum of intense on T1-weighted MR images, hyperintense lesions can arise in the suprasellar region and on T2-weighted MR images, and heterogeneous secondarily involve the cavernous sinus. More enhancement on gadolinium-enhanced MR im- common among these lesions are (a) germ cell ages. Bulky metastatic cervical lymphadenopathy tumors and (b) craniopharyngiomas. is usually seen (Fig E4). Intracranial germ cell tumors are a heterogeneous group of lesions that occur in the pineal Adenoid Cystic Carcinoma.—Adenoid cystic and suprasellar region. Of these lesions, 90% carcinomas are malignant tumors of the mi- occur in patients before the age of 20 years nor and major salivary glands, with a marked (42). Intracranial germ cell tumors are broadly propensity for perineural spread. These lesions divided into germinomatous and nongermino- account for about one-third of all minor salivary matous tumors (namely, embryonal carcinoma, gland tumors (33). Common sites of origin in yolk sac tumor, and choriocarcinoma). Supra- the head and neck are the palate, nasopharynx, sellar germinomas classically manifest with parapharyngeal space, buccal mucosa, and the diabetes insipidus, emaciation, or precocious tongue. Adenoid cystic carcinomas can occur in puberty. Peculiar to germ cell tumors is the se- a wide range of age groups, with a peak rate of cretion of protein markers, such as α-fetoprotein occurrence in the 5th and 6th decades. Adenoid and the beta subunit of human chorionic go- cystic carcinomas have an apparently indolent nadotropin, that can be detected in the serum course but have aggressive long-term behavior, and CSF. The combination of extremely high with high rates of recurrence. On the basis of levels of these proteins and the presence of a their architecture, adenoid cystic carcinomas suprasellar mass virtually clinches the diagnosis can be divided into three types—tubular, crib- of germ cell tumor. These tumors have a varied riform, and solid, in order of increasing aggres- appearance at imaging; germinomas usually are siveness (39). solid, and nongerminomatous lesions are said MRI is the modality of choice for staging to be more heterogeneous, with cystic and solid adenoid cystic carcinomas, owing to its superior areas. Nongerminomatous lesions tend to be delineation of perineural extension. Gadolin- more invasive (Fig E6). Imaging features are not ium-enhanced fat-suppressed MR images are specific enough to be used to distinguish be- useful for this purpose (Fig E5). Although the tween germinomatous and nongerminomatous presence of a small primary carcinoma with germ cell tumors. Teratomas can manifest as a extensive perineural spread may provide a clue heterogeneous cystic mass with fat and calcifica- to this diagnosis, this feature is not specific tion (43). and may be seen in other malignancies, such Craniopharyngiomas are sellar and/or supra- as squamous cell carcinoma, mucoepidermoid sellar tumors that arise from remnants of the carcinoma, melanoma, and lymphoma (40). craniopharyngeal duct. Cavernous sinus invasion is rare. Craniopharyngioma has a bimodal Sinonasal Carcinoma.—Carcinoma of the age distribution, with peaks in the 2nd decade paranasal sinus can involve the cavernous sinus and in the 4th to 6th decades. Craniopharyngio- by way of direct invasion and bone destruction. mas are divided into two types: (a) the adaman- Sphenoid sinus carcinoma, although rare and tinomatous type, which occurs predominantly in accounting for less than 1% of all sinonasal car- children and is characterized by the presence of cinomas, is the most common of the sinonasal wet keratin, stellate reticulum, and cholesterol carcinomas to invade the cavernous sinus, owing granuloma; and (b) the papillary type, which to its anatomic proximity (33). occurs in adults and shows more squamous differentiation. Adamantinomatous craniopha- Rhadomyosarcoma.—Rhabdomyosarcoma is a ryngiomas have a T1-hyperintense component tumor of the pediatric age group, with around owing to “motor oil cysts” (“machine oil cysts”) 808 May-June 2019 radiographics.rsna.org

Figure 12. Lymphoma in a 61-year-old man who presented with left-sided facial pain, diplopia, weight loss, and fever, which had been present for 2 months. (a) Axial T2-weighted fat-saturated MR image shows isointense soft tissue involving and expanding the left cavernous sinus (arrow). (b, c) Axial diffusion-weighted MR image (b) and apparent diffusion coefficient map (c) show diffusion restriction within the mass lesion (arrow on b) in the left cavernous sinus. (d) Axial PET/ CT fusion image shows intense uptake of fluorine 18 fluorodeoxyglucose (FDG) within the mass (arrow). Multiple other lesions with intense FDG uptake were also found in the lungs, kidneys, liver, and multiple lymph nodes (not shown). The findings from histopathologic examination of the specimen from biopsy disclosed high-grade non-Hodgkin lymphoma. and are frequently calcified; papillary craniopharyngiomas are solid and are not calcified (44).

Systemic Neoplasia

Lymphoma.—Systemic lymphoma and leukemia can involve the cavernous sinus either by direct extension from adjacent structures, such as the marrow of surrounding bones or the nasopharynx, or by hematogenous dissemination. Most of these lesions represent non-Hodgkin lymphoma. A primary lymphomatous lesion of the cavern- those seen in other aggressive neoplasms, such ous sinus without evidence of systemic disease as lymphoma and metastasis. is exceedingly rare (45). At MRI, lymphomatous lesions often are T2 hypointense and show Histiocytosis.—Histiocytosis is the term applied diffusion restriction owing to their high cel- to a group of disorders that are characterized by lularity. On gadolinium-enhanced MR images, proliferation of macrophages and dendritic cells these lesions demonstrate intense enhancement. and that occur predominantly in children. Ac- Lymphoma can mimic Tolosa-Hunt syndrome cording to the WHO classification, these disor- clinically and radiologically (46). PET plays an ders are divided into three groups: (a) dendritic important role in assessing the extent of sys- cell disorders, such as Langerhans cell histio- temic disease involvement (Fig 12). cytosis and Erdheim-Chester disease; (b) mac- rophage disorders, such as Rosai-Dorfman Myeloma or Plasmacytoma.—Cavernous sinus disease; and (c) malignant histiocytic disorders. involvement can be due to invasion from adja- The most commonly encountered entity among cent bone marrow disease (myeloma) or can be these disorders is Langerhans cell histiocytosis due to extramedullary plasmacytoma occurring (49). Langerhans cell histiocytosis is character- within the cavernous sinus (47,48). Patients ized histologically by myeloid dendritic cells that with primary extramedullary plasmacytoma are positive for CD1a and demonstrate Birbeck may go on to develop multiple myeloma later. granules at electron microscopic examination. Imaging features are nonspecific and mimic These cells are accompanied by lymphocytes RG • Volume 39 Number 3 Mahalingam et al 809

Figure 13. Cavernous sinus thrombosis in a 24-year-old woman who presented with headache, which had been present for 2 weeks, left-sided exophthalmos, and multiple episodes of seizures during the previous 24 hours. (a) Coronal T2-weighted MR image shows a bulky left cavernous sinus with a convex lateral margin (arrow). (b) Axial contrast-enhanced fat-suppressed T1-weighted MR image shows filling defects in the left cavernous sinus (arrow) and in the left superior ophthalmic vein (arrowhead). Also note the abnormal enhancement of the retro-orbital fat, with enhancing soft-tissue thickening in the preseptal space of the left orbit. and eosinophils. These disorders can occasion- the most common and is managed primarily by ally involve the cavernous sinus, either owing to controlling the source of sepsis with medical and contiguous invasion from a skull base lesion or surgical means. Digital subtraction angiography owing to dural disease. These lesions have been plays an important role in the management of described as being hypointense on T2-weighted CCF and ICA aneurysm. MR images and demonstrate variable contrast enhancement (50) (Fig E7). Cavernous Sinus Thrombosis Cavernous sinus thrombosis most often occurs Metastasis.—Metastasis to the cavernous sinus as a complication of bacterial or fungal sepsis in can occur by way of hematogenous, perineural, the paranasal sinuses, the face, the orbits, and or direct vascular spread. Head and neck ma- the skull base. The tributaries of the cavernous lignancies are the most common ones to me- sinus do not possess any valves and allow bidirec- tastasize to the cavernous sinus. Distant tumors tional flow, thus predisposing the sinus to septic that metastasize to the cavernous sinus are lung, involvement (51). The clinical manifestations of breast, renal, and gastric malignancies (14). An cavernous sinus thrombosis are often dramatic aggressive cavernous sinus lesion in the presence and are characterized by sudden-onset painful of a known malignancy at another site often ophthalmoplegia, exophthalmos, and vision loss. clinches the diagnosis of metastatic disease. Cavernous sinus thrombosis is more common in However, cavernous sinus syndrome owing to patients with diabetes and those with an immu- metastatic involvement may occasionally be the nocompromised status. presenting symptom of an occult malignancy. Imaging signs of cavernous sinus thrombosis Diagnosis of a metastatic lesion should be given include a bulky cavernous sinus, a convex con- consideration especially when a lesion with ag- figuration of the lateral wall, and filling defects gressive features, such as bone destruction, is within the sinus. Pitfalls in interpretation of cav- encountered. ernous sinus filling defects are highlighted in the section, “Pitfalls in Interpretation and Pseudole- Vascular Conditions sions.” Indirect signs that support the diagnosis Vascular lesions of the cavernous sinus—namely, of cavernous sinus thrombosis are back pressure cavernous sinus thrombosis, CCF, and ICA an- changes such as an engorged or thrombosed eurysm—are great clinical mimics, with a wide superior ophthalmic vein manifest as a loss of variety of clinical manifestations varying from its flow void, ipsilateral retro-orbital fat strand- trivial to life threatening. Among this category ing, bulky extraocular muscles, and exophthal- of cavernous sinus lesions, septic thrombosis is mos (52) (Fig 13). T1 and T2 signal intensity 810 May-June 2019 radiographics.rsna.org

Figure 14. CCF in a 20-year-old man with a history of head injury 1 month ago and progressive left exophthalmos during the previous 2 weeks. (a) Axial fat-suppressed T2-weighted MR image shows a bulky and hypointense left cavernous sinus (black arrowhead) with left-sided exophthalmos. Also note the stranding of the retrobulbar fat and the prominent extraocular muscles in the left orbit (white arrowheads). (b) Coronal T2-weighted MR image of the orbits shows a dilated left superior ophthalmic vein (arrow). (c) Digi- tal subtraction angiographic image of the left ICA obtained in the lateral view shows opacification of the left cavernous sinus (arrow) and its tributaries in the early arterial phase. SOV = superior ophthalmic vein. is not reliable for the diagnosis of cavernous ICA Aneurysm sinus thrombosis in isolation, because the signal Aneurysms arising from the cavernous segment intensity of a normal cavernous sinus is variable. of the intracranial ICA constitute around 2%– Diffusion-weighted MRI can be especially useful 9% of all intracranial aneurysms and around 5% in the acute stages of cavernous sinus throm- of giant aneurysms (>2.5 cm) (55). Most cav- bosis and can demonstrate diffusion restriction ernous ICA aneurysms are asymptomatic and within the sinus itself (Fig E8). are incidentally detected at imaging, most often in women older than 50 years (56). When these Carotid-Cavernous Fistula aneurysms are symptomatic, the most common CCF represents an abnormal communication manifestation is diplopia and headache owing to from the carotid artery to the cavernous sinus; this mass effect. Rupture can rarely occur and can communication can be either direct or indirect by manifest with symptoms unique to the location way of the branches of the carotid artery. CCF can of these aneurysms, such as epistaxis, spontane- be traumatic or spontaneous, with the traumatic ous CCF, subarachnoid hemorrhage, and cere- type being more common, representing 75% of all bral infarction owing to distal embolization. CCFs (53). Most of the posttraumatic CCFs are At CT, cavernous ICA aneurysms are mildly encountered in young male subjects. In contrast, hyperattenuating compared with brain paren- spontaneous CCFs are more common in older fe- chyma and can show peripheral curvilinear male subjects. The clinical manifestations of CCF, calcifications. The signal intensity within the especially the direct type, tend to be dramatic, aneurysm on MR images can be highly variable with progressive pulsatile exophthalmos, chemosis, and depends on the patency of and flow rate and diplopia. The indirect type of CCF has a more through the aneurysm. On T2-weighted MR insidious onset and can mimic an inflammatory images, the aneurysm can be seen as a flow void cause, with a waxing and waning course. or can be heterogeneously hyperintense ow- The reference standard for diagnosis of CCF ing to slow flow or partial thrombosis (Fig 15). is digital subtraction angiography. Features Pulsation artifacts can also be seen. Completely of CCF at routine MRI include a bulky ipsi- thrombosed aneurysms generally demonstrate lateral cavernous sinus, exaggerated adjacent iso- to hyperintense signal intensity on both flow voids, a dilated superior ophthalmic vein, T1- and T2-weighted MR images (57) (Fig E9). stranding of the retro-orbital fat, and bulky ex- Digital subtraction angiography plays an impor- traocular muscles (Fig 14). CT angiography has tant role in planning management of cavernous been shown to be equivalent to digital subtrac- ICA aneurysms. It is important to note that the tion angiography and better than MR angiogra- signal intensity of the lesion on MR images can phy in the detection of CCFs (54). Transarterial be misleading, and the clue to diagnosis is the or transvenous endovascular embolization is the round shape of the lesion and its continuity with preferred method of treatment. the ICA. RG • Volume 39 Number 3 Mahalingam et al 811

Figure 15. ICA aneurysm in a 50-year-old woman with a history of occasional headache for 2 years who presented with right hemiparesis, which had been present for 1 day after an episode of loss of conscious- ness. (a) Axial fat-suppressed T2-weighted MR image shows a rounded heterogeneous lesion in the left cavernous sinus. The heterogeneous signal intensity within the lesion is due to turbulent flow. A few small acute infarcts were seen in the left frontal lobe in the territory of the middle cerebral artery (not shown). (b) Digital subtraction angiographic image of the left ICA obtained in the lateral view shows a large aneurysm involving the cavernous segment of the ICA.

Infective and invasive, and chronic granulomatous invasive Inflammatory Conditions types on the basis of histologic criteria (58). A wide spectrum of infective and inflammatory The acute invasive, or fulminant, subtype of disorders can affect the cavernous sinus, includ- invasive fungal infection occurs in the setting ing fungal infections (acute or chronic), tuber- of immunocompromise, such as uncontrolled culosis, actinomycosis, sarcoidosis, immuno- diabetes mellitus or posttransplant immunosup- globulin G4 (IgG4)–related disease, idiopathic pression, and is characterized by a painless, ne- hypertrophic pachymeningitis, granulomatosis crotic black nasal septal or palatal ulcer that rap- with polyangiitis, and Tolosa-Hunt syndrome. idly progresses into full-blown cavernous sinus Considerable overlap exists in the radiologic syndrome and ICA thrombosis, with extremely findings of cavernous sinus involvement in infec- high mortality rates. Angioinvasion by fungal tive or inflammatory diseases; the most common hyphae is characteristic of this disease. The findings encountered are a bulky cavernous si- previously described imaging features of cavern- nus and increased enhancement, which may ex- ous sinus thrombosis are seen. MRI can be used tend to the orbit or the adjacent dura. Imaging to assess the extent of disease much better than clues that point to infection or inflammation as CT. Bone erosion, although a specific feature the possible cause, as compared with neoplasms, suggestive of invasive disease, often occurs late are a sheetlike configuration of the abnormal in the course of the disease. The infarcted tissue soft tissue and T2 hypointensity. However, characteristically has a nonenhancing T2-hy- certain neoplasms, such as lymphoma and en pointense nature; in the nasal turbinate, this fea- plaque meningioma, can mimic these findings. ture has been called the “black turbinate sign” Among this spectrum of infective and inflam- (Fig 16) (59). Diffusion-weighted MRI can matory disorders, Tolosa-Hunt syndrome is a show infarction of the optic nerve or the brain diagnosis of exclusion; other disease processes parenchyma either owing to direct parenchymal are diagnosed by specific serum or histopatho- invasion or ICA invasion and thrombosis. logic biomarkers. Individual disease processes The chronic invasive and chronic granu- are reviewed in the following paragraphs, with lomatous invasive subtypes of invasive fungal an emphasis on multidisciplinary evaluation. infection generally occur in immunocompetent patients, although diabetes mellitus and steroid Fungal Infection therapy are risk factors. The disease evolves Cavernous sinus involvement with fungal infec- during a period of months to years and is tion is due to spread from an invasive fungal characterized by dense accumulation of fungal infection of the paranasal sinus. Invasive fungal hyphae and mixed bone erosion and sclerosis infection is classified into acute invasive, chronic (60). CT shows hyperattenuating soft tissue 812 May-June 2019 radiographics.rsna.org

Figure 16. Acute invasive fungal infection in a 62-year-old man with uncontrolled diabetes mellitus who presented with right facial pain, which had been present for 1 week, loss of vision in the right eye,

and a fever, which had been present for 2 days. The level of hemoglobin A1c at admission was 13.6 g/ dL. (a) Coronal contrast-enhanced T1-weighted MR image shows mucosal thickening involving the right maxillary sinus (white arrow) and nonenhancing nasal turbinates (black arrow) on the right side. (b) Axial contrast-enhanced fat-suppressed T1-weighted MR image shows a filling defect in the right cavernous sinus (black arrowhead), as well as right exophthalmos (white arrowhead). (c) Photomicrograph shows necrotic debris with occasional broad aseptate basophilic fungal hyphae (arrow). Fungal culture (not shown) grew Aspergillus flavus and Rhizopus arrhizus. (H-E stain; original magnification,3 200.)

in the sinuses, which demonstrates markedly T2-hypointense signal intensity attributed to the accumulation of paramagnetic ions in the fungal hyphae. These chronic invasive subtypes are great mimics of the noninfective inflammatory spectrum of diseases, both clinically and at imaging. Moreover, if corticosteroid therapy is inadvertently administered to a patient with invasive fungal disease, the therapy can cause rapid worsening of the disease. Histopathologic examination hence plays a central role in diag- nosing invasive fungal disease.

Tuberculosis Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis that can rarely involve temic disease or rarely as isolated cavernous sinus the cavernous sinus, with both acute (61) and disease. Elevated serum angiotensin-converting chronic cavernous sinus syndrome (62) being enzyme levels may provide a clue to the diagno- reported in the literature. Disease manifestation sis, although this finding is not specific or sensi- of the chronic form can mimic meningioma and tive. The results of histopathologic examination other chronic inflammatory disorders, with the show noncaseating granulomas, with no organ- diagnosis being established by histopathologic isms or other causes of granulomatous reaction demonstration of granulomatous inflamma- (63) (Fig 17). tion with caseous necrosis (Fig E10). Culture of M tuberculosis from the biopsy sample is the only IgG4-related Disease definitive proof of diagnosis but is often elusive. IgG4-related disease is a recently recognized multisystemic fibroinflammatory disease entity Sarcoidosis characterized by lesions with a dense IgG4- Sarcoidosis is a multisystem granulomatous positive lymphoplasmacytic infiltrate, storiform disorder of unknown etiology. Cavernous sinus fibrosis, and elevated serum IgG4 levels (64). Al- involvement is rare. It can occur as part of sys- though first recognized in the context of autoim- RG • Volume 39 Number 3 Mahalingam et al 813

Figure 17. Sarcoidosis in a 64-year-old man who presented with cognitive impairment, which had been present for 1 year, polyuria, and polydipsia, which had been present for 2 months. There were no cranial nerve deficits. (a) Coronal T2-weighted MR image shows T2-hypointense soft tissue (arrow) involving the right sphenoid sinus and the right cavernous sinus. (b) Photomicrograph shows a supraclavicular lymph node with its architecture partially effaced by discrete granulomas composed of epithelioid histiocytes admixed with few lymphocytes, and Langhans- type (white arrows) and foreign body–type (straight black arrow) multinucleate giant cells. Basophilic concentric lamellar bodies (curved black arrow), resembling Schaumann bodies, are depicted. Serum angiotensin-converting enzyme levels were within normal limits. (H-E stain; original magnification,3 100.) mune pancreatitis, IgG4-related disease has now of the histopathologic findings exists with those been reported to involve almost all organ systems. of idiopathic hypertrophic pachymeningitis Similar to sarcoidosis, it is a unifying histologic and inflammatory pseudotumor, with only diagnosis for diverse clinical syndromes. Ume- the involved location being different. Tolosa- hara et al (65) have proposed comprehensive Hunt syndrome is a diagnosis of exclusion that diagnostic criteria for this disease on the basis of requires careful ruling out of alternative diagno- serum IgG4 levels and histologic criteria. Cav- ses. Common clinical features include orbital or ernous sinus involvement is often accompanied retro-orbital pain, paresis of the cavernous sinus by orbital and dural disease characterized by nerves, Horner syndrome, symptoms lasting for T2-hypointense thickening of involved tissue and a period of days to weeks, an absence of a sys- marked enhancement after administration of a temic or CSF inflammatory reaction, occasional gadolinium-based contrast agent (Fig E11). The spontaneous remissions, and dramatic improve- nerves of the cavernous sinus may show thicken- ment with administration of corticosteroid ing and enhancement (66). therapy (68). In contrast to other inflammatory disorders, biopsy is not essential to establish the Granulomatosis with Polyangiitis diagnosis. Biopsy is restricted to patients with Formerly known as Wegener granulomatosis, rapidly progressive disease and a lack of re- granulomatosis with polyangiitis is a necrotizing sponse to corticosteroid therapy. small-vessel vasculitis characterized by involve- In patients with Tolosa-Hunt syndrome, MRI ment of the nose and/or paranasal sinuses, the shows enhancing soft-tissue thickening of the lungs, and the kidneys. The findings at histo- cavernous sinus and superior orbital fissure (Fig pathologic examination reveal leukocytoclastic E12). The thickening is usually isointense to vasculitis with necrosis and palisading histiocytes gray matter on T1-weighted MR images and iso- (67). The levels of cytoplasmic antineutrophil to hypointense on T2-weighted MR images (69). cytoplasmic antibody (c-ANCA) are often but The cavernous ICA may show mild narrowing. not always elevated. Cavernous sinus involvement More important, imaging plays a crucial role is uncommon and can occur because of contigu- in demonstrating a lack of disease outside the ous extension from the orbit or paranasal sinus or region of the cavernous sinus, superior orbital because of de novo dural disease. fissure, and orbital apex region, as well as in ruling out mimics such as mass lesions (68). Be- Tolosa-Hunt Syndrome cause the diagnosis is made only on the basis of Tolosa-Hunt syndrome is a syndrome of painful the clinical and imaging features, close follow- ophthalmoplegia caused by a nonspecific inflam- up is usually recommended for at least 2 years mation of the superior orbital fissure–cavernous after establishing the diagnosis of Tolosa-Hunt sinus region on one side. Considerable overlap syndrome (70). 814 May-June 2019 radiographics.rsna.org

Figure 18. Epidermoid cyst in a 9-year-old girl who presented with intermittent headache, which had been present for 4 years, and preferential use of the left eye. (a) Axial fat-suppressed T2- weighted MR image shows a T2-hyperintense lesion (arrow) in the right cavernous sinus; the lesion was depicted medial to the lateral dura of the cavernous sinus. (b, c) Axial diffusion-weighted MR image (b) and apparent diffusion coefficient map (c) show diffusion restriction within the lesion. No enhancement was demonstrated (image not shown). (d) Photomicrograph shows the cyst wall composed of fibrocollagenous tissue lined by stratified squamous epithelial cells and lamellated keratin. Adnexal structures are not present. (H-E stain; original magnification,3 100.)

Congenital and Miscellaneous Lesions

Epidermoid and Dermoid Cysts Epidermoid cysts and dermoid cysts are congenital lesions that occur because of a disorder MRI are characteristic. The lesions are T2 hy- in the cleavage of cutaneous elements from the perintense, with signal intensity equal to that of neuroectoderm. Both of these types of cysts are the CSF, and T1 hypointense; they show partial lined by stratified squamous epithelium and suppression of signal intensity on FLAIR MR filled with desquamated skin cells. An epider- images; they show diffusion restriction; and they moid cyst is distinguished from a dermoid cyst do not enhance (Fig 18). High-spatial-resolution by the lack of dermal elements and append- steady-state or heavily T2-weighted MR images ages (sebaceous glands, apocrine glands, and help to clearly outline the wall of the lesion. hair). Dermoid and epidermoid cysts are slow Occasional lesions have T1-hyperintense signal growing and manifest in an insidious manner. intensity and have been described as “white Rarely, they can rupture, with resultant chemical epidermoids” (71). meningitis (71). Dermoid cysts are around 3–10 times less A parasellar location is the second most com- common than epidermoid cysts (73). Simi- mon location, after the cerebellopontine angle, lar to epidermoid cysts, dermoid cysts can be for intracranial epidermoid cysts. On the basis extradural or interdural in location. Extradural of their location, they can be classified into lesions tend to have adjacent skull base erosion (a) extracavernous (most commonly arising and encase the ICA; interdural lesions do not from the trigeminal cave) with cavernous sinus show skull base erosions and tend to displace invasion, (b) interdural (between the two layers the ICA medially. The signal intensity character- of the lateral wall of the cavernous sinus), or istics of dermoid cysts generally parallel those of (c) true intracavernous (tending to encase the fat at MRI, owing to their cholesterol content. ICA and push the nerves laterally). Interdural Dermoid cysts are hyperintense on T1-weighted lesions are adherent to the nerves and usually MR images and are of variable signal intensity cannot be resected completely (72). The features on T2-weighted MR images. Thin peripheral of epidermoid cysts of the cavernous sinus at enhancement can be seen (71). RG • Volume 39 Number 3 Mahalingam et al 815

Figure 19. CSF pseudocyst in a 55-year-old woman who presented with diplopia, which had been present for 2 months. She had undergone surgery for a pituitary macroadenoma 11 years ago. (a) Coronal T2-weighted MR image shows a thin-walled T2-hyperintense lesion (arrow) occupying the right cavernous sinus and the right side of the sella. (b) Coro- nal gadolinium-enhanced T1-weighted MR image shows no associated enhancement in the lesion (arrow). (c) Coronal contrast-enhanced T1-weighted MR image obtained 11 years ago (before the previous surgery) shows a hypoen- hancing pituitary macroadenoma (arrow) with right cavernous sinus invasion and complete encasement of the right ICA.

Arachnoid Cyst CSF signal intensity and showed no enhancement Arachnoid cysts are benign congenital CSF- (Fig 19). This lesion was surgically decompressed, containing unilocular cysts that are lined by a and the patient had an uneventful recovery. thin collagenous membrane and arachnoid cells. Arachnoid cyst of the cavernous sinus is extremely Pitfalls in Interpretation rare, with only a few case reports in the literature and Pseudolesions (74,75). The cranial nerves in the lateral wall of the cavernous sinus are sheathed by separate Asymmetry arachnoid membranes, and an arachnoid cyst may The cavernous sinuses are not always bilater- form when CSF gets trapped within these mem- ally symmetric at imaging. This finding could be branes. The signal intensity of the lesions parallels either related to the imaging technique (owing that of the CSF with use of all MRI sequences, to unintended obliquity in the plane of acquisi- and the lesions do not enhance. Heavily T2- tion) or related to the patient (owing to actual weighted MR images are useful in demonstrating difference in the shape and width of the cavern- the wall of the lesion. ous sinus). Asymmetry of the cavernous sinuses is a natural variation that can be mistaken for a CSF Pseudocyst lesion, especially on the contrast-enhanced im- Intracranial collections of CSF can occur after sur- ages, when the contrast material opacification gery or trauma. Such lesions can occasionally oc- within the cavernous sinus and within the ICA is cur in the cavernous sinus and cause symptoms by equal. One of the cavernous sinuses can appear exerting mass effect on the nerves. We encountered comparatively bulky. This finding needs to be a patient who had undergone surgery for a pitu- correlated with the patient’s symptoms. Other itary macroadenoma in the remote past and now ways of resolving this issue are (a) reviewing the presented with diplopia. Imaging showed a cystic T2-weighted axial and coronal MR images that lesion in a sellar-parasellar location; the lesion had clearly show a more tortuous course of the ICA 816 May-June 2019 radiographics.rsna.org

Table 2: Clues to the Differential Diagnosis of Cavernous Sinus Lesions on the Basis of Their Imaging Appearance

Imaging Clue Diagnosis T2 hypointensity Chronic inflammation, fungal infection, Langerhans cell histiocytosis, lymphoma, aneurysm with flow void Marked T2 hyperin- Cavernoma, hemangioma, chondrosarcoma tensity T1 hyperintensity Dermoid cyst, melanoma, adenoma with hemorrhage, aneurysm with thrombosis and/or slow flow, lipoma Calcifications Chondrosarcoma, chordoma CT hyperattenuation Meningioma, melanoma, highly cellular neoplasms, thrombosed aneurysm Hyperostosis Meningioma Hemorrhage Adenoma, schwannoma Intense homogeneous Meningioma, lymphoma, cavernous hemangioma, aneurysm, enhancement juvenile nasopharyngeal angiofibroma, chronic inflammatory disease Diffusion restriction Lymphoma, epidermoid cyst Dural disease Meningioma, inflammatory disease Perineural extension Neurogenic tumors, adenoid cystic carcinoma, nasopharyngeal carcinoma, melanoma, lymphoma Constriction of the Meningioma, inflammatory lesions ICA Flow voids Hemangiopericytoma, juvenile nasopharyngeal angiofibroma, CCF Dilated superior oph- CCF, cavernous sinus thrombosis thalmic vein within the bulky-appearing cavernous sinus and travenous catheters or owing to trauma. In patients (b) assessing the lateral border of the cavernous without symptoms of cavernous sinus syndrome, sinus—this border remains straight or concave this finding is not of much clinical importance (77). even if the cavernous sinus is apparently bulky owing to natural variation, as compared with a Incomplete Opacification of the convex lateral margin when the cavernous sinus is Cavernous Sinus involved by a lesion (Fig E13). The cavernous sinuses are opacified at a later time than other dural venous sinuses. First-pass Fat in the Cavernous Sinus multidetector CT angiographic images often show Fat can normally be seen within the cavernous si- inadequate contrast opacification of the cavern- nus, more commonly in the anterior part near the ous sinus (9). Even at delayed phase imaging superior orbital fissure and in the region posterior performed with a time delay of 40 seconds, not all to the ICA. The results of microanatomic stud- images show adequate cavernous sinus opacifica- ies have shown that intracavernous adipose tissue tion. Moreover, first-pass images can show partial has a dumbbell-shaped configuration between the opacification of the cavernous sinus, mimicking ICA and the cranial nerves (5). At CT, promi- thrombosis (Fig E14). Thus when cavernous sinus nent fat attenuation can be depicted in patients thrombosis is suspected, delayed phase imaging with Cushing syndrome or can even be a normal (scanning delay of at least 45 seconds after con- variant (76). This finding should not be mistaken trast material injection) is required to definitively for a mass lesion. At CT, inexperienced readers rule out filling defects (78). Acquisition can also be can mistake fat within the cavernous sinus for air planned in the craniocaudal direction, which pro- owing to its low attenuation; this problem is easily vides some extra time for cavernous sinus filling. resolved by using a wide window setting. Clues to Differential Diagnosis and Gas in the Cavernous Sinus Algorithmic Approach At head CT, air attenuation in the cavernous sinus Although in certain cases, imaging features are can occasionally be depicted. This finding occurs pathognomonic, considerable overlap often exists probably as a result of venous air emboli from in- among the imaging findings of the various patho- RG • Volume 39 Number 3 Mahalingam et al 817

Figure 20. Diagram of a diagnostic algorithm for an imaging-based differential diagnosis of cavernous sinus lesions. CS = cavernous sinus, JNA = juvenile nasopharyngeal angiofibroma, LCH = Langerhans cell histiocytosis, PPF = pterygopalatine fossa. logic conditions described in this article. Imaging 5. Liang L, Gao F, Xu Q, Zhang M. Configuration of fibrous and adipose tissues in the cavernous sinus. PLoS One clues can point toward one group of diseases, thus 2014;9(2):e89182. https://www.ncbi.nlm.nih.gov/pmc/ helping to provide a more targeted clinical ap- articles/PMC3935851/pdf/pone.0089182.pdf. Published proach to diagnosis. These clues are highlighted February 26, 2014. 6. Lee JH, Lee HK, Park JK, Choi CG, Suh DC. Cavernous in Table 2. A stepwise algorithmic approach to sinus syndrome: clinical features and differential diagnosis differential diagnosis that is based on imaging is with MR imaging. AJR Am J Roentgenol 2003;181(2): highlighted in Figure 20. 583–590. 7. van Overbeeke JJ. The cavernous sinus syndrome: an anatomical and clinical study. In: Samii M, ed. Surgery of Conclusion the sellar region and paranasal sinuses. Berlin, Germany: Cavernous sinus syndrome can manifest with Springer, 1991; 484–489. 8. Yagi A, Sato N, Taketomi A, et al. Normal cranial nerves ophthalmoplegia, ptosis, exophthalmos, chemo- in the cavernous sinuses: contrast-enhanced three-dimen- sis, vision loss, Horner syndrome, facial pain, or sional constructive interference in the steady state MR headache. A wide range of conditions can cause imaging. AJNR Am J Neuroradiol 2005;26(4):946–950. 9. Delgado Almandoz JE, Su HS, Schaefer PW, et al. Fre- cavernous sinus syndrome, including neoplasms, quency of adequate contrast opacification of the major infection, inflammation, and vascular pathologic intracranial venous structures with CT angiography in conditions. Knowledge of the imaging clues is es- the setting of intracerebral hemorrhage: comparison of 16- and 64-section CT angiography techniques. AJNR sential to arrive at a workable set of possible diag- Am J Neuroradiol 2011;32(5):839–845. noses. Although a few conditions have a pathog- 10. Radhakrishnan K, Mokri B, Parisi JE, O’Fallon WM, nomonic imaging appearance that can clinch Sunku J, Kurland LT. The trends in incidence of primary brain tumors in the population of Rochester, Minnesota. their diagnosis, a multidisciplinary approach is Ann Neurol 1995;37(1):67–73. often necessary to arrive at the final diagnosis in 11. Osborn AG. Meningiomas and other nonglial neoplasms. most scenarios. In: Osborne AG, ed. Diagnostic neuroradiology. St Louis, Mo: Mosby-Elsevier Science, 2004; 584–602. 12. Commins DL, Atkinson RD, Burnett ME. Review of me- References ningioma histopathology. Neurosurg Focus 2007;23(4):E3. 1. Parkinson D. Lateral sellar compartment O.T. (cavern- https://thejns.org/focus/view/journals/neurosurg-fo- ous sinus): history, anatomy, terminology. Anat Rec cus/23/4/article-pE3.xml. Published October 2007. 1998;251(4):486–490. 13. Klinger DR, Flores BC, Lewis JJ, Barnett SL. The treatment 2. Yasuda A, Campero A, Martins C, Rhoton AL Jr, de Oliveira of cavernous sinus meningiomas: evolution of a modern E, Ribas GC. Microsurgical anatomy and approaches to approach. Neurosurg Focus 2013;35(6):E8. https://thejns. the cavernous sinus. Neurosurgery 2005;56(1 suppl):4–27; org/focus/view/journals/neurosurg-focus/35/6/article-pE8. discussion 4–27. xml. Published December 2013. 3. Campero A, Campero AA, Martins C, Yasuda A, Rhoton 14. Bakan AA, Alkan A, Kurtcan S, et al. Cavernous sinus: a com- AL Jr. Surgical anatomy of the dural walls of the cavernous prehensive review of its anatomy, pathologic conditions, and sinus. J Clin Neurosci 2010;17(6):746–750. imaging features. Clin Neuroradiol 2015;25(2):109–125. 4. Kline LB, Acker JD, Post MJ, Vitek JJ. The cavernous sinus: 15. Nakagawa T, Uchida K, Ozveren MF, Kawase T. Abdu- a computed tomographic study. AJNR Am J Neuroradiol cens schwannoma inside the cavernous sinus proper: case 1981;2(4):299–305. report. Surg Neurol 2004;61(6):559–563; discussion 563. 818 May-June 2019 radiographics.rsna.org

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