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MR imaging of perineural tumor spread
Magn Reson Imaging Clin N Am 10 (2002) 511–525
MR imaging of perineural tumor spread Lawrence E. Ginsberg, MD Department of Diagnostic Radiology, University of Texas MD Anderson Cancer Center, Box 57, 1515 Holcombe Boulevard, Houston, TX 77030, USA
Perineural spread (PNS) is a mechanism whereby tumor, or other pathologic conditions, spreads along the tissues of the neural sheath. In the setting of head and neck cancer, this type of tumor spread is common, and is well described in the surgical and imaging literature [1–9]. PNS has significant implications for treatment planning and also represents a major negative prognostic indicator. Imaging is critical in the diagnosis of PNS, particularly because it may asymptomatic. A thorough understanding of the relevant cranial nerve anatomy is a prerequisite for the successful radiologic evaluation of possible PNS. This article reviews the clinical settings that may be associated with PNS and presents the imaging strategies and findings of PNS, with a focus on MR imaging.
Clinical settings associated with perineural spread Malignant disease The most common malignancies associated with head and neck PNS are tumors of salivary, mucosal, and cutaneous origin [8–15]. For salivary gland origin, typical primary sites include the parotid gland and minor salivary glands, mainly in the palate. Any histologic subtype can spread perineurally but adenoid cystic carcinoma is most notorious. Squamous cell carcinoma (SCC) of primary mucosal origin, and cutaneous SCC or desmoplastic melanoma are also commonly associated with PNS. PNS is often present at the time of diagnosis and rarely may present prior to the detection of a head and neck primary cancer (Fig. 1) [16]. It is
E-mail address: [email protected] (L.E. Ginsberg).
also common for PNS to constitute, or occur simultaneously to, disease recurrence [7]. A typical history might be a new cranial neuropathy in a patient who had previously undergone resection of a lesion, with PNS as the cause of the neuropathy (Fig. 2). In some cases, the patient may not recall the prior resection and might not have known that the lesion was malignant. There also have been cases in which the previously resected lesion was erroneously interpreted as benign by the pathologist. In addition to the primary cancers mentioned previously, any malignant tumor that involves certain staging areas has the potential to spread perineurally. These locations, which are all immediately adjacent to skull base foramina, include the masticator space (Fig. 3), Meckel’s cave or cavernous sinus, and the pterygopalatine fossa (PPF) [7]. This spread may be retrograde (toward the central nervous system [CNS], generally superiorly or posteriorly) or antegrade (away from the CNS, generally inferiorly or anteriorly; see Figs. 1, 2). This will be discussed further in the section on anatomy. Benign disease Certain benign disorders may have spread along cranial nerve branches that are either tantamount to PNS, or very closely resembling it radiologically. These conditions include benign tumors, such as schwannoma/neurofibroma (Fig. 4) and meningioma; infections, such as rhinocerebral mucormycosis; and granulomatous lesions, such as sarcoidosis [7,17,18]. Clinical signs and symptoms The most common signs and symptoms associated with PNS include pain and paresthesias. In the case of V3, the mandibular division of the
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Fig. 1. A 64-year-old woman with 10-month history of left cheek numbness. After unsuccessful treatment for sinusitis, the symptoms got worse. Physical examination showed no abnormality in the oral cavity. Diagnosis was submucosal adenoid cystic carcinoma of the left hard palate. (A) Coronal T1-weighted MR image shows a subtle submucosal mass in the left side of the hard palate (arrow). Note the infiltration of the normal marrow fat, which is seen to be normal on the right side (arrowhead). This lesion was not palpable. (B) Axial CT image, bone algorithm, showing destruction and widening of the left greater palatine foramen (arrowhead). The normal lesser palatine foramen (black arrow) and right palatine foramen (white arrows) are evident. In the absence of direct tumor extension to involve these foramen, this finding strongly suggests perineural tumor spread. (C) Axial T1-weighted MR image shows abnormal soft tissue replacing the fat in the left pterygopalatine fossa (PPF; arrowheads). The right PPF is normal (arrow). (D) Axial fatsuppressed postcontrast T1-weighted MR image shows tumor extending posteriorly through foramen rotundum (black dots) into the cavernous sinus (arrow) and Meckel’s cave (arrowhead ). The right Meckel’s cave (white dot) is normal. (E) Coronal fat-suppressed post-contrast T1-weighted MR image shows tumor within foramen rotundum (large arrow). The normal right foramen rotundum (arrowhead) is smaller and far less enhancing. Some foraminal enhancement is normal and to be expected. Note the normally enhancing vidian canals (small arrows). (F) Coronal fat-suppressed postcontrast T1-weighted MR image, anterior to (E). There is enlargement and abnormal enhancement in the left infraorbital nerve (arrowhead), representing antegrade perineural tumor spread. Note that, despite fat suppression, the primary cancer (black dots) is not as evident as it was on the precontrast image (A).
trigeminal nerve, weakness and denervation of the muscles of mastication may be present. For PNS involvement of the facial nerve, varying degrees of facial weakness or paralysis may be evident. For facial paralysis, ‘‘Bell’s palsy’’ should not be a diagnostic consideration if facial paralysis is sustained; such cases require careful radiologic evaluation to exclude mass lesions. Up to 40% of patients with PNS, however, may be asymptomatic [7,14,15]. Anatomic considerations Trigeminal nerve The most commonly affected nerves in PNS are the trigeminal and facial. All three trigeminal divi-
sions may be involved, sometimes more than one simultaneously. The maxillary (V2) and mandibular (V3) divisions are most commonly involved, but occasionally for a lesion in the appropriate location, the ophthalmic division (CN V1) may be affected [7,19]. Figs. 5–8 depict the anatomy relevant to PNS along the trigeminal nerve. The ophthalmic division of the trigeminal nerve, V1, provides purely sensory innervation to the eye, lacrimal gland, conjunctiva, part of the nasal mucosa, and skin of the nose, eyelids, forehead, and scalp (see Fig. 5) [20]. PNS along the ophthalmic nerve generally arises in the setting of a cutaneous malignancy in the distribution of V1, the supraorbital region (Fig. 9). Although it is feasible that an intraorbital tumor could spread
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Fig. 1 (continued )
perineurally along V1, this does not appear common. In the author’s experience, the branches of the ophthalmic nerve most likely to be affected by PNS are the medially situated supratrochlear nerve and the more laterally situated supraorbital branch (see Figs. 5, 9). Of course, tumor can then spread back along the main trunk of V1 to the superior orbital fissure and more posteriorly. The maxillary nerve, V2, provides sensory innervation to the mid- and upper lateral face; the mucosa of the palate, sinonasal region, and maxillary gingiva; and the maxillary teeth (see Fig. 6) [20]. This nerve is commonly involved in PNS, particularly from cutaneous lesions in its distribution, but also by mucosal and minor salivary cancers of the palate (see Figs. 1, 10), nasophar-
ynx, and maxillary sinus [7,8]. For nasopharyngeal cancer to spread perineurally along V2, the tumor must first gain access to the PPF [13]. This typically occurs first by anterior extension into the nasal cavity, then lateral extension through the sphenopalatine foramen into the PPF [7,13]. The author has seen one very unusual case in which nasopharyngeal cancer first spread upward into foramen lacerum (the posterior boundary of the vidian canal) and then anteriorly in the vidian canal to the PPF, in an antegrade fashion (Fig. 11). Skin cancers in the distribution of the maxillary division of the trigeminal nerve overwhelmingly affect the infraorbital nerve, but may also affect the zygomatic nerve. The zygomatic nerve branches off from the main maxillary trunk within
Fig. 2. A 53-year-old woman, 6 years postparotidectomy for adenocarcinoma, with new onset of ipsilateral facial numbness. This case demonstrates perineural spread along the auriculotemporal branch of the mandibular nerve in a setting of late tumor recurrence, which was not detectable on physical examination. (A) Coronal postcontrast T1weighted MR image without fat suppression. There is subtle evidence of prior left parotidectomy, and abnormal enhancement extending superiorly through foramen ovale (arrowhead). More bulky disease is seen within Meckel’s cave (asterisk). From the parotid gland, this tumor could only get onto the main trunk of V3 via the auriculotemporal nerve. Note the lack of any bulky disease in the surgical bed; no disease was palpable. This case illustrates that the diagnosis of perineural spread can be made without fat suppression. (B) Axial postcontrast T1-weighted MR image without fat suppression. There is antegrade extension of tumor, anteriorly from Meckel’s cave, through the cavernous sinus and foramen rotundum into the pterygopalatine fossa (black dots). The normal right Meckel’s cave is seen (white dot). (C) Coronal postcontrast T1-weighted MR image without fat suppression shows continued antegrade perineural tumor spread along the infraorbital nerve (arrowhead).
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Fig. 3. A 49-year-old man, postresection of squamous cell carcinoma of the right retromolar area. The patient experienced persistent, progressive trismus postoperatively. (A) Axial fat-suppressed postcontrast T1-weighted MR image shows extensive tumor recurrence in the right masticator space (brackets). Anteriorly, tumor has extended directly into the pterygopalatine fossa (black dots). Note the normal pterygoid plates on the left side (arrows). (B) Coronal fatsuppressed post-contrast T1-weighted MR image shows tumor extending superiorly through a grossly widened foramen ovale (small dots) into Meckel’s cave (large dot). (C) Axial fat-suppressed postcontrast T1-weighted MR image shows tumor extending posteriorly from MeckelÕs cave, along the main trigeminal trunk (arrowheads).
the PPF, enters the orbit through the inferior orbital fissure, runs along the lateral orbital wall, and divides into the zygomaticofacial and zygomaticotemporal branches [20]. The zygomaticotemporal nerve sends a small twig to the lacrimal nerve. The zygomaticotemporal and zygomaticofacial nerves exit the orbit through its lateral wall and supply innervation to the skin of the temporal region and lateral cheek (for anatomy of the
zygomatic nerve; see Figs. 6, 7). By this route, skin cancers arising in the cutaneous distribution of the zygomatic nerve may spread perineurally into the orbit (Fig. 12). Continued posterior spread into the PPF and more proximally may then ensue. For the maxillary nerve, the common final pathway is the PPF. The PPF is a pyramidal space located inferior to the orbital apex and posterior to the maxillary sinus (see Fig. 6) [21]. In addition to
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Fig. 5. The ophthalmic nerve (V1) anatomy, frontal view. Ant, anterior; n, nerve; post, posterior.
Fig. 4. A 38-year-old woman with a 30 year history of intermittent right facial pain. There was no history of head and neck malignancy. Diagnosis was neurofibroma. (A) Noncontrast axial T1-weighted MR image shows a very large mass extending from Meckel’s cave anteriorly through a massively widened foramen rotundum (arrowheads) into the pterygopalatine fossa (dots). Tumor extends laterally and then anteriorly to enter the orbit via the inferior orbital fissure (arrow), probably along the zygomatic branch of V2. (B) Axial CT image, bone algorithm, showing enlargement of the bony foramina, without destruction, suggesting a benign process.
the extracranial segment of V2, the PPF also contains the pterygopalatine ganglion and terminal branches of the internal maxillary artery. It is bounded posteriorly by the pterygoid plates, medially by the palatine bone, and anteriorly by the maxillary bone. Laterally, it communicates with the infratemporal fossa via the pterygomaxillary fissure. It also connects with the nasal cavity medially via the sphenopalatine foramen, the orbit via the inferior orbital fissure, and intracranial space via the foramen rotundum. Posteriorly, the anterior opening of the vidian canal permits the entrance of the vidian nerve, which constitutes the preganglionic parasympathetic component of the pterygopalatine ganglion. Inferiorly, the greater and lesser palatine foramina lead to the palate (see Fig. 6). Once tumor has spread perineurally to the PPF, it may continue posteriorly through the foramen rotundum (see Fig. 1), into the cavernous sinus, and can continue posteriorly through Meckel’s cave and on to the main trigeminal trunk (see Fig. 3). Tumor may also spread posteriorly along the vidian nerve within the vidian or pterygoid canal (see Fig. 10). This permits continued posterior PNS
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Fig. 6. V2, V3, and facial nerve anatomy, lateral view. (From Ginsberg LE. Imaging of perineural tumor spread in head and neck cancer. Semin Ultrasound CT MR 1999;2:176).
Fig. 7. The zygomatic branch of V2. br, branch; n, nerve; nn, nerves.
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Fig. 8. (A, B) The auriculotemporal branch of V3. (B) Cutaneous innervation of the auriculotemporal nerve. br, branch; n, nerve.
along the greater superficial petrosal nerve (GSPN; to be discussed later). Alternatively, once arriving in the PPF, tumor may spread in an antegrade fashion, anteriorly along the infraorbital nerve (common; see Figs. 1, 2) or inferiorly along the palatine nerves (uncommon). Tumor that has spread posteriorly from V2 into the Meckel’s cave
may also spread inferiorly along V3 through foramen ovale. The mandibular nerve, V3, provides sensory innervation to the skin of the lower face and preauricular/temporal region; the mandibular teeth; and the mucosa of the mandibular gingiva, floor of mouth, and tongue (anterior two thirds); and
Fig. 9. A 55-year-old man, with postsurgery followed by XRT for recurrent squamous cell carcinoma of the left forehead. At the time of this scan, the patient was experiencing pain and paresthesias in the supraorbital region. (A) More anterior and (B) more posterior coronal, fat-suppressed, contrast-enhanced T1-weighted MR images show abnormal enhancement of the frontal branch of V1 (arrowhead), located between the orbital roof and the superior muscle complex.
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Fig. 10. A 64-year-old man with adenoid cystic carcinoma of the hard palate extending into the nasal cavity. (A) Coronal fat-suppressed contrast-enhanced T1-weighted MR image shows a large mass encompassing the hard palate and extending upward into the nasal cavity bilaterally (brackets). (B) Axial noncontrast T1-weighted MR image shows abnormal soft tissue in the left pterygopalatine fossa (dots). This is more subtle than what was seen in Fig. 1C. (C) Axial fat-suppressed postcontrast T1-weighted MR image shows tumor extending posteriorly into the anterior aspect of the left vidian canal (arrows). More posteriorly, the canal appears normal (small arrowhead). The right vidian canal is also seen (large arrowheads).
the buccal mucosa [20]. The mandibular nerve also provides motor innervation to the muscles of mastication, the mylohyoid, and anterior belly of the digastric muscles. Mandibular nerve neuroanatomy relevant to PNS can be seen in Figs. 6 and 8. Tumors that most commonly spread perineurally along the mandibular nerve include cancers of the lower lip and any tumor that arises primarily within, or spreads secondarily to, the masticator
space. Examples of the latter include lateral extension of nasopharyngeal cancer or deeply invasive oral malignancies (see Fig. 3) [7,13]. There is a lateral branch of the mandibular nerve, the auriculotemporal nerve (ATN), which splits from the main trunk just beneath foramen ovale, courses laterally and then superiorly, and provides sensory innervation to the upper lateral face and preauricular region (see Fig. 8) [20]. The
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Fig. 11. A 39-year-old woman with adenoid cystic carcinoma of the nasopharynx. (A) Axial T2-weighted MR image showing the primary lesion (arrow). (B) Axial fat-suppressed postcontrast T1-weighted MR image shows the upper extent of the primary skull base involvement in the foramen lacerum (asterisk). From here, tumor extends anteriorly, in an antegrade fashion, through a grossly widened vidian canal (arrowheads). The pterygopalatine fossa, which represents the anterior boundary of the vidian canal, is also filled with tumor (dots). The left vidian canal is normal (arrows). (C) Coronal fat-suppressed postcontrast T1-weighted MR image shows the enlarged right vidian nerve (dot).
ATN also transmits postganglionic parasympathetic innervation (originating from cranial nerves VII and IX in the form of the lesser superficial petrosal nerve) to the parotid gland [20,22]. Cutaneous malignancies arising in the distribution of the ATN may spread perineurally and ultimately
gain access to the main trunk of V3. Because of the ATN, parotid malignancies may spread perineurally along the mandibular nerve (see Fig. 2) and the more widely appreciated facial nerve [7]. Once tumor has accessed a branch of the mandibular nerve, it may continue on to the main
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Fig. 12. Recurrent desmoplastic melanoma in the right lateral orbital region. Coronal noncontrast T1-weighted MR image shows the recurrence site (asterisks). Intraorbital tumor is also seen (black arrowheads), representing perineural extension along the zygomatic branches of the maxillary nerve. Secondary to other facial recurrences not shown, there is also V1 (arrow) and infraorbital (V2; white arrowhead) perineural tumor spread. The pterygopalatine fossa was also involved.
branch of V3 and course upward through foramen ovale into the MeckelÕs cave. From there, regardless of whether tumor arrived from V3 or from posterior extension of V2 PNS, tumor may spread posteriorly along the main trigeminal trunk and into the brainstem (see Fig. 3). Alternatively, from the MeckelÕs cave, tumor may spread anteriorly, in an antegrade fashion, into the cavernous sinus, foramen rotundum, and all the way into the PPF and beyond (see Fig. 2).
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mucoepidermoid carcinoma. Lesions that secondarily invade the parotid gland are generally cutaneous malignancies, such as SCC and desmoplastic melanoma. Once tumors have gained access to the main facial trunk, they may spread all the way up to the geniculate ganglion, and even through the labyrinthine segment to involve the internal auditory canal (intracanalicular segment). PNS of this type often represents or accompanies tumor recurrence that may be otherwise clinically silent (see Fig. 13). The other facial nerve branch that may be involved in PNS is the GSPN. The GSPN is a small branch of the facial nerve that leaves the geniculate ganglion and exits the superior surface of the temporal bone through the facial hiatus to become intracranial (Fig. 14) [20,24]. It then courses inferiorly and anteromedially, under Meckel’s cave, to the foramen lacerum, where it is joined by the deep petrosal nerve of the carotid sympathetic plexus to enter the pterygoid or vidian canal as the vidian nerve (see Fig. 1E) [24]. More anteriorly, within the PPF, the vidian nerve synapses in the pterygopalatine ganglion, and postganglionic parasympathetic fibers are distributed to the nasopharynx, the nasal cavity, the palate, and the lacrimal gland. These postganglionic parasympathetic fibers use distal trigeminal nerve branches as a conduit to arrive at their terminal destinations. For instance, the fibers that provide vasomotor innervation to the palate actually run within the palatine branches of the maxillary nerve [7,10]. This has the practical implication that tumors that arise within sites that are primarily thought of as innervated by the trigeminal nerve may give rise to perineural tumor spread that ultimately involves the facial nerve (Fig. 15). Also, because the GSPN courses immediately beneath Meckel’s cave, any tumor within Meckel’s cave, regardless of how it got there, may access the GSPN and spread posteriorly into the geniculate ganglion [24].
Facial nerve The facial nerve is complex, with multiple functions and a complicated course. A thorough review would be beyond the scope of this article; however, for PNS, only two facial nerve branches are typically affected. Diagrams of the facial nerve can be found in Figs. 6–8. Most commonly, the descending facial nerve segment is involved perineurally by malignancies that originate within or secondarily invade the parotid gland (Fig. 13) [7,11,24]. Examples of the former include adenoid cystic carcinoma, SCC, adenocarcinoma, and
Imaging of perineural tumor spread Imaging of PNS with MR imaging is analogous to imaging with CT but is far more sensitive. Many cases of PNS are probably missed because the imaging technique is inadequate. First, the field of view must be small enough to allow visualization of the often very small structures involved: 18 cm should be the largest field of view used in imaging PNS. For pulse sequences, a minimum set of sequence would include axial T1- and T2weighted images and axial and coronal postcontrast
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Fig. 13. A 54-year-old woman post parotidectomy for adenocarcinoma, which resulted in facial paralysis. At the time of this scan, physical examination was unrevealing and there were no new symptoms. In the setting of postoperative facial palsy, recurrent tumor may initially be clinically silent. (A) Axial noncontrast T1-weighted MR image shows abnormal soft tissue (arrows), representing tumor recurrence in the region of the left stylomastoid foramen. Note the normal hyperintense fat within the right stylomastoid foramen (dot). (B) Axial fat-suppressed postcontrast T1-weighted MR image shows enlargement and excessive enhancement (arrowhead) consistent with upward perineural tumor extension along the descending segment of the left facial nerve. The contralateral facial nerve is only faintly seen (arrow).
Fig. 14. The greater superficial petrosal nerve. a, artery; n, nerve; sup, superior. (From Ginsberg LE, DeMonte F, Gillenwater AM. Greater superficial petrosal nerve: anatomy and MR findings in perineural tumor spread. AJNR Am J Neuroradiol 1996;17.)
T1-weighted images. At the MD Anderson Cancer Center, all postcontrast head and neck imaging includes fat suppression, which is critical in the detection of PNS. PNS can be seen on non–fatsuppressed postcontrast MR imaging as well (see Fig. 2). As important as the postcontrast imaging is, the precontrast T1-weighted images are also crucial, because PNS generally causes replacement of the normal hyperintense fat that is present within PPF and at the opening of the basilar foramina of the skull base. Other technique considerations include slice thickness and spacing. Very large slices and intervals should be avoided to prevent partial voluming effects or missing a lesion entirely. We generally use 5-mm slices at 1-mm intervals for skull base imaging. Finally, though not strictly speaking an imaging technique, too many images per sheet of film may result in images that are too small to read, even if they were acquired properly. For the skull base, the author and his colleagues film 12 on 1. Of course, with the transition to soft reading, this potential problem will be obviated. Findings that suggest PNS include widening or excessive enhancement of the foramina through which cranial nerves and their branches traverse [5–9,23,25]. These include, for V3, foramen ovale
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Fig. 15. Advanced adenoid cystic carcinoma of the palate with massive intracranial disease. From Meckel’s cave (asterisk), tumor is spreading posterolaterally along the greater superficial petrosal nerve (dots), through the facial hiatus, and into the geniculate ganglion of the right facial nerve (large arrow). There is also early involvement of the proximal tympanic (small arrow) and labyrinthine (arrowhead) segments [16].
Fig. 16. Subacute hypoglossal denervation. Axial fat-suppressed postcontrast T1-weighted MR image shows faint but definite abnormal enhancement in the right hemitongue (arrowheads).
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Fig. 17. Chronic hypoglossal denervation. Axial noncontrast T1-weighted MR image shows hyperintensity in the right hemitongue, consistent with fatty infiltration. Also note the anteroposterior elongation of the right hemitongue, commonly seen in hypoglossal denervation.
and the mandibular foramen for the inferior alveolar nerve (the branch that enters the mandible, providing sensory innervation to the lower teeth and gingiva, and ends as the mental nerve providing cutaneous innervation of the chin; see Figs. 2, 3). For V2, important foramina/spaces include foramen rotundum, the PPF, the canal and foramen for the infraorbital nerve, the vidian canal, and the palatine foramen (see Figs. 1, 10, 12). For the facial nerve, the stylomastoid foramen and descending facial canal should be scrutinized (see Fig. 13). More proximally, enlargement and excessive enhancement of the cavernous sinus or Meckel’s cave strongly suggests perineural tumor spread in the appropriate clinical setting (see Figs. 1–3; Fig. 15). Of course, benign lesions such as meningioma and peripheral nerve tumors might appear very similar to perineural tumor spread (see Fig. 4). Indirect findings of PNS for the mandibular nerve include denervation of the masticator muscles, anterior belly of the digastric muscles, and mylohyoid [7,26,27]. In the early stages of denervation, the involved muscles may be observed on MR imaging to be abnormally hyperintense on T2-weighted images, and enhance excessively following contrast administration (Fig. 16) [27]. This type of denervation may be
the first sign of PNS and direct the radiologist to it, but it is undetectable on CT. Later, often months, denervation is manifested by atrophy and fatty infiltration, and is obvious on CT and MR imaging (Fig. 17). Recently, Fischbein et al [28] described denervation in the muscles of facial expression caused by disease involvement of the facial nerve. Of course, denervation is a phenomenon that is not unique to PNS but may be seen in other disease affecting cranial nerves. In conclusion, it is imperative that the radiologist, when faced with a clinical scenario such as new cranial neuropathy or a head and neck malignancy of the type or in the location that typically gives rise to PNS, consider this possibility when planning and interpreting cross-sectional imaging procedures. It is common that the radiologist first suggests or confirms the clinical suspicion of perineural tumor spread in these patients, and this diagnosis often has profound implications for treatment and prognosis. References [1] Ballantyne AJ, McCarten AB, Ibanex ML. The extension of cancer of the head and neck through peripheral nerves. Am J Surg 1963;106:651–67.
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[16] Ginsberg LE, DeMonte F. Palatal adenoid cystic carcinoma presenting as perineural spread to the cavernous sinus. Skull Base Surg 1998;8:39–43. [17] McLean FM, Ginsberg LE, Stanton CA. Perineural spread of rhinocerebral mucormycosis. AJNR Am J Neuroradiol 1996;17:114–6. [18] Mazziotti S, Gaeta M, Blandino A, et al. Perineural spread in a case of sinonasal sarcoidosis: case report. AJNR Am J Neuroradiol 2001;22:1207–8. [19] McNab AA, Francis AC, Benger R, et al. Perineural spread of cutaneous squamous cell carcinoma via the orbit. Ophthalmology 1997;104: 1457–62. [20] Berry M, Bannister LH, Stranding SM. Nervous system. In: Bannister LH, Berry MM, Collins P, Dyson M, Dussek JE, Ferguson MWJ, editors. Gray’s anatomy. 38th edition. New York: Churchill Livingston; 1995. p. 901–1937. [21] Daniels DL, Mark LP, Ulmer JL, et al. Anatomic moment: osseus anatomy of the pterygopalatine fossa. AJNR Am J Neuroradiol 1998;19: 1423–32. [22] Ginsberg LE, Pruett SW, Chen MY, et al. Skullbase foramina of the middle cranial fossa: reassessment of normal variation with high-resolution CT. AJNR Am J Neuroradiol 1994;15:283–91. [23] Caldemeyer KS, Mathews VP, Righi RR, et al. Imaging features and clinical significance of perineural spread or extension of head and neck tumors. Radiographics 1998;18:97–110. [24] Ginsberg LE, DeMonte F, Gillenwater AM. Greater superficial petrosal nerve: anatomy and MR findings in perineural tumor spread. AJNR Am J Neuroradiol 1996;17:389–93. [25] Curtin HD, Williams R. Computed tomographic anatomy of the pterygopalatine fossa. Radiographics 1985;5:429–40. [26] Russo CP, Smoker WRK, Weissman JL. MR appearance of trigeminal and hypoglossal motor denervation. AJNR Am J Neuroradiol 1997;18: 1375–83. [27] Davis SB, Mathews VP, Williams DW. Masticator muscle enhancement in subacute denervation atrophy. AJNR Am J Neuroradiol 1995;16:1292–4. [28] Fischbein NJ, Kaplan MJ, Jackler RK, et al. MR imaging in two cases of subacute denervation change in the muscles of facial expression. AJNR Am J Neuroradiol 2001;22:880–4.
MR imaging of perineural tumor spread Lawrence E. Ginsberg, MD Department of Diagnostic Radiology, University of Texas MD Anderson Cancer Center, Box 57, 1515 Holcombe Boulevard, Houston, TX 77030, USA
Perineural spread (PNS) is a mechanism whereby tumor, or other pathologic conditions, spreads along the tissues of the neural sheath. In the setting of head and neck cancer, this type of tumor spread is common, and is well described in the surgical and imaging literature [1–9]. PNS has significant implications for treatment planning and also represents a major negative prognostic indicator. Imaging is critical in the diagnosis of PNS, particularly because it may asymptomatic. A thorough understanding of the relevant cranial nerve anatomy is a prerequisite for the successful radiologic evaluation of possible PNS. This article reviews the clinical settings that may be associated with PNS and presents the imaging strategies and findings of PNS, with a focus on MR imaging.
Clinical settings associated with perineural spread Malignant disease The most common malignancies associated with head and neck PNS are tumors of salivary, mucosal, and cutaneous origin [8–15]. For salivary gland origin, typical primary sites include the parotid gland and minor salivary glands, mainly in the palate. Any histologic subtype can spread perineurally but adenoid cystic carcinoma is most notorious. Squamous cell carcinoma (SCC) of primary mucosal origin, and cutaneous SCC or desmoplastic melanoma are also commonly associated with PNS. PNS is often present at the time of diagnosis and rarely may present prior to the detection of a head and neck primary cancer (Fig. 1) [16]. It is
E-mail address: [email protected] (L.E. Ginsberg).
also common for PNS to constitute, or occur simultaneously to, disease recurrence [7]. A typical history might be a new cranial neuropathy in a patient who had previously undergone resection of a lesion, with PNS as the cause of the neuropathy (Fig. 2). In some cases, the patient may not recall the prior resection and might not have known that the lesion was malignant. There also have been cases in which the previously resected lesion was erroneously interpreted as benign by the pathologist. In addition to the primary cancers mentioned previously, any malignant tumor that involves certain staging areas has the potential to spread perineurally. These locations, which are all immediately adjacent to skull base foramina, include the masticator space (Fig. 3), Meckel’s cave or cavernous sinus, and the pterygopalatine fossa (PPF) [7]. This spread may be retrograde (toward the central nervous system [CNS], generally superiorly or posteriorly) or antegrade (away from the CNS, generally inferiorly or anteriorly; see Figs. 1, 2). This will be discussed further in the section on anatomy. Benign disease Certain benign disorders may have spread along cranial nerve branches that are either tantamount to PNS, or very closely resembling it radiologically. These conditions include benign tumors, such as schwannoma/neurofibroma (Fig. 4) and meningioma; infections, such as rhinocerebral mucormycosis; and granulomatous lesions, such as sarcoidosis [7,17,18]. Clinical signs and symptoms The most common signs and symptoms associated with PNS include pain and paresthesias. In the case of V3, the mandibular division of the
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Fig. 1. A 64-year-old woman with 10-month history of left cheek numbness. After unsuccessful treatment for sinusitis, the symptoms got worse. Physical examination showed no abnormality in the oral cavity. Diagnosis was submucosal adenoid cystic carcinoma of the left hard palate. (A) Coronal T1-weighted MR image shows a subtle submucosal mass in the left side of the hard palate (arrow). Note the infiltration of the normal marrow fat, which is seen to be normal on the right side (arrowhead). This lesion was not palpable. (B) Axial CT image, bone algorithm, showing destruction and widening of the left greater palatine foramen (arrowhead). The normal lesser palatine foramen (black arrow) and right palatine foramen (white arrows) are evident. In the absence of direct tumor extension to involve these foramen, this finding strongly suggests perineural tumor spread. (C) Axial T1-weighted MR image shows abnormal soft tissue replacing the fat in the left pterygopalatine fossa (PPF; arrowheads). The right PPF is normal (arrow). (D) Axial fatsuppressed postcontrast T1-weighted MR image shows tumor extending posteriorly through foramen rotundum (black dots) into the cavernous sinus (arrow) and Meckel’s cave (arrowhead ). The right Meckel’s cave (white dot) is normal. (E) Coronal fat-suppressed post-contrast T1-weighted MR image shows tumor within foramen rotundum (large arrow). The normal right foramen rotundum (arrowhead) is smaller and far less enhancing. Some foraminal enhancement is normal and to be expected. Note the normally enhancing vidian canals (small arrows). (F) Coronal fat-suppressed postcontrast T1-weighted MR image, anterior to (E). There is enlargement and abnormal enhancement in the left infraorbital nerve (arrowhead), representing antegrade perineural tumor spread. Note that, despite fat suppression, the primary cancer (black dots) is not as evident as it was on the precontrast image (A).
trigeminal nerve, weakness and denervation of the muscles of mastication may be present. For PNS involvement of the facial nerve, varying degrees of facial weakness or paralysis may be evident. For facial paralysis, ‘‘Bell’s palsy’’ should not be a diagnostic consideration if facial paralysis is sustained; such cases require careful radiologic evaluation to exclude mass lesions. Up to 40% of patients with PNS, however, may be asymptomatic [7,14,15]. Anatomic considerations Trigeminal nerve The most commonly affected nerves in PNS are the trigeminal and facial. All three trigeminal divi-
sions may be involved, sometimes more than one simultaneously. The maxillary (V2) and mandibular (V3) divisions are most commonly involved, but occasionally for a lesion in the appropriate location, the ophthalmic division (CN V1) may be affected [7,19]. Figs. 5–8 depict the anatomy relevant to PNS along the trigeminal nerve. The ophthalmic division of the trigeminal nerve, V1, provides purely sensory innervation to the eye, lacrimal gland, conjunctiva, part of the nasal mucosa, and skin of the nose, eyelids, forehead, and scalp (see Fig. 5) [20]. PNS along the ophthalmic nerve generally arises in the setting of a cutaneous malignancy in the distribution of V1, the supraorbital region (Fig. 9). Although it is feasible that an intraorbital tumor could spread
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Fig. 1 (continued )
perineurally along V1, this does not appear common. In the author’s experience, the branches of the ophthalmic nerve most likely to be affected by PNS are the medially situated supratrochlear nerve and the more laterally situated supraorbital branch (see Figs. 5, 9). Of course, tumor can then spread back along the main trunk of V1 to the superior orbital fissure and more posteriorly. The maxillary nerve, V2, provides sensory innervation to the mid- and upper lateral face; the mucosa of the palate, sinonasal region, and maxillary gingiva; and the maxillary teeth (see Fig. 6) [20]. This nerve is commonly involved in PNS, particularly from cutaneous lesions in its distribution, but also by mucosal and minor salivary cancers of the palate (see Figs. 1, 10), nasophar-
ynx, and maxillary sinus [7,8]. For nasopharyngeal cancer to spread perineurally along V2, the tumor must first gain access to the PPF [13]. This typically occurs first by anterior extension into the nasal cavity, then lateral extension through the sphenopalatine foramen into the PPF [7,13]. The author has seen one very unusual case in which nasopharyngeal cancer first spread upward into foramen lacerum (the posterior boundary of the vidian canal) and then anteriorly in the vidian canal to the PPF, in an antegrade fashion (Fig. 11). Skin cancers in the distribution of the maxillary division of the trigeminal nerve overwhelmingly affect the infraorbital nerve, but may also affect the zygomatic nerve. The zygomatic nerve branches off from the main maxillary trunk within
Fig. 2. A 53-year-old woman, 6 years postparotidectomy for adenocarcinoma, with new onset of ipsilateral facial numbness. This case demonstrates perineural spread along the auriculotemporal branch of the mandibular nerve in a setting of late tumor recurrence, which was not detectable on physical examination. (A) Coronal postcontrast T1weighted MR image without fat suppression. There is subtle evidence of prior left parotidectomy, and abnormal enhancement extending superiorly through foramen ovale (arrowhead). More bulky disease is seen within Meckel’s cave (asterisk). From the parotid gland, this tumor could only get onto the main trunk of V3 via the auriculotemporal nerve. Note the lack of any bulky disease in the surgical bed; no disease was palpable. This case illustrates that the diagnosis of perineural spread can be made without fat suppression. (B) Axial postcontrast T1-weighted MR image without fat suppression. There is antegrade extension of tumor, anteriorly from Meckel’s cave, through the cavernous sinus and foramen rotundum into the pterygopalatine fossa (black dots). The normal right Meckel’s cave is seen (white dot). (C) Coronal postcontrast T1-weighted MR image without fat suppression shows continued antegrade perineural tumor spread along the infraorbital nerve (arrowhead).
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Fig. 3. A 49-year-old man, postresection of squamous cell carcinoma of the right retromolar area. The patient experienced persistent, progressive trismus postoperatively. (A) Axial fat-suppressed postcontrast T1-weighted MR image shows extensive tumor recurrence in the right masticator space (brackets). Anteriorly, tumor has extended directly into the pterygopalatine fossa (black dots). Note the normal pterygoid plates on the left side (arrows). (B) Coronal fatsuppressed post-contrast T1-weighted MR image shows tumor extending superiorly through a grossly widened foramen ovale (small dots) into Meckel’s cave (large dot). (C) Axial fat-suppressed postcontrast T1-weighted MR image shows tumor extending posteriorly from MeckelÕs cave, along the main trigeminal trunk (arrowheads).
the PPF, enters the orbit through the inferior orbital fissure, runs along the lateral orbital wall, and divides into the zygomaticofacial and zygomaticotemporal branches [20]. The zygomaticotemporal nerve sends a small twig to the lacrimal nerve. The zygomaticotemporal and zygomaticofacial nerves exit the orbit through its lateral wall and supply innervation to the skin of the temporal region and lateral cheek (for anatomy of the
zygomatic nerve; see Figs. 6, 7). By this route, skin cancers arising in the cutaneous distribution of the zygomatic nerve may spread perineurally into the orbit (Fig. 12). Continued posterior spread into the PPF and more proximally may then ensue. For the maxillary nerve, the common final pathway is the PPF. The PPF is a pyramidal space located inferior to the orbital apex and posterior to the maxillary sinus (see Fig. 6) [21]. In addition to
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Fig. 5. The ophthalmic nerve (V1) anatomy, frontal view. Ant, anterior; n, nerve; post, posterior.
Fig. 4. A 38-year-old woman with a 30 year history of intermittent right facial pain. There was no history of head and neck malignancy. Diagnosis was neurofibroma. (A) Noncontrast axial T1-weighted MR image shows a very large mass extending from Meckel’s cave anteriorly through a massively widened foramen rotundum (arrowheads) into the pterygopalatine fossa (dots). Tumor extends laterally and then anteriorly to enter the orbit via the inferior orbital fissure (arrow), probably along the zygomatic branch of V2. (B) Axial CT image, bone algorithm, showing enlargement of the bony foramina, without destruction, suggesting a benign process.
the extracranial segment of V2, the PPF also contains the pterygopalatine ganglion and terminal branches of the internal maxillary artery. It is bounded posteriorly by the pterygoid plates, medially by the palatine bone, and anteriorly by the maxillary bone. Laterally, it communicates with the infratemporal fossa via the pterygomaxillary fissure. It also connects with the nasal cavity medially via the sphenopalatine foramen, the orbit via the inferior orbital fissure, and intracranial space via the foramen rotundum. Posteriorly, the anterior opening of the vidian canal permits the entrance of the vidian nerve, which constitutes the preganglionic parasympathetic component of the pterygopalatine ganglion. Inferiorly, the greater and lesser palatine foramina lead to the palate (see Fig. 6). Once tumor has spread perineurally to the PPF, it may continue posteriorly through the foramen rotundum (see Fig. 1), into the cavernous sinus, and can continue posteriorly through Meckel’s cave and on to the main trigeminal trunk (see Fig. 3). Tumor may also spread posteriorly along the vidian nerve within the vidian or pterygoid canal (see Fig. 10). This permits continued posterior PNS
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Fig. 6. V2, V3, and facial nerve anatomy, lateral view. (From Ginsberg LE. Imaging of perineural tumor spread in head and neck cancer. Semin Ultrasound CT MR 1999;2:176).
Fig. 7. The zygomatic branch of V2. br, branch; n, nerve; nn, nerves.
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Fig. 8. (A, B) The auriculotemporal branch of V3. (B) Cutaneous innervation of the auriculotemporal nerve. br, branch; n, nerve.
along the greater superficial petrosal nerve (GSPN; to be discussed later). Alternatively, once arriving in the PPF, tumor may spread in an antegrade fashion, anteriorly along the infraorbital nerve (common; see Figs. 1, 2) or inferiorly along the palatine nerves (uncommon). Tumor that has spread posteriorly from V2 into the Meckel’s cave
may also spread inferiorly along V3 through foramen ovale. The mandibular nerve, V3, provides sensory innervation to the skin of the lower face and preauricular/temporal region; the mandibular teeth; and the mucosa of the mandibular gingiva, floor of mouth, and tongue (anterior two thirds); and
Fig. 9. A 55-year-old man, with postsurgery followed by XRT for recurrent squamous cell carcinoma of the left forehead. At the time of this scan, the patient was experiencing pain and paresthesias in the supraorbital region. (A) More anterior and (B) more posterior coronal, fat-suppressed, contrast-enhanced T1-weighted MR images show abnormal enhancement of the frontal branch of V1 (arrowhead), located between the orbital roof and the superior muscle complex.
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Fig. 10. A 64-year-old man with adenoid cystic carcinoma of the hard palate extending into the nasal cavity. (A) Coronal fat-suppressed contrast-enhanced T1-weighted MR image shows a large mass encompassing the hard palate and extending upward into the nasal cavity bilaterally (brackets). (B) Axial noncontrast T1-weighted MR image shows abnormal soft tissue in the left pterygopalatine fossa (dots). This is more subtle than what was seen in Fig. 1C. (C) Axial fat-suppressed postcontrast T1-weighted MR image shows tumor extending posteriorly into the anterior aspect of the left vidian canal (arrows). More posteriorly, the canal appears normal (small arrowhead). The right vidian canal is also seen (large arrowheads).
the buccal mucosa [20]. The mandibular nerve also provides motor innervation to the muscles of mastication, the mylohyoid, and anterior belly of the digastric muscles. Mandibular nerve neuroanatomy relevant to PNS can be seen in Figs. 6 and 8. Tumors that most commonly spread perineurally along the mandibular nerve include cancers of the lower lip and any tumor that arises primarily within, or spreads secondarily to, the masticator
space. Examples of the latter include lateral extension of nasopharyngeal cancer or deeply invasive oral malignancies (see Fig. 3) [7,13]. There is a lateral branch of the mandibular nerve, the auriculotemporal nerve (ATN), which splits from the main trunk just beneath foramen ovale, courses laterally and then superiorly, and provides sensory innervation to the upper lateral face and preauricular region (see Fig. 8) [20]. The
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Fig. 11. A 39-year-old woman with adenoid cystic carcinoma of the nasopharynx. (A) Axial T2-weighted MR image showing the primary lesion (arrow). (B) Axial fat-suppressed postcontrast T1-weighted MR image shows the upper extent of the primary skull base involvement in the foramen lacerum (asterisk). From here, tumor extends anteriorly, in an antegrade fashion, through a grossly widened vidian canal (arrowheads). The pterygopalatine fossa, which represents the anterior boundary of the vidian canal, is also filled with tumor (dots). The left vidian canal is normal (arrows). (C) Coronal fat-suppressed postcontrast T1-weighted MR image shows the enlarged right vidian nerve (dot).
ATN also transmits postganglionic parasympathetic innervation (originating from cranial nerves VII and IX in the form of the lesser superficial petrosal nerve) to the parotid gland [20,22]. Cutaneous malignancies arising in the distribution of the ATN may spread perineurally and ultimately
gain access to the main trunk of V3. Because of the ATN, parotid malignancies may spread perineurally along the mandibular nerve (see Fig. 2) and the more widely appreciated facial nerve [7]. Once tumor has accessed a branch of the mandibular nerve, it may continue on to the main
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Fig. 12. Recurrent desmoplastic melanoma in the right lateral orbital region. Coronal noncontrast T1-weighted MR image shows the recurrence site (asterisks). Intraorbital tumor is also seen (black arrowheads), representing perineural extension along the zygomatic branches of the maxillary nerve. Secondary to other facial recurrences not shown, there is also V1 (arrow) and infraorbital (V2; white arrowhead) perineural tumor spread. The pterygopalatine fossa was also involved.
branch of V3 and course upward through foramen ovale into the MeckelÕs cave. From there, regardless of whether tumor arrived from V3 or from posterior extension of V2 PNS, tumor may spread posteriorly along the main trigeminal trunk and into the brainstem (see Fig. 3). Alternatively, from the MeckelÕs cave, tumor may spread anteriorly, in an antegrade fashion, into the cavernous sinus, foramen rotundum, and all the way into the PPF and beyond (see Fig. 2).
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mucoepidermoid carcinoma. Lesions that secondarily invade the parotid gland are generally cutaneous malignancies, such as SCC and desmoplastic melanoma. Once tumors have gained access to the main facial trunk, they may spread all the way up to the geniculate ganglion, and even through the labyrinthine segment to involve the internal auditory canal (intracanalicular segment). PNS of this type often represents or accompanies tumor recurrence that may be otherwise clinically silent (see Fig. 13). The other facial nerve branch that may be involved in PNS is the GSPN. The GSPN is a small branch of the facial nerve that leaves the geniculate ganglion and exits the superior surface of the temporal bone through the facial hiatus to become intracranial (Fig. 14) [20,24]. It then courses inferiorly and anteromedially, under Meckel’s cave, to the foramen lacerum, where it is joined by the deep petrosal nerve of the carotid sympathetic plexus to enter the pterygoid or vidian canal as the vidian nerve (see Fig. 1E) [24]. More anteriorly, within the PPF, the vidian nerve synapses in the pterygopalatine ganglion, and postganglionic parasympathetic fibers are distributed to the nasopharynx, the nasal cavity, the palate, and the lacrimal gland. These postganglionic parasympathetic fibers use distal trigeminal nerve branches as a conduit to arrive at their terminal destinations. For instance, the fibers that provide vasomotor innervation to the palate actually run within the palatine branches of the maxillary nerve [7,10]. This has the practical implication that tumors that arise within sites that are primarily thought of as innervated by the trigeminal nerve may give rise to perineural tumor spread that ultimately involves the facial nerve (Fig. 15). Also, because the GSPN courses immediately beneath Meckel’s cave, any tumor within Meckel’s cave, regardless of how it got there, may access the GSPN and spread posteriorly into the geniculate ganglion [24].
Facial nerve The facial nerve is complex, with multiple functions and a complicated course. A thorough review would be beyond the scope of this article; however, for PNS, only two facial nerve branches are typically affected. Diagrams of the facial nerve can be found in Figs. 6–8. Most commonly, the descending facial nerve segment is involved perineurally by malignancies that originate within or secondarily invade the parotid gland (Fig. 13) [7,11,24]. Examples of the former include adenoid cystic carcinoma, SCC, adenocarcinoma, and
Imaging of perineural tumor spread Imaging of PNS with MR imaging is analogous to imaging with CT but is far more sensitive. Many cases of PNS are probably missed because the imaging technique is inadequate. First, the field of view must be small enough to allow visualization of the often very small structures involved: 18 cm should be the largest field of view used in imaging PNS. For pulse sequences, a minimum set of sequence would include axial T1- and T2weighted images and axial and coronal postcontrast
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Fig. 13. A 54-year-old woman post parotidectomy for adenocarcinoma, which resulted in facial paralysis. At the time of this scan, physical examination was unrevealing and there were no new symptoms. In the setting of postoperative facial palsy, recurrent tumor may initially be clinically silent. (A) Axial noncontrast T1-weighted MR image shows abnormal soft tissue (arrows), representing tumor recurrence in the region of the left stylomastoid foramen. Note the normal hyperintense fat within the right stylomastoid foramen (dot). (B) Axial fat-suppressed postcontrast T1-weighted MR image shows enlargement and excessive enhancement (arrowhead) consistent with upward perineural tumor extension along the descending segment of the left facial nerve. The contralateral facial nerve is only faintly seen (arrow).
Fig. 14. The greater superficial petrosal nerve. a, artery; n, nerve; sup, superior. (From Ginsberg LE, DeMonte F, Gillenwater AM. Greater superficial petrosal nerve: anatomy and MR findings in perineural tumor spread. AJNR Am J Neuroradiol 1996;17.)
T1-weighted images. At the MD Anderson Cancer Center, all postcontrast head and neck imaging includes fat suppression, which is critical in the detection of PNS. PNS can be seen on non–fatsuppressed postcontrast MR imaging as well (see Fig. 2). As important as the postcontrast imaging is, the precontrast T1-weighted images are also crucial, because PNS generally causes replacement of the normal hyperintense fat that is present within PPF and at the opening of the basilar foramina of the skull base. Other technique considerations include slice thickness and spacing. Very large slices and intervals should be avoided to prevent partial voluming effects or missing a lesion entirely. We generally use 5-mm slices at 1-mm intervals for skull base imaging. Finally, though not strictly speaking an imaging technique, too many images per sheet of film may result in images that are too small to read, even if they were acquired properly. For the skull base, the author and his colleagues film 12 on 1. Of course, with the transition to soft reading, this potential problem will be obviated. Findings that suggest PNS include widening or excessive enhancement of the foramina through which cranial nerves and their branches traverse [5–9,23,25]. These include, for V3, foramen ovale
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Fig. 15. Advanced adenoid cystic carcinoma of the palate with massive intracranial disease. From Meckel’s cave (asterisk), tumor is spreading posterolaterally along the greater superficial petrosal nerve (dots), through the facial hiatus, and into the geniculate ganglion of the right facial nerve (large arrow). There is also early involvement of the proximal tympanic (small arrow) and labyrinthine (arrowhead) segments [16].
Fig. 16. Subacute hypoglossal denervation. Axial fat-suppressed postcontrast T1-weighted MR image shows faint but definite abnormal enhancement in the right hemitongue (arrowheads).
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Fig. 17. Chronic hypoglossal denervation. Axial noncontrast T1-weighted MR image shows hyperintensity in the right hemitongue, consistent with fatty infiltration. Also note the anteroposterior elongation of the right hemitongue, commonly seen in hypoglossal denervation.
and the mandibular foramen for the inferior alveolar nerve (the branch that enters the mandible, providing sensory innervation to the lower teeth and gingiva, and ends as the mental nerve providing cutaneous innervation of the chin; see Figs. 2, 3). For V2, important foramina/spaces include foramen rotundum, the PPF, the canal and foramen for the infraorbital nerve, the vidian canal, and the palatine foramen (see Figs. 1, 10, 12). For the facial nerve, the stylomastoid foramen and descending facial canal should be scrutinized (see Fig. 13). More proximally, enlargement and excessive enhancement of the cavernous sinus or Meckel’s cave strongly suggests perineural tumor spread in the appropriate clinical setting (see Figs. 1–3; Fig. 15). Of course, benign lesions such as meningioma and peripheral nerve tumors might appear very similar to perineural tumor spread (see Fig. 4). Indirect findings of PNS for the mandibular nerve include denervation of the masticator muscles, anterior belly of the digastric muscles, and mylohyoid [7,26,27]. In the early stages of denervation, the involved muscles may be observed on MR imaging to be abnormally hyperintense on T2-weighted images, and enhance excessively following contrast administration (Fig. 16) [27]. This type of denervation may be
the first sign of PNS and direct the radiologist to it, but it is undetectable on CT. Later, often months, denervation is manifested by atrophy and fatty infiltration, and is obvious on CT and MR imaging (Fig. 17). Recently, Fischbein et al [28] described denervation in the muscles of facial expression caused by disease involvement of the facial nerve. Of course, denervation is a phenomenon that is not unique to PNS but may be seen in other disease affecting cranial nerves. In conclusion, it is imperative that the radiologist, when faced with a clinical scenario such as new cranial neuropathy or a head and neck malignancy of the type or in the location that typically gives rise to PNS, consider this possibility when planning and interpreting cross-sectional imaging procedures. It is common that the radiologist first suggests or confirms the clinical suspicion of perineural tumor spread in these patients, and this diagnosis often has profound implications for treatment and prognosis. References [1] Ballantyne AJ, McCarten AB, Ibanex ML. The extension of cancer of the head and neck through peripheral nerves. Am J Surg 1963;106:651–67.
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