Peripheral trigeminal nerve branch lesions: CT and MRI findings in a pathologically confirmed case series

Abstract

Purpose

The peripheral branches of the trigeminal nerve (V1, V2, and V3) follow an intricate and tortuous course through various skull base foramina and soft tissue spaces. Due to the rarity of lesions specifically involving these distal segments, radiological diagnosis remains a significant challenge. This study aims to summarize the characteristic imaging patterns of diverse pathologically confirmed lesions affecting the peripheral trigeminal branches using CT and MRI.

Methods

We retrospectively reviewed 18 patients (2008–2022) with pathologically proven peripheral trigeminal lesions. The cohort included schwannoma (n = 10), neurofibroma (n = 3), adenoid cystic carcinoma (n = 1), intraneural perineurioma (n = 1), malignant peripheral nerve sheath tumor (n = 1), lymphoid hyperplasia (n = 1), and IgG4-related disease (n = 1). All patients underwent comprehensive multi-planar CT and contrast-enhanced MRI.

Results

V1, V2, and V3 divisions were involved in 5, 6, and 5 cases, respectively. We identified three descriptive imaging groupings: Benign Neurogenic Grouping: Characterized by fusiform or nodular thickening with “smooth expansile remodeling” of bony foramina (e.g., foramen rotundum and ovale). Malignant Infiltrative Grouping: Exemplified by adenoid cystic carcinoma, showing aggressive “creeping” spread along neural pathways, often involving the pterygopalatine fossa hub and traversing multiple anatomical compartments. Diffuse/Symmetric Grouping: Observed in intraneural perineurioma and lymphoproliferative disease/IgG4-related disease, manifesting as long-segment, uniform, and often bilateral nerve thickening without focal mass formation.

Conclusion

Accurate diagnosis of peripheral trigeminal lesions requires a segmental anatomical approach. While MRI is superior for evaluating neural architecture and signal changes, CT provides critical surrogate markers via bone remodeling patterns. Recognizing these descriptive imaging groupings as observed in our series—ranging from indolent remodeling to aggressive perineural spread—is helpful for differentiating rare neural pathologies and guiding clinical management.

Introduction

The trigeminal nerve, as the largest cranial nerve, provides critical sensory and motor innervation to the maxillofacial region. Its complex anatomical trajectory is conventionally divided into five segments: brainstem, cisternal, Meckel’s cave, cavernous sinus, and peripheral divisions [1]. Recent microanatomical studies have further elucidated the complex meningeal architecture surrounding Meckel’s cave. Wysiadecki et al. [2] demonstrated that Meckel’s cave is completely surrounded by a dural sleeve that separates it from the lateral sellar compartment, with arachnoid granulations consistently found near the trigeminal ganglion and its divisions. Zhang et al. [3] provided quantitative morphometric data on the trigeminal ganglion, revealing significant side-to-side differences that may influence the laterality of lesion spread. While intracranial pathologies are well-documented, lesions originating in or extending to the distal peripheral branches—the ophthalmic (V1), maxillary (V2), and mandibular (V3) nerves—present a distinct diagnostic challenge due to the intricate bony architecture and diverse deep facial spaces they traverse [4].

Precise localization and characterization of peripheral trigeminal neuropathy are of paramount clinical importance, as these branches serve as potential conduits for both benign neoplastic growth and aggressive perineural invasion (PNI) [5]. However, isolated involvement of these distal segments is relatively rare in clinical practice. The existing literature largely consists of isolated case reports or studies focused on the proximal trigeminal segments, leaving a significant gap in the systematic understanding of imaging patterns affecting the distal V1-V3 pathways [6, 7].

The diagnostic cornerstone for evaluating these “hidden” segments lies in the synergy of multi-modal imaging. MRI is the gold standard for visualizing intrinsic neural architecture and signal alterations, such as the “target sign” in neurofibromas or the enhancement patterns in inflammatory conditions [8]. Conversely, CT provides indispensable surrogate markers of disease chronicity; for instance, the “smooth expansile remodeling” of the foramen rotundum or ovale is highly suggestive of indolent neurogenic tumors, whereas permeative bone destruction often heralds malignancy [9, 10].

Recent advancements in head and neck imaging emphasize the role of anatomical “hubs,” such as the pterygopalatine fossa (PPF), in the multi-directional spread of disease [11]. Understanding how different pathologies exploit these pre-existing neural pathways—whether through the indolent remodeling seen in schwannomas or the aggressive “creeping” spread typical of adenoid cystic carcinoma (ACC)—is essential for surgical planning and radiation oncology [12]. Furthermore, rare systemic conditions like IgG4-related disease (IgG4-RD) and intraneural perineurioma (INP) further complicate the diagnostic landscape, often manifesting as diffuse, symmetric nerve thickening that can mimic more common entities [13, 14].

In this study, we retrospectively analyzed 18 pathologically confirmed cases to provide a comprehensive, pattern-based approach to peripheral trigeminal lesions. By integrating CT and MRI findings, we aim to categorize these rare pathologies into three distinct imaging patterns—Benign Neurogenic, Malignant Infiltrative, and Diffuse/Symmetric—thereby potentially aiding in the differential diagnosis and informing clinical management in this anatomically complex region.

Methods

Subjects

Study design and patient selection

This retrospective study was approved by Peking University Third Hospital Medical Science Research Ethics Committee and the requirement for informed consent was waived. We reviewed our institutional pathology and radiology databases from January 2008 to December 2022 to identify patients with pathologically confirmed lesions involving the trigeminal nerve. Inclusion criteria were: (1) histopathological diagnosis obtained via surgical resection or biopsy; (2) availability of preoperative contrast-enhanced MRI and CT examinations; and (3) imaging studies of sufficient quality for detailed evaluation of the trigeminal nerve and its branches.

Patient cohort

A total of 18 patients (12 females, 6 males; mean age 45.2 years; range 17–85 years) met these criteria and were enrolled in this study. The pathological spectrum included schwannoma (n = 10), neurofibroma (n = 3), adenoid cystic carcinoma (ACC, n = 1), intraneural perineurioma (INP, n = 1), malignant peripheral nerve sheath tumor (MPNST, n = 1), lymphoid hyperplasia (n = 1), and IgG4-related disease (IgG4-RD, n = 1). All patients underwent both contrast-enhanced MRI and CT with multiplanar reconstructions prior to treatment.

Imaging approach

CT protocol

CT imaging the trigeminal nerve include helical acquisition scans from the orbital roof to the mandibular symphysis reconstructed in the axial, coronal and sagittal planes, on both soft tissue and bony algorithms.Slice thickness, 2 mm, without interslice gap.

MRI protocol

MRI was performed using a 3.0T scanner (uMR 770, United Imaging, Shanghai, China). The protocol included: axial T2-weighted fast spin-echo (FSE) [TR/TE, 3480/82.24 ms; slice thickness, 3 mm; matrix, 320 × 256], and pre- and post-contrast axial and coronal T1-weighted FSE [TR/TE, 614/10.18 ms; slice thickness, 3 mm; matrix, 320 × 224] with fat suppression. Gadolinium-based contrast agent was administered intravenously at a dose of 0.1 mmol/kg.

General principles

CT and MRI serve as complementary modalities for evaluating patients with suspected trigeminal nerve pathology. A systematic, segmental approach to imaging the trigeminal nerve is essential for accurate localization and characterization of lesions. Based on the established framework in the literature [1, 4], we subdivided the nerve into five distinct segments along its course:

1. Brainstem segment: Intraparenchymal portion from the trigeminal nuclei to the root exit zone.

2. Cisternal segment: Pre-pontine portion from the brainstem to the porus trigeminus.

3. Meckel’s cave segment: Trigeminal ganglion and cistern within the trigeminal impression.

4. Cavernous sinus segment: V1 and V2 branches traversing the lateral wall of the cavernous sinus.

5. Peripheral divisions: Extracranial portions of V1 (ophthalmic), V2 (maxillary), and V3 (mandibular) branches, continuing as the supraorbital nerve, infraorbital nerve, and inferior alveolar nerve, respectively.

Imaging analysis

Two experienced head and neck radiologists, blinded to the specific pathological diagnosis, independently reviewed the images. Discrepancies were resolved by consensus. A systematic segmental approach was employed to assess the trigeminal nerve from its brainstem nuclei to its distal peripheral branches (V1: ophthalmic, V2: maxillary, V3: mandibular).

Image interpretation should systematically assess each segment for abnormalities, including nerve thickening or atrophy, signal alteration, abnormal contrast enhancement, and mass effect. Particular attention should be paid to the skull base foramina (superior orbital fissure, foramen rotundum, foramen ovale) and their associated canals (infraorbital canal, inferior alveolar canal), as osseous changes often provide indirect evidence of underlying neural pathology. Multiplanar reformations, especially coronal and oblique sagittal planes parallel to the nerve course, are invaluable for visualizing the smaller peripheral branches and their relationship to adjacent structures.

Results

The involvement of various intracranial segments and peripheral branches of the trigeminal nerve in the 18 cases is summarized in Table 1. The ophthalmic (V1), maxillary (V2), and mandibular (V3) branches were involved in 5, 6, and 5 cases, respectively. Isolated involvement of a single branch was observed in four cases, two branches in three cases, and all three branches bilaterally in two cases. The imaging features commonly demonstrated irregular thickening and enhancement of the affected nerves, with associated widening of the corresponding skull base foramina.

Table 1.

Demographic and clinical characteristics of 18 patients with trigeminal neuropathy

Location and/or branches  involved
Case	Age,y/Gender	Pathology	Side	Brain stemsegment	Cisternal segment	Meckel’s cavesegment	Cavernoussinussegment	Peripheral branches
								V1	V2	V3	Number of branches involved
1	35/F	ACC	L				+		+		1
2	51/F	SN	R	+	+	+	+		+		1
3	85/F	SN	R		+	+	+			+	1
4	43/F	SN	R				+	+			1
5	40/F	SN	R		+	+	+	+		+	2
6	23/M	NF	L						+	+	2
7	33/F	INP	R, L			+	+	+	+	+	3
8	51/M	SN	L			+					None
9	52/F	SN	R			+					None
10	48/M	SN	R		+						None
11	24/F	SN	L		+	+					None
12	27/F	MPNST	L		+						None
13	55/F	NF	R		+	+					None
14	63/F	NF	R	+	+	+	+				None
15	75/F	SN	R		+						None
16	17/M	SN	L		+	+	+				None
17	47/M	LH	R, L				+	+	+		2
18	42/M	IgG4-RD	R, L				+	+	+	+	2

F Female, M Male, L Left, R Right, V1 Ophthalmic division, V2 Maxillary division, V3 Mandibular division, ACC Adenoid cystic carcinoma, NF neurofibroma, SN Schwannoma, INP Intraneural perineurioma, MPNST Malignant peripheral nerve sheath tumor, LH Lymphoid hyperplasia, IgG4-RD IgG4 related disease

“+” indicates involved; “None” indicates no peripheral branch involvement (lesion confined to intracranial segments)

Table 1 summarizes the demographic and clinical characteristics of all 18 patients, including age, gender, pathology, side of involvement, and the specific branches and segments affected. Table 2 provides a detailed overview of the imaging findings, and Table 3 presents the treatment approach and clinical outcome for each case, including nerve morphology, enhancement pattern, and key bony changes. Based on the systematic analysis of morphology, enhancement, and bony changes, the 18 cases were found to cluster into three different imaging groupings.

Table 2.

Imaging findings in 18 patients with trigeminal neuropathy

Case	Pathology	Nerve Morphology	Enhancement Pattern	Key Bony Changes
1	ACC	Fusiform thickening	Moderate, heterogeneous	Widened foramen rotundum, pterygopalatine fossa, infraorbital canal
2	SN	Nodular mass	Heterogeneous	Not applicable (intracranial)
3	SN	Nodular mass	Heterogeneous	Enlarged foramen ovale
4	SN	Nodular mass	Heterogeneous with cystic necrosis	Widened superior orbital fissure
5	SN	Lobulated mass	Heterogeneous	Enlarged foramen ovale, widened superior orbital fissure
6	NF	Tubular thickening	Mild, homogeneous	Widened foramen rotundum, infraorbital canal
7	INP	Long-segment serpentine thickening (bilateral)	Slight, homogeneous	No significant bony changes
8	SN	Ovoid mass	Homogeneous	Enlarged Meckel’s cave
9	SN	Ovoid mass	Homogeneous	Enlarged Meckel’s cave
10	SN	Small nodule	Homogeneous	None
11	SN	Lobulated mass	Heterogeneous	Enlarged Meckel’s cave
12	MPNST	Infiltrative thickening (multifocal)	Heterogeneous	None (aggressive, no chronic remodeling)
13	NF	Fusiform thickening	Mild, homogeneous	Enlarged Meckel’s cave
14	NF	Diffuse thickening	Mild, homogeneous	Enlarged Meckel’s cave, cavernous sinus erosion
15	SN	Small nodule	Homogeneous	None
16	SN	Lobulated mass	Heterogeneous	Enlarged Meckel’s cave
17	LH	Smooth, uniform thickening (bilateral)	Homogeneous	Widened foramen rotundum, infraorbital canal, pterygopalatine fossa
18	IgG4-RD	Smooth, uniform thickening (bilateral)	Homogeneous	Widened foramen ovale, foramen rotundum

ACC Adenoid cystic carcinoma, NF Neurofibroma, SN Schwannoma, INP Intraneural perineurioma, MPNST Malignant peripheral nerve sheath tumor, LH Lymphoid hyperplasia, IgG4-RD IgG4-related disease

Table 3.

Treatment approach and clinical outcome in 18 patients with trigeminal neuropathy

Case	Pathology	Treatment	Clinical Outcome
1	ACC	gross total resection + adjuvant radiotherapy	symptom improvement
2	SN	gross total resection	symptom relief
3	SN	observation	stability
4	SN	gross total resection	symptom relief
5	SN	subtotal resection	symptom improvement
6	NF	partial resection	symptom improvement
7	INP	intramuscular vitamin B1 and mecobalamin treatment.	symptom improvement
8	SN	gross total resection	symptom relief
9	SN	gross total resection	symptom relief
10	SN	gross total resection	symptom relief
11	SN	gross total resection	symptom relief
12	MPNST	Intracranial lesion: observation; Brachial plexus mass: resection + adjuvant radiotherapy	symptom improvement
13	NF	observation	stability
14	NF	gross total resection	symptom relief
15	SN	observation	stability
16	SN	Gamma Knife radiosurgery	symptom relief
17	LH	partial resection	symptom improvement
18	IgG4-RD	corticosteroid therapy	symptom improvement

ACC Adenoid cystic carcinoma, NF Neurofibroma, SN Schwannoma, INP Intraneural perineurioma, MPNST Malignant peripheral nerve sheath tumor, LH Lymphoid hyperplasia, IgG4-RD IgG4-related disease

Grouping 1 obersed in our series: focal mass with indolent bone remodeling (n = 13)

This pattern, characterized by circumscribed expansion and secondary osseous adaptation, was observed in benign nerve sheath tumors.

Schwannomas (n = 10): These were the most frequent lesions in our series. They typically appeared as well-defined, ovoid, or lobulated masses. As demonstrated by the imaging of Case 5, MRI showed heterogeneous hyperintensity on T2-weighted images and robust contrast enhancement, with internal cystic necrosis often present in larger tumors. CT revealed smooth, expansile remodeling of the associated foramina, such as the superior orbital fissure or foramen ovale (Fig. 1). In Case 5, subtotal resection of the mass was performed. The tumor was found intraoperatively to originate from and occupy the right foramen ovale region, with partial tumorous infiltration of the trigeminal ganglion. During resection, careful attention was required to protect the intracranial segment of the right internal carotid artery as well as the adjacent oculomotor nerve (CN III), trochlear nerve (CN IV), and abducens nerve (CN VI).

Fig. 1.

CT and MR images of a 40-year-old female with a right-sided trigeminal schwannoma involving the ophthalmic and mandibular branches. MR shows a mass running along the ophthalmic branch of the trigeminal nerve passing through the cavernous sinus (a, red arrow), and T1 enhancement image shows heterogeneous enhancement of the mass in the right foramen ovale area (b, area within the irregular red circle). CT axial image shows enlargement of the right superior orbital fissure (c, blue arrow). CT axial images at another level show an enlarged and deformed foramen ovale and carotid canal on the right side (d, area within the irregular red circle), compared to a normal foramen ovale on the left (d, green arrow)

Neurofibromas (n = 3): These presented as fusiform or tubular nerve thickening. Compared to schwannomas, neurofibromas showed more homogeneous, mild to moderate enhancement and less frequent cystic changes. Associated bony changes included a widened Meckel’s cave or cavernous sinus erosion in more diffuse cases.

Grouping 2 observed in our series: infiltrative spread with multi-compartmental Involvement (n = 2)

This pattern reflected the aggressive, path-of-least-resistance growth characteristic of malignant or recurrent lesions.

Adenoid Cystic Carcinoma (ACC) (n = 1): Case 1 exhibited infiltrative thickening with a “creeping” spread along the maxillary nerve (V2). The tumor utilized the pterygopalatine fossa as a strategic “hub,” extending posteriorly to the foramen rotundum and anteriorly along the infraorbital canal (Fig. 2). In Case 1, the main tumor mass was located in the pterygopalatine fossa, with involvement of the infraorbital nerve, maxillary nerve (V2), pterygopalatine ganglion, and vidian nerve. The tumor extended along the maxillary nerve into the foramen rotundum, anteriorly along the infraorbital nerve canal into the infraorbital foramen and subcutaneous tissues, medially through the pterygopalatine ganglion into the sphenopalatine foramen, and along the vidian nerve into the vidian canal.

Fig. 2.

CT and MR images of a 35-year-old female with postoperative recurrence of adenoid cystic carcinoma show a mass occupying the pterygopalatine fossa (a, red arrow). The tumor spreads along the maxillary branch of the trigeminal nerve, extending posteriorly through the foramen rotundum (a, blue arrow) and anteriorly along the inferior orbital fissure (b, yellow arrow)

Malignant Peripheral Nerve Sheath Tumor (MPNST) (n = 1): Representing Pattern 2 in its most aggressive form, Case 12 demonstrated multifocal, infiltrative thickening of multiple cranial nerves (V, III, VIII) and the brachial plexus (Fig. 3). Post-resection pathology of the brachial plexus mass confirmed a MPNST. Unlike Pattern 1, it showed ill-defined margins and lacked chronic bony remodeling due to its rapid growth.

Fig. 3.

MR images of a 27-year-old female with malignant peripheral nerve sheath tumor show the lesion involving the cisternal segment of the left trigeminal nerve (a, red arrow), the right oculomotor nerve (b, blue arrow), the right auditory nerve (c, green arrow), and the right brachial plexus (d, pink arrow)

Grouping 3 observed in our series: diffuse, symmetric thickening (n = 3)

This pattern was identified by long-segment, uniform enlargement, typically lacking a focal extraneural mass component.

Intraneural Perineurioma (INP) (n = 1): This rare case (Case 7) showed pathognomonic symmetric, serpentine, and long-segment thickening of all three trigeminal branches bilaterally. The thickened nerves remained isointense on T1W images and showed slight, homogeneous enhancement (Fig. 4).The patient presented with external ophthalmoplegia, which was partially relieved following intramuscular vitamin B1 and mecobalamin treatment.

Fig. 4.

MR images of a 33-year-old female with intraneural perineurioma involving all the three branches- ophthalmic branch (V1), maxillary branch (V2) and mandibular branch (V3) of bilateral trigeminal nerve (a, d, axial T2-fat suppression images; b, e, axial T1-fat suppression; c, T1 coronal image; f, T1-enhancement image; g ~ i, saggital T2-fat suppression images of the right-side). V1 enters the orbit after exiting the skull through the cavernous sinus and superior orbital fissure, runs between the superior rectus muscle and the superior orbital wall, then transitions into the supraorbital nerve (a, b, c, f, g, red arrow), and finally exits the orbit through the supraorbital foramen. V2 (d, e, g, yellow arrow) passes through the cavernous sinus and enters the pterygopalatine fossa through the foramen rotundum, continuing through the infraorbital foramen as the infraorbital nerve (c, d, e, f, g, orange arrow). V3 exits the skull from the foramen ovale (h, green arrow) and enters the space between the masticator, extending downwards as the inferior alveolar nerve (i, blue arrow).Coronal T1-weighted image demonstrates enlargement of the bilateral V1 (c, red arrow) and infraorbital nerve (c, orange arrow), signal enhancement on coronal T1-weighted postgadolinium images (f)

Lymphoid Hyperplasia (n = 1): Case 17 presented with smooth, uniform thickening of bilateral V1 and V2 branches.CT and MRI traced the process through an enlarged foramen rotundum into the pterygopalatine fossa and infraorbital canal, showing homogeneous enhancement (Fig. 5).

Fig. 5.

CT and MR images of a 47-year-old male with bilateral lymphoid hyperplasia involving the trigeminal nerves. (a, b, c, CT images; d, e, f, MR images); The affected and thickened maxillary nerve (pink arrows in c, d) passes through the enlarged foramen rotundum (pink dotted line in c) into the pterygopalatine fossa, then traverses the inferior orbital fissure to enter the orbit, where it continues as the thickened infraorbital nerve (blue arrows in b, c, d, e, f). Due to the thickening of the infraorbital nerve, the corresponding infra-orbital canal is widened (blue dotted line in b). The ophthalmic branch enters the orbit through the superior orbital fissure and continues as the frontal nerve (red arrows in b, c, e, f), which later divides into the supratrochlear and supraorbital nerves

IgG4-related Disease (IgG4-RD) (n = 1): Case 18 exhibited a radiographic picture indistinguishable from lymphoid hyperplasia, featuring smooth thickening of the trigeminal ganglion and its V1/V2/V3 branches. A key diagnostic feature was its significant responsiveness to corticosteroid therapy, with post-treatment images showing marked resolution (Fig. 6). Notably, in both lymphoid hyperplasia and IgG4-related disease, the affected nerves demonstrated smooth, uniform thickening rather than focal nodular enlargement, with homogeneous enhancement on post-contrast imaging. This pattern, distinct from the often-heterogeneous appearance of schwannomas, may serve as a helpful distinguishing feature.

Fig. 6.

CT and MR images of a 42-year-old male with IgG4-related disease. (a, d, g, CT image; b, e, h, MR image before treatment; c, f, i, MR image after treatment with Prednisone for 7 months); Both CT and MR images clearly demonstrate proptosis, eyelid swelling, and thickening of the extraocular muscles. Contrast-enhanced MR images reveal an enlarged and thickened trigeminal ganglion with marked homogeneous enhancement (yellow arrows in b, h).The ophthalmic branch (V1) enters the orbit and continues as the thickened frontal nerve (red arrow), with the thickened superior rectus muscle visible beneath it. The maxillary division (V2) is seen passing through the foramen rotundum into the pterygopalatine fossa (green triangle in h), with some branches traversing the inferior orbital fissure to enter the orbit and continue as the infra-orbital nerve (blue arrows in e, h), above which the thickened inferior rectus muscle is visible. The mandibular division (V3) passes through the foramen ovale (short pink solid lines in d, g) into the infratemporal fossa. Follow-up MR images obtained 7 months after corticosteroid therapy (c, g, i) show a significant reduction in lesion volume compared to previous scans

Discussion

The peripheral branches of the trigeminal nerve (V1–V3) function as critical “anatomical highways” for a wide array of neoplastic and inflammatory pathologies. Based on our retrospective analysis of 18 pathologically confirmed cases, we observed that while these branches are encased in complex bony and soft-tissue structures, their imaging manifestations follow predictable biological patterns. Our study proposes a shift from simple lesion identification to a descriptive grouping-based approach, emphasizing the synergy between MRI-defined neural morphology and CT-detected osseous surrogate markers.

The most prevalent findings in our series were benign peripheral nerve sheath tumors (PNSTs), including schwannomas and neurofibromas, whose imaging appearances align with established literature.Mechanisms of Bone Remodeling: Unlike the cisternal segment where masses expand freely, the peripheral branches are confined within rigid skull base foramina. The “smooth expansile remodeling” of the superior orbital fissure (V1), foramen rotundum (V2), and foramen ovale (V3) observed on CT is highly characteristic of an indolent, chronic process [15]. This finding indicates that the lesion’s pressure has been applied slowly enough to permit periosteal bone adaptation, a feature that distinguishes benign PNSTs from aggressive malignancies.Intra-pattern Differentiation: Schwannomas frequently exhibited internal cystic necrosis—a radiographic reflection of Antoni B hypocellular areas. Conversely, neurofibromas tended toward more uniform, fusiform thickening.

The transition from Grouping 1 to Gourping 2 marks a fundamental shift from expansion to infiltration, characteristic of perineural invasion (PNI).The Pterygopalatine Fossa (PPF) as a strategic hub: Our findings in Case 1 (ACC) visulize the concept of the PPF as a strategic “hub” for perineural spread, as emphasized by Biau et al. [5]. The PPF functions as a critical anatomical crossroads connecting the infraorbital canal, foramen rotundum, and sphenopalatine foramen. Biological behavior: This “creeping” spread reflects the biological behavior of ACC, which follows paths of least resistance along nerve sheaths while initially preserving the underlying skeletal architecture [16, 17]. Recognition of this infiltrative pattern is important for accurate radiotherapy planning and surgical margin assessment. ACC involving the orbital nerves represents a highly challenging head and neck malignancy. Due to its high propensity for perineural invasion and its characteristic of late recurrence, treatment strategies must achieve a delicate balance between radical tumor eradication and preservation of neurological functions (such as eye movement and vision). “Surgery plus postoperative radiotherapy” is currently the main treatment paradigm. Surgery requires resection of the main tumor mass, along with tracking of the involved nerves (e.g., branches of the trigeminal nerve) to their skull base foramina of exit (e.g., foramen rotundum, foramen ovale), in order to ensure clearance of the perineural spread pathway. For patients with extensive involvement of the orbital apex, cavernous sinus, or critical neurovascular structures, functional subtotal resection may be performed to preserve function, with residual lesion subsequently controlled by radiotherapy.

Grouping 3 represents the most significant diagnostic challenge, as it typically lacks a focal mass and often presents bilaterally. Intraneural Perineurioma (INP): The bilateral, multi-branch involvement in Case 7 is exceptionally rare. While Mauermann et al. [14] describe INP as a focal hypertrophic neuropathy, our case expands this phenotypic spectrum to include long-segment, serpentine thickening. Wang et al. [18] also reported INP involving the intracranial segment, further illustrating the diverse presentation of this rare entity. Fibroinflammatory Mimicry: IgG4-RD and lymphoid hyperplasia (Cases 17, 18) present a “smooth, uniform thickening” rather than a focal nodular mass. As described by Wang et al., these conditions are characterized by intrinsic nerve enlargement without an extraneural soft-tissue component. The dramatic response to corticosteroid therapy in Case 18 confirms the inflammatory nature of the process and can serve as a diagnostic-therapeutic test.

The differential diagnosis for diffuse, symmetric cranial nerve thickening, as observed in our series (INP, lymphoid hyperplasia, and IgG4-RD), is not exhaustive. Other entities should be considered, most notably IgG4-related inflammatory pseudotumor of the trigeminal nerve. Katsura et al. [19] described a case where this pseudotumor presented as isolated trigeminal nerve thickening, occurring in the absence of systemic IgG4-RD. This highlights that even without multi-organ involvement, a localized IgG4-related process can produce the same imaging phenotype and must be included in the differential. Other inflammatory conditions, such as neurosarcoidosis, can also present with diffuse or asymmetric thickening of the cavernous sinus and trigeminal nerve branches. As reported by Gao et al. [20], neurosarcoidosis may manifest as meningeal thickening and enhancement along the cavernous sinus wall, extending to the superior orbital fissure, with involvement of the ophthalmic division (V1). Unlike the indolent bone remodeling seen in schwannomas (Grouping 1) or the aggressive ‘creeping’ spread of ACC (Grouping 2), neurosarcoidosis typically lacks a discrete mass and shows no characteristic bony changes. It should be considered in the differential diagnosis of Grouping 3 (diffuse/symmetric thickening), particularly when accompanied by systemic findings such as hilar lymphadenopathy or elevated serum/CSF angiotensin converting enzyme(ACE) levels. Furthermore, morphometric variations in skull base neurovascular canals may influence imaging interpretation. Dedeoglu et al. [21] demonstrated that pathological conditions can induce measurable changes in the diameters of key skull base foramina, including the foramen rotundum. This finding underscores the value of CT-based bone assessment in evaluating trigeminal nerve pathology, as quantitative canal measurements may serve as surrogate markers for chronic pathological processes.

Several limitations of this study should be acknowledged. First, the retrospective design and small sample size (n = 18) limit the statistical power and generalizability of our findings. Second, the pathological heterogeneity of the included lesions, while reflecting real-world clinical practice, makes it difficult to draw definitive conclusions about any single entity. Third, the proposed three imaging groupings are descriptive observations based on our single-center case series and have not undergone external validation. Consequently, they should be interpreted as exploratory and hypothesis-generating rather than as a formally validated classification system. Future multicenter prospective studies with larger cohorts and standardized quantitative imaging parameters (e.g., nerve thickness ratios, standardized enhancement values) are needed to validate these preliminary observations. Furthermore, given the complexity of the trigeminal nerve system and the rarity of these lesions, continued integration of detailed microanatomical studies [2, 3], high-resolution imaging of peripheral neural pathways, and clinical validation cohorts will be essential to improve diagnostic precision and to better understand lesion spread patterns.Recent morphometric analyses of skull base canals [21] suggest that quantitative CT parameters may offer additional value in future research.

Conclusions

Accurate evaluation of the peripheral trigeminal branches requires a segmental approach that integrates morphology with biological behavior. By recognizing these three descriptive imaging groupings as observed in our series—indolent remodeling, infiltrative spread, and diffuse symmetry thickening—clinicians may better approach the wide differential diagnosis of lesions in this complex region. This framework not only aids in accurate diagnosis but also directs appropriate management, ranging from steroid therapy in inflammatory cases to aggressive surgical margins in perineural malignancies.

Abbreviations

ACC

Adenoid cystic carcinoma

INP

Intraneural perineurioma

MPNST

Malignant peripheral nerve sheath tumor

IgG-RD

IgG4-related disease

PNI

Perineural invasion

PPF

Pterygopalatine fossa

ACE

Angiotensin converting enzyme

Authors’ contributions

Aonan Wang and Haibo Wu conceived and designed the study. Huishu Yuan supported the study.Aonan Wang and Haibo Wu performed the imaging analysis. Aonan Wang and Suwei Liu drafted the initial manuscript. Haibo Wu revised the manuscript. All authors reviewed and approved the final manuscript for publication.

Funding

This work was supported by the Start-up Fund for Returned Scholars of Peking University Third Hospital (Grant No.Y75509-02) and the Beijing Natural Science Foundation (Grant No.7212126).

Data availability

The data supporting the findings of this study are available from the corresponding author upon reasonable request.

Declarations

Ethics approval and consent to participate

This study was conducted in accordance with the Declaration of Helsinki and received approval from Peking University Third Hospital Medical Science Research Ethics Committee (Approval Number: IRB00006761-M2022386). The requirement for informed consent was waived by Peking University Third Hospital Medical Science Research Ethics Committee (Approval Number: IRB00006761-M2022386) due to the retrospective nature of the study.

Consent for publication

We confirm that all participants/patients involved in this study gave written informed consent for their personal or clinical details, along with any identifying images, to be published in this study.

Competing interests

The authors declare no competing interests.