Concurrent Complete Spinal Cord Syndrome and Sixth Cranial Nerve Palsy in Advanced Adenoid Cystic Carcinoma: A Case Report and Literature Review

Abstract

Adenoid cystic carcinoma (ACC) with intracranial metastasis and sixth cranial nerve (CN VI) palsy, spinal metastases, and malignant spinal cord compression is an uncommon clinical entity. We present a case of a patient exhibiting this constellation of findings secondary to the parotid ACC. A 55-year-old man with no identifiable risk factors for ACC presented with a 10-year history of a left parotid tumor. He underwent two surgical resections and received one cycle of chemotherapy. Subsequently, his disease progressed locoregionally and systemically. He developed diplopia due to left sixth cranial nerve palsy caused by an intracranial metastatic lesion, together with complete spinal cord syndrome secondary to thoracic spinal metastases with malignant spinal cord compression. The patient was treated with whole-brain radiotherapy for intracranial metastasis and palliative spinal radiotherapy for spinal cord compression, achieving neurological stabilization without further deterioration. Systemic therapy with a tyrosine kinase inhibitor was subsequently initiated (lenvatinib 24 mg QD). The lungs are the most common site of distant metastasis in ACC, followed by bone and liver involvement. However, intracranial dissemination may occur rarely and should be considered in the clinical evaluation of these patients.

Introduction

Adenoid cystic carcinoma (ACC) is a rare malignancy arising from the salivary glands, accounting for approximately 1% of all head and neck cancers [1]. Despite its indolent growth pattern, ACC is characterized by a high incidence of local recurrence and metastasis. ACC most commonly metastasizes to the lungs (70%), bone (6%), and liver (3%) [2]; whereas metastasis to the central nervous system (CNS) is exceedingly uncommon [3]. Cranial neuropathies are uncommon manifestations in adenoid cystic carcinoma and are most often associated with perineural spread or direct extension to the skull base rather than hematogenous dissemination. Among the cranial neuropathies reported, sixth cranial nerve palsy is particularly rare [4]. Likewise, spinal metastases leading to malignant spinal cord compression and complete spinal cord syndrome are infrequently reported in ACC patients [5]. We describe a unique case of advanced ACC presenting with concurrent intracranial and spinal metastases, manifesting as sixth cranial nerve (CN VI) palsy and complete spinal cord syndrome, highlighting the importance of early recognition and multidisciplinary management.

Case presentation

Family and past medical history

The patient had a family history significant for colon cancer, as one brother was diagnosed with the disease at the age of 36 years. The patient's past medical history was notable for hypertension, occasional tobacco and alcohol use, and mild exposure to wood smoke.

Present illness

The patient first noted a mass on the left side of his neck approximately 11 years before definitive surgical management, without associated symptoms or medical evaluation. Approximately 10 years after the initial onset, the tumor increased in size, and several months later, pain developed, prompting medical consultation. He subsequently underwent surgical resection of an 8 × 10 cm tumor located in the tail of the left parotid gland. Histopathology confirmed invasive ACC with lymphovascular and perineural invasion. The tumor was classified as stage IV-A according to the American Joint Committee on Cancer (AJCC) 8th edition TNM classification [6].

Locoregional progression was documented within the following 1-2 months, and a second tumor resection was performed approximately 3 months after the first procedure. Pathology (Figure 1) again demonstrated ACC of the parotid gland with lymphovascular and perineural invasion, as well as metastasis to one of the six lymph nodes examined.

Figure 1. Histopathological report of the second surgical resection of the left parotid gland.

Hematoxylin and eosin (H&E) stain. A. Intermediate-power view (40x) showing perineural invasion; nerve fasciculus (red arrow) surrounded by tumor cells (black arrow). B. Low-power view (20x) demonstrating cysts (green stars) surrounded by tumor cells (black arrows).

Approximately 3 weeks after the second resection, the patient received one cycle of chemotherapy consisting of carboplatin, epirubicin, and paclitaxel at an outside institution. The clinical indication and rationale for selecting this regimen could not be determined because this information was not available in the medical records received from the treating institution. After completion of the first chemotherapy cycle, the patient was lost to follow-up and did not receive the planned radiotherapy. The reasons for interruption of follow-up were not documented in the available medical records.

The patient exhibited continued locoregional progression over the following 7 months (Figure 2). He subsequently received definitive radiotherapy consisting of 70 Gy in 35 fractions to the tumor bed and ipsilateral lymph node levels I-V, concurrently with triweekly cisplatin (three cycles), completing this treatment phase approximately 2 months later. 

Figure 2. Computed tomography study.

A. Contrast-enhanced chest-abdomen CT, sagittal view, showing no lytic lesions in the thoracic spine or spinal canal involvement (red box). B and C. Contrast-enhanced neck CT, axial sections at the level of the hyoid cartilage, demonstrating a tumor-like lesion at level III of the left neck (white arrow). Lymphadenopathy is noted in the left-sided levels IB, II, III, IV, and V (white arrows).

While awaiting imaging to assess the response, further locoregional (Figure 3) and distant progression (Figure 4) were identified.

Figure 3. Non-contrasted CT of the head.

A. Sagittal view; B. Coronal view. Infratentorial extra-axial mass located anterior to the pons and medulla oblongata (white arrow), adjacent to the clivus (white arrow), measuring 29 × 23 × 34 mm; this lesion is consistent with intracranial metastatic disease causing left sixth cranial nerve palsy.

Figure 4. Non-contrast magnetic resonance imaging of the thoracolumbar spine.

A. T2-weighted sequence; B. T1-weighted sequence. Infiltrative lesions (white arrows) with extension into the epidural space causing severe spinal canal stenosis and changes consistent with compressive myelopathy (yellow arrow) at the T3–T7 levels, corresponding to the patient's complete spinal cord syndrome. Additional infiltrative lesions are observed in the vertebral bodies of C7, T1, T2, and T12.

Approximately 3 months after completing chemoradiotherapy, he presented with left CN VI palsy (Figure 5), lower-extremity weakness and sensory loss, as well as urinary and fecal incontinence, prompting hospitalization. Complete neurological examination revealed left sixth cranial nerve palsy characterized by impaired abduction of the left eye and horizontal diplopia. In addition, the patient presented with complete paraplegia of both lower extremities (Medical Research Council grade 0/5), a sensory level at T6 with complete loss of all sensory modalities below this level, absent voluntary anal contraction, urinary and fecal incontinence, and loss of sacral sensation. Deep tendon reflexes in the lower extremities were absent at presentation. These findings were consistent with a complete spinal cord syndrome at the T6 level, corresponding to the American Spinal Injury Association (ASIA) Impairment Scale, grade A. As part of the diagnostic evaluation, cranial computed tomography was performed shortly after presentation and demonstrated an intracranial metastatic lesion corresponding to the patient's neurological presentation. He was assessed by a multidisciplinary team, including the Neurosurgery service. Surgical decompression was considered but not recommended because of the extensive metastatic disease burden, poor overall prognosis, and the prolonged duration of the neurological deficits before presentation.

Figure 5. Ocular movements examination.

A. Full abduction to the right (white arrows). B. Left sixth cranial nerve palsy (yellow arrows).

Initial management consisted of intravenous dexamethasone 4 mg every 6 hours for 7 days. The intracranial metastatic lesion was treated with whole-brain radiotherapy to a total dose of 30 Gy delivered in 10 fractions over a 3-week period. The rationale for selecting whole-brain radiotherapy rather than stereotactic radiotherapy was not documented in the available medical records. Concurrently, palliative thoracic spinal radiotherapy was administered at a total dose of 20 Gy in five fractions over 1 week. Following completion of radiotherapy, the patient's neurological status remained stable without further deterioration, and systemic therapy with lenvatinib was initiated at a dose of 24 mg once daily because of progressive metastatic disease despite prior surgery, platinum-based chemotherapy, and definitive chemoradiotherapy. Lenvatinib was selected based on its reported clinical activity in recurrent or metastatic adenoid cystic carcinoma when curative treatment options are no longer feasible. Unfortunately, the patient was lost to follow-up after treatment initiation and did not attend subsequent outpatient visits. Therefore, treatment response, adverse events, toxicities, dose modifications, and long-term clinical outcomes could not be assessed.

Figure 6 illustrates the diagnostic and therapeutic approaches used from the initial presentation to the last medical encounter. 

Figure 6. Clinical timeline illustrating disease progression, multidisciplinary management, and treatment interventions.

ACC: adenoid cystic carcinoma; CN VI: sixth cranial nerve

Discussion

Natural history and disease progression

The present case illustrates an uncommon pattern of metastatic progression in adenoid cystic carcinoma. Although ACC is typically characterized by slow growth and a marked tendency for perineural invasion [2], our patient developed concurrent involvement of two anatomically distinct levels of the neuroaxis, resulting in sixth cranial nerve palsy and complete thoracic spinal cord syndrome. To our knowledge, the combination of intracranial metastatic disease causing sixth cranial nerve palsy together with thoracic spinal metastasis producing complete spinal cord syndrome has rarely been reported. Although pulmonary metastases represent the most common site of distant spread in ACC, central nervous system involvement remains distinctly uncommon [3]. Tumor size, positive margins, lymphovascular invasion, perineural invasion, histological grade, and advanced TNM stage have all been associated with an increased risk of recurrence and distant dissemination [7].

An additional noteworthy aspect of this case is the prolonged interval of approximately 10 years between the patient's initial recognition of the parotid mass and his first medical evaluation. Although a direct causal relationship cannot be established, this delay may have facilitated the advanced locoregional disease observed at diagnosis. The typically slow-growing nature of adenoid cystic carcinoma may lead patients to underestimate the clinical significance of persistent salivary gland masses, allowing continued tumor growth, perineural invasion, and, ultimately, the development of distant metastatic disease. This case underscores the importance of early evaluation of persistent salivary gland lesions, even when they appear clinically indolent.

Intracranial involvement and sixth nerve palsy

Unlike the classical pattern of ACC progression, which is typically characterized by slowly progressive locoregional spread with subsequent distant metastases, our patient developed concurrent intracranial and thoracic spinal involvement during a relatively short period of systemic progression. This unusual pattern suggests that more than one metastatic pathway may have contributed to the observed neuroaxis dissemination. Intracranial spread in adenoid cystic carcinoma most commonly occurs through direct extension or perineural spread to the skull base, whereas hematogenous dissemination is less frequent [2]. In our patient, both surgical specimens demonstrated perineural invasion, and the intracranial lesion was located adjacent to the clivus and anterior to the pons. These findings make perineural spread with skull base extension the most plausible mechanism of intracranial involvement. Moreover, this location is anatomically consistent with the patient's left sixth cranial nerve palsy, as the abducens nerve traverses Dorello's canal over the clivus before entering the cavernous sinus, making it particularly vulnerable to lesions involving the skull base [8]. Nevertheless, because histopathological confirmation of the intracranial lesion was not available, hematogenous dissemination cannot be completely excluded. Published reports describing intracranial involvement in ACC remain scarce [3], and only a limited number of cases presenting with sixth cranial nerve palsy have been described [9, 10].

Spinal metastases and malignant spinal cord compression

Likewise, spinal metastases resulting in malignant spinal cord compression are exceptionally uncommon [5]. The simultaneous occurrence of these two neurological manifestations in the same patient appears to be exceedingly rare and represents the principal distinguishing feature of the present case. These findings illustrate that advanced ACC may involve multiple levels of the neuroaxis through more than one metastatic pathway, emphasizing the need for comprehensive neurological evaluation and targeted neuroimaging when new focal neurological deficits arise. Because this report describes a single patient, these observations should be regarded as hypothesis-generating and should not be interpreted as supporting changes to current surveillance recommendations.

Review of the available literature demonstrates that intracranial involvement in ACC most commonly occurs through skull base extension or perineural spread, whereas spinal metastatic disease producing malignant spinal cord compression is exceptionally uncommon. Although isolated cases of sixth cranial nerve palsy and spinal metastases have been reported separately, their concurrent occurrence in a single patient has rarely been described. Compared with the previously reported cases summarized in Table 1, our patient is unique in presenting simultaneous petroclival involvement causing sixth cranial nerve palsy together with thoracic malignant spinal cord compression.

Table 1. Summary of published cases of adenoid cystic carcinoma with central nervous system involvement, cranial neuropathies, and spinal metastatic disease.

Cases are presented in chronological order according to year of publication. The table summarizes the primary tumor site, neurological manifestations, treatment, and clinical outcome to facilitate comparison with the present case (final row). 

CNS: central nervous system; TKI: tyrosine kinase inhibitor.

Author	Year	Sex	Age	Primary tumor	CNS involvement	Cranial nerve involvement	Spinal metastases	Malignant spinal cord compression	Treatment	Outcome
Riela, et al [11]	1983	Female	54	Left submandibular gland	-	-	Present	Yes (T12-L1)	Surgery + Vertebral stabilization + Radiotherapy	Routine follow-up
Kaur, et al [12]	1999	Male	32	Right hard palate	Right temporal lobe and left cavernous sinus	Right seventh nerve	-	-	Surgery + Radiotherapy + Chemotherapy	Death
		Female	29	Left lacrimal gland	Right temporal lobe	Left third nerve	Present	No	Surgery + Radiotherapy	Death
Abdul-Hussein, et al [9]	2007	Female	49	Minor salivary gland	Pterygoid plate and right cavernous sinus	Right fifth and sixth nerves	-	-	Surgery + Radiotherapy	Unknown
Lee, et al [13]	2008	Male	52	Left lacrimal gland	Frontal and left temporal lobes	Left second, third and fifth nerves	Present	No	Surgery + Chemotherapy + Radiotherapy	Routine follow-up
Thariat, et al [14]	2008	Female	54	Submandibular gland	-	-	Present	Yes (T5)	Surgery + Steroids + Palliative radiotherapy + Chemotherapy + TKI (Imatinib)	Death
Fukai, et al [15]	2014	Male	29	Minor salivary gland	Left middle and infratemporal cranial fossa	Left fifth nerve	-	-	Surgery + Radiotherapy	Unknown
Nair, et al [10]	2018	Male	75	Right hard palate	Right cavernous sinus	Right sixth nerve	-	-	Palliative radiotherapy	Death
Bozkurt, et al [16]	2020	Female	70	Left parotid gland	Left posterior fossa	Left seventh nerve	-	-	Surgery + Radiotherapy	Routine follow-up
Pires, et al [17]	2020	Female	56	Left submandibular gland	Right occipital and left temporal lobes, cerebellum	-	Present	Yes	Surgery + Chemotherapy + Radiotherapy + Vertebral stabilization	Death
Shen, et al [18]	2022	Female	61	Right external auditory canal ceruminous gland	-	-	Present	Yes (L2)	Surgery + Radiotherapy + Vertebral stabilization	Death
Hassouneh, et al [19]	2025	Male	56	Right parotid gland	Right temporal lobe	Right fifth and seventh nerves	-	-	Surgery + Chemotherapy	Unknown
Present case	2026	Male	55	Left parotid gland	Retroclival	Left sixth nerve	Present	Yes (T6)	Surgery + Chemotherapy + Whole-brain radiotherapy + Palliative radiotherapy + TKI (lenvatinib)	Lost to follow-up

Management considerations

Management of advanced ACC should be individualized according to disease extent, neurological status, and overall prognosis. In our patient, multidisciplinary evaluation favored a palliative approach because of extensive metastatic disease, Eastern Cooperative Oncology Group (ECOG) Performance Status 4, and the prolonged duration of the neurological deficits before presentation. Consequently, surgical decompression was not considered appropriate, and treatment focused on symptom control and local disease stabilization through corticosteroids and radiotherapy [2, 7].

Whole-brain radiotherapy and palliative thoracic spinal radiotherapy achieved neurological stabilization without further deterioration. Because the disease progressed despite prior surgery, platinum-based chemotherapy, and definitive chemoradiotherapy, systemic therapy with lenvatinib was initiated as salvage treatment [2]. Although tyrosine kinase inhibitors have demonstrated modest activity in recurrent or metastatic ACC, long-term treatment response could not be evaluated because the patient was subsequently lost to follow-up.

The present case also illustrates the potential consequences of interrupted oncological follow-up. Although a causal relationship cannot be established, the prolonged interruption in surveillance after the initial chemotherapy cycle likely delayed definitive locoregional treatment and subsequent recognition of metastatic progression. Taken together, these findings highlight that advanced ACC may rarely progress beyond its classical pattern of indolent locoregional disease to involve multiple levels of the neuroaxis. The coexistence of petroclival disease causing sixth cranial nerve palsy and thoracic spinal metastasis resulting in complete spinal cord syndrome represents an exceptionally uncommon presentation that broadens the recognized spectrum of neurological manifestations associated with advanced ACC.

Alternative management strategies may include surgical resection, stereotactic radiosurgery for selected intracranial lesions, and surgical decompression for carefully selected patients with malignant spinal cord compression and preserved neurological function [20]. However, these options were not considered appropriate in the present case because of the patient's extensive metastatic disease, poor functional status (ECOG Performance Status 4), and the prolonged duration of neurological deficits before presentation. The prognosis of metastatic ACC involving the central nervous system remains poor, particularly when neurological deficits are already established at presentation and treatment is primarily palliative [1, 2]. Overall, the management decisions in the present case were consistent with the predominantly palliative approaches reported in previously published cases of advanced ACC with central nervous system involvement (Table 1).

Limitations

This case has several limitations. First, part of the patient's initial oncologic management was performed at two outside institutions. Consequently, histopathological slides from the initial surgical resection were unavailable for review, precluding direct comparison of the pathological findings between the first and second resections and limiting assessment of potential changes in tumor morphology or histological grade over time. In addition, the clinical rationale for the chemotherapy regimen consisting of carboplatin, epirubicin, and paclitaxel, as well as the selection of whole-brain radiotherapy, could not be determined from the available medical records.

Second, the reasons for the interruption of follow-up after the initial cycle of chemotherapy were not documented in the available medical records. Therefore, no conclusions can be drawn regarding possible socioeconomic, healthcare access, or personal factors contributing to the interruption of care. Nevertheless, loss to follow-up may delay timely oncologic treatment and disease surveillance.

Third, only the imaging studies available in the medical records could be reviewed. Higher-resolution images and contrast-enhanced spinal MRI were not available because they were not obtained during the patient's clinical care. These limitations reduced the radiological characterization of the intracranial and spinal lesions.

Fourth, after initiation of lenvatinib at our institution, the patient was again lost to follow-up. Consequently, treatment response, adverse events, dose modifications, and long-term clinical outcomes could not be assessed.

Finally, as this is a single-case report, the findings should be interpreted cautiously and cannot be generalized to the broader population of patients with adenoid cystic carcinoma.

Conclusions

Although typically indolent, adenoid cystic carcinoma may occasionally exhibit aggressive behavior with rare intracranial and spinal metastatic involvement. In the present case, comprehensive neurological evaluation together with cranial computed tomography and spinal magnetic resonance imaging established the diagnosis of intracranial and spinal metastatic disease, manifesting as sixth cranial nerve palsy and complete thoracic spinal cord syndrome. Multidisciplinary management with corticosteroids, whole-brain radiotherapy, palliative spinal radiotherapy, and subsequent systemic therapy achieved neurological stabilization without further deterioration. In patients with advanced ACC who develop focal neurological deficits, prompt neurological evaluation and appropriate neuroimaging should be considered to facilitate timely diagnosis and multidisciplinary management. As a single-case report, these findings should be interpreted cautiously and are not intended to establish causal relationships or treatment recommendations. Rather, this report highlights the importance of maintaining a high index of suspicion for central nervous system involvement in patients with adenoid cystic carcinoma who develop new neurological symptoms, thereby contributing to clinical awareness of this exceptionally rare presentation. Further studies and additional reported cases are needed to better define the mechanisms, optimal management, and prognosis of central nervous system involvement in advanced adenoid cystic carcinoma.