Delhi Journal of Ophthalmology

Adie’s Tonic Pupil in a Case of Recurrent Adenoid Cystic Carcinoma of Maxillary Sinus – An Ophthalmic Perspective

Prithviraj Udaya, Sairani Karanam 
Paediatric Ophthalmology, Sankara Eye Hospital, Guntur, Andhra Pradesh, India

Corresponding Author:

Prithviraj Udaya 
Paediatric Ophthalmology, 
Sankara Eye Hospital, Guntur, 
Andhra Pradesh, India
Email id:

Published Online: 30-JUL-2018


A gentleman without signs of tumour recurrence until a year following surgery for adenoid cystic carcinoma (ACC) of the maxillary sinus, presented with binocular diplopia, defective vision in the right eye and numbness in the right forehead. Examination revealed a right Adie’s pupil that concurred with positive infraorbital nerve margins on intraoperative frozen section, indicating a perineural tumour spread. Diplopia and Hess charting verified a combined right sixth nerve and partial third nerve palsy. Neuroimaging confirmed extension of residual tumour to the right cavernous sinus apart from buckling of the right optic nerve. We report a unique case of recurrent ACC of maxillary sinus with partial cavernous sinus syndrome and an acquired Adie’s pupil consequent to intracranial extension and perineural spread.

Keywords :Adenoid cystic carcinoma; maxillary sinus; perineural; Adie’s tonic pupil

Adenoid cystic carcinomas are rare malignant neoplasms of epithelial cell origin, constituting 5% of all paranasal sinus malignancies.1-3 The most common primary sites are maxillary sinus (48-54.7%) followed by ethmoid sinus (4.2-16%) and sphenoid sinus (3-12%).3,4 These carcinomas are typified by their local invasiveness, perineural spread (50%), lung metastases and delayed recurrence.3,5,6 Diagnostic delay is common due to non-specific symptomatology like orbital discomfort, pain and altered sensations in the trigeminal distribution.1,3,7 Common neuro-ophthalmic signs due to primary growth of tumour or its recurrence include movement limitation and diplopia secondary to cranial nerve involvement, which include III, IV, V and VI suggestive of cavernous sinus syndrome, either partial or complete.7-10 Considering the proximity of the tumour to adjacent anatomical structures (e.g., cranial nerves), incomplete surgical oncologic clearance can predispose the patient to tumour recurrence despite palliative radiotherapy and chemotherapy.11 Prognosis is guarded in neoplasms with perineural invasion, extension to skull base and positive surgical margins on frozen section.12 Invariably, the treatment of choice is surgical resection.13 Adjuvant radiotherapy and chemotherapy is implemented additionally in cases of residual tumour disease, positive surgical margins or advanced tumour stage.14-16

Case Report
A 39-year-old gentleman presented to the outpatient department a year ago (in November 2016) with intermittent, pricking pain in the right half of the face radiating to the right temporal region. CT scan of paranasal sinuses (Figure 1) had revealed a lesion in the right pterygopalatine region involving the posterior wall of maxillary sinus with bone destruction and extension to the skull base. A week later, medial maxillectomy was done to excise the visible tumour. Histopathology of intra-operative frozen section from the infraorbital nerve and periorbital margin revealed tumour cells in glandular, trabecular and cribriform pattern suggestive of adenoid cystic carcinoma with perineural spread. The patient did well post-operatively. A month later, he underwent adjuvant radiotherapy and chemotherapy for 5 weeks in view of positive surgical margins on frozen section. There was no sign of tumour recurrence until a year after surgery.

At presentation, he reported recent onset binocular diplopia since November 2017, associated with limited movements and defective distant vision in the right eye apart from numbness in the right forehead. A follow-up MRI of the orbit/brain with contrast in November 2017 revealed buckling of the right optic nerve.
Physical examination was negative for lymphadenopathy. Currently, his best corrected distance visual acuity was 6/12 in the right eye and 6/6 in the left eye. Near visual acuity was N6 in both eyes with +1.25DS. A 3 cm linear vertical scar lateral to the nose above the right naso-labial fold corresponded to the site of surgery. The right eye was enophthalmic secondary to a bony surgical defect in the maxilla. In the absence of any lid signs, a right face turn was associated with limitation of movements in the right eye - abduction, elevation in adduction and primary gaze (Figure 2). Altered sensations in the periorbital area were associated with reduced corneal sensations in the right eye. Pupil diameter was measured to be 4 mm in the right eye as against 2 mm in the left eye. The anisocoria increased in light and was coexistent with vermiform constriction of the pupil, an absent consensual reflex in the right eye, in the presence of a brisk near response. Supersensitivity to 0.125% pilocarpine revealed an Adie’s tonic pupil (Figure 3). The lens was clear with a normal fundus picture. Assessment of colour vision was normal in both eyes. The remaining cranial nerves were intact. Motor system examination was normal. Diplopia and Hess charting verified a combined right sixth nerve and partial third nerve palsy. A repeat contrast MRI of brain/orbit with fat suppression sequencing in February 2018 confirmed an ill-defined heterogeneously enhancing plaque like soft tissue lesion involving the distal portion of the right orbit with extension into the right cavernous sinus apart from encasing the retrobulbar portion of the optic nerve (Figure 4) indicating tumour recurrence. An observation of right Adie’s tonic pupil with partial cavernous sinus syndrome secondary to dural invasion in recurrent adenoid cystic carcinoma of maxillary sinus was made.

Adenoid cystic carcinoma is known for its frequent occurrence from the fourth decade to the sixth decade with a female predilection.17 Initial manifestations of the disease include subtle discomfort and altered sensations in the trigeminal distribution.7 In our case, the patient reported right hemifacial pain, probably indicating a direct involvement of the second division of the trigeminal nerve that innervates the maxillary sinus. Concurrent involvement of cranial nerves III, IV, V and VI is common, either as a primary manifestation of an evolving tumour or an indication of its recurrence.7-10 The time between onset of incipient symptoms and partial cavernous sinus syndrome ranged between 6 months and 6 years.2 The patient was in remission for a year post surgery when he presented with clinching neuro-ophthalmic signs in the affected eye including Adie’s pupil, reduced corneal sensations and diplopia secondary to restricted abduction and elevation. The possible mechanism for the course of events could be either a perineural spread, direct invasion of cavernous sinus by tumour cells or intracranial invasion (intraparenchymal or dural). A case series by Alleyne et al. has documented involvement of the trigeminal ganglion in 35.8%, temporal lobe or middle fossa in 20.7%, cavernous sinus in 15.1%, chiasma in 7.5%, cerebellopontine angle in 5.7% and posterior fossa in 5.7% of cases with intracranial invasion.7 In our case, the plausible mechanism is that the drainage of maxillary sinus has probably induced direct seeding of the tumour cells in the cavernous sinus or direct passage of tumour cells from the right orbit via the superior ophthalmic vein. Multiple cranial nerve involvement in our case (III, V and VI) is probably suggestive of tumour cell activity in the cavernous sinus. Radiologic signs suggestive of cavernous sinus involvement include: sinus enlargement, convexity of lateral dural margins and replacement of the trigeminal cistern with soft tissue.18 Adie’s pupil in the affected eye is probably due to perineural spread of tumour cells from the cavernous sinus along the first division of the trigeminal nerve, tracking along the nasociliary nerve to the ciliary ganglion upon entering the orbit through the annulus of Zinn.19 Intraoperative frozen section of proximal structures during surgical excision of tumour was positive for the margins of infraorbital nerve indicative of perineural activity at the initial presentation. Contrast enhanced MRI with fat suppression is essential to identify perineural enhancement.2 Literature review suggests a greater risk of distant metastasis and local recurrence in tumours with perineural spread.10,20,21 Skull base extension, an unfavourable prognostic factor for survival, may occur along the Eustachian tube, internal carotid artery, maxillary and mandibular nerves.22 Gandour-Edwards et al. have reported that tumours with dural invasion express neural cell adhesion molecules increasing their affinity for the dura.23 Tumour cells may also hematogenously invade the lungs, bones, liver and occasionally the brain.24-26
Histological growth patterns of ACC reported include tubular, cribriform and solid, with the cribriform pattern being the most frequent as in our case.27 Solid type correlates with aggressive behavior and poorer prognosis.4 Immunohistochemical staining for c-kit accords a poorer prognosis in tubular and solid ACC subtypes.4 The treating physician is faced with multiple treatment challenges due to incomplete resection owing to local invasion and perineural spread, increasing the possibility of recurrence upon completion of treatment.3,17 The benefit of concurrent radiotherapy and chemotherapy still remains uncertain, with surgical resection the most effective treatment modality.3 In our case, Adie’s pupil secondary to perineural spread of tumour, necessitates shift in treatment goal from cure to palliation.2 
Prognosis in ACC is determined by histological subtype, tumour location, tumour stage and perineural spread at time of diagnosis.28 Though biopsy revealed a cribriform subtype, prognosis is more circumspect in our case due to evidence of skull base extension and subsequent perineural invasion.

We report a unique case of recurrent, cribriform variant of ACC of the maxillary sinus with partial cavernous sinus syndrome and an acquired Adie’s pupil consequent to intracranial extension and perineural spread This case is a reminder that subtle neuro-ophthalmic signs like an Adie’s pupil can give essential clues regarding the site of tumour cell activity. Keeping in mind the clinical behavior of ACC, a high index of clinical suspicion is mandatory to help the radiologist outline signs of recurrence through appropriate imaging techniques. Early identification of tumour extension will have an essential impact on long term survival negating any diagnostic or therapeutic challenge. The most effective treatment of ACC is still uncertain, justifying the need for further prospective clinical trials to evaluate the impact of adjuvant radiotherapy and chemotherapy in the presence or absence of positive tumour margins. The future outcome of this case is questionable even with palliative therapy, warranting the need for a strict vigilance of further clinical course of the disease through a multidisciplinary collaboration to ensure minimal interference with activities of daily living. 

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Prithviraj Udaya, Sairani KaranamAdie’s Tonic Pupil in a Case of Recurrent Adenoid Cystic Carcinoma of Maxillary Sinus – An Ophthalmic Perspective.DJO 2018;29:60-63


Prithviraj Udaya, Sairani KaranamAdie’s Tonic Pupil in a Case of Recurrent Adenoid Cystic Carcinoma of Maxillary Sinus – An Ophthalmic Perspective.DJO [serial online] 2018[cited 2022 Nov 30];29:60-63. Available from: