Journal of Neuro-Ophthalmology, September 1997, Volume 17, Issue 3

Neuro-Ophthalmologic Manifestations of Adenoid Cystic Carcinoma

Intracranial adenoid cystic carcinoma is uncommon. We report two unusual cases of intracranial adenoid cystic carcinoma. The first patient presented with a steroid-responsive optic neuropathy from an orbital mass that simulated orbital pseudotumor, and subsequently developed intracranial involvement, presumably by contiguous perineural spread. The second patient presented with proptosis of the left eye, right facial weakness and numbness, and an intracranial mass, presumably from hematogenous metastatic spread.

Journal of Neuw- Ophthulmolosy 17( 3): 183- 188, 1997. © 1997 Lippincoll- Ravcn Publishers, Philadelphia Neuro- Ophthalmologic Manifestations of Adenoid Cystic Carcinoma Andrew G. Lee, M. D., Paul H. Phillips, M. D., Nancy J. Newman, M. D., L. Anne Hayman, M. D., Jade S. Schiffman, M. D., Scott E. Segal, M. D., Hering J. Nauta, M. D., Mitchell J. Wolin, M. D., and Rosa A. Tang, M. D., M. P. H. Intracranial adenoid cystic carcinoma is uncommon. We report two unusual cases of intracranial adenoid cystic carcinoma. The first patient presented with a steroid- responsive optic neurop­athy from an orbital mass that simulated orbital pseudotumor, and subsequently developed intracranial involvement, presum­ably by contiguous perineural spread. The second patient pre­sented with proptosis of the left eye, right facial weakness and numbness, and an intracranial mass, presumably from hema­togenous metastatic spread. Key Words: Adenoid cystic carcinoma- intracranial. Adenoid cystic carcinoma ( ACC) arises most fre­quently from the salivary, lacrimal, and other exocrine glands ( 1,2) and may be locally invasive. There are few reports, however, of intracranial ACC ( 3- 12). We report the clinical and neuroradiologic findings in two unusual cases and review the literature on intracranial ACC ( 3 - 12). CASE REPORTS Case 1 A 36- year- old pregnant white woman complained of a 2- month history of right facial pain, intermittent numb­ness of the right cheek, and diffuse, moderately severe headaches. Her symptoms began in March 1995, at the end of her first trimester of pregnancy. In April 1995, she Manuscript received December 19, 1996; accepted March 31, 1997. From the Departments of Ophthalmology, Neurology, and Neuro­surgery ( A. G. L.) and the Department of Radiology, ( L. A. H.), Baylor College of Medicine, Houston, Texas; the Departments of Ophthalmol­ogy ( N. J. N., P. H. P.), Neurology ( N. J. N.), and Neurosurgery ( N. J. N.), Emory University School of Medicine, Atlanta, Georgia; University of Miami School of Medicine ( J. S. S.), Miami, Florida; the Anderson Eye and Ear Associates ( M. J. W.), Anderson, South Carolina; and the De­partments of Ophthalmology and Neurosurgery ( R. A. T, H. J. N.), Uni­versity of Texas Medical Branch at Galveston, Houston, Texas and the Division of Neurosurgery, University of Texas, M. D. Anderson Cancer Center, Houston, Texas, U. S. A. Address correspondence and reprint requests to Dr. A. G. Lee, Cullen Eye Institute, Baylor College of Medicine, 6501 Fannin, NC 200, Houston, TX 77030, U. S. A. Presented in part at the Frank B. Walsh Society Meeting, Salt Lake City, Utah, February 11, 1996. noted decreased vision in the inferior field of her right eye associated with a pressure sensation behind the right eye. Her past medical, surgical, and social history were noncontributory. A general medical, neurologic, and oto­laryngologic evaluation were unremarkable. Results from a computed tomography ( CT) scan of the head, without contrast, on June 15, 1995, were normal. She then noted progressive loss of visual acuity, in­creasing proptosis, and retrobulbar pain of the right eye. She was seen by an ophthalmologist on July 7, 1995, and had a visual acuity of counting fingers in the right eye and 20/ 20 in the left eye. There was a relative afferent pupillary defect and 4 mm of proptosis in the right eye. Ophthalmoscopic study revealed mild disc edema in the right eye. A magnetic resonance ( MR) scan of the head and orbits without contrast showed a nonspecific soft tissue mass in the right orbital apex, extending posteri­orly into the cavernous sinus with enlargement of the extraocular muscles in the right orbital apex ( Fig. I). The lacrimal glands were felt to be normal clinically, and appeared normal on the MR scan of the orbit. She was treated with an empiric trial of oral prednisone ( 60 mg per day) for the presumed diagnosis of pseudotumor of the orbit. One week after treatment with oral steroids, she experienced a dramatic improvement in visual acuity in the right eye to 20/ 40, the proptosis of the right eye had decreased by 1 mm, and the visual field defect had im­proved in the right eye. On July 20, 1995, the patient reported improvement in her headache and visual func­tion, and the prednisone dosage subsequently was re­duced to 40 mg per day. On August 16, 1995, the visual acuity measured 20/ 60 in the right eye, and the oral pred­nisone dosage was increased to 60 mg per day, alternat­ing with 30 mg per day. Neuro- ophthalmologic examination on August 23, 1995, revealed a visual acuity of 20/ 60 in the right eye and 20/ 20 in the left eye. Hertel exophthalmometer mea­surements were 26 mm in the right eye and 22 mm in the left eye. The right pupil reacted sluggishly to light, and there was a right relative afferent pupillary defect. Gold-mann perimetry revealed a relative inferior nerve fiber bundle- related defect involving central fixation to the 183 184 A. G. LEEETAL. FIG. 1. Case 1. Axial T1 - weighted MR image without contrast of the orbit reveals an isointense mass in the right orbital apex ( arrow). I4e and III4e stimuli in the right eye and a normal visual field in the left eye. Results of slit lamp biomicroscopy, intraocular pressure measurements, and ocular motility examination were normal in each eye. Ophthalmoscopic study revealed mild right optic disc swelling. Findings on corneal reflex testing were normal in each eye. Sensation in the cutaneous distribution of the second division of the trigeminal nerve was decreased on the right. A second MR scan of the head and orbits, without contrast, on September 1, 1995, revealed an increase in the size of the soft tissue mass at the right orbital apex ( Fig. 2) and involvement of the pterygopalatine fissure and skull FIG. 2. Case 1. Axial T2- weighted MR image shows hyperin-tense signal intensity in the right orbital apex ( arrow) and along the right posterior optic nerve sheath. FIG. 3. Case 1. Histopathologic examination of the lesion re­veals aggregates or islands of poorly differentiated, small, tightly packed epithelial cells that are outlined sharply against the sur­rounding hyaline- like stroma, consistent with adenoid cystic car­cinoma. base. On September 6, 1995, the visual acuity was count­ing fingers in the right eye with worsening of the visual field defect in the right eye. A third MR scan, without contrast, revealed slight enlargement of the right orbital apex mass. At 37 weeks' gestation, she underwent an induced vaginal delivery without complication. The following day, she underwent a right frontal craniotomy. At the time of surgery, an irregular tan and pink soft tissue mass involving the meninges of the lesser wing of the sphe­noid and the right optic canal was encountered. The mar­gin of the lesion could not be grossly identified, and the mass seemed to infiltrate the meninges of the cavernous sinus and superior orbital fissure, as well as the greater wing of the sphenoid bone. The right optic nerve was decompressed by removing the roof of the optic canal, and the optic nerve appeared grossly normal. Histopath­ologic examination of the mass revealed ACC ( Fig. 3). No ectopic lacrimal gland tissue was seen. An extensive otolaryngologic and general medical examination failed to uncover a primary tumor site or other metastatic le­sions. Results of a chest radiograph and bone scan were normal. A biopsy of the right lacrimal gland did not reveal any evidence of ACC. The patient underwent fractionated radiation therapy consisting of 6300 cGy over 5 weeks to the right sphe­noid wing and posterior orbit. Examination on January 24, 1996, revealed a visual acuity of 20/ 30, a small para­central scotoma to the I4e stimulus on Goldmann perim­etry, and optic atrophy in the right eye. MR imaging revealed postoperative changes in the right orbital apex from the previous craniotomy. The lesion in the ptery­gopalatine fossa was better demonstrated after the ad­ministration of contrast material ( Fig. 4). Case 2 A 32- year- old Hispanic man presented with a 2- month history of increasing " fullness" of the left upper lid and ./ Neuro- Ophlhalmol. Vol. 17, No. 3, 1997 NEURO- OPHTHALMOLOGIC MANIFESTATIONS OF ACC 185 FIG. 4. Case 1. Axial T1 - weighted MR image demonstrates con­trast enhancement of lesion on the right side ( arrow) in the area of the pterygopalatine fossa. proptosis of the left eye. He was treated by his local physician with topical antibiotic drops without relief of symptoms. One month before referral, he developed de­creased vision in the left eye, binocular vertical diplopia in upgaze, mild weakness of the right face, and numb­ness in the left hand. His past medical history was un­remarkable. Neuro- ophthalmologic examination revealed a visual acuity of 20/ 20 in the right eye and 20/ 30 in the left eye. There was a palpable fullness in the left upper eyelid, left infraplacement of the globe, 3 mm of left- sided propto­sis, and decreased retropulsion in the left eye. The pupils were of equal size, and there was no relative afferent pupillary defect. Ocular motility examination revealed full movement of the right eye, but the left eye had limited elevation ( Fig. 5). Visual fields performed by Goldmann perimetry were normal in each eye. Ophthal­moscopic study revealed choroidal folds superiorly in the left eye. The remainder of the findings from retinal and optic nerve examination in each eye was normal. Neu­rologic examination revealed decreased sensation in the cutaneous distribution of the first and second divisions of the trigeminal nerve on the right side, a right peripheral seventh cranial nerve paresis, mild weakness and de­creased sensation to light touch of the left upper and lower extremities, and agraphesthesia of the left hand. General physical examination revealed mild tenderness over the right mandibular angle and an enlarged, non-tender right cervical lymph node. MR scan of the brain and orbits revealed a left superior orbital mass with intracranial extension ( Fig. 6), and a 4- cm extraaxial mass in the right parietal region with surrounding meningeal enhancement. There was mini- < 5- FIG. 5. Case 2. Motility photographs demonstrate full movement of the right eye, but the left eye was limited in elevation. J Neum- Ophlhalmol, Vol. 17, No. 3, 1997 186 A. G. LEEETAL. FIG. 6. Case 2. Coronal T1- weighted MR image demonstrates slightly hypointense abnormal signal intensity in the left superior orbit with erosion of the orbital roof and intracranial extension. mal surrounding tissue edema, mass effect, or midline shift. A second mass was identified in the left superior orbital ridge compressing the superior portion of the left globe. CT of the brain and orbits revealed a lytic bone lesion in the right calvarium adjacent to the right parietal mass ( Fig. 7), a lytic bone lesion in the right mandibular angle, and a superior orbital mass with adjacent orbital bone destruction. CT of the chest, abdomen, and pelvis yielded normal results. A bone survey revealed the lytic bone lesions in the right calvarium and right mandibular angle, and a bone scan revealed increased uptake in the left orbit, right mandible, and midline of the skull. Bi­opsy of the right parietal mass revealed ACC. The patient was treated with palliative radiation and chemotherapy, but he developed metastatic lesions of the cervical and sacral vertebrae. DISCUSSION Adenoid cystic carcinoma most commonly arises from the major and minor salivary glands, and the mucous glands of the upper respiratory tract ( 1- 23). In the orbit, ACC usually arises from the lacrimal gland. Less com­monly, ACC may develop from the cerumen glands of the external auditory canal, ectopic lacrimal gland tissue, and other organs such as breast, bronchus, intestine, pan­creas, vulva, sweat glands, or genital organs ( 3,5,11,17). ACC usually grows slowly over many years, with pro­gressive local extension and multiple local recurrences ( 17,21). Metastatic disease is a late finding and usually involves the lungs, but also may involve bone, liver, regional lymph nodes of the head and neck, and rarely, brain ( 5). Nevertheless, patients may continue to live for several years despite the development of metastases ( 7). The overall 5- year survival rate for all ACC is about 47%, and the 15- year survival rate is about 10% to 22% ( 7). The median age of patients with ACC is 38 years, with an equal incidence in male and female pa­tients. ACC of the head and neck usually presents with a local mass or swelling with or without pain ( 2). Patients with orbital ACC may have proptosis, orbital pain, dip­lopia, or visual loss, depending on the location and in­filtrating character of the tumor ( 2). Intracranial exten­sion of ACC may occur in 4% to 22% of cases ( 3- 12,18,20). Most of these cases invade the skull base and are thought to extend directly or by perineural spread from lesions in adjacent structures, such as the lacrimal glands, salivary glands, paranasal sinuses, or from the nasopharynx ( 3- 12,18,20). Hematogenous metastasis to the brain are rare ( 4,5,24- 26). In Case 1, there was no clinical or radiologic evidence of a primary orbital or ectopic lacrimal gland origin of the ACC, and a lacrimal gland biopsy revealed no evi­dence of ACC. There was involvement of the pterygo­palatine fissure on the initial imaging studies, suggesting that the tumor originated from minor salivary glands within the pterygopalatine fossa. An extensive general medical evaluation failed to disclose another primary tu­mor site or metastatic lesions. The intraorbital and intra­cranial tumor likely occurred through perineural or con­tiguous spread from the pterygopalatine fossa. The ptery­gopalatine fossa is located directly posterior to the maxillary sinus and is in communication with the orbit through the inferior and superior orbital fissures, as well as the cranium through the foramen rotundum. The max­illary division of the trigeminal nerve travels through the pterygopalatine fossa, and it is likely that involvement of this nerve in this location was the source of the intermit­tent numbness of the cheek experienced by this patient ( Fig. 8). Contiguous spread of tumor from the pterygo­palatine fossa to the orbit has been reported ( 27- 29). FIG. 7. Case 2. Coronal CT scan of the head demonstrates a slightly hyperdense lesion in the right parietal region with erosion of the skull. J Neiiro- Oplilluilmol, Vol. 17, No. 3, 1997 NEURO- OPHTHALMOLOGIC MANIFESTATIONS OF ACC 187 I'll llAOROITAL FlSSUflf WAXILLAHT H. S. HFATER PETROSAL N inFTnenBirAi, u, S^ H¥ f. T\ KT\ C3 ' \ DLbP PETROSAL N PTFR^ COPMATlUti GANGLION in PTEHTOOP^ LATIrtE HOSSft SAGITTAL VIEW OF EEEUL. ORBIT^ L WALL FIG. 8. Schematic sagittal view of the infraorbital nerve and pterygopalatine fossa. ( Reproduced with permission from Wolin MJ. Neuro- ophthalmic manifestations of paranasal sinus dis­ease. Ophthalmol Clin North Am 1991; 4: 585- 603.) Peipmeier and others reported on a patient with an in­tracranial ACC with involvement of the orbit, extraocu­lar muscles, and optic nerve ( 10). These authors believed that the intracranial and intraorbital tumor was from peri­neural invasion of the trigeminal nerve ( 10). Our patient had symptoms of an ipsilateral trigeminal neuropathy and may have likewise experienced perineural trigeminal invasion. In Case 2, the left lacrimal gland is the most likely primary site. However, the right salivary glands may have been an alternative primary site, since this patient had a right CN VII palsy and a lytic lesion in the right mandibular angle. Although this patient had no discrete mass on neuroimaging of this region suggestive of a primary site, Cummings described two cases of ACC in which local signs occurred 4 to 6 years before the de­velopment of a clinically detectable parotid mass ( 24). Our patient in Case 2 likely had intracranial involve­ment from hematogenous metastatic spread, since the intracranial mass was anatomically isolated and on the opposite side of the orbital mass. Hematogenous me­tastases to the brain are rare ( 4,5,24- 26). Gelber and coworkers ( 25) described a patient with ACC of the right parotid gland with a histologically confirmed metastatic lesion to the inner table of the left frontal calvaria, epi­dural compartment, and brain parenchyma. Variakojis and associates ( 26) described a patient with ACC arising in the right submaxillary salivary gland with a metastatic lesion to the left frontoparietal region of the skull, which invaded the underlying dura and brain. Hara and col­leagues ( 4) reported on a patient with an isolated ACC of the frontal lobe from an unknown primary site. These metastatic CNS lesions occurred in anatomic positions inconsistent with direct or retrograde perineural spread from the primary site. Intracranial ACC usually appears on CT as a well-demarcated, hyperdense, extraaxial mass that shows ho­mogeneous enhancement after contrast administration ( 4, 6,9,11). The features of intracranial ACC seen on MR imaging include isointense signal intensity on Tl-weighted images, hyperintense signal intensity on T2- weighted images, and homogeneous enhancement after the administration of gadolinium- DTPA. Morioka and others reported linear meningeal thickening and en­hancement adjacent to an intracranial ACC similar to the " dural tail" seen more commonly in meningiomas ( 9). The natural history of ACC seems to be a prolonged course with local recurrences and variable metastatic dis­ease. Treatment regimens include chemotherapy, radia­tion therapy, and surgical excision. Radical complete surgical excision, when possible at the time of initial diagnosis, seems to be the best treatment option, but often is not feasible because of infiltrative involvement of contiguous vital structures ( 1,2,12,17,20). ACC is ra­diosensitive but not radiocurable ( 7,9,11,12,15,18,20). Chemotherapy has been tried for ACC, but with limited success, presumably secondary to the slow growth rate of these tumors ( 2,11,19,20). Gormley and colleagues ( 12) presented 16 cases of ACC with cranial base and intra­cranial extension. These authors focused on neurosurgi­cal treatment and recommended the following: ( 1) pre­liminary cerebral revascularization with cervical carotid to middle cerebral artery bypass in cases with carotid artery involvement; ( 2) as complete as possible removal of tumor from the cavernous sinus with attempts to pre­serve the ocular motor cranial nerves; ( 3) orbital ex­enteration in cases with intraconal involvement; and ( 4) consideration for palliative surgery even in cases where local disease precludes surgical cure. The dramatic re­sponse to steroid therapy in Case 1 suggested the erro­neous diagnosis of orbital pseudotumor, but the transient numbness of the cheek and intracranial extension of the tumor were atypical features that prompted biopsy. ACC should be considered in the differential diagnoses of painful, steroid- responsive optic neuropathies and of in­traorbital as well as intracranial masses. 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