INTRACRANIAL ADENOID CYSTIC CARCINOMA: CASE REPORT AND REVIEW OF THE LITERATURE Cargill H. Alleyne, Jr., M.D.,* Roy A. E. Bakay, M.D.,* Donal Costigan, M.D.,T Bill Thomas, M.D.,** and Greg J. Joseph, M.D.+ Departments of Neurosurgery, * Neurology, f Pathology, * * and Radiology, $ Emory ~nive~i~ School of medicine, Atlanta, Georgia
Alleyne CH, Bakay RAE, Costigan D, Thomas B, Joseph GJ. Intracranial adenoid cystic carcinoma: case report and review of the literature. Surg Neural 1996:~~265-71. BACKGROUND
Adenoid cystic carcinoma (cylindroma) is a relatively common head and neck tumor that is slow growing, but locally aggressive and thus prone to recurrence. It is of particular interest to neurosurgeons and neurologists because of its tendency to locally infiltrate neural structures and to spread perineurally. Intracranial involvement has been regarded as rare. METHODS
A case report of a patient with adenoid cystic carcinoma involving the Gasserian ganglion region is presented. The world literature on intracranial involvement of adenoid cystic carcinoma is reviewed. A discussion of the characteristics of this lesion is provided. RESULTS
Our literature review revealed 119 previously reported cases of adenoid cystic carcinoma with intracranial involvement. Our case represents only the tenth reported intracranial case with an unknown primary site. CONCLUSIONS
Although intracranial adenoid cystic carcinoma is regarded as rare, we have accumulated over 100 such reports. A wide variety of primary sites and intracranial sites have been described. KEY WORDS
Adenoid cysiic curcinom~, cy~ind~ma, brain neoplasm, perineural spread.
he malignant epithelial neoplasm, adenoid cystic carcinoma, was first described in 1856 by Billroth  under the name “cylindroma.” A wide array of terms has been applied to this tumor, including adenocystic carcinoma, cribriform adenocarcinoma, adenocystic basal-cell (or basaloid) Address reprint requests to: Cargill H. Alleyne, Jr., M.D., The Emory Clinic, 1327 Clifton Rd., N.E., Atlanta, GA 30322. Received August 19, 1994; accepted November 16, 1994. 0 1996 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010
carcinoma, pseudoadenomatous carcinoma, adenomyoepithelium, and basaloma. it most commonly arises in the major and minor salivary glands, nasopharynx, and lacrimal glands but has also been found in the lung, trachea, mammary gland, and skin. These tumors are slow growing but are locally aggressive and are prone to recurrence. Distant metastases are not uncommon. Neurosurgeons and neurologists need to be familiar with this tumor in view of a tendency to local extension into neural structures, both in the intracranial compartment, and by perineural spread along the trigeminal nerve. The incidence of intracranial involvement has been variously reported as 4% to 22% [4,7,24]. In Conley’s series , 22% of 134 patients with adenoid cystic carcinoma in the head and neck had intracranial involvement. In a report by Font et al , 15% of 79 patients with adenoid cystic carcinoma of the lacrimal gland had intracranial invasion. A review of the world literature has revealed an additional 77 cases of intracranial adenoid cystic carcinoma bringing the total to 119 [1,5,6,8-15, 17,19,21-26,29-37,39-42,44,46,48]. Reports of bony involvement without meningeal, cranial root, or parenchymal involvement have been excluded from this review. To this growing number of cases, we report a patient with an adenoid cystic carcinoma with prominent symptoms of Gasserian ganglion involvement and asymptomatic cavernous sinus involvement. To our knowledge, this is only the tenth reported case of intracranial adenoid cystic carcinoma with an unknown primary site.
CASEREPORT HISTORY A 38year-old left-handed Caucasian woman sought a fifth neurologic opinion at our institution for an 0090-3019/96/$15.00 SSDI 0090-3019(95)00235-V
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(A): Coronal T,-weighted MRI with contrast q(shorfshows an enlarged right cavernous sinus umw) with enhancement along the course of the mandibular nerve through the foramen ovale (long arrow). (B): Slightly anterior coronal contrast-enhanced MRI shows an enlarged foramen rotundum (curued arrow) and dural enhancement around the floor of the middle fossa (&on’ arrows). (C): Axial contrast-enhanced T,-weighted image at the level of Me&elk cave shows enhancement of the cisternal portion of the trigeminal nerve (arrowhead). Abnormal dural enhancement extends around the temporal tip (shoti arrows).
undiagnosed 3-year history of facial pain. She described initially laminating but subsequently more continuous pain and numbness in the distribution of the right second and third divisions of the trigeminal nerve (V2 and V3), including the tongue. Her pain was partially responsive to carbamazepine (200 mg po BID) and baclofen (20 mg po QID). She noted deviation of the jaw to the right on opening her mouth. There were no symptoms of right abdutens or oculomotor nerve weakness, although a familial partial optic neuropathy became evident. The family history was remarkable for a brother who had suffered insidiously progressive visuaf loss to legal blindness. He was not available for evaiuation. EXAMINATION On physical examination, the patient was in chronic but severe distress. There was bilateral exophoria,
without signs of abducens or oculomotor paresisSevere loss of all sensory modalities was noted in the distribution of right V2 and V3, with no reduction of the cornea1 reflex. There was deviation of the jaw to the right on opening the mouth, with palpable weakness of right pterygoid muscle. The remainder of the neurologic examination was normal. Prior investigations had revealed normal complete blood count and erythrocyte sedimentation rate. Syphilitic serology and serum protein electrophoresis were negative. Multiple studies of the cerebrospinal fluid, including myelin basic protein, cryptococcal antigen, oligoclonal banding, and cytology were negative or normal. Magnetic resonance imaging (MFU) performed 2?4 years previously had suggested a right Gasserian ganglion abnormality, but this was subsequently dismissed as artifact. A computed tomo~aphy (CT) scan of
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shaped tan tissue was noted emerging through the strands of dura covering the trigeminal nerve. This was very suggestive of perineural ascent of the tumor. A small irregularly eroded hole measuring less than 1 millimeter was noted in the middle fossa floor. This hole did not seem to represent a neural foramen. The tumor was debulked and sent to pathology. The procedure was well tolerated. Microscopically, the tumor consisted of cytologically bland-appearing cells forming a tubular and cribriform glandular arrangement. Duct-lining secretory cells were present in the tubular arrangement, while the cystic spaces in the cribriform pattern contained a stringy secretion. The tumor infiltrated the dura and connective tissue. These features of the lesion were consistent with adenoid cystic carcinoma (see Figure 2 A and B).
Histologic photomicrographs of adenoid cystic carcinoma infiltrating the dura. In figure 2 (A), the characteristic cribriform pattern is seen @I & E X 400). Figure 2 B shows the tubular pattern (H & E X 200). the brain without contrast, obtained 9 months prior to admission, was normal. Another more recent MRI with gadolinium, obtained 5 months prior to admission, was interpreted as normal. At the time of evaluation, needle electromyography of the right masseter muscle showed active axonal denervation. A repeat MRI with gadolinium (Figure 1 A, B, and C) showed abnormal dural enhancement over the anterior floor of the right middle fossa and involving the right cavernous sinus. There was abnormal enhancement of the proximal trigeminal nerve in its cisternal course and the mandibular division as it coursed through the foramen ovale. The foramina ovale and rotundum were enlarged. A high signal abnormality in the infratemporal fossa on the right represented a small focus of tumor extension. There was no evidence of orbital apex extension. In retrospect, similar abnormalities were seen upon reexamination of the previous MRI study. OPERATION The patient underwent a craniotomy with a right pterional approach to the middle fossa. Irregularly
POSTOPERATIVE COURSE The patient’s postoperative course was uneventful. Further workup, including fiberoptic examination of the nasopharynx and hypopharynx, contrast MRI of the neck, indirect laryngoscopy, CT scan of the chest, abdomen, and pelvis, and mammogr~s, was negative for a primary site. She was discharged to home on postoperative day 4 in stable condition. Radiation therapy was administered on an outpatient basis. On subsequent follow-up, she developed worsening facial pain and a repeat contrast MRI showed more involvement of the right cavernous sinus and more meningeal enhancement over the right temporal lobe.
DISCUSSION A review of the world literature has revealed a wide variety of primary sites from which intracranial adenoid cystic carcinomas arise. These include the n~oph~x [ 17,23,37,48], lacrimal gland [36,46,25], parotid gland [ 15,241, submaxillary gland 1431, submandibular gland , minor salivary glands , maxillary sinus [26,46], sphenoid sinus [44,48], ethmoid sinus [ 261, tongue [ 241, nasal septum [ 351, and mandible . Metastatic adenoid cystic carcinomas with primary sites in the lung , breast 1141, and scalp  have also been reported. There is even an unusual report of an adenoid cystic carcinoma arising in heterotopic salivary gland tissue in the cerebellopontine angle . As in the case we now report, a negative workup for a primary source is not uncommon. At least nine patients in the literature presented with an apparently primary intracranial lesion and without evidence of a primary source (Table 1) [8,10,11,21,23,25,29,40,47]. In most
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of the cases, histologic confirmation of the diagnosis was obtained at surgery or autopsy. Intracranial involvement by adenoid cystic carcinomas can occur in one of three ways: direct extension, hematogenous spread, and perineural spread. Perineural spread of adenoid cystic carcinomas has long been recognized [3,18] Larson et al  showed that perineural spread occurs contiguously along neural planes and not in perineural lymphatits. Vrielinck et al  found a 52.6% incidence of perineural invasion in primary resection specimens from 37 patients with adenoid cystic carcinomas. They also found that this factor was associated with a significantly lower survival rate and with the development of distal metastases. Parker et al  showed, by MRI, a relationship between the primary tumor site and the involved nerve. For example, masticator space tumors, including adenoid cystic carcinomas, spread along the mandibular division of the trigeminal nerve, while maxillary sinus tumors spread along the maxillary division. Perineural spread of adenoid cystic carcinomas intracranially has been reported f 17,46,49]. Direct extension of adenoid cystic carcinomas into the brain with bony destruction has also been described [35,36,42,46,4&J. In some cases of intracranial adenoid cystic carcinoma, metastasis by a hematogenous route must be invoked to explain the location of the lesions [10,11,14]. Of the 37 cases wherein age and sex of the patients were reported in the English literature, the average age was 53 years (with a range of 24 to 90 years). A slight male predominance was noted (22 male and 15 female patients). Gonzalez and Zulch  reported two major regions of intracranial invasion by adenoid cystic carcinomas-the optic chiasm and the Gasserian ganglion. The former was thought to arise from primary lesions in the nasal fossae or paranasal sinuses traversing the cribriform plate, and the latter from the glandular epithelium of the eustachian tube. Our review of the 53 cases with documentation of the site of intracranial involvement demonstrated involvement of the Gasserian ganglion in 35.8% [8,9,37,41,49], temporal lobe, or middle fossa in 20.7% [14,19,21,23,42,44,36,4?], cavernous sinus in 15.1% [23,29,32,34,44,48], frontal lobe or anterior fossa in 15.1% [10,11,25,35,36,43,46], chiasmal region in 7.5% , cerebellopontine angle in 5.7% [5,15,17], and posterior fossa in 5.7% of cases [25,40,47]. In some cases, the intracranial extent of the lesion was formidable [42,47]. Presenting signs and symptoms were referable to the anatomic location of the lesion. Facial paresthesiae and pain in the trigeminal distribution were
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commonly reported, reflecting the frequent involvement of the Gasserian ganglion and underscoring the importance of possible perineural spread. The duration between onset of neurologic symptoms and treatment ranged from 3 months to 3 years. Our patient’s course prior to diagnosis is typical. Her initial s~ptoms clearly reflect involvement of the trigeminal nerve, probably distal to the ganglion, with subsequent invasion of the middle cranial fossa. The remarkable selectivity of her trigeminal nerve involvement (V2 and V3, sparing Vl) at presentation, and the lack of clinical signs of a cavernous sinus lesion, underline the indolent pattern of local invasion. In spite of cavernous sinus abnormality on the MRI, there was no clinical effect on Vl and the third, fourth, and sixth cranial nerves. This emphasizes the need for careful radiographic inspection of the region of the Gasserian ganglion when confronted with this syndrome. The most common treatment modality implemented was surgical decompression of the lesion, Radiation therapy was also utilized as a palliative measure since this tumor is regarded as radiosensitive but not radiocurable [26,31,46]. There are rare reports of tumor shrinkage with chemotherapy [35,46]. Brachytherapy was used in one instance with complete radiographic resolution of the tumor . This mode of therapy may prove useful in selected cases. The relationship between histologic appearance of the tumor and prognosis has been examined. Perzin et al  found that the predominantly tubular pattern had the best prognosis, while the predominantly solid pattern had the worst. Spiro et al , however, found no difference between histologic type and result of treatment. Detailed reports on follow-up of patients with intracranial adenoid cystic carcinoma are lacking, but Spiro et al  documented a lo-year survival rate of 72%, 42%, and 29% in patients with stage 1, 2, and 3 tumors, respectively. In summary, we present a case of an intracranial adenoid cystic carcinoma with an unknown primary site. Although intracranial adenoid cystic carcinoma is regarded as rare, a review of the world literature has revealed an increasing number of such reports, totaling 119. A wide variety of primary sites and intracranial sites has been reported.
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The authors report on a 3%year-old woman who presented with a S-year history of facial pain. MRl of the head showed abnormal enhancement of the right trigeminal nerve, enlarged foramina ovale and rotundurn, as well as abnormal dural enhancement along the floor of the right middle cranial fossa. At surgery, tumor was found in the middle cranial fossa emerging through the strands of dura covering the trigeminal nerve. The tumor was debulked. Pathology revealed adenoid cystic carcinoma. Investigation for primary site was negative. Intracranial involvement of adenoid cystic carcinoma may be due to direct extension; however, often it is related to perineural and perivascular spread of adenoid cystic carcinomas in the head and neck, arising from major and minor salivary glands as well as lacrimal glands. In cases like the one reported by the author, careful clinical and imaging studies of the salivary glands, lacrimal glands, oral cavity, pharynx, sinonasal cavities, and other parts of the upper respiratory airway should be done to search for a primary site. In the authors’ case, due to involvement of the mandibular and