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Cerebellopontine angle metastasis from papillary carcinoma of the thyroid: Case report and literature review
By Sung Tae Cha, M.D., Reza Jarrahy, M.D., Ronald A. Mathiesen, M.D., Richard Suh, M.D., Hrayr K. Shahinian, M.D.


Papillary thyroid carcinoma is the most common type of well-differentiated thyroid malignancy and typically has an excellent prognosis and a low incidence of distant metastasis. However, once metastasis has developed in a distant site, prognosis is markedly diminished. Brain metastases from papillary thyroid carcinoma are extremely rare. Currently, there are no established therapeutic guidelines for treating brain metastases from thyroid carcinoma.


We report on the case of a patient who presented with deteriorating neurological symptoms 3 years following resection of a thyroid papillary carcinoma. Magnetic resonance imaging identified a lesion of the cerebellopontine angle that encased the lower cranial nerves. The patient underwent a left retrosigmoid craniotomy with a 98% resection of the mass and received postoperative adjuvant radioiodine therapy, external beam radiation, and Gamma Knife radiosurgery.


The patient tolerated the procedure well and demonstrated significant progressive improvement in her neurological symptoms postoperatively. Following the multimodal approach to therapy, she remains symptom-free at three-year follow-up. Radiographic monitoring of the small tumor remnant reveals a decrease in size from the postoperative period.


This paper is the first formal case report of cerebellopontine angle metastasis from papillary thyroid carcinoma. Therapeutic protocols for brain metastases of papillary thyroid carcinoma are not firmly established. This case illustrates the unique event of a cerebellopontine angle metastasis from papillary thyroid carcinoma, which was successfully treated with a combination of surgical, chemical, and radiological modalities. This aggressive course of therapy has resulted in an excellent outcome in this instance.

distant metastases, papillary carcinoma, thyroid, cerebellopontine angle


Papillary thyroid carcinoma (PTC) is the most common type of well-differentiated thyroid carcinoma. It is classically described as having an indolent nature of progression and consequently a favorable prognosis. Metastasis usually occurs to regional lymph nodes, especially the cervical and mediastinal nodes. Locoregional lymph node metastases do not typically affect the overall prognosis of PTC [16,17], but distant metastases, most commonly to lung and bone and present in 1 to 7% of patients with PTC, alter survival dramatically [5,10,16,17,].

Metastases to the brain are extremely rare, constituting 0.1-5% of distant metastases of papillary carcinoma [4,5,10,17,28]. Only 71 cases of brain metastases have been reported in the English literature. To date, however, there have been no formal case reports of CP angle metastasis from PTC. Our patient's lesion was located anterior to the cerebellum and extended medially into the brainstem, encasing the lower cranial nerves. An aggressive multimodal approach to treatment was undertaken with excellent results. We review the literature of this rare clinical entity and discuss therapeutic modalities available for distant metastases of PTC.

Case report

The patient is a 78-year-old woman who initially presented in January 1994 with complaints of a neck mass. She was noted to have a palpable mass in the left lobe of the thyroid gland, and she eventually underwent a left thyroidectomy with an intraoperative fine needle aspiration from the right lobe. Histopathology confirmed papillary carcinoma in both specimens. This prompted a completion thyroidectomy and isthmusectomy, which was performed during the same hospitalization two days later. The patient was discharged home on postoperative day 5 after an uneventful recovery.

In March 1997, the patient returned with complaints of increasing dizziness, frequent falls and persistent headaches. She was noted to have bilateral horizontal gaze nystagmus and an ataxic gait on examination with the remainder of her detailed physical examination being normal. A magnetic resonance imaging (MRI) scan was then performed, demonstrating a 4.2 x 3.0 x 2.5 cm mass in the left CP angle with associated mild hydrocephalus. The patient was seen in surgical consultation and was scheduled for elective resection of the mass.

Over the next week, she developed intractable vomiting and an inability to walk for which she was admitted to the hospital. She was placed on intravenous Dexamethasone and underwent a cerebral angiogram with attempted preoperative embolization of the tumor. The angiogram revealed a left posterior fossa mass with its blood supply originating mainly from the left occipital artery. Additionally, arterial collaterals from the left cerebellar branches were present. Angiographic embolization was not technically possible.

She was taken to the operating room two days later. A left retrosigmoid craniotomy and microsurgical resection of the tumor was performed. Intraoperatively, the tumor was found to be immediately anterior to the cerebellum compressing it posteriorly. The tumor extended medially to the brainstem, encased the lower cranial nerves, and displaced the acousticofacial bundle superiorly. The anterior inferior cerebellar and vertebral arteries were identified and were dissected free from the tumor. Microdissection of the tumor from the skull base confirmed that the mass was adherent superiorly to the acousticofacial bundle. Facial nerve monitoring was performed during the entire dissection, and the tumor was dissected free without injury to the VIIth or VIIIth cranial nerves. The anterior and inferior borders of the mass also completely encased the ninth cranial nerve and partially involved the tenth and eleventh cranial nerves. The glossopharyngeal nerve was sacrificed but both the vagus and spinal accessory nerves were preserved. A 98% resection of the tumor was performed with a minute amount left at the junction of the cranial nerves and the brainstem as the tumor infiltrated the latter. Frozen section was diagnostic for metastatic tumor with epithelial cells, but more specific etiology could not be identified at that time.

Postoperatively, the patient was extubated in the operating room and was observed for 24 hours in the Surgical Intensive Care Unit. She remained free from neurologic deficits but complained of throat soreness that was partially attributed to the loss of the IXth cranial nerve. Her postoperative course was otherwise uncomplicated, and she received two weeks of inpatient rehabilitation prior to being discharged home.

Histopathology was diagnostic for metastatic carcinoma from a primary papillary carcinoma of the thyroid gland. Hemotoxlyn and eosin stained sections showed papillae with a fibrovascular core lined by tall cells with an abundant cytoplasm. The neoplastic cells showed positive immunohistochemistry staining for thyroglobulin and low molecular weight keratin. Psammoma bodies were rare.

One month later, the patient was evaluated for systemic metastasis with a thyroid I131 scan, which showed a small amount of residual thyroid tissue in the thyroid bed without evidence of intracranial residual tissue or systemic metastases. Serum thyroglobulin was elevated at 27 ug/l (Normal = < 0.1 ug/l), and the patient then underwent I131 radioiodine therapy with 147.1 mCi of I131 given orally.

A postoperative MRI was taken one month later and revealed a small residual tumor in the CP angle measuring 0.7 cm in maximal diameter. The patient then underwent adjuvant whole brain radiation therapy (WBRT) with parallel opposed 6 Megavolt photon beams to a dose of 44 Gy in 22 fractions over 31 calendar days at 2 Gy per fraction.

The patient was then referred for Gamma Knife radiosurgery in an effort to further reduce any residual tumor. She underwent this procedure in February 1998.

Subsequent serial MRI scans performed at 6-month intervals revealed progressive resolution of the mass. At 3-year follow-up, the patient is symptom free, her ataxia, headaches, and throat discomfort have resolved entirely, she is independent in her daily activities, and she exhibits no signs of dementia.


The incidence of thyroid carcinoma is estimated to be 1 in 25,000 population [28]. Papillary carcinoma is the most common type of well-differentiated carcinoma of the thyroid constituting 81.2% of all thyroid malignancies [16]. The typical clinical course of papillary carcinoma is indolent, and overall prognosis is usually excellent. Reported survival rates for non-metastatic lesions are 97.8% at 5 years and 94.9% at 10 years [16]. The peak prevalence is the third decade of life for both men and women, and the tumors behave differently in patients of different ages. In younger patients, the tumor is usually confined to the neck with or without spread to regional lymph nodes, but in older patients papillary carcinoma tends to be more aggressive and may give rise to distant metastases [6].

PTC usually metastasizes to local regional lymph nodes and extrathyroidal tissue. Spread to lymph nodes has been reported to range from 37% to 43% of patients with metastatic disease with cervical and upper mediastinal lymph nodes being the most common sites of regional lymph node invasion [16,17]. Long term prognosis, however, is not influenced by locoregional invasion [16,17].

The incidence of distant metastasis from PTC ranges from 1 to 7% [4,16,17]. McConahey et al. [17] and Hoie et al. [10] describe risk factors for distant metastasis of PTC. These include a male gender, advanced age, histologic grade, and extrathyroidal invasion at initial examination. Other risk factors reported by Dinneen et al. [6] are completeness of surgical resection of the primary tumor and nuclear DNA content. Lung is the most common site of distant metastasis, comprising 77% of all metastases followed by bone with rate of 20% [6,17]. Distant metastasis seriously affects survival rates. Dinneen et al. [6] report 5 and 10-year survival rates of 37% and 24%, respectively, for patients with metastatic PTC.

Metastases to the brain from PTC are extremely rare. Large retrospective series of papillary carcinoma report an intracranial metastasis frequency of 0.1-5% [4,10,17,28]. Only 71 references to brain metastases from PTC have been made in the medical literature [1,2,4,5,7,9-13,15,17,18,20,21,24,28]; of these only 13 have been presented as isolated case reports [1,2,9,11,12,13,15,18,20,21]. (Table 1) The intracranial distribution of lesions in these case reports is varied. Nine of these cases were supratentorial cerebral masses [2, 9,12,13,18,21,28], 2 were cerebellar [12,20], and 2 involved the pituitary gland [15]. In a retrospective review of 241 cases of PTC, Carcangiu [4] briefly noted one case of an intracranial metastasis specifically affecting the CP angle without elaborating upon the details of the case. This represents the only other direct reference at PTC CP angle metastasis aside from this case report.

There is no clearly defined treatment protocol for patients with intracranial metastatic lesions from PTC. Therapy must therefore be tailored to each individual patient. Such lesions could induce life-threatening complications such as increased intracranial pressure, cerebral edema, tonsillar herniation, or intracranial hemorrhage. Early recognition of the presence of an intracranial mass should prompt immediate attention and the institution of a treatment plan.

Other than the information obtained from the patient's history, physical exam, diagnostic studies, there are no definitive methods for diagnosing metastases of PTC to the brain. Only histologic examination provides confirmation of lesion. As demonstrated in our patient, a high serum thyroglobulin level may be helpful for detecting distant metastases or residual tumor in cases of well-differentiated thyroid carcinoma [7]. I131 may or may not accumulate into metastatic tumor tissue in cases of PTC [9,23]; therefore utilizing I131 to detect metastatic brain lesions from metastatic thyroid carcinoma may not be reliable. There are several theories as to why I131 accumulates poorly in metastatic thyroidal cancerous tissues [27]. It has been reported that metastatic PTC that does accumulate I131 carries a better prognosis, as these tumors tend to be more well-differentiated, less aggressive, and more susceptible to radioiodine therapy [6].

Several treatment modalities have been used in the limited number of cases of intracranial metastatic PTC, including surgical resection, external beam radiation, and radioiodine therapy. Results have been equivocal (Table 1). Although the presence of a brain metastsis is an overall negative prognostic indicator, Chiu [5] has found that surgical resection of brain metastases may help to significantly prolong survival in patients with differentiated thyroid carcinoma.

Due to our patient's otherwise excellent physical and mental health, collaboration between the patient and a multidisciplinary team of surgeons, neurologists, oncologists, and radiation oncologists resulted in the decision to pursue an aggressive course of therapy. Surgery was scheduled on a semi-urgent basis due to the patient's deteriorating neurological exam. The resection was incomplete due to the involvement of critical neurovascular structures in the posterior fossa, but did achieve the primary goal of halting the progressive decline in neurological function. Subsequent adjuvant therapy was based upon several factors. Discovery of residual thyroid tissue in the neck prompted radioiodine therapy targeted toward that remnant. As the likelihood of uptake by the remaining intracranial disease was unlikely [6,9,23,27], radiation therapy was implemented to address the possible presence of other intracranial metastases that might have been undetectable as well as the potential for the development of subsequent secondary sites of intracranial metastasis. Occurrence of both of these phenomena has been documented [5, 26]. WBRT has been commonly used in the management of patients with incomplete resection of brain tumors [5, 22]. Furthermore, several reports have documented improved tumor control with combined WBRT and radiosurgery in comparison to the use of either modality alone [8,14,19,25].

In the absence of established treatment protocols to followed in patients with intracranial metastasis from PTC, the practitioner is especially challenged when faced with this disease. Our experience has demonstrated the importance of specifically tailoring the treatment to the individual case. This patient underwent an aggressive multimodal approach to therapy and has had and excellent result. Although guidelines for clinical practice cannot be derived from a solitary report, this case exemplifies how surgery, radioiodine therapy, and radiation may be combined to yield prolonged and asymptomatic survival.


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Table 1. Distant metastases of papillary thyroid carcinoma to the brain
  Initial Dx of PTC
Initial therapy Interval from initial Dx Location Treatment Other DM Brain reactivity to scan Evolution After Surgery
Ibanez11 (1966) 42/F None 12 years Rt parietal Surgery Lung Bone N/A Immediatepostop death
Parker21 (1986) 31/M Rt radical neck dissec-tion & XRT 35 Years Rt fronto-parietal Surgery+ I 125 seeding Lung Bone Negative Alive and well
74/M TT 4 years Rt temporo-parietal Surgery None Negative Recurr in the brain after 4 months
Michie18* (1986) 47/M None None Lt occipital Surgery + XRT None N/A Recurr in the brain after 6 months
Goolen9 (1990) 52/F Radio-iodine ablation 4 years Rt frontal XRT None Negative Death after 6 months
Aihara1 (1991) 40/F SubTT & XRT 15 years Rt parietal Surgery Bone N/A No recurr for 1 year
Biswal2 (1994) 26/F Near TT & Radio-iodine therapy 8 weeks Rt frontal XRT Lung Negative Death after 4 months
Jyothir-mayi12 (1995) 31/M TT 19 years Rt cere-bellum Surgery Lung N/A Recurr in the ileum & bone after 14 months
59/M TT 2 years Rt frontal Surgery None N/A N/A
Pacak20 (1998) 82/F TT 8 years Lt cere-bellum Surgery Lung Bone Negative No recurr for 1 year
Kapusta13**(1999) 13/F TT & Radio-iodine therapy 30 years Rt Inf-forntal, Lt Parietal XRT Lung N/A N/A
Masiuki-ewicz15 (1999) 56/M TT & node disection & Radio-iodine therapy 5 Years Pituitary Radioiodine therapy Lung Focal positive Recurr in bone and lung after 1 year
35/F SubTT 20 years Rt cavernous -sinus & Pituitary Sterotactic radiosurgery

Lung, retoorbital & lower neck

Positive Recurr in submandi-bular & parapharygeal space after 5 months
This case 78/F TT 3 years Lt CP angle Surgery + Radioiodine therapy+ XRT+ Radio-surgery None Negative Alive and well for 3 years

Dx: Diagnosis, DM: Distant metastasis, PTC: papillary thyroid carcinoma, XRT: Radiotherapy, TT: Total thyroidectomy, CP: Cerbellopontine angle

* Cerebral metastases from occult papillary carcinoma. Brain surgery was performed before thyroidectomy.
** Two focus of metastasis in the brain has been developed in chronological order.