By Ali Mesiwala, MD

Craniopharyngiomas are typically a tumor of childhood, presenting with hypothalamic-pituitary dysfunction or visual deficits. They are occasionally found in adults, and cause similar problems. While these tumors are not malignant, they are difficult to cure. These tumors often densely adhere to normal tissue and, in some cases, cannot be completely removed without risk to vital structures. Surgical treatment, however, of these complex lesions can yield tremendous benefit to the patient. We present one such case.

(Scans of the patient's craniopharyngioma. Click on the images to enlarge.)

A 48-year-old man was emergently transferred to Cedars-Sinai Medical Center (CSMC) in early November 2004 because he had recently slipped into a coma and was found to have several brain masses causing significant distortion of the brain. The patient was 400 lbs and had been admitted to the hospital because he had become very lethargic. The patient was a resident in a nursing care facility who had originally become so obese that he was unable to care for himself. At the time he became a resident in this facility, he weighed 750 lbs. Over the course of the next two years, his weight progressively decreased from 750 to 400 lbs, while his mental status and level of consciousness gradually deteriorated. When he became comatose, he was rushed to a local emergency department and subsequently admitted to the hospital for a comprehensive work-up. A multitude of tests and imaging studies were performed that revealed an underlying pneumonia and metabolic abnormalities - none of which would explain his comatose state. An astute internist felt that his work-up was incomplete without an imaging study of the brain, and thus he ordered an MRI. Surprisingly, this demonstrated a collection of solid and cystic masses that occupied one-half of the intracranial space and extended from the pituitary region to the top of the skull. Concerned that this represented an atypical infection or unusual pituitary tumor, a neurosurgeon at the Maxine Dunitz Neurosurgical Institute was contacted regarding transferring the patient to Cedars-Sinai for further treatment.

Arrangements were made for the patient's transfer. Upon arrival in the evening, he was found to be completely unresponsive and comatose. He was immediately transferred to the intensive care unit, intubated, and placed on a ventilator. A review of the MRI of the brain which had been performed at the outside hospital led the attending neurosurgeon to believe that this mass was a craniopharyngioma and not an infection. He subsequently started the patient on high dose steroids and hyper-osmotic agents to decrease swelling within the brain. By morning the patient began to move spontaneously and stabilized. Meanwhile, preparations were made to take the patient to the operating room to remove as much of the mass as possible and to obtain tissue for a definitive diagnosis.

The patient's family was contacted and informed of recent events. They were startled to learn of his condition, as they had lost touch with him several years before. According to his brother, the patient had become progressively more reclusive and less like himself as his weight had increased over the years. As his personality changed, the patient's family had less and less contact with him, eventually losing all contact when he was admitted to a care facility. Further discussions with his family revealed that he had three brothers, all at least 6 feet in height and weighing 250 - 400 lbs. By all accounts, his progressive weight gain and personality changes were simultaneous. Understanding the seriousness of his condition, his family provided consent to proceed with his surgery.

The patient was taken to the operating room later that morning. He underwent a left craniotomy for resection of the mass. Intraoperative pathology was consistent with a craniopharyngioma. The cystic portions of the tumor were removed and the solid component along the skull base was decompressed. Normal anatomical landmarks were grossly distorted by the tumor; only the left carotid artery, left optic nerve, and left olfactory nerve could be identified. After several hours of microsurgical dissection, no further tumor could be safely removed. The patient tolerated the procedure well and was brought back to the intensive care unit for postoperative recovery and observation.

The following day the patient suddenly awoke. He motioned to his nurse to have the breathing tube removed and promptly sat up in bed and surveyed his room. The neurosurgical team was called to his bedside. He calmly said, "Hello, how are you?" The nurses, physicians, and other personnel felt as if a switch had been flipped, and the patient had been turned on. The next several hours were spent reviewing with the patient where he was, how he came to be at Cedars-Sinai, and what had transpired over the last few weeks. It became clear that the tumor had not only resulted in his coma, but had caused a profound retrograde amnesia. Medically stable and in surprisingly good spirits, he was transferred out of the ICU the next day.

The next five weeks saw the emergence of the patient as an individual. His medical problems were addressed and his nutritional and physical rehabilitation began. He gradually pieced together his life's story, remembering who he was, where he came from, and what had happened over the course of the last several years. He reestablished ties with his family and friends, and remained thankful for all that had transpired. His daily struggles with forgotten memories and family ties moved all who were involved with his care. His unwavering positive outlook and joi d' vivre inspired us all and reaffirmed for many why they became health professionals. By the time he began radiation therapy to treat the remaining solid tumor, his weight had decreased to 380 lbs and he was able to be transferred from his bed to a wheelchair for the first time in more than three years.

Daily radiation treatments did little to dampen his spirits or outlook. He continued with aggressive physical therapy and often wheeled himself around the hospital ward speaking with nurses and other patients. His positive nature and genuine good will made tangible differences on a daily basis. As his radiation treatment concluded, his physical therapy advanced. Within a week, nearly eight weeks after his operation, he was able to ambulate for the first time in years. Several days later, the patient was discharged to an outpatient rehabilitation setting.

Craniopharyngiomas are typically a benign, extra-axial, slow-growing tumor that usually involve the sella and suprasellar space. Despite their benign histologic appearance, these tumors can behave like a malignant tumor, causing rapid onset of severe symptoms. They are usually treated with surgery and/or radiation therapy.

Craniopharyngiomas occur equally in males and females. They have a bimodal age distribution, with a first peak occurring predominantly from age five - 10 years, and a second peak occurring from age 40 - 60 years. They account for approximately three to five percent of intracranial tumors and six to 10 percent of pediatric brain tumors. In children, craniopharyngiomas represent approximately 50 percent of all sellar and prechiasmatic tumors. They have a five-year survival rate of more than 80 percent when the tumor is treated with surgery and radiation. For tumors that cannot be completely removed, postoperative radiation has shown significant benefit. When treated with radiation, local control rates of up to 75 to 89 percent at 10 years have been reported, compared with a nearly 100% progression rate without radiation. Many patients suffer permanent endocrinologic deficits as a result of this tumor; this may be due to the destructive nature of the tumor, or the surgery and radiation required for its treatment. Depending on growth of the tumor, visual disturbances may or may not be reversible. Craniopharyngiomas are slow-growing and typically cause problems from their compression of nearby structures. Early intervention in both children and adults remains the standard of care and results in a significant reduction in symptoms and recurrence rate.

Patients with craniopharyngiomas suffer from a broad range of symptoms, ranging from none to endocrine, visual, or psychological disorders. Some patients have only mild headaches, while others have a progressively deteriorating course. The most common presenting symptoms include headache, nausea, vomiting, and visual disturbances. The most common visual problems include bitemporal hemianopsia, homonomous hemianopsia, and amblyopia. Other findings may include oculomotor palsies, scotomas, blindness, asymmetric acuity deficiencies, and optic atrophy. Hydrocephalus may result from a tumor that obstructs the third ventricle and papilledema frequently occurs. Seizures and chemical meningitis (from rupture of the tumor's cyst contents) may also result. Endocrine abnormalities include pituitary and adrenal dysfunction, diabetes insipidus, obesity, weakness, ataxia, and coma. Children may present with growth failure, obesity (33 - 50 percent), and hypothyroidism (67 percent), and precocious puberty. Poor school performance and psychological problems may also be early manifestations of the tumor's neurocognitive effects. Due to their anatomical location and associated endocrine dysfunction, a complete endocrine work-up is generally performed prior to surgical intervention; replacement of those hormones that are deficient often leads to dramatic improvements.

Craniopharyngiomas generally arise in the region of the sella turcica, suprasellar cistern, or third ventricle. These locations are along the course of the craniopharyngeal duct, the embryonal structure that gives rise to the hypothalamus, pituitary stalk, and pituitary gland. It is thought that craniopharyngiomas originate from epithelial rests derived from the Rathke's cleft, the embryonal precursor to these neuroendocrine structures. Tumors can occur anywhere along the course of this duct from the pharynx to the sella turcica and third ventricle. The etiology of this tumor is unknown, but two types exist.

The classic and most common type of craniopharyngioma is the adamantinomatous type. It has a cystic and solid appearance, with a wide variation in size. The cyst contains fluid that can vary in color, but typically resembles "crank case oil." The color is the result of suspended cholesterol crystals within the cyst fluid, which may be the result of intermittent hemorrhage within the cyst cavity. Extensive fibrosis and inflammation is observed with this type of tumor, resulting in dense adhesion to adjacent structures and vessels. In many cases the tumor completely encases critical blood vessels and structures. This accounts for the surgical difficulty in complete removal of craniopharyngiomas, and often accounts for the frequent recurrences of tumors.

The other type of craniopharyngioma, the papillary variant, generally consists of only a solid component, typically without calcifications. It is commonly located within the third ventricle and is encapsulated; it is thus more amenable to complete surgical resection.

Craniopharyngiomas remain a challenging tumor to treat. Their location and growth pattern cause a variety of symptoms and signs that may be missed by many patients and clinicians. Once diagnosed, however, surgical resection and radiation can lead to significant improvements and tumor control.