Symptomatic pituitary metastases

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Object. The diagnosis and treatment of metastasis to the pituitary gland can be difficult to determine. The goal of this study was to analyze the clinical presentation, treatment, and prognosis of patients who presented with symptomatic pituitary metastasis.

Methods. The cases of 36 patients with symptomatic pituitary metastases were reviewed. The most common primary cancers were breast (33%) and lung (36%). The presenting symptoms included diabetes insipidus, anterior pituitary insufficiency, and retroorbital pain. The overall median length of patient survival following diagnosis of pituitary metastasis was 180 days. In 20 patients (56%), symptoms stemming from pituitary metastasis were the first manifestation of illness. Local control of tumor was associated with significant improvement in survival times (p < 0.05) and amelioration of disabling symptoms including painful ophthalmoplegia and visual field deficits.

Conclusions. Aggressive treatment including both surgical decompression and radiation therapy improves the quality of life in patients suffering from symptomatic pituitary metastasis.

Metastatic spread of neoplasms to the pituitary gland is a relatively common finding in autopsy series of cancer patients.1,7,24,26 However, the majority of these patients were asymptomatic or succumbed without identification of pituitary metastasis because of overwhelming systemic complications of malignancy, including fatigue, weight loss, or central nervous system involvement, which may mask symptoms of hypopituitarism.4,18 With improving rates of survival in patients with cancer, there have been some case reports3,5,11,23 and published series2,10,12,20,22 in which pituitary metastases have been examined. Tumors that have metastasized to the pituitary gland are often difficult to differentiate from pituitary adenoma or other sellar-suprasellar tumors on radiographic studies.2,19,20 In addition, there has been little discussion regarding treatment options.2,10,12,20,22 The purpose of this paper is to analyze the clinical presentation, differential diagnosis, prognosis, and treatment of patients who presented with symptomatic pituitary metastasis.

Clinical Material and Methods

From 1973 through 1996, 36 patients with symptoms arising from tumor metastasis to the pituitary region were evaluated at the Mayo Clinic. We reviewed all 36 case histories and the patients' radiological and pathological studies. Fourteen of the cases have been the subject of a prior report.2

There were 18 men and 18 women in this group. The patients' ages at presentation ranged from 36 to 84 years (median 65 years). The primary malignancies and the duration from diagnosis of primary tumor to recognition of pituitary metastasis are listed in Table 1. The most common primary sources for metastasis were breast and lung cancer. In two patients, the primary malignancy was not identified. Comparisons of survival times between clinical groups were made with relation to patient age and gender, tumor grade and type, status of other metastases within 1 month after diagnosis of pituitary metastasis, local tumor control, and treatment.

TABLE 1

Primary malignancy and interval to pituitary metastasis in 36 patients

Primary TumorNo. of CasesInterval From Primary Diagnosis*
breast120–12 yrs (median 4.5 yrs) 
lung
 small cell50 
 nonsmall cell80–3 yrs 
prostate10 
hepatocellular10 
renal clear cell15 yrs 
colon adenocarcinoma13 yrs 
plasmacytoma16 yrs 
nasopharyngeal10 
squamous cell cancer12 yrs 
retroperitoneal sarcoma10 
pancreas13 mos† 
unknown20 
total36 

Zero signifies malignancy was diagnosed at the time of surgery or at workup for surgery.

Malignancy was diagnosed 3 months after surgery.

Treatment Options and Indications

Surgical exploration was performed in 21 cases in which there was significant mass effect and/or uncertainty surrounding the diagnosis. Transsphenoidal surgery was performed in 16 cases. In five cases, transcranial removal was performed because the tumor mass had significant extension in the suprasellar or cavernous sinus region. Radiation therapy was administered as adjunctive treatment in 17 cases. The dose of radiation ranged from 900 to 6000 cGy (median 3600 cGy). Adjunctive chemotherapy was administered in 19 cases. Two patients received no treatment. Local tumor control was defined as tumor regression that could be demonstrated by computerized tomography (CT) or magnetic resonance (MR) imaging and improvement in clinical symptoms other than hormonal imbalance.

Statistical Analysis

The overall duration of patient survival following diagnosis of pituitary lesions was estimated using the Kaplan—Meier method, and the clinical groups were compared using the log-rank test.

Results
Clinical Presentation

In the 36 patients with metastatic pituitary tumors, symptoms related to the pituitary metastasis were the first manifestation of malignancy in 20 cases. Eleven patients were found to have malignant tumor metastasis at the time of pituitary surgery and a diagnosis of pituitary malignancy during the preoperative medical workup was made in nine. Of 17 patients in whom the pituitary gland was the only site of metastatic spread at the time of presentation, 13 died of disseminated metastasis or other metastasis within 18 months. In the 19 patients who had other metastases at the time of presentation, the sites included bone in nine, lung in six, and liver in five. Nine patients had additional brain metastases.

The clinical presentation of patients is shown in Table 2. Diabetes insipidus, anterior pituitary insufficiency, and retroorbital pain were the most common presenting symptoms. The duration from the onset of symptoms to diagnosis ranged from 10 days to 3 years (median 3 months).

TABLE 2

Presenting symptoms and signs in 36 patients with symptomatic pituitary metastasis

PresentationNo. of Cases
diabetes insipidus22
anterior hypopituitarism17
 panhypopituitarism8
retroorbital pain/headache14
visual field deficit12
fatigue11
ophthalmoplegia9
nausea/anorexia/vomiting3
cognitive deficit4
facial numbness2

Diagnostic Evaluation

Computerized tomography and/or MR images were obtained in all patients (Figs. 1 and 2). Angiography was also performed in 13 patients. Plain skull radiographs were available in 23 patients. The radiographic findings are depicted in Table 3. On plain sellar radiographs, enlargement of the sella turcica was seen in five patients, and destruction or erosion of the floor or dorsum sellae in nine. On cerebral angiography, a tumor stain was noted in nine patients and mass effect was present in five. Computerized tomography scanning or MR imaging displayed homogeneously enhancing lesions in the sella in 22 patients and cavernous sinus invasion in seven. Pituitary stalk enlargement/enhancement was noted in 11 patients; this proved to be a common characteristic finding of pituitary—hypothalamic axis metastases. Hypothalamic and optic nerve invasions were noted in two cases. Suprasellar extension was observed in 14 cases.

Fig. 1.
Fig. 1.

Illustrative Case 1. Sagittal (left) and axial (right) gadolinium-enhanced MR images obtained in a 47-year-old man with unknown primary and pituitary adenocarcinoma who presented with a 2-month history of retroorbital pain, bitemporal visual field defects, and bilateral ophthalmoplegia. The images show a homogeneously enhancing lesion in the sella and suprasellar areas with bilateral cavernous sinus invasion. The patient underwent transsphenoidal tumor debulking, followed by external-beam radiation therapy (3750 cGy). Although the patient's preoperative symptoms improved, he died 2 months later from disseminated metastases.

Fig. 2.
Fig. 2.

Illustrative Case 2. Gadolinium-enhanced coronal (left) and noncontrast-enhanced sagittal (right) MR images obtained in a 43-year-old woman with metastatic colon adenocarcinoma who presented with headache, diabetes insipidus, visual field defects, and facial numbness. The images demonstrate an enhancing mass in the sella that extends upward to the hypothalamic and infundibular regions along the pituitary stalk. Serum cortisol and thyroxin levels were low. The patient underwent transsphenoidal decompression followed by focal radiation therapy (3600 cGy). Although her headache and vision improved temporarily, she died 9 months later from disseminated disease.

TABLE 3

Radiographic characteristics in 36 patients with symptomatic pituitary metastasis

CharacteristicNo. of Cases
plain skull radiograph (23 cases)
 sellar destruction/erosion9
 sellar enlargement, ballooning5
 deformity of sella3
 sphenoid sinus abnormality3
 sellar calcification1
 frontal base erosion1
 normal6
cerebral angiogram (13 cases)
 tumor stain, blush9
 mass effect5
 normal3
CT/MR imaging (35 cases)
 homogeneous enhancing sellar mass22
 suprasellar enhancing mass14
 stalk enhancement, enlargement11
 cavernous sinus invasion7
 mass in sphenoid sinus3
 hypothalamus, optic nerve invasion2
 other sellar abnormality4
 negative findings1
 other brain lesions3

All patients underwent a pretreatment endocrinological evaluation. The most common finding was posterior pituitary dysfunction, which was identified in 22 cases. Abnormal anterior pituitary function included low thyroxine levels in 12, low cortisol levels in 11, high prolactin levels in four, and low testosterone levels in four patients. Panhypopituitarism was noted in eight patients.

Treatment Outcome

A Kaplan—Meier survival curve extending from the time of diagnosis is depicted in Fig. 3. The mean length of survival was 180 days, whereas the longest survival time was 5 years. Because of the small numbers in each group, no statistically significant data could be determined regarding treatment options. Thirteen patients survived longer than 1 year and this appeared to be more common in those treated with surgery (seven cases). This group consisted primarily of patients who harbored slow-growing malignancies that included breast cancer in six patients, grade 2 colon adenocarcinoma in one, grade 2 renal cell cancer in one, plasmacytoma in one, and lung cancer in four. Although it is not statistically significant, among all patients older than 65 years, those with metastasis from small-cell lung cancer and those who had a short duration (< 1 year) from initial diagnosis to pituitary metastasis tended to have poorer outcomes. The completeness of surgical resection and the radiation doses did not alter the patients' survival time. Local control of tumor, which was achieved in 14 cases, improved the length of survival significantly (p < 0.05) (Fig. 4). Good local control was achieved in nine of 16 patients who underwent transsphenoidal surgery. In Table 4 symptom outcome is detailed. Surgical treatment resulted in improvement in pain and visual field deficits. Improvement in cranial nerve palsies was less common and hormonal dysfunction present before treatment did not improve.

Fig. 3.
Fig. 3.

Kaplan—Meier survival life table of patients with tumors that have metastasized to the pituitary gland, following diagnosis. Three patients with pituitary metastasis survived for longer than 5 years. Expected survival (E) for a matched United States population is shown by the dotted line. O = observed life expectancy in patients with pituitary metastasis.

Fig. 4.
Fig. 4.

Graph displaying a comparison of survival duration between patients with and without local tumor control. A statistically significant difference is shown.

TABLE 4

Clinical improvement after treatment in 36 patients with symptomatic pituitary metastasis

No. of Patients*
Clinical FindingsTotalImprovedUnchangedWorse/New Deficit
hormonal abnormality31 (14) 0 28 (13) 3 (2)
pain14 (7) 13 (7) 1 (0) 0
visual field defect12 (7) 9 (6) 3 (1) 0
ophthalmoplegia9 (4) 4 (3) 4 (1) 1 (1)
facial numbness2 (2) 0 2 (2) 0

Numbers in parentheses indicate the number of patients who underwent transsphenoidal surgery.

Complications following transsphenoidal surgery included cerebrospinal fluid leak in two patients, carcinomatous meningitis in one, and worsening of endocrine function in three. After transcranial surgery, two patients developed persistent focal epilepsy that was difficult to control. Subsequently, pulmonary emboli developed in one of these patients and a significant subdural hygroma in the other patient. These two patients died as a result of these complications.

The causes of death in this group of patients included disseminated metastasis in 20, brain metastasis in five, pulmonary emboli in four (postsurgical complication in three), pituitary mass growth in one, meningeal carcinomatosis in one, and primary malignancy growth in four cases.

Discussion
Clinicopathological Review

Metastasis of a malignant tumor to the pituitary gland is a relatively common finding in autopsy or hypophysectomy specimens obtained in cancer patients. The reported incidence of pituitary metastasis is 1 to 26.6%.1,7,14,24,25 Cases of breast carcinoma have an unusually high incidence of pituitary metastasis, ranging from 9 to 29%.1,7,16 The reason for the high incidence of breast cancer that has metastasized to the pituitary is not well known. It has been hypothesized that an environment rich in hormones, especially prolactin, may provide a preferred environment for the breast cancer cells that enhances their proliferation.6,16 In patients who have leukemia or lymphoma, the incidence of pituitary involvement is reported to range from 2 to 46%.17 Pituitary metastasis is typically seen in cases in which there is widespread metastasis (more than five locations) or in cases in which there is bone metastasis.8,14,16,18

There has been some controversy regarding the most common location of metastasis within the pituitary gland. Because the posterior pituitary lobe is alleged to receive direct blood flow from the systemic circulation, it has been reported that tumor metastasis is more commonly found in the posterior lobe than in the anterior lobe, which is secondarily supplied by the pituitary portal vasculature. The frequent clinical presentation of diabetes insipidus may be explained by this hypothesis. Anterior pituitary insufficiency has been attributed to pituitary damage due to vascular occlusion by tumor or due to direct tumor invasion or compression of the anterior lobe.18,26 In a review by Max and colleagues,18 metastases identified in pathological pituitary specimens were located in the posterior lobe alone in 52%, in the anterior lobe alone in 21%, and in both lobes in 27%. However, a more recent study of breast cancer cases conducted by Marin and colleagues16 demonstrated that the more common metastatic location was the anterior gland. Metastasis to the anterior lobe has been thought to occur through the pituitary portal vessels. It has been speculated that there are four basic metastatic pathways to the pituitary gland: 1) direct blood-borne metastasis to the posterior lobe with subsequent expansion; 2) blood-borne metastasis to the pituitary stalk with growth into the anterior and posterior pituitary lobes; 3) blood-borne metastasis to the clivus, dorsum sellae, or cavernous sinus, which then spreads into the pituitary gland; and 4) leptomeningeal spread with involvement of the pituitary capsule.18,22,25

Although there have been sporadic case reports,3,11,23 cases of symptomatic pituitary metastasis are relatively rare.2,12,20 According to an autopsy report by Teears and Silverman,26 only 6.8% of cases were symptomatic. Branch and Laws2 reported that approximately 1% of pituitary lesions treated by transsphenoidal surgery were metastatic tumors. In one surgical series, there were two patients with cancer that had metastasized to pituitary adenomas.21 In the review by Max and colleagues18 of 178 reported cases of pituitary metastases, only 28 cases (16%) were symptomatic. As stated by Bynke and Ottosson,4 these metastases are often seen in patients with terminal malignancy who present with malaise, weight loss, generalized pain, central nervous system involvement, or treatment-associated symptoms. Thus, the symptoms of pituitary insufficiency can be masked. In addition, if the anterior pituitary dysfunction is severe, diabetes insipidus may also be concealed by reduced mineral corticoid function.4,10 Accordingly, there may be a significant number of patients with primary cancers whose pituitary insufficiency is not appropriately diagnosed. With the advent of adjunctive treatments for patients suffering from metastatic disease, survival periods have improved. Therefore, it is becoming clinically more relevant to consider the possibility that tumor has metastasized to the pituitary gland; this should be done early so that symptoms from these lesions may be improved by appropriate endocrine replacement.

Clinical Features and Diagnostic Aspects

Diabetes insipidus is the most common clinical presentation of metastasis in these patients.10,13 In the Mayo Clinic series of patients who had pituitary tumors associated with visual symptoms,9 only 1% of those who had a pituitary adenoma presented with diabetes insipidus. In 14 to 20% of adult patients who present with spontaneous diabetes insipidus, the disease is caused by metastatic pituitary tumors.10,13 Accordingly, when a patient first presents with a pituitary mass and diabetes insipidus, the initial differential diagnosis should include metastatic tumor in addition to craniopharyngioma, germinoma, histiocytosis X, or pituitary adenoma. Because pituitary adenomas rarely invade the cavernous sinus, cranial nerve deficits alone are not pathognomonic. However, increasing pain and a rapid progression of symptoms strongly suggest the presence of metastatic disease.11,12 If a patient presents with diabetes insipidus and painful ophthalmoplegia with rapid progression, malignancy should be strongly suspected.12,18 A history of malignancy or concurrent metastatic disease is, of course, very important diagnostic information. However, even when patients with breast carcinoma are found to have a pituitary lesion, there is a significant chance (16%) that it is a pituitary adenoma or some other pituitary lesion.16 Furthermore, as our review indicates, there are many cases in which the first manifestation of malignancy is a metastatic tumor deposit in the pituitary gland. Therefore, a history of malignancy is not an absolute diagnostic necessity.

Because pituitary adenomas also present with invasion into surrounding structures, radiological diagnosis has been relatively less pathognomonic.2,20 Enlargement or enhancement of the pituitary stalk with a pituitary mass detected by CT or MR imaging is the most characteristic feature. The degree of destruction of surrounding structures and the rapidity of radiologically confirmed progression can be possible clues indicating malignancy.19,22

Treatment and Prognosis

There were no significant differences in survival times between the surgical and nonsurgical treatment groups. Although the completeness of surgical resection or radiation dosage did not affect survival times, they did alter local tumor control and, subsequently, resulted in improved symptom outcome. Accordingly, the role of direct treatment of pituitary metastases should be focused on symptomatic relief.12,23 Our current indications for surgery in the treatment of metastatic pituitary tumors include: symptomatic mass lesions, especially those causing pain and visual deficits, and lesions with an uncertain diagnosis. Transsphenoidal surgical decompression and radiation treatment were well tolerated by our patients and were associated with minimal complications and a decrease in patient morbidity rates. Most impressively, aggressive treatment led to a significant improvement in pain and visual field deficits. Furthermore, in selected cases of metastatic breast or prostate cancer, a transsphenoidal hypophysectomy may be beneficial in attenuating metastatic bone pain.15

Acknowledgments

The authors are indebted to W. Michael O'Fallon, Ph.D., and Ms. Crowson of the Biostatistics Department at the Mayo Clinic for their assistance in performing the statistical analysis.

References

  • 1.

    Abrams HLSpiro RGoldstein N: Metastases in carcinoma. Analysis of 1000 autopsied cases. Cancer 3:74851950Cancer 3:

  • 2.

    Branch CL JrLaws ER Jr: Metastatic tumors of the sella turcica masquerading as primary pituitary tumors. J Clin Endocrinol Metab 65:4694741987J Clin Endocrinol Metab 65:

  • 3.

    Buonaguidi RFerdeghini MFaggionato Fet al: Intrasellar metastasis mimicking a pituitary adenoma. Surg Neurol 20:3733781983Surg Neurol 20:

  • 4.

    Bynke OOttosson AM: Is metastatic breast carcinoma in the pituitary a concealed manifestation? Lancet 2:133613371982Lancet 2:

  • 5.

    Cox EV III: Chiasmal compression from metastatic cancer to the pituitary gland. Surg Neurol 11:49501979Cox EV III: Chiasmal compression from metastatic cancer to the pituitary gland. Surg Neurol 11:

  • 6.

    de la Monte SMHutchins GMMoore GW: Endocrine organ metastases from breast carcinoma. Am J Pathol 114:1311361984Am J Pathol 114:

  • 7.

    Gurling KJScott GBDBaron DN: Metastases in pituitary tissue removed at hypophysectomy in women with mammary carcinoma. Br J Cancer 11:5195231957Br J Cancer 11:

  • 8.

    Hägerstrand ISchönebeck J: Metastases to the pituitary gland. Acta Pathol Microbiol Scand 75:64701969Acta Pathol Microbiol Scand 75:

  • 9.

    Hollenhorst RWYounge BR: Ocular manifestations produced by adenomas of the pituitary gland: analysis of 1000 casesKohler PORoss GT (eds): Diagnosis and Treatment of Pituitary Tumors. Amsterdam: Excerpta Medica19735368Diagnosis and Treatment of Pituitary Tumors.

  • 10.

    Houck WAOlson KBHorton J: Clinical features of tumor metastasis to the pituitary. Cancer 26:6566591970Cancer 26:

  • 11.

    Juneau PSchoene WCBlack P: Malignant tumors in the pituitary gland. Arch Neurol 49:5555581992Arch Neurol 49:

  • 12.

    Kattah JCSilgals RMManz Het al: Presentation and management of parasellar and suprasellar metastatic mass lesions. J Neurol Neurosurg Psychiatry 48:44491985J Neurol Neurosurg Psychiatry 48:

  • 13.

    Kimmel DWO'Neill BP: Systemic cancer presenting as diabetes insipidus. Clinical and radiographic features of 11 patients with a review of metastatic-induced diabetes insipidus. Cancer 52:235523581983Cancer 52:

  • 14.

    Kovacs K: Metastatic cancer of the pituitary gland. Oncology 27:5335421973Kovacs K: Metastatic cancer of the pituitary gland. Oncology 27:

  • 15.

    Leclercq TAKnisley RED'Amico RPet al: Evaluation of transsphenoidal hypophysectomy in the management of metastatic breast carcinoma. Hormone responsiveness and the interval between initial diagnosis and hypophysectomy provide the most reliable predictors of success. R I Med J 67:4374401984R I Med J 67:

  • 16.

    Marin FKovacs KTScheithauer BWet al: The pituitary gland in patients with breast carcinoma: a histologic and immunocytochemical study of 125 cases. Mayo Clin Proc 67:9499561992Mayo Clin Proc 67:

  • 17.

    Masse SRWolk RWConklin RH: Peripituitary gland involvement in acute leukemia in adults. Arch Pathol 96:1411421973Arch Pathol 96:

  • 18.

    Max MBDeck MDFRottenberg DA: Pituitary metastasis: incidence in cancer patients and clinical differentiation from pituitary adenoma. Neurology 31:99810021981Neurology 31:

  • 19.

    Mayr NAYuh WTCMuhonen MGet al: Pituitary metatases: MR findings. J Comput Assist Tomogr 17:4324371993J Comput Assist Tomogr 17:

  • 20.

    McCormick PCPost KDKandji ADet al: Metastatic carcinoma to the pituitary gland. Br J Neurosurg 3:71801989Br J Neurosurg 3:

  • 21.

    Molinatti PAScheithauer BWRandall RVet al: Metastasis to pituitary adenoma. Arch Pathol Lab Med 109:2872891985Arch Pathol Lab Med 109:

  • 22.

    Morita AFukushima TMiyazaki Set al: [Clinical features, diagnosis, and treatment of metastatic pituitary tumors. Report of four cases.] Neurol Med Chir 27:4364421987 (Jpn)Neurol Med Chir 27:

  • 23.

    Nelson PBRobinson AGMartinez AJ: Metastatic tumor of the pituitary gland. Neurosurgery 21:9419441987Neurosurgery 21:

  • 24.

    Roessmann UKaufman BFriede RL: Metastatic lesions in the sella turcica and pituitary gland. Cancer 25:4784801970Cancer 25:

  • 25.

    Takakura KSano KHojo Set al: Metastatic Tumors of the Central Nervous System. Tokyo: Igaku-Shoin1982101104Metastatic Tumors of the Central Nervous System.

  • 26.

    Teears RJSilverman EM: Clinicopathologic review of 88 cases of carcinoma metastatic to the pituitary gland. Cancer 36:2162201975Cancer 36:

Article Information

Address reprint requests to: Fredric B. Meyer, M.D., Department of Neurological Surgery, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905.

© AANS, except where prohibited by US copyright law."

Headings

Figures

  • View in gallery

    Illustrative Case 1. Sagittal (left) and axial (right) gadolinium-enhanced MR images obtained in a 47-year-old man with unknown primary and pituitary adenocarcinoma who presented with a 2-month history of retroorbital pain, bitemporal visual field defects, and bilateral ophthalmoplegia. The images show a homogeneously enhancing lesion in the sella and suprasellar areas with bilateral cavernous sinus invasion. The patient underwent transsphenoidal tumor debulking, followed by external-beam radiation therapy (3750 cGy). Although the patient's preoperative symptoms improved, he died 2 months later from disseminated metastases.

  • View in gallery

    Illustrative Case 2. Gadolinium-enhanced coronal (left) and noncontrast-enhanced sagittal (right) MR images obtained in a 43-year-old woman with metastatic colon adenocarcinoma who presented with headache, diabetes insipidus, visual field defects, and facial numbness. The images demonstrate an enhancing mass in the sella that extends upward to the hypothalamic and infundibular regions along the pituitary stalk. Serum cortisol and thyroxin levels were low. The patient underwent transsphenoidal decompression followed by focal radiation therapy (3600 cGy). Although her headache and vision improved temporarily, she died 9 months later from disseminated disease.

  • View in gallery

    Kaplan—Meier survival life table of patients with tumors that have metastasized to the pituitary gland, following diagnosis. Three patients with pituitary metastasis survived for longer than 5 years. Expected survival (E) for a matched United States population is shown by the dotted line. O = observed life expectancy in patients with pituitary metastasis.

  • View in gallery

    Graph displaying a comparison of survival duration between patients with and without local tumor control. A statistically significant difference is shown.

References

1.

Abrams HLSpiro RGoldstein N: Metastases in carcinoma. Analysis of 1000 autopsied cases. Cancer 3:74851950Cancer 3:

2.

Branch CL JrLaws ER Jr: Metastatic tumors of the sella turcica masquerading as primary pituitary tumors. J Clin Endocrinol Metab 65:4694741987J Clin Endocrinol Metab 65:

3.

Buonaguidi RFerdeghini MFaggionato Fet al: Intrasellar metastasis mimicking a pituitary adenoma. Surg Neurol 20:3733781983Surg Neurol 20:

4.

Bynke OOttosson AM: Is metastatic breast carcinoma in the pituitary a concealed manifestation? Lancet 2:133613371982Lancet 2:

5.

Cox EV III: Chiasmal compression from metastatic cancer to the pituitary gland. Surg Neurol 11:49501979Cox EV III: Chiasmal compression from metastatic cancer to the pituitary gland. Surg Neurol 11:

6.

de la Monte SMHutchins GMMoore GW: Endocrine organ metastases from breast carcinoma. Am J Pathol 114:1311361984Am J Pathol 114:

7.

Gurling KJScott GBDBaron DN: Metastases in pituitary tissue removed at hypophysectomy in women with mammary carcinoma. Br J Cancer 11:5195231957Br J Cancer 11:

8.

Hägerstrand ISchönebeck J: Metastases to the pituitary gland. Acta Pathol Microbiol Scand 75:64701969Acta Pathol Microbiol Scand 75:

9.

Hollenhorst RWYounge BR: Ocular manifestations produced by adenomas of the pituitary gland: analysis of 1000 casesKohler PORoss GT (eds): Diagnosis and Treatment of Pituitary Tumors. Amsterdam: Excerpta Medica19735368Diagnosis and Treatment of Pituitary Tumors.

10.

Houck WAOlson KBHorton J: Clinical features of tumor metastasis to the pituitary. Cancer 26:6566591970Cancer 26:

11.

Juneau PSchoene WCBlack P: Malignant tumors in the pituitary gland. Arch Neurol 49:5555581992Arch Neurol 49:

12.

Kattah JCSilgals RMManz Het al: Presentation and management of parasellar and suprasellar metastatic mass lesions. J Neurol Neurosurg Psychiatry 48:44491985J Neurol Neurosurg Psychiatry 48:

13.

Kimmel DWO'Neill BP: Systemic cancer presenting as diabetes insipidus. Clinical and radiographic features of 11 patients with a review of metastatic-induced diabetes insipidus. Cancer 52:235523581983Cancer 52:

14.

Kovacs K: Metastatic cancer of the pituitary gland. Oncology 27:5335421973Kovacs K: Metastatic cancer of the pituitary gland. Oncology 27:

15.

Leclercq TAKnisley RED'Amico RPet al: Evaluation of transsphenoidal hypophysectomy in the management of metastatic breast carcinoma. Hormone responsiveness and the interval between initial diagnosis and hypophysectomy provide the most reliable predictors of success. R I Med J 67:4374401984R I Med J 67:

16.

Marin FKovacs KTScheithauer BWet al: The pituitary gland in patients with breast carcinoma: a histologic and immunocytochemical study of 125 cases. Mayo Clin Proc 67:9499561992Mayo Clin Proc 67:

17.

Masse SRWolk RWConklin RH: Peripituitary gland involvement in acute leukemia in adults. Arch Pathol 96:1411421973Arch Pathol 96:

18.

Max MBDeck MDFRottenberg DA: Pituitary metastasis: incidence in cancer patients and clinical differentiation from pituitary adenoma. Neurology 31:99810021981Neurology 31:

19.

Mayr NAYuh WTCMuhonen MGet al: Pituitary metatases: MR findings. J Comput Assist Tomogr 17:4324371993J Comput Assist Tomogr 17:

20.

McCormick PCPost KDKandji ADet al: Metastatic carcinoma to the pituitary gland. Br J Neurosurg 3:71801989Br J Neurosurg 3:

21.

Molinatti PAScheithauer BWRandall RVet al: Metastasis to pituitary adenoma. Arch Pathol Lab Med 109:2872891985Arch Pathol Lab Med 109:

22.

Morita AFukushima TMiyazaki Set al: [Clinical features, diagnosis, and treatment of metastatic pituitary tumors. Report of four cases.] Neurol Med Chir 27:4364421987 (Jpn)Neurol Med Chir 27:

23.

Nelson PBRobinson AGMartinez AJ: Metastatic tumor of the pituitary gland. Neurosurgery 21:9419441987Neurosurgery 21:

24.

Roessmann UKaufman BFriede RL: Metastatic lesions in the sella turcica and pituitary gland. Cancer 25:4784801970Cancer 25:

25.

Takakura KSano KHojo Set al: Metastatic Tumors of the Central Nervous System. Tokyo: Igaku-Shoin1982101104Metastatic Tumors of the Central Nervous System.

26.

Teears RJSilverman EM: Clinicopathologic review of 88 cases of carcinoma metastatic to the pituitary gland. Cancer 36:2162201975Cancer 36:

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