metastatic lesions comprise approximately 1% of the tumors in the sellar / parasellar ( sps ) area for which patients undergo transsphenoidal surgery ( tss ) [ 1 , 2 ] ; however , it has been reported in autopsy series that the rate of metastasis to these areas could be as high as 28% . breast and lung cancer are the two most common types of malignant tumors that metastasize to the sps region , with respective rates of 40% and 33% . metastases of prostate , renal cell , gastrointestinal , thyroid [ 8 , 9 ] , and pancreatic cancers , and lymphoma , leukemia , melanoma , and plasmocytoma   have also been reported . despite the advancement in the imaging modalities , tumors that have metastasized to the sps areas may still be difficult to differentiate from pituitary adenoma on radiographic studies [ 2 , 14 , 15 ] . thickening of the pituitary stalk and invasion of the cavernous sinus may be suggestive of such lesions , but invasion of the cavernous sinus may commonly occur with pituitary adenomas . this distinction is also clinically challenging , although there are very few symptoms that suggest a metastatic lesion . management options are multimodal and vary depending on whether a primary source is known or on the likely differential diagnoses based on the clinical and radiological findings . multimodal options include radiation therapy , chemotherapy , and/or surgery [ 16 , 17 ] , although the tumor invasiveness renders surgical resection limited . although surgical series have not shown any survival benefits , the patient 's quality of life may be improved [ 10 , 14 ] . in this paper , we review the clinical , endocrine , and radiological features of the metastatic sps tumors with currently accepted therapeutic options based on the pertinent literature . in addition , we report six cases from our institution and discuss their management with long - term clinical outcome . a systematic review of the literature was performed using pubmed and the bibliographies of reviewed articles . the medical records of six patients admitted to the university of utah health sciences center between 2001 and 2011 were reviewed retrospectively . clinical presentation , radiographic studies , treatment , histopathological confirmation , outcome , and prognosis were recorded ( table 1 ) . a 77-year - old man with known prostate cancer presented with a four - month history of left retro - orbital pain followed by left eye ptosis . at presentation , he had complete left third nerve palsy . his visual acuity was intact in both eyes , with full visual fields to confrontation . brain magnetic resonance ( mr ) imaging ( figure 1 ) showed a heterogeneously enhancing mass lesion that measured 29  17  29  mm involving the sella , with invasion of the left cavernous sinus and the upper clivus . the lesion extended to the inferior orbital fissure and was centered in the sella turcica and the cavernous sinus . he subsequently underwent chemotherapy and focused radiation to the sellar region and was noted to have stable neurological examination findings two months after surgery , with no change in his ophthalmoplegia . an 82-year - old woman with known history of breast cancer presented with several weeks ' complaint of progressive left - sided hearing loss as well as facial pain and numbness in the first and the second divisions of the trigeminal nerve , respectively . on neurological examination , left - sided hearing loss and facial numbness along the v1 and v2 distributions were confirmed . mr imaging showed evidence of a heterogeneously enhancing mass in the left petrous apex that extended to involve meckel 's cave , the lateral cavernous sinus , and the internal auditory canal ( figure 2 ) . she was discharged home on postoperative day three in stable condition for followup with oncology . a 79-year - old man with known history of prostate cancer presented with several weeks ' history of progressively worsening double vision and eventual right eye ptosis . mr imaging disclosed an enhancing soft tissue mass involving the clivus , pituitary fossa , cavernous sinus , and posterior nasal cavity ( figure 3 ) that surrounded both internal carotid arteries in the cavernous sinuses . an endonasal transsphenoidal approach to the sphenoid sinus was carried out to obtain a biopsy of the lesion .   a histopathological diagnosis of metastatic melanoma was made , and evaluation was undertaken by the oncology team . ) a 21-year - old man with a remote history of osteosarcoma and newly diagnosed metastatic renal cell carcinoma had complaints of worsening vision and facial pain . because there was a discrepancy in the pupillary size between his eyes , he underwent a computed tomography ( ct ) scan of the head , followed by craniofacial mr imaging , which revealed an enhancing mass in the right sphenoid sinus with adjacent extension . on neurological examination , he was noted to have complete hemifacial numbness and horner 's syndrome on the right side . mr imaging of the face demonstrated a homogeneously contrast - enhancing lesion centered within the right sphenoid sinus measuring 33  20  27  mm ( figure 4 ) . the lesion extended into the carotid canal , pterygopalatine fossa , and optic nerve canal with destruction of the vidian canal and foramen rotundum on the right . a 42-year - old woman with several weeks of frontal headaches initially presumed to be secondary to a sinus infection underwent mr imaging after antibiotic medications failed to alleviate her symptoms . brain mr imaging demonstrated a lobulated , 25  20-mm sellar and suprasellar lesion with extension into the right cavernous sinus and encasement of the right internal carotid artery . this lesion was isointense on t1- and t2-weighted images and heterogeneously enhancing with gadolinium administration . a ct scan was consistent with a lytic lesion involving the central skull base extending laterally and posteriorly to involve the bilateral medial sphenoid wings and the clivus , respectively . histopathologic evaluation was consistent with a diagnosis of diffuse large b - cell lymphoma ( figure 5 ) . a 53-year - old woman presented with a known diagnosis of breast cancer and a one - year history of worsening left eye vision with a more precipitous decline in the last month . mr imaging of the brain demonstrated a skull base lesion involving the left sphenoid bone , the anterior clinoidal process , and the cavernous sinus .   on neurological assessment , the patient was noted to have an acutely diminished visual acuity in her left eye to a level of finger counting with left temporal visual field cut . mr imaging ( not shown ) showed a homogenously contrast - enhancing lesion of the skull base involving the greater sphenoid wing and the anterior clinoidal process with encasement of the optic nerve on the left . a left frontotemporal craniotomy was performed for biopsy of the lesion and to decompress the optic nerve and the cavernous sinus with a subtotal resection . one year after surgery , her neurological findings were unchanged , and her systemic disease was under control . neoplasms originating from a multitude of sites have been reported to metastasize to the sps region . breast and lung cancer account for approximately two - thirds of sps metastases , being the most common sources in women and men , respectively , [ 11 , 1821 ] . histological examinations of the tissue samples obtained during palliative hypophysectomy performed in patients with end - stage breast cancer and from autopsy series have documented metastasis to the sps region in 6% to 29% of cases [ 3 , 2225 ] . one hypothesis put forth to explain this prevalence is that the prolactin - rich environment of the pituitary enhances the proliferation of breast tumor cells . after carcinoma of breast and lung , lymphoma and prostate cancer have been reported to be the most common sources of metastasis to sps region . liver , renal cell , colon , and thyroid cancers and melanoma are rare sources of distant metastases to this region . the relatively rarer occurrence of our other cases , prostate , melanoma , renal cell , and lymphoma , is consistent with the literature . most cases are found in the sixth or the seventh decade of life as a part of a generalized metastatic spread , commonly associated with multiple , particularly osseous metastases [ 18 , 20 ] ; however , metastases can occur in young patients . the age of presentation ranged from 21 to 82 years in our small series , with an average age of 60 years . very occasionally , these lesions are the first manifestation of an occult cancer or the only site of metastasis [ 14 , 20 ] . thus , in a patient without any prior history of cancer , an sps lesion can not be assumed to be an adenoma , just as in a patient with a known primary cancer , it is not always metastatic . clinically , metastasis is generally suspected in patients with rapid onset and progressive symptoms , irrespective of a history of malignancy . the possible metastatic pathways to the pituitary and parasellar region include direct blood - borne metastasis to the posterior pituitary lobe , pituitary stalk , clivus , dorsum sellae , or cavernous sinus or leptomeningeal spread with involvement of the pituitary capsule [ 10 , 26 , 27 ] . there has been some controversy regarding the most common location of metastasis within the pituitary gland . authors of early series have reported that the majority of pituitary metastasis occurs in the posterior pituitary , but some dispute this claim . teears and silverman   reported that 57% of the lesions localized to the posterior pituitary alone , 13% to the anterior pituitary alone , 12% to both lobes , and the remaining 18% to the capsule or stalk . they hypothesized that the posterior pituitary , by receiving direct arterial supply , is more likely to develop metastases than the adenohypophysis , which receives its blood supply from the hypophyseal portal system . the posterior lobe has a larger area of contact with the adjacent dura , which may be another contributing factor [ 4 , 18 ] . metastatic inoculation in the anterior lobe is usually the result of contiguous spread from the posterior lobe . these may be isolated , such as diplopia or ptosis , with the third ( oculomotor ) and the sixth ( abducens ) nerves being the most commonly involved , followed by the fourth ( trochlear ) nerve [ 14 , 2931 ] , or they may appear in a constellation of symptoms characterized by unilateral , rapidly progressive ophthalmoplegia with retroorbital pain . this latter presentation is the usual presentation of the cavernous sinus syndrome , also known as parasellar syndrome . if the branches of the trigeminal nerve are affected , alteration in the facial sensation , facial pain , or dysesthesia occurs . headache has been reported as a rather common symptom , with an incidence as high as 70% [ 14 , 34 , 35 ] ; however , the majority of pituitary metastases are clinically silent . in the autopsy study by teears and silverman , these metastases are often seen in patients with terminal malignancy who present with malaise , generalized pain , central nervous system involvement , or treatment - associated symptoms , although symptoms of pituitary insufficiency may be masked . several studies have indicated that diabetes insipidus ( di ) was the most common symptom [ 10 , 20 , 24 , 36 , 37 ] . in the series of mccormick et al . , di developed in 70% of patients ; however , if the anterior pituitary function is compromised , di may be concealed by reduced mineralocorticoid function . in some recent series , di has not been reported , which is likely because modern imaging techniques are able to detect abnormalities earlier than the timeframe required for di development . other rarer hormonal findings may be hypothyroidism and hypoadrenalism , hypogonadism , or overproduction of adrenocorticotropic hormone ( acth ) , growth hormone ( gh ) , or prolactin [ 10 , 3840 ] . because of their invasiveness , pituitary metastatic lesions have a high potential to cause visual deficits from suprasellar extension , with an incidence as high as 50% reported by branch jr . and laws jr .   and others [ 10 , 34 , 41 ] . in both the series by chiang et al .   and that of sioutos et al cranial nerve palsies involving the third and the sixth nerves and facial pain with numbness ( trigeminal origin ) were the most common presentation ( 33% ) in our cases with cavernous sinus involvement . retro - orbital pain , vision compromise , gait instability , horner 's syndrome , and hearing loss were infrequent and associated with petroclival and sphenoorbital extension of the lesions . all these symptoms were experienced with a relatively rapid onset from a few weeks to a few months that suggested the aggressive character of the lesions . symptoms strongly suggesting metastasis in the parasellar or sellar space include painful ophthalmoplegia in association with the sudden onset of di [ 10 , 26 , 34 , 42 ] . the pain may be retro - orbital or may be due to trigeminal dysfunction [ 4345 ] . in our series , 5 of the 6 ( 83% ) patients had a previous history of malignant disease . one of the patients that had prior history developed a malignancy ( melanoma ) other than the original one . only one patient without a prior history of malignancy first presented with lymphoma metastasis to the sps region . because pituitary adenomas also present with invasion of the sellar floor , cavernous sinus , or clivus , no specific neuroimaging criteria to define metastatic lesions in sps region have been reported . the diagnostic imaging tools for sps metastasis mainly include high - resolution ct and mr imaging . although ct is superior to mr imaging in detecting the bone involvement , the latter is preferable to determine the relationship of the lesion to the surrounding neurovascular structures .   although nonspecific , the characteristics of these lesions on mr imaging are an iso- or hypointense mass on t1-weighted imaging with a usually hyperintense signal on t2-weighted imaging , and homogeneously enhancing mass in images obtained after the administration of contrast agent . invasion of the cavernous sinus , sclerotic changes around the sella turcica and clivus , isointense signal on both t1- and t2-weighted imaging , and loss of high - intensity signal in the posterior pituitary have been reported to be helpful in differentiating metastatic lesions from benign   ones [ 15 , 30 , 48 ] . .   found that thickening or enhancement of the infundibulum was the most characteristic ct or mr imaging feature . schubiger and halter   reported that the invasion of the infundibular recess by a suprasellar mass is suggestive of metastasis . because of the rapid growth of metastatic lesions , a dumbbell - shaped intra- and suprasellar tumor with indentation at the diaphragm level is generally indicative for these cases [ 20 , 37 , 49 ] . the radiodiagnostic findings that suggested a malignant / metastatic process in our cases were the involvement of multiple compartments in the anterior , middle , posterior cranial fossae , extension to the infratemporal and pterygopalatine fossae , sphenoid sinus , and nasal cavity with bony destruction in the cranial base and asymmetric or bilateral invasion into the cavernous sinus . the management of sps metastases is multimodal , including surgical resection , radiation therapy , and chemotherapy . treatment is mainly palliative and depends on the symptoms and the extent of systemic disease [ 10 , 51 ] . because of the invasiveness and the high vascularity of the tumor , total surgical resection is generally not undertaken [ 1 , 20 ] . therefore , surgical treatment should aim for symptomatic relief and the preservation of visual function , even in patients with widespread primary disease , and should be followed by local radiation treatment and/or chemotherapy [ 10 , 51 ] . the body of evidence is inconclusive on the effect of the latter two modalities on survival [ 14 , 52 ] . laws jr .   reported improvement in symptoms , especially in pain and visual field defects , with no difference in survival after complete resection compared with subtotal or partial resection [ 10 , 14 ] . on the other hand , others have supported the concept of improvement in survival after surgical resection of the lesion [ 5355 ] . surgical exploration is also essential if tissue diagnosis is likely to affect therapy in patients with no known primary malignancy . resection is most commonly done via transsphenoidal route , although subfrontal or pterional approaches are also options depending on the location and the extension of the lesion . four out of six patients in our series underwent surgical biopsy through either transsphenoidal or transcranial route and then underwent subsequent radiation / chemotherapy . one patient who had visual compromise had subtotal resection for palliation followed by radiation / chemotherapy . one patient who had renal cell carcinoma was directly referred to radiation oncology for immediate radiation and subsequent chemotherapy . besides its role as an adjunct after surgery [ 14 , 42 , 56 ] , radiosurgery or conventional radiation is recommended as the initial course of treatment in patients with systemic disease out of control , recurrence in the systemic disease with concomitant sps metastasis , or medical comorbidities that put the patient at risk for a surgical intervention [ 2 , 7 , 18 , 41 , 5762 ] . radiosurgery , which is considered less invasive than conventional radiation , has been reported to achieve good tumor control [ 63 , 64 ] . in a series of 23 patients by iwai et al . , the rates of tumor control and symptom improvement were 67% and 53% , respectively ; however , radiosurgery to the sps region is limited by its potential to cause radiation injury to the surrounding neurovascular structures such as optic apparatus , pituitary gland , or cranial nerves coursing in cavernous sinus . doses reported in the literature for these structures range from 8 to 40 gy [ 63 , 6568 ] , and the optimal dose may be quite variable depending on the proximity of the lesion . furthermore , the debate about whether the radiation should be directed to the sps region alone or to the entire brain continues . chemotherapy is commonly used alone or along with radiation therapy mostly for palliation in the treatment of metastatic disease in sps region . its value has not been adequately studied and reported in the literature . the prognosis of patients with metastases to the sps region is grim in a majority of cases because of the aggressive character of the primary disease . even in patients with no other metastasis at the initial evaluation , the prognosis remains poor because of radiologically undetectable microscopic metastases ; however , it has been suggested that the extent of systemic disease affects survival in these patients . patients with a single sps region metastasis may have a better outcome [ 10 , 20 ] . median survival is less than 2 years independent of the management strategy [ 10 , 14 , 70 ] . the records on the long - term follow - up of the majority of our patients are lacking because the patients were not monitored for surgical outcome , or the follow - up periods were too short . the only patient that had palliative surgery for vision compromise was seen at one year after the surgery with stable neurological findings . suggestive symptoms include rapid onset of progressive ophthalmoplegia with retro - orbital or facial pain , visual impairment , and/or di . management varies depending on whether a primary source is identified , the symptomatology , the location and extent of the lesion , the stage of the primary disease , and the medical comorbidities . subtotal or partial surgical resection is aimed mainly for symptom relief . a multimodal approach involving subtotal resection of the lesion followed by radiation and/or chemotherapy is widely accepted , especially in symptomatic patients whose primary disease is under control . radiation with or without chemotherapy is generally recommended as first - line treatment in patients with advanced primary disease or in those with high - risk medical comorbidities . a biopsy usually precedes radiation therapy if the primary source of the metastasis is unknown . the prognosis for patients is generally poor , independent of the therapeutic modality , and the overall survival is less than two years .
the sellar and parasellar ( sps ) region is a complex area rich in vital neurovascular structures and as such may be the location of first manifestation of a systemic malignancy . 
 metastases to this region are rare ; breast cancer is the most common source among those that metastasize to the sps region . 
 ophthalmoplegia , headache , retroorbital or facial pain , diabetes insipidus , and visual field defects are the most commonly reported symptoms . 
 lack of specific clinical and radiological features renders sps metastases difficult to differentiate from the other frequently encountered lesions in this area , especially when there is no known history of a primary disease . 
 currently accepted management is multimodality therapy that includes biopsy and/or palliative surgical resection , radiation , and chemotherapy . 
 although no significant survival benefits have been shown by the surgical series , surgical resection may improve quality of life . here 
 we review the relevant literature and present six illustrative cases from our own institution .