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Manish K. Aghi, M.D., Ph.D. Manish K. Aghi, M.D., Ph.D. Assistant ProfessorAssistant Professor

California Center for Pituitary DisordersCalifornia Center for Pituitary DisordersDepartment of NeurosurgeryDepartment of Neurosurgery

University of California, San Francisco (UCSF)University of California, San Francisco (UCSF)

Differential Diagnosis of Sellar Lesions

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Introduction Introduction -- Sellar AnatomySellar Anatomy

ANTERIOR POSTERIOR

INFERIOR

SUPERIOR

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Sellar anatomy on MRISellar anatomy on MRIPituitary gland boundaries:Pituitary gland boundaries:

Superior Superior –– pituitary stalk (deviates away from tumors), optic pituitary stalk (deviates away from tumors), optic chiasm (pushed up by macroadenomas)chiasm (pushed up by macroadenomas)

Inferior Inferior –– sphenoid sinus, sellar bonesphenoid sinus, sellar bone

Right/left Right/left –– cavernous sinus/carotid arteriescavernous sinus/carotid arteries

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Differential Diagnosis of Sellar MassesDifferential Diagnosis of Sellar Masses1.1. Cystic LesionsCystic Lesions

Rathke’sRathke’s cleft cyst, Craniopharyngioma, cleft cyst, Craniopharyngioma, ArachnoidArachnoidCystCyst

2. Other Neoplasms2. Other Neoplasms

MeningiomaMeningioma , Germ Cell Tumor, , Germ Cell Tumor, ChordomaChordoma , Granular , Granular Cell Tumor, Cell Tumor, PituicytomaPituicytoma , Glioma, Metastases, , Glioma, Metastases, LymphomaLymphoma

3. Inflammation/Infection3. Inflammation/Infection

SarcoidosisSarcoidosis , Tuberculosis, Pituitary Abscess, , Tuberculosis, Pituitary Abscess, LangerhansLangerhans ’ ’ HistiocytosisHistiocytosis , Lymphocytic , Lymphocytic HypophysitisHypophysitis

4. Empty 4. Empty sellasella syndromesyndrome

5. Pituitary Adenomas (91%)5. Pituitary Adenomas (91%)

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CaseCase34 34 yoyo F presents with headache, that eventually led her F presents with headache, that eventually led her

primary care physician to get a brain MRI.primary care physician to get a brain MRI.

T1T1

ProlactinProlactin 55 ng/mL, other hormones within normal limits.55 ng/mL, other hormones within normal limits.T1 T1 gadogado T2T2

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Rathke’sRathke’s cleft cystcleft cystOriginate between anterior and posterior lobe from embryologic Originate between anterior and posterior lobe from embryologic

Rathke’sRathke’s pouch. Anterior lobe forms from anterior wall of pouch. Anterior lobe forms from anterior wall of Rathke’sRathke’s pouch and pars pouch and pars intermediaintermedia forms from posterior forms from posterior wall of wall of Rathke’sRathke’s pouch.pouch.

Symptoms Symptoms –– headache most common; visual disturbance or headache most common; visual disturbance or hypopituitarism less commonhypopituitarism less common

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Rathke’sRathke’s Cleft Cyst Cleft Cyst -- MRIMRIDifferential diagnosis is usually cystic adenoma Differential diagnosis is usually cystic adenoma vsvs

Rathke’sRathke’s cleft cyst, cleft cyst, Rathke’sRathke’s cleft cyst defined by:cleft cyst defined by:

•• Stalk typically midlineStalk typically midline

•• abnormality between anterior and posterior lobeabnormality between anterior and posterior lobe

1.1. Two types:Two types:i.i. T1 dark, T2 bright (one third) T1 dark, T2 bright (one third) –– fluid like CSFfluid like CSF

ii.ii. T1 bright, T2 variable (two third) T1 bright, T2 variable (two third) –– fluid is mucus, higher fluid is mucus, higher rate of presenting with h/a (100%) or gland dysfun ction rate of presenting with h/a (100%) or gland dysfun ction (40%); higher rate of (40%); higher rate of postoppostop diabetes diabetes insipidusinsipidus than than adenomasadenomas

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Rathke’sRathke’s Cleft Cyst TreatmentCleft Cyst Treatment

1.1. transsphenoidal surgery if larger than 1 transsphenoidal surgery if larger than 1 cm or clearly symptomatic; need to cm or clearly symptomatic; need to drain cyst and remove as much wall as drain cyst and remove as much wall as possiblepossible

2.2. 20% recur within first 2 years20% recur within first 2 years

3.3. rate of headache improvement 60rate of headache improvement 60 --80%80%

4.4. rate of hormone dysfunction rate of hormone dysfunction improvement 20%improvement 20%

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Rathke’sRathke’s Cleft CystCleft CystCyst wall typically has columnar or Cyst wall typically has columnar or

cuboidalcuboidal epithelium, but epithelium, but squamoussquamousmetaplasiametaplasia can occur and increases risk can occur and increases risk of recurrence by as much as 3of recurrence by as much as 3 -- to 4to 4 --foldfold

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Pituitary Pituitary ArachnoidArachnoid CystCystCongenital or acquired; Congenital or acquired; herniationherniation of of arachnoidarachnoid membrane membrane

through incompetent diaphragm or arises from through incompetent diaphragm or arises from arachnoidarachnoid rests rests below the below the diaphgragmdiaphgragm

Symptoms Symptoms –– 90% have headaches, 35% have visual field defect, 90% have headaches, 35% have visual field defect, 35% have hypopituitarism35% have hypopituitarism

MRI MRI –– similar to similar to Rathke’sRathke’s cleft cyst containing watery contents cleft cyst containing watery contents rather than mucus, T2 bright T1 darkrather than mucus, T2 bright T1 dark

Treatment Treatment –– transsphenoidal drainage and wall biopsy, headache transsphenoidal drainage and wall biopsy, headache gets better but endocrine function improvement wors e than gets better but endocrine function improvement wors e than with other cysts. 20% recurrence at 10 years.with other cysts. 20% recurrence at 10 years.

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CraniopharyngiomaCraniopharyngiomaAge 5 to 10Age 5 to 10

Histologically benign looking tumor (developing fro m nests Histologically benign looking tumor (developing fro m nests of epithelium derived from of epithelium derived from Rathke’sRathke’s pouch) with pouch) with malignant behavior due to invasion of surrounding malignant behavior due to invasion of surrounding structures and recurrence after gross total resecti on. structures and recurrence after gross total resecti on.

Single large or multiple cysts filled with turbid, Single large or multiple cysts filled with turbid, proteinaceousproteinaceous brownbrown --yellow material that sparkles due to yellow material that sparkles due to cholesterol crystals.cholesterol crystals.

Usually start sellar, can have Usually start sellar, can have suprasellarsuprasellar extension with extension with invasion into hypothalamus.invasion into hypothalamus.

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CraniopharyngiomaCraniopharyngioma

Radiation used for residual tumor after Radiation used for residual tumor after surgery, although hypopituitarism and surgery, although hypopituitarism and other side effects in the pediatric other side effects in the pediatric population will ensue.population will ensue.

1010--year recurrence rate year recurrence rate –– 83% for tumors 83% for tumors larger than 5 cm, 20% for tumors smaller larger than 5 cm, 20% for tumors smaller than 5 cmthan 5 cm

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Overview of cystic pituitary lesionsOverview of cystic pituitary lesions

Psychiatric disturbances Psychiatric disturbances unique to unique to craniopharyngioma, get craniopharyngioma, get better with surgerybetter with surgery

ArachnoidArachnoid cyst patients cyst patients present older (fifth decade present older (fifth decade of life)of life)

Endocrine dysfunction rare in Endocrine dysfunction rare in arachnoidarachnoid cyst, if present in cyst, if present in arachnoidarachnoid cyst won’t get cyst won’t get better with surgerybetter with surgery

Source: JCEM 84: 3972, 1999

Cra

nio

Rat

hke

Ara

ch

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Cystic Pituitary Lesions Cystic Pituitary Lesions -- RecurrenceRecurrence

ArachnoidArachnoid cysts cysts –– 20% recur after 10 years; 20% recur after 10 years; Rathke’sRathke’s –– 20% 20% recur within first year or 2; Craniopharyngioma recur within first year or 2; Craniopharyngioma –– most most recur, spread over 10 yearsrecur, spread over 10 years

Source: JCEM 84: 3972, 1999

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CaseCase33 year old female with severe headaches, 33 year old female with severe headaches,

n/vn/v , weight loss, , weight loss, hyperprolactinemiahyperprolactinemia , , hypoadrenalismhypoadrenalism , , hypothyroidsmhypothyroidsm ..

MRI with intrinsically T1 bright, T2 MRI with intrinsically T1 bright, T2 intermediate signal 3intermediate signal 3 --4 mm lesion in left 4 mm lesion in left inferoposteriorinferoposterior sellasella

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PituicytomaPituicytomaNew diagnosis created by WHO in 2007 New diagnosis created by WHO in 2007 –– WHO grade I tumor WHO grade I tumor

of the of the pituicytespituicytes , which are stromal (supporting) cells of the , which are stromal (supporting) cells of the posterior lobe or stalk.posterior lobe or stalk.

Present with visual field defect, or asymptomatic i ncidental Present with visual field defect, or asymptomatic i ncidental finding on MRIfinding on MRI

More vascular than pituitary adenoma and tough to a ccess More vascular than pituitary adenoma and tough to a ccess (posterior lobe, sometimes stalk) so surgery risky.(posterior lobe, sometimes stalk) so surgery risky.

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PituicytomaPituicytoma

•• Five cases at UCSF 2007Five cases at UCSF 2007 --20092009

•• Mean age 53 (range 33Mean age 53 (range 33 --71)71)

•• 3 men, 2 women3 men, 2 women

•• 1 incidental finding; 2 1 incidental finding; 2 panhypopituarismpanhypopituarism , 1 visual , 1 visual symptoms; 2 with over 20 lb symptoms; 2 with over 20 lb weight lossweight loss

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PituicytomaPituicytoma•• GFAP+GFAP+

•• MIBMIB--1 0.51 0.5--2.0%2.0%

•• No hormones, no No hormones, no neurosecretoryneurosecretory granulesgranules

•• Well circumscribedWell circumscribed

•• Low recurrence rate but readily symptomatic Low recurrence rate but readily symptomatic due to locationdue to location

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Metastasis to the Pituitary GlandMetastasis to the Pituitary Gland1% of sellar lesions are 1% of sellar lesions are metsmets -- Breast, Lung most commonBreast, Lung most common

Posterior Lobe more common than anterior lobe (dire ct Posterior Lobe more common than anterior lobe (dire ct blood supply), also can grow along stalkblood supply), also can grow along stalk

Patients 5Patients 5 --10 years younger than average brain met patient10 years younger than average brain met patient

Posterior lobe Posterior lobe metsmets often present with diabetes often present with diabetes insipidusinsipidusand are often treated with radiosurgeryand are often treated with radiosurgery

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CaseCase33 year old male presents with right eye sealed shu t for 10 33 year old male presents with right eye sealed shu t for 10

days and several months of abdominal pain. Exam days and several months of abdominal pain. Exam –– R R 33rdrd nerve palsy, but acuity intact. Hormone function nerve palsy, but acuity intact. Hormone function reveals low testosterone, low thyroid hormone.reveals low testosterone, low thyroid hormone.

T1 gado coronal T1 sag gado

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Pituitary LymphomaPituitary LymphomaMRI MRI –– isointenseisointense to brain on T1 and T2, enhance to brain on T1 and T2, enhance

homogeneously after homogeneously after gadogado (pituitary adenoma is (pituitary adenoma is hypointensehypointense on T1, on T1, hyperintensehyperintense on T2, and have delayed on T2, and have delayed gadogado enhancement compared to normal gland)enhancement compared to normal gland)

Treatment Treatment –– transsphenoidal biopsy then chemotherapytranssphenoidal biopsy then chemotherapy

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Pituitary Pituitary GerminomaGerminoma

Most common causes of central DI in children/adoles cents Most common causes of central DI in children/adoles cents are are LangerhansLangerhans ’ ’ histiocytosishistiocytosis and and germinomagerminoma ..

MRI MRI –– thick homogeneously enhancing stalk; sometimes thick homogeneously enhancing stalk; sometimes associated with pineal lesion.associated with pineal lesion.

Treatment Treatment –– Transsphenoidal biopsy, then radiation to 40 Transsphenoidal biopsy, then radiation to 40 Gy, 90% longGy, 90% long --term survivalterm survival

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CaseCase24 24 yoyo F with intermittent h/a for 6 months, F with intermittent h/a for 6 months,

1 month of amenorrhea, 2 weeks of 1 month of amenorrhea, 2 weeks of polyuria/polydipsiapolyuria/polydipsia . No other . No other sxsx . Sp . Sp gravgrav 1.005, daily urine output 7 L, 1.005, daily urine output 7 L, decreased decreased estradiolestradiol , low T3/T4, , low T3/T4, prolactinprolactin25 ng/mL, low GH, ESR 14, WBC 6.225 ng/mL, low GH, ESR 14, WBC 6.2

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Pituitary AbscessPituitary AbscessCan be primary (in normal gland) or secondary (in p reCan be primary (in normal gland) or secondary (in p re--

existing pathology like adenoma or existing pathology like adenoma or Rathke’sRathke’s cleft cleft cyst).cyst).

Presenting symptom Presenting symptom –– hypopituitarism, headache, hypopituitarism, headache, visual field cut. Fever and visual field cut. Fever and meningismusmeningismus are rare.are rare.

Source of infection unclear Source of infection unclear –– hematogenoushematogenous versus versus local spread from sphenoid sinus both speculatedlocal spread from sphenoid sinus both speculated

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Pituitary AbscessPituitary Abscess

MRI MRI -- cystic lesion with heterogeneous cystic lesion with heterogeneous signal and peripheral enhancement signal and peripheral enhancement causing causing hypopituitarismhypopituitarism . Restricted . Restricted diffusion highly predictive when diffusion highly predictive when present.present.

Only 50% grow out organisms, when they Only 50% grow out organisms, when they do gram + and gram do gram + and gram –– equally common, equally common, fungi less common.fungi less common.

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Culture Negative May Still Benefit Culture Negative May Still Benefit from Antibiotic Treatmentfrom Antibiotic Treatment

Culture negative infected Culture negative infected Rathke’sRathke’s cysts recur cysts recur more frequently than culture positive cysts treated more frequently than culture positive cysts treated with antibiotics; antibiotic treatment restores the with antibiotics; antibiotic treatment restores the recurrence rate to that of recurrence rate to that of noncultured/noninfectednoncultured/noninfectedcystscysts

0 10 20 30 400

10

20

30

40

50

60CULTURED

NONCULTUREDANTIBIOTIC-TREATED

NO ANTIBIOTIC CULTURE-NEGATIVE

Months

Per

cent

rec

urre

nce

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Same case continuedSame case continued

One year later all hormone function One year later all hormone function except GH has resolved and MRI except GH has resolved and MRI shows:shows:

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Empty Empty sellasella syndromesyndromeSellaSella filled with CSF causing pituitary gland to be flat tened filled with CSF causing pituitary gland to be flat tened

against floor of against floor of sellasella . In these patients, the diaphragm . In these patients, the diaphragm sellaesellae is limited to a thin rim of tissue around a huge is limited to a thin rim of tissue around a huge infundibularinfundibular foramen. foramen.

Much more common in females than males. Seen in 6% of Much more common in females than males. Seen in 6% of autopsies. 30% of empty autopsies. 30% of empty sellasella patients are hypertensive. patients are hypertensive.

Can be primary or secondary to burned out pituitary Can be primary or secondary to burned out pituitary tumors after apoplexy, posttumors after apoplexy, post --radiationradiation

Headache most common symptom. 30% GH deficient.Headache most common symptom. 30% GH deficient.

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CaseCase

28 28 yoyo F with severe h/a 4 days after normal F with severe h/a 4 days after normal vaginal delivery. Labs reveal low vaginal delivery. Labs reveal low prolactinprolactin 0.5 0.5 ng/mL (normal 0ng/mL (normal 0 --20) and low ACTH20) and low ACTH

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Another caseAnother case

39 year old male with 4 weeks of h/a, 39 year old male with 4 weeks of h/a, n/vn/v , and left eye , and left eye visual lossvisual loss

To OR at another institution where left carotid inj ury To OR at another institution where left carotid inj ury occurredoccurred

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Another case (continued)Another case (continued)Transferred to our institution for carotid Transferred to our institution for carotid

injury/injury/ pseudoaneurysmpseudoaneurysm management (management ( stentingstenting of of left left supraclinoidsupraclinoid ICA)ICA)

On On coumadincoumadin postpost --stent and on replacement stent and on replacement steroid therapy. steroid therapy.

3 month follow3 month follow --up imagingup imaging

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Lymphocytic Lymphocytic HypophysitisHypophysitis

Lymphocytic pituitary infiltration during or after pregnancyLymphocytic pituitary infiltration during or after pregnancy

Symptoms Symptoms –– present with ACTH deficiency (whereas present with ACTH deficiency (whereas nonfunctional adenoma presents with GH or FSH/LH nonfunctional adenoma presents with GH or FSH/LH deficiency), 1/3 get deficiency), 1/3 get hyperprolactinemiahyperprolactinemia (stalk effect) 2/3 (stalk effect) 2/3 get get hypoprolactinemiahypoprolactinemia (gland compression)(gland compression)

MRI MRI –– anterior gland enhancement that may extend to stalkanterior gland enhancement that may extend to stalk

Diagnosed by transsphenoidal Diagnosed by transsphenoidal endonasalendonasal pituitary biopsypituitary biopsy

Treated with steroidsTreated with steroids

3 weekssteroids

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LangerhansLangerhans ’ ’ HistiocytosisHistiocytosis

In pediatric/adolescent patients, most common cause s In pediatric/adolescent patients, most common cause s of DI are of DI are LangerhansLangerhans ’ ’ histiocytosishistiocytosis and and germinomagerminoma ..

MRI MRI –– thick stalk, posterior lobe loses its T1 brightness thick stalk, posterior lobe loses its T1 brightness but now enhances.but now enhances.

Need biopsy to differentiate from Need biopsy to differentiate from germinomagerminoma ..

Treat with Treat with alkylatingalkylating agent + steroid. Prognosis good.agent + steroid. Prognosis good.

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Pituitary Pituitary SarcoidosisSarcoidosis5% of 5% of sarcoidsarcoid cases have CNS involvement, but cases have CNS involvement, but

hypothalamus, pituitary stalk, and pituitary are mo st hypothalamus, pituitary stalk, and pituitary are mo st common sites of CNS involvement. common sites of CNS involvement.

DI is most common presenting symptom, followed by a nterior DI is most common presenting symptom, followed by a nterior pituitary hormone deficiencypituitary hormone deficiency

MRI with enhancing fullness of posterior gland.MRI with enhancing fullness of posterior gland.

Treatment Treatment –– transsphenoidal biopsy, transsphenoidal biopsy, treat with 40 mg prednisone daily, treat with 40 mg prednisone daily, lesion will likely resolve, but patient lesion will likely resolve, but patient will likely continue to need will likely continue to need ddAVPddAVP if if presented with DI.presented with DI.

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CaseCase

35 35 yoyo F with F with galactorrheagalactorrhea and amenorrhea. and amenorrhea. Labs reveal Labs reveal prolactinprolactin 43 ng/mL (normal 043 ng/mL (normal 0 --20), 20), TSH 283 TSH 283 µµU/mLU/mL (normal 0(normal 0 --3).3).

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Pituitary HyperplasiaPituitary HyperplasiaSxSx –– high high prolactinprolactin , high TSH but , high TSH but prolactinprolactin

symptoms predominatesymptoms predominate

Cause Cause –– hypothyroidism, TRH drives hypothyroidism, TRH drives prolactinprolactinreleaserelease

Treatment Treatment –– thyroid hormonethyroid hormone

Path Path –– hyperplasia of hyperplasia of thyrotrophsthyrotrophs and and lactotrophslactotrophs ..

4 months

synthroid

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Pituitary Adenoma Pituitary Adenoma -- NonsecretoryNonsecretoryRadiographic features: abnormality in anterior lobe Radiographic features: abnormality in anterior lobe

of gland usually of gland usually anteroinferioranteroinferior aspect of gland; aspect of gland; tend to be on one side and push stalk to opposite tend to be on one side and push stalk to opposite side; most are somewhat T2 bright indicating side; most are somewhat T2 bright indicating softness, fibrous adenomas can be T2 dark; softness, fibrous adenomas can be T2 dark; characteristic T1 enhancement pattern causing characteristic T1 enhancement pattern causing adenoma to appear darker than adjacent gland.adenoma to appear darker than adjacent gland.

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Pituitary Adenoma Pituitary Adenoma -- NonsecretoryNonsecretory

Stalk effect Stalk effect –– increased increased prolactinprolactin due to tumor due to tumor size, increased adenoma size up to 3 cm makes a size, increased adenoma size up to 3 cm makes a higher higher prolactinprolactin attributable to stalk effect.attributable to stalk effect.

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Pituitary Adenoma Pituitary Adenoma -- NonsecretoryNonsecretory

Pathologist should stain tumors for hormones, Pathologist should stain tumors for hormones, especially ACTH, because “silent especially ACTH, because “silent corticotrophiccorticotrophic ” ” adenomas may have higher risk of recurrence and adenomas may have higher risk of recurrence and risk of delayed Cushing’s disease.risk of delayed Cushing’s disease.

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