Pocket Oncology (Pocket Notebook Series), 1st Ed.

SELLAR TUMORS

Jane L. Meisel, Monica Girotra, Kevin C. De Braganca, and Thomas J. Kaley

Sellar Masses

• Presentation

• Neuro sx: HA (expansion of sella), diplopia (oculomotor nerve compression), pituitary apoplexy (sudden hemorrhage into the mass), CSF rhinorrhea (inferior extension of mass), visual field deficits

• Hormonal abnormalities (hyper- or hyposecretion; see below)

• Incidental finding on MRI done for other reason (“incidentaloma”)

• Causes

• Pituitary adenomas = most common cause; ∼85% of sellar masses

• Also: Physiologic pituitary enlargement (pregnancy, 1° hypothyroidism, 1° hypogonadism); cyst, abscess or AV fistula of cavernous sinus; hypophysitis (lymphocytic = most common kind, seen in postpartum  or in anti-CTLA-4 tx of malignancies); benign tumors (craniopharyngioma, meningioma); 1° malignant tumors (germ cell, chordoma, 1° CNS lymphoma, sarcoma, pituitary carcinoma-rare); met disease (breast/lung 1° most common)

• In a large registry of pituitary tumors (N = 4122), 84.6% were adenomas, 3.2% were craniopharyngioma, 1.8% were Rathke cysts, 1.8% were Crooke cells (w/o adenoma), ∼1% were meningiomas, 0.6% were mets, & 0.5% were chordomas. Sellar tumors of all other types each occurred no more often <0.5% of the time (CNS lymphoma 0.02%, GCT 0.15% as described below) (Eur J Endocrinol 2007;156(2):203)

• Evaluation

• Sellar MRI to better characterize the lesion

• Evaluation of hypothalamic-pituitary hormonal function

Pituitary Adenoma

• Classification: By size & cell of origin

• Size: <1 cm = microadenoma; >1 cm = macroadenoma

• Cell type: Arise from any type of cell of the anterior pituitary; can lead to ↑ secretion of hormone(s) produced by that cell and/or ↓ secretion of other hormones due to compression of other cell types

• Gonadotroph: Usu clinically nonfunctional

• Corticotroph: Usu causes Cushing

• Lactotroph: ↑ PRL → hypogonadism (/)

• Thyrotroph: Can be clinically nonfunctional (secreting only α or TSH-β subunits, or can cause hyperthyroidism from ↑ secretion of intact TSH)

• Somatotroph: ↑ GH → acromegaly

• Lactotroph/somatotroph combinations also occur, leading to sx of both

• Evaluation

• MRI: Best imaging procedure to evaluate sellar masses

• Evaluation of hypothalamic-pituitary hormonal function:

• Hormonal hypersecretion is caused only by pituitary adenomas & defines the sellar mass as such

• Hormonal hyposecretion can be caused by any hypothalamic or pituitary lesion; does not help narrow the ddx (unless DI is found, as this indicates a lesion/ ↓ ADH release from hypothalamus or stalk)

• Tx

• Gonadotroph/other clinically nonfunctioning adenomas: If large enough to cause neuro sx (visual field abnormalities, etc.), TSS is 1st line; if no neuro sx, can consider TSS if extrasellar extension present (ie, elevating optic chiasm) or monitor w/q6–12 mos exams/MRIs. Post-op monitoring is w/MRI; if residual tissue grows progressively, consider repeat surgery or XRT.

• Corticotroph: Complete removal of tumor via transsphenoidal adenectomy or anterior pituitary resection is 1st line; repeat surgery or XRT for persistent/recurrent disease; medical Rx for persistent/recurrent disease or while waiting for RT effect (adrenal enzyme inhibitors- ketoconazole, metyrapone; somatostatin analog- pasireotide; cabergoline). B/l total adrenalectomy can be considered in pts not cured by pituitary surgery, RT, &/or medical Rx

• Lactotroph: Tx if existing/impending neuro sx due to size (ie, >1 cm), hypogonadism or other sx due to inc PRL; DA agonist (cabergoline, bromocriptine) is 1st line to ↓ tumor size & dec prl. Pts w/nl PRL & no adenoma on MR while on low-dose DA agonist for at least 2 y, suggest trial of stopping drug w/careful monitoring of PRL/MR. If drugs ineffective (ie, substantial tumor/macroadenoma remains or sx due to ↑ PRL persist after tx), consider TSS. In pts w/very large macroadenoma who have considerable residual tumor after TSS not amenable to further surgery, consider DA agonist tx and/or XRT.

• Thyrotroph: Transsphenoidal resection is 1st line & cures 1/3, improves 1/3, leads to no Δ in 1/3 → many need additional tx (DA agonist/octreotide). βB can ameliorate s/s of hyperthyroidism.

• Somatotroph: TSS unless not fully resectable/surgical risk is too high, then consider medical tx w/LA somatostatin analog (if no impending neuro sx). If surgery results in normalization of serum IGF-1, no further tx. If IGF-1 still high, treat w/somatostatin analog. If ineffective, add cabergoline; if this is ineffective, stop cabergoline & give pegvisomant alone or w/somatostatin analog. If still not successful, XRT or repeat operation.

Primary Malignant Tumors

• Intracranial GCTs

• Arise from the pineal/suprasellar region (pineal = 2× as common)

• Usu occur in children & through the third decade of life (up to 40% in young adults; M > F (particularly in pineal region)

• Intracranial GCTs make up ∼0.5–3% of pediatric CNS tumors in USA (more frequent in Asian countries) (Oncologist 2008;13:690)

• Sx: Pineal region- HA, nausea, vomiting, lethargy, diplopia, pyramidal tract signs, & ataxia (from ↑ ICP/hydrocephalus), paralysis of upward gaze; suprasellar – hypopituitarism, DI

• Intracranial GCTs = germinomas & NGGCTs; the latter includes embryonal carcinoma, endodermal sinus tumor/yolk sac tumor, choriocarcinoma, teratoma (immature & mature), mixed tumors consisting of a combination of these types

• Histology: Germinomas = lg polygonal undifferentiated cells w/abundant cytoplasm arranged in nests separated by bands of connective tissue; NGGCTs = varies depending on cell types present

• W/u/eval: CSF & serum levels of AFP & B-hCG, (elevated levels primarily seen in NGGCT; CSF AFP > 1000 correlated w/poor prognosis); eval of pituitary/hypothalamic function, CSF cytology, MRI brain/spine for staging as 10–15% will have leptomeningeal spread at time of dx (Oncologist 2000;5:312), bx

• Tx: Localized pure germinoma: Whole-ventricle RT (21–24 Gy) w/boost to 1° tumor (total tumor dose 40–45 Gy) (Int J Radiat Oncol Biol Phys 2003;56:511); neoadj chemo w/bleomycin & etoposide w/either CIS (BEP) or carboplatin (BEJ) can be used followed by a reduced dose of radiation, but chemo alone is a/w an unacceptable rate of relapse (Pediatr Blood Cancer 2004;43:126). Note: Tx bifocal tumors (pineal & suprasellar components) as localized tumors if MRI spine & CSF cytology are negative (Int J Radiat Oncol Biol Phys 82(4):1341–1351). Disseminated germinoma (as identified by MRI and/or CSF cytology) or tumors that do not demonstrate PR to chemo: Craniospinal irradiation NGGCTs: CIS-based chemotherapy followed by resection of residual tumor & craniospinal RT (Neuropediatrics 2005;36(2):71). Mature teratoma: Surgical resection (these do not respond to chemo/RT).

• Chordomas

• Rare (diagnosed in ∼300 pts in USA annually), slow growing, locally aggressive neoplasms of bone that arise from embryonic remnants of the notochord; can arise in the clivus

• Common sx: HA, visual impairment, & anterior pituitary hormonal deficiencies

• Histologic subtypes: Conventional (most common, cartilaginous or other mesenchymal components absent), chondroid (chordomatous & chondromatous features; predilection for the sphenooccipital region of the skull base); sarcomatous transformation (2–8% of chordomas; the sarcomatous component is interspersed w/areas of conventional chordoma; poorer prognosis)

• IHC: + CK; + EMA >80% of cases; other stains variable

• Tx: Surgical resection followed by RT; proton beam RT is best if available given importance of minimizing damage to surrounding structures (Neurosurg Rev 2009;32(4):403).

• Primary CNS Lymphoma involving the pituitary

• Common sx: HA & visual/oculomotor impairment and/or deficiencies of anterior pituitary hormones & ADH/DI

• W/u: Contrast-enhanced MRI = sellar mass w/variable extrasellar extension

• Tx: Remains controversial- some treat as a systemic lymphoma; some w/CNS lymphoma regimens; some w/a combination of both (see Primary CNS Lymphoma)

Metastases to the Pituitary Gland

• Mets to the hypothalamus & pituitary gland = ∼1–2% of sellar masses

• Most common w/BC in women & lung CA in men but also occurs rarely in other CA (renal cell, hepatocellular, prostate, colon)

• Presentation (sx occur in ∼7% of pts): DI (most common presenting sx, if sx are present), anterior pituitary dysfunction, visual field defects, retroorbital pain, ophthalmoplegia

• Tx: Often involves local Rx (surgery or XRT) for sx mets; systemic Rx is dictated by 1° tumor type

• OS very poor (between 6 & 22 mos) (Neurosurg Focus 2004;16:E8)