Figure 78-1. A: Sagittal view. B: Coronal view. ICA, internal carotid artery; CN, cranial nerve.
PATHOLOGY OF SELLAR LESIONS
Tables 78-1 and 78-2). The true incidence of adenomas is difficult to determine as it varies depending on whether the series is based upon clinically significant tumors, autopsy findings, or imaging data. The prevalence of incidental sellar masses found in imaging studies is about 10% to 22%, while it is about 14% in autopsy series.1 The original pathologic classification was based upon staining affinity for histologic dyes, that is, acidophilic, basophilic, or chromophobe. A more recent and clinically useful pathologic classification from the WHO is based upon immunocytochemistry of various hormone subtypes. These include:, Pituitary adenomas are the most common tumors of the sella and most important surgical pathology, but the differential diagnosis of sellar lesions is broad (
Prolactinomas (Lactotroph Adenomas)
Although less important in surgical series since the advent of dopamine agonist treatment, these are one of the most common pituitary adenomas with an incidence of 6 to 10 per million per year and a prevalence of 60 to 100 cases per million.2 Also known as lactotroph adenomas, they arise from the prolactin-secreting cells of the adenohypophysis. They are commonly microadenomas in women, but especially in men may become large and invasive.
Table 78-1 Tumors of the Pituitary
Growth Hormone-Secreting Adenomas (Somatotroph Adenomas)
These tumors secrete excess levels of growth hormone, leading to gigantism in children and acromegaly in adults. The incidence of acromegaly is about 2 to 4 cases per million per year.3 These tumors may sometimes coexpress prolactin (mammosomatotroph adenomas) and rarely TSH, as these cellular subtypes appear to arise from a common stem cell origin. They are typically invasive macroadenomas.
ACTH-Secreting Adenomas (Corticotroph Adenomas)
These tumors secrete excess levels of ACTH, leading to excess production of cortisol by the adrenal glands (Cushing disease). They are uncommon, with an estimated incidence of 1.2 to 1.7 cases per million per year.4 Pathologic diagnosis can be difficult, given that these tumors are often quite small and surgical specimens limited. Corticotroph adenomas typically manifest loss of normal glandular architecture, with positive immunocytochemistry for ACTH.
Table 78-2 Differential Diagnosis of Nonpituitary Sellar Lesions
TSH-Secreting Adenomas (Thyrotroph Adenomas)
These tumors are uncommon and typically comprise less than 1% of surgical series. Patients will sometimes present with hyperthyroidism, but TSH staining without clinical hyperthyroidism is a more common scenario.5
These tumors are common and comprise most of the “nonfunctioning” adenomas, as they express primarily hormone subunits, including beta FSH, LH, or alpha subunits. They become symptomatic via mass effect, with compression of normal gland leading to pituitary hypofunction, or compression of the chiasm leading to visual field abnormalities. Very rarely, patients with these tumors may present with symptoms attributed to excess gonadal steroids, such as precocious puberty, irregular menses, or psychiatric manifestations.
Null Cell Adenomas
These tumors are uncommon; they manifest no clinical or immunocytochemical evidence of hormone secretion, but this may be a function of the sensitivity of the immunocytochemical technique.
“Atypical” Adenomas and Pituitary Carcinomas
Pituitary carcinoma is extraordinarily rare. It is defined by the presence of distant metastases or CSF dissemination. While pituitary carcinomas may demonstrate extensive pleomorphism and/or necrosis, these pathologic findings are also seen in benign adenomas. The factors correlated with aggressive clinical behavior include an elevated Ki-67 labeling index (MIB-1 fraction, proliferation index) and extensive p53 reactivity.6 “Atypical” adenomas have been defined as those tumors manifesting an MIB-1 fraction of greater than 3%, excessive p53 immunoreactivity, and increased mitotic activity.7 Atypical adenomas are usually larger and invasive, but are not uncommon (15% in some surgical series), and the factors predisposing to malignant degeneration and metastasis are not well defined.8
Nonadenomatous Lesions of the Sella
Other neoplasms of the sella are uncommon but remain important in the differential diagnosis. Craniopharyngiomas are benign, solid, or partially cystic masses which presumably arise from remnants of Rathke pouch.11 They occur in a bimodal distribution with peaks in childhood and in older adults. The adamantinomatous type is typical in children, and is often cystic and partially calcified. The cysts contain a “motor oil” appearing fluid, which can produce severe chemical meningitis when in contact with the CSF. The epithelium produces keratinaceous debris and cholesterol clefts. There is often a pronounced inflammatory reaction. The papillary type is seen almost exclusively in older adults. It may be cystic and/or solid, and can be densely adherent to surrounding neural structures, especially the optic nerves and hypothalamus. Meningiomas can arise anywhere along the intracranial dura, including within the sella. Meningiomas arising from the diaphragm sella or tuberculum sella can mimic pituitary adenomas and lead to endocrine dysfunction and chiasm compression. Germ cell tumors are most common in children and young adults and occur predominantly in males. The sella is the second most common location after the pineal; the most common subtype is the germinoma followed by teratomas. Metastases to the sella are fortunately rare, most commonly from breast and lung.12
A variety of nonneoplastic cysts can occur within the sella. Although most are incidental findings seen on routine MRI imaging, large cysts can sometimes lead to endocrine dysfunction or chiasm compression. The most common cystic structure is Rathke cleft cyst, arising from a remnant of Rathke pouch within the pars intermedia. Rathke cysts can sometimes enlarge with time and compress surrounding structures; they may then require drainage and/or resection. Most, however, are incidental findings, and require no treatment. Epidermoid or dermoid cysts arise from ectopic squamous or dermoid tissue and can fill with keratinaceous debris. Arachnoid cysts are CSF containing structures which may also occur within the sella, presumably arising by means of a “one-way valve” mechanism allowing CSF to enter the cyst cavity but not exit; enlarging cysts may become clinically symptomatic.
Inflammatory lesions of the sella are rare. Lymphocytic hypophysitis, the most common, is thought to represent an autoimmune phenomenon and is seen usually in women during or after pregnancy, often in association with other autoimmune disorders (Hashimoto thyroiditis, atrophic gastritis.) The gland is enlarged and infiltrated with inflammatory cells and pituitary dysfunction may occur. Granulomatous hypophysitis can arise from infections, that is, tuberculosis or fungal, or idiopathic granulomatous inflammation, either alone or in association with sarcoidosis. The recent introduction of ipilimumab antibody therapy for melanoma has led to the recognition of a presumed immune-mediated hypophysitis associated with pituitary enlargement and dysfunction.13 Other uncommon types of hypophysitis include xanthomatous, necrotizing, and IgG4 related.
14,15 The majority of pituitary adenomas are monoclonal in origin.16,17 The adenoma presumably arises from a single mutated cell, but the relative contributions of intrinsic genetic events and stimulation by hypothalamic hormones and local growth factors remain to be determined. Progression to malignancy with metastasis is rare, although local invasion is common. Genetic mutations predisposing to the development of pituitary adenomas include mutations in the AIP gene (aryl hydrocarbon receptor interacting protein) which has been found in some familial pituitary adenoma cohorts as well as some sporadic adenomas, especially in young acromegalic patients. The MEN1 (multiple endocrine neoplasia) gene is also associated with familial adenomas, but is uncommon in sporadic disease, as is the GNAS mutation associated with McCune Albright syndrome. The PRKAR1A gene encodes a type 1A regulatory subunit of protein kinase A. Inactivating mutations of this gene are identified in 60% to 70% of patients with Carney complex, a condition of dominant inheritance, which may lead to acromegaly as a result of somatotroph hyperplasia or adenoma, as well as a variety of extrapituitary manifestations. Epigenetic modification has been suggested as a mechanism to influence gene expression without alteration in the underlying genome. Altered expression of genes encoding CDKN2A (cyclin-dependent kinase inhibitor), DAPK (death-associated protein kinase), FGFR2 (fibroblast growth factor receptor 2), among others, have been associated with sporadic pituitary adenomas. Loss of tumor suppressor genes may also be involved in adenoma pathogenesis. Loss of the GADD45y gene expression occurs in the majority of human pituitary adenomas, and products of the AIP, PRKAR1A, and MEN1 genes may also act as tumor suppressors, with loss of these products in familial syndromes predisposing to the development of pituitary adenomas, in a “two-hit” model. Dysregulation of micro RNAs, which can regulate translation of target mRNAs, has recently been found in pituitary adenomas, and differential expression can be associated with specific tumor subtypes. It is unclear which, if any, of these abnormalities are primary as opposed to epiphenomena in pituitary tumorigenesis.The molecular pathogenesis of pituitary adenomas remains unclear, although a number of possibilities have been suggested.
All patients with a pituitary mass require endocrine evaluation for pituitary hypofunction, and patients with possible pituitary adenomas require evaluation for hypersecretory syndromes as well. This is best done in conjunction with an endocrinologist experienced in the management of pituitary disease.
Pituitary Hypofunction (Hypopituitarism)
It is important to determine the presence of hypopituitarism, especially in patients requiring surgical treatment, as unrecognized hypothyroidism or hypoadrenalism may have a profound effect on response to anesthesia and complicate recovery from surgery. Determination of anterior pituitary dysfunction requires measurement of free thyroxine (free T4) and thyrotropin (TSH), gonadal hormones (estradiol and testosterone), as well as gonadotropins (LH and FSH), basal and stimulated cortisol levels, and sometimes growth hormone levels and IGF1 (insulin-like growth factor 1) if clinically indicated. Central (secondary) hypothyroidism is characterized by low free T4 levels in association with low or inappropriately normal TSH. Central hypogonadism is characterized by low morning testosterone levels in men, and low estradiol levels in women, associated with low or inappropriately normal FSH and LH. Central hypoadrenalism is characterized by low morning cortisol levels in association with low or inappropriately normal ACTH. Morning serum cortisol ≤3 mcg/dL is diagnostic of adrenal insufficiency, whereas morning serum cortisol ≥18 mcg/dL assures sufficient adrenal function. Intermediate cortisol levels are indeterminate with regard to adrenocortical function and require further evaluation, including stimulation with cosyntropin or insulin tolerance testing. Growth hormone levels are normally pulsatile, which can make growth hormone insufficiency difficult to diagnose; it can be presumed in the presence of multiple hormone insufficiencies, and confirmed by appropriate stimulation testing, which can be undertaken after definitive treatment of the underlying pituitary lesion and replacement of other pituitary hormone deficiencies have been implemented. Replacement therapy, especially levothyroxine and glucocorticoid (prednisone or hydrocortisone), should be considered as soon as the diagnosis of insufficiency is confirmed, especially in those patients who require surgery. Glucocorticoid replacement should precede thyroid hormone replacement in order to avoid precipitating adrenal crisis. Posterior pituitary dysfunction, typically diabetes insipidus (DI) is uncommon as a presenting symptom; when seen in association with sellar mass, the diagnosis is unlikely to represent a pituitary adenoma. Diabetes insipidus is characterized by polyuria/polydipsia, hyposthenuria and tendency to hyperosmolar dehydration if access to water is limited or thirst is deficient; confirmation may require a water deprivation test in uncertain cases. Hyponatremia may also occur in patients at the time of their initial presentation as a consequence of the syndrome of inappropriate antidiuretic hormone secretion (SIADH), central hypoadrenalism, or hypothyroidism.
Pituitary adenomas may be associated with excess hormone secretion, giving rise to well-characterized clinical syndromes. It is important to recognize these preoperatively, especially since surgical treatment in some instances is not first-line therapy. In particular, patients with prolactin-secreting pituitary adenomas may be offered a trial of medical therapy, as dopamine agonists are effective in controlling tumor size and relieving mass effect.
Excess Prolactin (Prolactinomas)
Prolactin levels in women are physiologically increased during pregnancy, and are responsible for lactation; prolactin levels in healthy men are typically low. Excess prolactin in women leads to the syndrome of amenorrhea/galactorrhea, and hypogonadism with sexual dysfunction in men. Mildly elevated prolactin levels may be related to medication effects (dopamine antagonists, e.g., psychotropic medications), a microprolactinoma, or “stalk effect.” (Table 78-3). This phenomenon occurs from the loss of tonic dopamine inhibition on the lactotrophs of the pituitary by any nonspecific mass compressing the pituitary stalk. Thus a nonfunctioning tumor or other pituitary lesion of sufficient size can lead to a moderately elevated prolactin level, usually less than 200 ng/mL, and this must be distinguished from a prolactinoma, as treatments are potentially different. A large tumor in the setting of a mildly elevated prolactin level likely represents “stalk effect” rather than a true prolactinoma; a mildly elevated prolactin level in the setting of a microadenoma likely represents a true microprolactinoma. Caution is advised in the interpretation of prolactin levels in patients with large sellar masses. Giant macroprolactinomas may secrete prolactin exuberantly, giving rise to the “hook effect,” an immunoassay artifact that occurs in the presence of very high serum concentrations of prolactin, leading to substantial underreporting of prolactin levels. To avoid this artifact, prolactin should be measured in serially diluted serum specimens in patients with large sellar lesions.
Excess Cortisol (Cushing Syndrome)
Hypercortisolemia of any cause is known as “Cushing syndrome.” These patients may present with a wide variety of manifestations, including metabolic (central adiposity, glucose intolerance), catabolic (muscle wasting, increased fracture risk, skin thinning, spontaneous ecchymoses, increased risk of infection), cardiovascular (hypertension, thromboembolism, coronary artery disease), mineralocorticoid (edema, hypokalemia), hypogonadal, hyperandrogenic (hirsutism, acne), and psychiatric symptoms. There are a number of causes of Cushing syndrome, including (most commonly) iatrogenic, but important neoplastic causes potentially requiring surgical treatment include pituitary adenomas, adrenal adenomas/carcinomas, or the ectopic secretion of ACTH by a nonpituitary/adrenal source, usually carcinoid tumors or small cell lung cancers. Approximately 70% to 80% of patients with noniatrogenic causes of Cushing syndrome will have a pituitary adenoma (Cushing disease). The diagnosis of Cushing disease can be difficult, and is best performed by an endocrinologist experienced in pituitary evaluation. Hypercortisolemia is determined by measurement of 24-hour urine free cortisol levels, elevated serum cortisol levels on dexamethasone suppression testing, and, more recently, by elevated late-night salivary cortisol levels. These tests help establish the presence of cortisol excess and differentiate between Cushing syndrome and other states associated with high cortisol levels (Table 78-4). ACTH dependence or independence is determined by the measurement of plasma ACTH levels; low ACTH levels (ACTH independence) is seen with adrenal disease, as the increased cortisol levels are secreted independently of central ACTH production, resulting in normal feedback inhibition of pituitary ACTH production. High or inappropriately normal ACTH levels (ACTH dependence) are seen with pituitary or ectopic sources. Normal ACTH levels in association with hypercortisolemia can also occur when diurnal variation is lost, and typically point to a central rather than adrenal source. Dexamethasone suppression testing can be performed to biochemically differentiate pituitary from ectopic sources. Classically, failure to suppress cortisol levels with high-dose dexamethasone is associated with an ectopic source, though this may also be seen with some pituitary macroadenomas. While pituitary MRI imaging may demonstrate an adenoma, typically the microadenomas of Cushing disease are very small, and may not appear on MRI in 30% to 40% of patients. In these cases confirmation of a pituitary source requires bilateral inferior petrosal sinus sampling, where ACTH levels obtained from the inferior petrosal sinuses (both before and after the intravenous administration of corticotropin-releasing hormone [CRH]) are compared to levels obtained in the vena cava; a central-peripheral ACTH ratio of greater than 3:1 after the administration of CRH is considered diagnostic of a central source, even in the absence of tumor visualization on MRI.18
Table 78-3 Causes of Hyperprolactinemia
Table 78-4 Conditions Associated with Cortisol Excess
Excess Growth Hormone (Acromegaly)
Excess growth hormone secretion by a pituitary adenoma in childhood, prior to epiphyseal closure, leads to gigantism, while growth hormone excess in adulthood leads to acromegaly. Adult patients will typically report increased ring and shoe size, dental and jaw abnormalities with malocclusion, coarsening of facial features (often falsely attributed to aging), headache, hoarseness, skin tags, increased sweating, carpal tunnel syndrome, arthralgias, frequent snoring, and sleep apnea. Because these changes occur slowly over time, diagnosis can be delayed, and these tumors are often larger and invasive at the time of detection. Systemic changes include glucose intolerance or frank diabetes mellitus, hypertension, and cardiomyopathy. There is an increased risk of colon polyps, and possibly colon and thyroid cancer. Acromegalic patients have a mortality risk on the order of 2 to 3 times that of the general population, if growth hormone excess is not adequately controlled. Many of these changes are reversible with successful control of the disease, but skeletal abnormalities are not. Because growth hormone secretion is pulsatile, random growth hormone measurements are not diagnostic. IGF1 (somatomedin C) is a protein produced mostly in the liver in response to growth hormone levels over time; it acts to integrate the pulsatile growth hormone levels and serves as the best single indicator of disease activity. IGF1 assays are technically challenging and require gender and age adjustment, as growth hormone levels increase during childhood and adolescent development and decrease with aging, and are higher in males than females. Because growth hormone is physiologically suppressed by a glucose load, glucose-suppressed growth hormone levels have been used as an indicator of disease activity, since acromegalic patients fail to suppress and may paradoxically increase. The criterion for adequate suppression has varied with the available growth hormone assay; current best available assays require suppression to at least GH <1 ng/mL (ideally below 0.4 ng/mL). Growth hormone measurements over time (day curve) have also been used in diagnosis, but are cumbersome to determine in an outpatient setting.
While immunocytochemical staining for TSH is not uncommon, secretion of active thyrotropin in excess leading to central hyperthyroidism is rare. These patients will manifest the clinical syndrome of hyperthyroidism with attendant systemic manifestations. The majority of these tumors are macroadenomas and may therefore be associated with mass effect. Biochemically, they demonstrate a nonsuppressed (inappropriately normal or increased) TSH level, in the setting of elevated thyroid hormones, that is, one does not see the feedback-inhibited TSH levels associated with primary hyperthyroidism. This syndrome needs to be distinguished from resistance to thyroid hormone which can lead to a similar hormone profile.
Endocrine Evaluation of a Pituitary “Incidentaloma”
With the widespread availability of MRI imaging, it is not uncommon for the radiologist to report the incidental finding of a pituitary mass. The endocrine evaluation requires screening of pituitary hormone levels to determine possible hypo- or hyperfunction, which will help to guide further therapy. Physiologic pituitary hypertrophy can be difficult to distinguish from a true pituitary adenoma, but requires an appreciation of the clinical setting to guard against unnecessary surgical intervention. Typically, adolescents, especially adolescent females, can demonstrate physiologic hypertrophy during puberty and for a few years thereafter, and women during pregnancy or during lactation can demonstrate physiologic enlargement of the gland from lactrotroph hyperplasia. Patients with unrecognized severe primary hypothyroidism can present with pituitary enlargement, sometimes striking, as a result of thyrotroph hyperplasia, which resolves with appropriate thyroid replacement. Rarely, ectopic secretion of growth hormone releasing hormone or corticotropin releasing hormone may lead to somatotroph or corticotroph hyperplasia, respectively. All these conditions need to be distinguished from true pituitary adenomas.
NEUROLOGIC EVALUATION IN PITUITARY ADENOMAS
The primary neurologic manifestation of a pituitary mass is ophthalmologic, from compression of the optic nerves or chiasm traveling through the suprasellar cistern. Because the ipsilateral retinal ganglion cell axons cross in the optic chiasm en route to the contralateral occipital cortex, the pathognomonic finding on visual field examination is a bitemporal hemianopsia (“pie-in-the-sky”). The chiasm may sometimes be associated with a relatively short intracranial optic nerve segment (“prefixed”) or a relatively long intracranial optic nerve segment (“post fixed”). Depending upon the relative position of the tumor and chiasm, compression may also lead to uni- or bilateral optic nerve dysfunction, or compression of an optic tract, with a homonymous hemianopsia. Patients may sometimes report decreased acuity, although central vision is usually preserved unless compression is severe. A unilateral decrease in color vision is a sensitive sign of an early optic neuropathy, as is an afferent pupillary defect (Marcus Gunn pupil). This can be demonstrated by the “swinging flashlight test,” where light shown into the affected eye leads to a paradoxical increase in pupillary size, as the ipsilateral pupillo-constrictor fibers have been damaged by ipsilateral optic nerve compression and transmit relatively decreased retinal activity. Although pituitary adenomas will often invade the cavernous sinus and displace the cranial nerves within, cranial nerve dysfunction other than optic is uncommon. When present, and especially if of sudden onset, one should suspect a rapidly expanding mass, that is, pituitary apoplexy, or a more aggressive tumor, for example, a malignancy. Similarly, pituitary adenomas will often circumscribe but rarely constrict the cavernous carotid artery or cause neurovascular dysfunction; when present an alternate pathologic diagnosis (especially meningioma) should be considered.
IMAGING OF PITUITARY ADENOMAS
Magnetic Resonance Imaging
MRI has revolutionized the visualization of intracranial lesions in general and pituitary tumors in particular. Useful pulse sequences for imaging the sella include T1 coronal and sagittal imaging before and after gadolinium administration. Other sequences (e.g., T2 coronal) may be useful, especially in the evaluation of cystic structures (fluid is generally hyperintense on T2) and previous hemorrhage (which may be dark on T2). Because of the relative decreased vascularity of adenomas as opposed to normal gland, timing of scanning relative to the administration of gadolinium is important; adenomas are generally focally hypointense to normal gland. Dynamic scanning using thin section gradient echo sequences may improve the sensitivity of visualization with small microadenomas (e.g., in Cushing disease), but gland heterogeneity may lead to decreased specificity.
CT scanning has largely been supplanted by MRI, but remains useful in the delineation of bony anatomy for surgical planning and navigation. In those patients who cannot have an MRI, thin section coronal CT after contrast administration can be used to demonstrate a pituitary lesion. The presence of calcification on CT scanning can assist with the differential diagnosis, for example, a calcified cystic lesion, especially in a child, is highly likely to represent a craniopharyngioma.
The normal gland enhances relatively homogenously. It should be no greater than about 8 mm in coronal height in males and 10 mm in females. The infundibulum should be midline. The posterior pituitary may be bright on T1 without contrast (thought to represent secretory granules in axon terminals), although this is not a constant finding.
Pituitary adenomas should be focally hypointense relative to normal gland on T1 sequences after contrast. Microadenomas (<1 cm) may not significantly disrupt gland architecture. Macroadenomas (>1 cm) show upward bowing of the diaphragm sella associated with stalk deviation, and larger macroadenomas will demonstrate compression of the chiasm. The normal gland can be compressed, usually superiorly and posteriorly. The cavernous sinus is variably involved; it can be difficult to distinguish invasion as opposed to compression. Lesions surrounding the cavernous carotid are obviously invasive; lesions which circumscribe less than 25% are usually compressive. It has been suggested than lesions which circumscribe less than 67% of the carotid diameter are not invasive, but this is very variable. Adenomas can also be cystic, which may show T1 bright signal before contrast consistent with high protein fluid or hemorrhage.
Craniopharyngiomas may be cystic or solid, and intra- or suprasellar. Characteristics of the cyst fluid can vary with the protein content, with greater T1 hyperintensity associated with higher protein. The cyst wall is commonly calcified on CT, especially in children. Since the tumor is often suprasellar or arises along the stalk, the gland is typically compressed inferiorly from above.
Pituitary cysts can demonstrate variable imaging characteristics also depending upon their protein content. Rathke cleft cysts arise posteriorly in the sella, or sometimes along the stalk. They can be T1 hypo- or hyperintense depending on protein content, and can compress the gland anteriorly or from above. The cyst wall is usually thin with minimal enhancement. If there is a solid component or calcification, the diagnosis is more likely to represent a craniopharyngioma. Arachnoid cysts of the sella contain fluid isointense to CSF. There will be minimal if any enhancement of the wall, as the cyst is lined with a thin arachnoid layer. The gland is usually compressed inferiorly or anteriorly.
Other Sellar Lesions
Germinomas usually involve the posterior gland, stalk, and/or hypothalamus. They are typically brightly enhancing, and the borders are relatively indistinct. An enhancing lesion of the posterior sella associated with a pineal mass is highly likely to represent a germinoma. Germ cell tumors may disseminate along CSF pathways, leading to enhancement around the fourth ventricle. Meningiomas are usually brightly enhancing, often more so than the gland itself. As they arise from the dura, they can be variably located in and around the sella. If they arise from the diaphragm, they can be difficult to distinguish from adenomas, but usually compress the gland from above. Meningiomas are often associated with a dural “tail,” which spreads out from the central mass of the tumor, and sometimes with focal hyperostosis. Meningiomas of the cavernous sinus can lead to carotid constriction, best seen on coronal images when comparing the transverse diameter of the intracavernous carotids, while adenomas rarely do. Metastases are typically locally invasive, brightly enhancing, and rapidly growing. They can spread hematogenously to the gland, or represent focal metastases to parasellar bony structures. When invading the cavernous sinus they can lead to a cavernous sinus syndrome, while adenomas rarely do.
Although the first reported pituitary operation was a craniotomy done in 1889 by Sir Vincent Horsley,19 the first transsphenoidal approach was described in 1907 by Hermann Schloffer, a Viennese otolaryngologist, when he reached the sphenoid via a lateral rhinotomy incision.20 Less disfiguring approaches were devised by the American neurosurgeon Harvey Cushing, who, with William Halsted, devised the sublabial approach in 1910, and another Viennese otolaryngologist, Oscar Hirsch, who described a fully endonasal procedure.21 Variants of these approaches remain in use today. Cushing performed over 200 transsphenoidal operations with an overall mortality rate of 5% – amazingly low given the lack of imaging, antibiotics, hormone replacement, and modern visualization – but decided in 1927 that the craniotomy was the more preferred procedure. With his decision, the transsphenoidal approach fell into relative disfavor, although kept alive by Dott in Edinburgh and Guiot in Paris, who introduced the use of intraoperative fluoroscopy as a navigation technique. When Jules Hardy of Montreal described the use of the operating microscope and reported the first removal of a pituitary microadenoma in 1962, pituitary surgery entered the modern era.22
The transsphenoidal approach is relatively noninvasive, as it employs the nasopharynx and sphenoid sinus to access the skull base, but the surgeon is constrained to operate through a narrow corridor, to a relatively deep target, surrounded by important structures (carotids and optic apparatus). The surgeon must (1) approach and navigate to the tumor, (2) visualize the pathology, and (3) maximally resect the tumor while minimizing damage to the adjacent structures, that is, normal gland.
There are three transsphenoidal approaches to the sella in use today, in addition to the seldom necessary subfrontal craniotomy (Fig. 78-2). The sublabial approach, described by Cushing and Halsted, employs an incision in the gingiva with a submucosal dissection to the bony nasal aperture, and then a submucosal dissection along the septum to the sphenoid. Because the approach is not constrained by the width of the nares, the degree of access is relatively wide, but the gingival incision is painful, can be associated with numbness of the teeth and gums, and usually requires nasal packing to reapproximate the mucosa. The two endonasal approaches are constrained by the width of the nasal aperture, but avoid the complications associated with a gingival incision. The approach described by Hirsch uses a submucosal tunnel along the septum through an anterior mucosal incision immediately posterior to the columella; Hirsch felt that the submucosal tunnel gave him a relatively sterile field through which to access the sphenoid, important in the days prior to antibiotics, but this approach also requires nasal packing to reapproximate the mucosa to the septum, which patients find uncomfortable. The direct endonasal approach described by Griffith and Veerapen23 and Cooke and Jones24 uses either an incision at the insertion of the septum into the face of the sphenoid, or an enlargement of the natural ostia, with a posterior septectomy. Because there is no submucosal tunnel, nasal packing is usually not required.
Figure 78-2. Surgical approaches to the sella.