fibrosis, depending on the chronicity of the condition. Several lines of evidence suggest that this process has an autoimmune basis (177-180). First, the cellular infiltrate present in affected glands is similar to other autoimmune reactions occurring in other organs. Antipituitary antibodies have been identified in the serum of some patients with the condition. Finally, patients with lymphocytic hypophysitis frequently have a concurrent or prior history of other autoimmune diseases (Hashimoto's thyroiditis, idiopathic adrenalitis, pancreatitis, and others), thus suggesting that lymphocytic hypophysitis is but one component of a generalized polyglandular autoimmune disorder.
The clinical profile of lymphocytic hypophysitis is fairly characteristic. Although the condition was once believed to affect women exclusively, ever-
increasing reports of its occurrence in men have established that males, too, may be affected, although considerably less often (181,182) (Fig. 8). One of the most typical features of the condition concerns its temporal association with pregnancy; almost 70% of reported cases occur during pregnancy or more commonly during the first postpartum year. Indeed the condition is sometimes called postpartum hypophysitis. Clinically, the picture is one of progressive anterior pituitary failure in association with an expansile sellar mass. The pituitary insufficiency may involve any or all anterior pituitary hormones; manifestations of hypocortisolism have been especially prominent among reported cases.
Amenorrhea or failure of appropriate resumption of menses following parturition is a common presenting complaint; galactorrhoea occurs less frequently. The amenorrhoea is at least in part related to the compression, a common accompaniment to the condition. Because the posterior lobe escapes injury, DI is not ordinarily a feature of the condition. Because there is often considerable enlargement of the gland, the majority of patients also have symptoms of mass effect, including headache and visual loss. The radiologic appearance of lymphocytic hypohysitis is nonspecific. Plain films may demonstrate sellar enlargement and suprasellar extension, and MRI scanning shows a sellar/suprasellar mass that is homogeneously isointense to brain parenchyma.
In its most typical clinical context, such as that involving the pregnant or postpartum female presenting with a sellar region mass, lymphocytic hypophysitis should be an obvious diagnostic consideration. Prolactin-producing pituitary adenomas, given their known tendency to enlarge during pregnancy, are probably the most commonly considered differential diagnosis. In other clinical situations not related to pregnancy, or those involving male patients, a prospective diagnosis of a lymphocytic hypophysitis cannot be made with any certainty. In all cases, however, the definitive diagnosis requires histologic confirmation. Accordingly, the management of this condition involves establishing a tissue diagnosis and chiasmal decompression—objectives best served by the transsphenoidal route. The gland typically appears firm and diffusely enlarged and has a pale-yellow appearance. The surgical goal is to remove sufficient tissue for histologic diagnosis and chiasmal decompression while preserving as much of the viable gland as possible, thus maximizing prospects for residual pituitary function.
Given the presumed autoimmune origins of lymphocytic hypophysitis, the therapeutic use of immunosuppressive agents has met with some success as an adjuvant form of therapy for this condition. In some patients, corticosteroid therapy has resulted in reduction in the size of the sellar mass and improvement in visual function, prompting some authors to recommend such therapy from the start, thus avoiding the immediate need for surgical decompression or tissue diagnosis (179). It is acknowledged, however, that experience with this approach has been limited and that steroids have not proven uniformly successful in ameliorating the inflammatory process (183).
Endocrine replacement therapy is an essential component of the management of this disorder. Pituitary insufficiency should be carefully assessed and appropriately treated both at presentation and during long-term follow-up. Because the degree of anterior pituitary destruction is typically quite severe, most patients with lymphocytic hypophysitis require chronic long-term replacement therapy.
Known as one of the "great imitators," sarcoidosis is well recognized for its periodic affinity for parasellar structures, serving as an occasional diagnosis of exclusion for masses and other inflammatory processes affecting this region (178,184,185). As a chronic multisystem granulomatous disease of unknown origin, sarcoidosis can affect any organ or tissue, with uveoparotitis, pulmonary, and lymph node involvement being its classical manifestations.
Five percent of all cases exhibit nervous system involvement, most commonly in the form of dense adhesive granulomatous arachnoiditis involving the base of the brain (185). Cranial nerves, the pituitary gland stalk, hypothalamic, and anterior third ventricular structures may all be engulfed in the inflammatory process. Less frequently, neurosarcoidosis can assume the form of discrete masses, both in the parasellar region and elsewhere in the neuroaxis.
The clinical features of neurosarcoidosis are variable and reflect the degree of anatomic involvement. The hypothalamus and pituitary stalk are favored targets, and accordingly features of hypothalamic dysfunction often predominate (186). The single most common feature of CNS involvement—one occasionally serving as the presenting feature of the disease in general—is DI. This usually reflects hypothalamic involvement and, less often, damage to the stalk. Additional evidence of hypothalamic disease in the form of somnolence and alterations of eating, emotion, and thermoregulation often coexist. Damage to hypo-physiotropic areas of the hypothalamus or the stalk can result in hypopituitarism and low-grade hyperprolactinemia. Primary involvement of the anterior pituitary may also be the source of hypopituitarism, but less commonly. Visual dysfunction secondary to optic nerve and chiasmal involvement also occurs. Depending on the extent of basilar meningeal involvement, other cranial nerve palsies may also occur. Hydrocephalus, reflecting basilar meningeal or third ventricular obstruction, may be present.
Imaging studies, when positive, generally reveal an enhancing meningeal process, or evidence of a discrete mass of the sellar region. A search for active disease in the lungs or elsewhere is often informative in providing corroborative evidence of sarcoidosis; however, definite diagnosis requires biopsy. Because the histopa-thology of sarcoidosis is often characteristic but falls short of being diagnostic, this is a diagnosis of exclusion. A compatible clinical profile, histologic evidence of noncaseating granulomas, and negative bacterial and fungal cultures of biopsy specimens are the practical diagnostic criteria used for this entity. CSF studies, though frequently abnormal (lymphocytic pleocytosis, elevations of protein and immunoglobins, decreased glucose concentrations), are nonspecific.
From the surgical perspective most cases of sarcoidosis involving the sellar region present as undiagnosed mass lesions, occurring in the absence of recognized systemic sarcoidosis. Therefore, the surgical objectives primarily include establishing a tissue diagnosis and decompression of the visual apparatus. Once the diagnosis is established, corticosteroids are often effective therapy. In cases unresponsive to steroids, chloroquine, azathioprine, and methotrexate have all been used with varying degrees of success. The prognosis is variable, being most favorable in patients with limited disease, where spontaneous remission is also occasionally seen. In other patients, particularly those with pulmonary involvement and disease in more than three organ systems, the prognosis is poor.
Langerhans Cell Histiocytosis (Histiocytosis X)
Langerhans cell histiocytosis is an umbrella term encompassing a collection of poorly understood clinically heterogeneous but pathologically interrelated entities. Unified pathologically and pathognomonically by a destructive infiltrate of foamy histiocytes in affected organs, the clinical expression of Langerhans cell histiocytes is variable, depending on the extent and nature of organ involvement. Ranging from the fulminant, disseminated, and frequently fatal Letterer-Siwe disease seen in childhood, through the multifocal eosinophilic
granulomas of Hand-Schuller-Christian disease, and to the relatively innocent solitary eosinophilic granulomas of bone, involvement of parasellar structures may be a feature of each.
CNS involvement, usually in association with multifocal bony lesions, occurs in almost one quarter of all patients with systemic Langerhans cell histiocytosis; isolated CNS involvement is, however, rare (187). There is an apparent predilection for involvement of the hypothalamus, infundibulum, and posterior pituitary, with adenohypophyseal involvement occurring less frequently (188-194). In some cases, the disease is discretely localized in the hypothalamus or posterior pituitary. In other cases the process is less restricted, with bony disease of the skull base and secondary infiltrates both compressing and permeating meningeal and multiple parasellar structures. DI is the most common presenting feature of CNS disease and commonly is the first sign of unrecognized systemic disease. Hyperprolactinemia on the basis of stalk or hypothalamic involvement may also present. Involvement of the optic apparatus occurs less frequently, and anterior pituitary function is often spared. Imaging studies are nonspecific, typically revealing obvious bony disease, with a contiguous soft tissue component.
If the diagnosis is already known, owing to the multisystem nature of the disease, there is no role for surgical intervention. In the rare situation of an isolated parasellar granuloma, the surgical objective in this condition is directed primarily at establishing a histologic diagnosis, and possibly decompression of compromised sellar structures. A definitive diagnosis rests on the identification of the intracytoplasmic organelles known as Birbeck granules, the demonstration that cells of the histiocytic infiltrate bear the CD1 antigenic determinant, and the confirmation that bacterial and fungal cultures of the surgical specimen are negative.
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