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Practical Pituitary Pathology What Does the Pathologist Need to Know?

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Practical Pituitary Pathology What Does the Pathologist Need to Know? Practical Pituitary Pathology What Does the Pathologist Need to Know? Sylvia L. Asa, MD, PhD ● Context.—The sellar region is the site of frequent pa- Conclusions.—The initial examination requires routine thology. The pituitary is affected by a large number of path- hematoxylin-eosin to establish whether the lesion is a pri- ologic entities arising from the gland itself and from adja- mary adenohypophysial proliferation or one of the many cent anatomical structures including brain, blood vessels, other types of pathology that occur in this area. The most nerves, and meninges. The surgical pathology of this area common lesions resected surgically are pituitary adeno- requires the accurate characterization of primary adeno- mas. These are evaluated with a number of special stains hypophysial tumors, craniopharyngiomas, neurologic neo- and immunohistochemical markers that are now available plasms, germ cell tumors, hematologic malignancies, and metastases as well as nonneoplastic lesions such as cysts, to accurately classify these tumors. The complex subclas- hyperplasias, and inflammatory disorders. sification of pituitary adenomas is now recognized to re- Objective.—To provide a practical approach to the di- flect specific clinical features and genetic alterations that agnosis of pituitary specimens. predict targeted therapies for patients with pituitary dis- Data Sources.—Literature review and primary material orders. from the University of Toronto. (Arch Pathol Lab Med. 2008;132:1231–1240) number of pathologic processes occur in the region of ment of new pharmacotherapeutic agents, improved min- A the pituitary gland. They include primary pituitary imally invasive surgical approaches, and targeted radio- lesions that are unique to this site, as well as disorders therapeutic techniques. The surgical pathologist must arising in adjacent anatomical structures such as brain, therefore recognize the important role of morphologic blood vessels, nerves, and meninges. The surgical pathol- analysis in classifying sellar pathology for the diagnosis ogy of this area requires the accurate characterization of and management of the pituitary patient. neoplastic lesions, including pituitary adenoma and car- cinoma, craniopharyngioma, neurologic neoplasms, germ THE ROLE OF CLINICAL INFORMATION cell tumors, and hematologic malignancies, and their dis- The importance of clinical information cannot be over- tinction from nonneoplastic disorders such as cysts, hy- emphasized in this field. Patients with pituitary disease perplasias, and inflammatory lesions.1,2 The spectrum of may present with symptoms and signs of hormone excess, pituitary pathologies that represent the surgical pathology or they may manifest features of a mass lesion, including of the pituitary is outlined in Table 1. headache, visual impairment, and hypopituitarism. The The commonest disorder is the pituitary adenoma, a le- former usually indicates a primary adenohypophysial dis- sion that is increasingly recognized as a highly prevalent order, but it should be recognized that hyperprolactinemia finding. A recent meta-analysis has shown that the post- may be a nonspecific finding because of a mass lesion that mortem prevalence of pituitary adenoma is 14.4% and that obstructs the pituitary stalk, interrupting blood flow that radiologic studies identify a lesion consistent with pitui- maintains prolactin (PRL) under tonic inhibition. The lat- tary adenoma in 22.2% of the population, providing an ter can be the result of any mass lesion in the region of overall estimated prevalence of 16.9%.3 Although many of the sella. The finding of diabetes insipidus or cranial nerve these lesions are considered to be incidental findings, dysfunction make the diagnosis of a primary adenohy- many have unrecognized impact on fertility, longevity, pophysial cell proliferation unlikely and instead suggest and quality of life, and their clinical significance is increas- other tumor types or inflammatory disorders. ingly gaining attention. Moreover, the management of Despite the importance of clinicopathologic correlation, these lesions has seen major changes with the develop- the reality is that many pathologists are faced with diag- nosing a lesion without clinical information. In most in- stances it is possible to determine a remarkable amount Accepted for publication January 30, 2008. of information with careful morphologic evaluation using From the Department of Pathology, University Health Network, To- a targeted approach. ronto, Ontario. The author has no relevant financial interest in the products or com- AT THE TIME OF SURGERY panies described in this article. Reprints: Sylvia L. Asa, MD, PhD, Department of Pathology, Univer- The initial handling of tissue obtained at pituitary sur- sity Health Network, 200 Elizabeth St, 11th Floor, Toronto, Ontario, gery should ensure adequate fixation in formalin for his- Canada M5G 2C4 (e-mail: [email protected]). tology and immunohistochemistry. In rare cases, there Arch Pathol Lab Med—Vol 132, August 2008 Pituitary Pathology—Asa 1231 Table 1. Classification of Pituitary Pathology* gland intact. In the case of a large lesion, the sella may be eroded to the point where it must be resected en bloc. Neoplastic However, in most patients the sellar diaphragm can be Benign† opened and the dorsum sellae fractured to push it pos- Pituitary adenoma teriorly, allowing the gland to be removed intact. The Craniopharyngioma Gangliocytoma/ganglioglioma gland then can be evaluated grossly and sectioned for Granular cell tumor complete histologic evaluation. Meningioma There are 2 approaches to the sectioning and embed- Schwannoma ding of the pituitary (Figure 1). Many investigators use Chordoma sagittal sections through the gland; others prefer trans- Vascular and mesenchymal tumors verse sections. The former permit examination of the stalk; Malignant the latter provide a more thorough examination of the Pituitary carcinoma gland and more accurate determination of the geographic Gliomas distribution of the various cell types, at the expense of Germ cell tumor examining the stalk carefully. Lymphoma/leukemia/Langerhans cell histiocytosis Vascular and mesenchymal tumors HISTOLOGY Metastases Miscellaneous (salivary gland lesions, melanoma, etc) The initial evaluation of a pituitary specimen involves Nonneoplastic review of material stained with hematoxylin-eosin. This Hyperplasia routine stain allows the distinction of primary adenohy- pophysial pathologies from other entities. Rathke cleft Inflammatory lesions cysts, arachnoid cysts, and dermoid cysts (Figure 2) are Infectious recognized based on preoperative clinical and radiologic Immune findings and confirmed with the identification of the ap- Cysts propriate cyst lining.4 Hypophysitis of any type5 can be Rathke cleft cysts readily recognized with this conventional stain (Figure 3). Arachnoid The various tumors that arise in the sella—gliomas, me- Dermoid/epidermoid ningiomas, schwannomas, and chordomas—are consid- Aneurysms ered based on this analysis and their workup is different Meningoencephalocele than that of a pituitary adenoma. Unusual hypothalamic Hamartoma Brown tumor of bone neuronal gangliocytomas and gangliogliomas can give rise to clinical features of hormone excess that can mimic * Surgical pathology only, not including developmental and meta- 6 bolic lesions that are not biopsied. pituitary adenoma, but must be recognized, either dis- † Although classified as benign, many of these lesions are locally tinct from an adenoma or associated with one. invasive and cause significant morbidity and mortality. Craniopharyngioma is a unique tumor of the sellar re- gion that is derived from the oropharyngeal remnants of Rathke pouch. These lesions have a characteristic mor- may be a need for ultrastructural analysis; because this phology that requires only routine hematoxylin-eosin situation is not often predicted clinically, it is recommend- staining for identification and classification (Figure 4). ed that a small piece of tissue be routinely fixed for elec- They are composed of cords or islands of squamoid epi- tron microscopy and retained in the event that it is need- thelial cells in a loose fibrous stroma with varying degrees ed. Currently there is no need for special handling of tis- of desquamation and intervening cysts that often contain sue for other diagnostic techniques. a thick oily fluid.1 They can be subclassified as adaman- Most pituitary specimens are very small and the tissue tinomatous and papillary types; the former are known to may be compromised by freezing artifact when surgeons harbor mutations of the ␤-catenin gene as a specific mo- request intraoperative consultation and frozen sections are lecular pathogenetic mechanism.7,8 These lesions have a performed. In some centers, pathologists use smear tech- bimodal distribution with peaks in childhood and in the nology for intraoperative consultation to prevent this ar- sixth decade. Although adamantinomatous lesions pre- tifact; this method uses less tissue but requires experience dominate in childhood, most craniopharyngiomas in for interpretation. Sometimes, the only diagnostic tissue is adults have a mixed pattern and the clinical significance in the material used for the intraoperative procedure and of subclassification remains uncertain. it is fraught with artefact that precludes accurate evalua- Germ cell tumors of the sella resemble germ cell tumors tion. Because valid indication for intraoperative consulta- in other sites of the body.9 Hematologic malignancies
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