Review of xanthomatous lesions of the sella

Abstract

Xanthomatous lesions of the sellar region have traditionally been divided into two separate categories, xanthomatous hypophysitis (XH) and xanthogranuloma (XG) of the sellar region. The seminal article on XH, a condition typified by foamy histiocytes and lymphoplasmacytic infiltrates in the pituitary gland/sellar region, but usually little or no hemosiderin pigment, detailed three patients. However, most reports since that time have been single cases, making understanding of the entity difficult. In contrast, the seminal report on XG, characterized by sellar region cholesterol clefts, lymphoplasmacytic infiltrates, marked hemosiderin deposits, fibrosis, multinucleated giant cells around cholesterol clefts, eosinophilic granular necrotic debris, and accumulation of macrophages, included 37 patients, allowing more insights into etiology. Few examples could be linked to adamantinomatous craniopharyngioma, and although ciliated epithelium similar to that of Rathke cleft cyst (RCC) was identified up to 35% of the 37 cases, it could not be proven that XG was related to hemorrhage into RCC. Case reports since that time, however, occasionally linked XG to RCC when an etiology could be identified at all, and a few recognized that a spectrum exists in xanthomatous lesions of the sella. They review literature, adding 23 cases from our own experience, to confirm that overlap occurs between XH and XG, and that the majority-but not all-can be linked to RCC leakage/rupture/hemorrhage. It was suggested that progressive accumulation of hemosiderin pigment in the lesion, possibly caused by the multiple episodes of bleeding, could account for the transition of at least some cases of XH to XG.

Keywords: cholesterol clefts; histiocytes; xanthoma.

Figure 1

Coronal magnetic resonance images (MRI), with gadolinium of patients #1 and #4. a. Although the neuroimaging appearance was variable amongst xanthomatous lesions of the sella, many cases of xanthomatous hypophysitis manifest a ring‐enhancing appearance, prompting consideration of infection. b. This xanthogranuloma had the unusual appearance of a fluid–fluid level.

Figure 2

Coronal magnetic resonance images (MRI), with gadolinium. a, b. This patient (#2) required two neurosurgical resections to control the growth of her sellar region mass; the appearance prior to each resection is shown. c. Patient #9 was one of two that was monitored over time with serial MRIs, which clearly show the growth of the lesion over time.

Figure 3

Intraoperative transnasal endoscopic images from patient #22 are illustrated. Intraoperative impressions of xanthomatous hypophysitis and xanthogranuloma of the sella were also quite varied but in several instances contributed significantly to the understanding of the lesion as a whole. Despite dry flaky keratin and focal keratohyaline layer in the squamous epithelium of the cystic lesion in this case, the neurosurgeon intraoperatively identified and photographed the mucoid material shown, which is not typical for epidermoid cyst contents. No mucin was received in the pathology specimen.

Figure 4

Xanthomatous hypophysitis (XH) manifested grumous material, sometimes with a few cholesterol clefts or neutrophils embedded within it (a), admixed macrophages (b), occasional hemosiderin within macrophages as seen on Perl's iron stain (c), and more cohesive sheets of foamy histiocytes admixed with lymphoplasmacytic infiltrates (d). Macrophages within the grumous debris often showed degenerative features and thus were best highlighted by CD68 immunostaining for macrophages (e), as seen here in the predominant XH component of an example with a small focus of xanthogranuloma (XG) development (f). Where present in the surgical specimen in XH, the anterior pituitary gland showed inflammation and sometimes considerable disruption of architecture (g). XGs consisted of abundant cholesterol clefts surrounded by multinucleated giant cells (h) and embedded in fibrotic background. Occasional examples of either XG or XH showed metaplastic ossification (i). All H&E except CD68 immunostaining with light hematoxylin counterstain (e) and Perl's iron (c).

Figure 5

Most cases of XH and XG had strips of columnar epithelium (a), usually ciliated (b) and sometimes best seen on touch preparation (b), although ciliation could be easily identified on permanent sections, especially using oil immersion (c, e, f, h, i). Focal goblet cells in the epithelium could be found in the highly‐ciliated epithelium of several cases (e, f, h) and squamous metaplasia (d, g) had to be distinguished from basal cell hyperplasia. Collections of neutrophils contributed to the impression of possible infection (c), although infectious organisms could not be demonstrated. Russell bodies within plasma cells were often conspicuous (h). All H&E.

Figure 6

Case 21 had a XG with abundant cholesterol clefts and giant cells associated with wet keratin (a), although focal small glands contained mucin and showed adjacent mononuclear cell inflammation in the specimen (b). The columnar, focally pseudostratified epithelium contained occasional goblet cells (c) and showed abrupt change to squamous epithelium containing wet keratin (d, e). Despite this, no nuclear beta catenin was found on immunostaining, even adjacent to wet keratin (f).