Pituitary adenoma associated with xanthogranuloma

Abstract

Xanthogranuloma (XG) of the sellar region is a non-neoplastic inflammatory lesion characterized histologically by recent and remote hemorrhage, necrotic debris, fibrosis, chronic inflammation, and cholesterol clefts with associated foreign-body giant cells. The inflammatory lesion was recognized by the World Health Organization in 2000. XG of the sellar region is rare. Cases of pituitary adenoma (PA) with an associated XG (PA/XG) are extremely rare, with a total of 16 cases in the literature. PA/XG lacks specific clinical and radiologic signs, making pre-operative diagnosis challenging. Herein, we report a case of PA/XG, describe the radiologic and pathologic findings, and discuss the role of so-called silent or “subclinical pituitary apoplexy” in the possible histogenesis of PA/XGs.

Introduction

Xanthogranuloma (XG) of the sellar region is a non-neoplastic inflammatory lesion characterized histologically by recent and remote hemorrhage, necrotic debris, fibrosis, chronic inflammation, and cholesterol clefts with associated foreign-body giant cells [1]. The inflammatory lesion was recognized by the World Health Organization in 2000 [2]. XG of the sellar region is rare, with an incidence ranging from 0.6% to 1.2% [1]. Cases of pituitary adenoma (PA) with an associated XG (PA/XG) are extremely rare, with a total of 16 cases in the literature [1,3]. PA/XG lacks specific clinical and radiologic signs, making preoperative diagnosis challenging [1]. Herein, we report a case of PA/XG, describe the radiologic and pathologic findings, and discuss the possible histogenesis of PA/XGs.

Case report

A 40-year-old male presented to an outside hospital with a 1-month history of progressive deterioration of vision in the left eye. Ophthalmologic examination revealed a bitemporal visual field defect, and brain MRI revealed a large intrasellar and suprasellar mass with compression of the optic chiasm, consistent with a pituitary macroadenoma (Fig. 1 A-D). The patient was referred to our institution for evaluation and treatment. Endocrinologic evaluation revealed mild hyperprolactinemia, presumably due to stalk effect, and hypogonadotropic hypogonadism. The clinical findings were consistent with a clinically nonfunctioning pituitary macroadenoma. Gross total resection of the sellar mass was performed using an endoscopic endonasal transsphenoidal approach. There were no procedural complications. Postoperative pathological examination revealed a pituitary adenoma, which was immunophenotypically consistent with a silent corticotroph adenoma, and a contiguous xanthogranuloma. The XG showed chronic inflammation, focal necrotic debris, hemorrhage, hemosiderin deposition, fibrosis, and cholesterol clefts associated with foreign-body giant cells (Fig. 1 E-I). Brain MRI at 4 months after surgery showed no evidence of residual or recurrent disease. Five months after surgery an endocrinologic evaluation revealed no need for hormone replacement therapy, and ophthalmologic evaluation revealed resolution of the bitemporal visual field defect.

Fig. 1.

MRI (A-D) and histopathology (E-I) of pituitary adenoma associated with xanthogranuloma. (A) Sagittal T1-weighted MR image showing lesion with hyperintense foci, reflecting hemorrhage, calcium, lipid or cholesterol (arrow). (B) Axial T2-weighted image showing lesion with mixed signal intensity (arrow). (C) Axial T1-weighted image with contrast showing lesion's cystic component with peripheral rim enhancement (arrow). (D) Coronal T1-weighted image with contrast showing lesion's heterogeneously enhancing solid component (white arrow), cystic component (orange arrow), peripheral rim enhancement (blue arrow) and optic nerve compression (green arrows). There was no evidence of cavernous sinus invasion by Knosp classification [10]. (E and F) Photomicrographs showing pituitary adenoma (PA) and a contiguous xanthogranuloma (XG). (G) Xanthogranuloma comprising focal hemorrhage, necrotic debris and numerous cholesterol clefts. (H) Pituitary adenoma showing a neoplastic proliferation of epithelial cells with a monotonous appearance. (I) Xanthogranuloma showing abundant cholesterol clefts surrounded by foreign-body giant cells (asterisks). [(E-I). paraffin sections stained with hematoxylin and eosin; (E), original magnification 10x; (F and G), original magnification 20x; (H and I), original magnification 40x].

Discussion

Intracranial XGs arise most commonly within the choroid plexus in the region of the trigone of the lateral ventricle [4]. XG of the sellar region is rare. Although sellar XG may occur as an isolated lesion, it is usually accompanied by a Rathke's cleft cyst (RCC) or, or more rarely, by a craniopharyngioma (CP) or pituitary adenoma (PA) [1,5]. Clinical presentation of sellar XGs often includes headache, visual disturbances and symptoms related to endocrine deficits [2,3]. Degradation of hemorrhage and necrotic debris within the lesion is generally assumed to be responsible for the cholesterol clefts and associated foreign-body giant cells.

Notably, our case shares several characteristic features previously described in the neuroradiology literature. In a neuroimaging case series of consecutive surgically treated PAs, all PAs associated with XGs (5/231) were nonfunctioning macroadenomas and showed mixed signal abnormalities on both T1-and T2-weighted images as well as heterogeneous gadolinium enhancement [6]. The majority of PAs/XGs displayed suprasellar extension, intratumoral cyst, and absence of cavernous sinus invasion. In cases of PA associated with XG where there has been no clinical history of an apoplectic event, such as sudden onset of severe headache or rapid deterioration of vision, it has been suggested that the XG arose from prior subclinical hemorrhage/necrosis within a macroadenoma, so-called silent or “subclinical apoplexy [6].” Subclinical apoplexy is not rare. In 1 large case series of surgically resected PAs, 10% were associated with subclinical “apoplectic changes” of hemorrhage and necrosis [7].

A recent comprehensive neuroimaging review emphasizes the challenges of differentiating sellar XGs from other sellar lesions [8]. The usual, albeit nonspecific, MRI features of sellar XGs include hyperintense signal in both T1- and T2-weighted sequences, cystic or partially cystic morphology, ovoid shape, intratumoral calcifications (best depicted by CT), linear rim enhancement, sellar or intra- and suprasellar location, and absence of cavernous sinus invasion [8]. These imaging characteristics are not unique to sellar XGs, so that the differential diagnosis would include cystic, hemorrhagic, or degenerative PA, RCC, CP, meningioma, germinoma, lymphoma [8], lymphocytic hypophysitis, and Langerhans cell histiocytosis [9].

Conclusion

PA/XGs are extremely rare, slowly growing lesions. Preoperative imaging diagnosis is challenging due to the lesion's nonspecific features. There is a paucity of postoperative neuroimaging surveillance data of PA/XGs, with the longest reported follow-up at 27 months showing no progression of the residual lesion [3]. Recognition and long-term follow-up of PA/XGs will contribute to a better understanding of the natural history of these rare composite lesions.

Ethical standards

This case report was reviewed by the UNC Biomedical Institutional Review Board and determined that it does not constitute human subjects research and does not require IRB oversight.

Patient consent

While details that might identify the patient have been removed, consent was obtained from the individual described in this case report prior to submission for publication.