Pediatric Pituitary Adenoma: Case Series, Review of the Literature, and a Skull Base Treatment Paradigm

Abstract

Background Pediatric pituitary adenoma is a rare skull base neoplasm, accounting for 3% of all intracranial neoplasms in children and 5% of pituitary adenomas. Compared with pituitary tumors in adults, secreting tumors predominate and longer disease trajectories are expected due to the patient age resulting in a natural history and treatment paradigm that is complex and controversial. Objectives The aims of this study were to describe a large, single-institution series of pediatric pituitary adenomas with extensive long-term follow-up and to conduct a systematic review examining outcomes after pituitary adenoma surgery in the pediatric population. Methods The study cohort was compiled by searching institutional pathology and operative reports using diagnosis and site codes for pituitary and sellar pathology, from 1956 to 2016. Systematic review of the English language literature since 1970 was conducted using PubMed, MEDLINE, Embase, and Google Scholar. Results Thirty-nine surgically managed pediatric pituitary adenomas were identified, including 15 prolactinomas, 14 corticotrophs, 7 somatotrophs, and 4 non-secreting adenomas. All patients underwent transsphenoidal resection (TSR) as the initial surgical treatment. Surgical cure was achieved in 18 (46%); 21 experienced recurrent/persistent disease, with secondary treatments including repeat surgery in 10, radiation in 14, adjuvant pharmacotherapy in 11, and bilateral adrenalectomy in 3. At the last follow-up (median 87 months, range 3-581), nine remained with recurrent/persistent disease (23%). Thirty-seven publications reporting surgical series of pediatric pituitary adenomas were included, containing 1,284 patients. Adrenocorticotropic hormone (ACTH)-secreting tumors were most prevalent (43%), followed by prolactin (PRL)-secreting (37%), growth hormone (GH)-secreting (12%), and nonsecreting (7%). Surgical cure was reported in 65%. Complications included pituitary insufficiency (23%), permanent visual dysfunction (6%), chronic diabetes insipidus (DI) (3%), and postoperative cerebrospinal fluid (CSF) leak (4%). Mean follow-up was 63 months (range 0-240), with recurrent/persistent disease reported in 18% at the time of last follow-up. Conclusion Pediatric pituitary adenomas are diverse and challenging tumors with complexities far beyond those encountered in the management of routine adult pituitary disease, including nuanced decision-making, a technically demanding operative environment, high propensity for recurrence, and the potentially serious consequences of hypopituitarism with respect to fertility and growth potential in a pediatric population. Optimal treatment requires a high degree of individualization, and patients are most likely to benefit from consolidated, multidisciplinary care in highly experienced centers.

Keywords: hypopituitarism; pediatric pituitary adenoma; radiotherapy; stereotactic radiosurgery; transsphenoidal surgery.

Fig. 1

Schematic depicting search strategy for systematic literature review

Fig. 2

Gadolinium-enhanced T1-weighted MRI of the brain in the coronal and sagittal planes ( A and B ) demonstrates a hypo-enhancing eccentric left sellar masses (red arrows) surrounded by briskly enhancing normal hypophyseal tissue, characteristic of pituitary microadenoma. Pre-contrast sagittal T1-weighted and coronal MPRAGE images ( B ) demonstrate a large, well-circumscribed, sellar mass with surrounding benign bony remodeling, significant superior displacement of the optic chiasm (red arrow), and internal heterogeneity, consistent with a partially hemorrhagic pituitary macroadenoma. Gadolinium-enhanced T1-weighted coronal and axial images ( C ) demonstrate a large, vividly enhancing sellar mass, with invasion of the bilateral cavernous sinuses, encasement of the internal carotid arteries, and significant suprasellar and middle fossa extension, suggestive of an aggressive pituitary macroadenoma. MPRAGE, magnetization prepared rapid acquisition gradient echo; MRI, magnetic resonance imaging.

Fig. 3

Histopathologic photomicrographs demonstrating a corticotroph-type tumor with typical features including diffuse adenoma cells ( A , H&E, 200X), loss of typical reticulated nesting ( B , Reticulin, 200X), and diffusely positive immunohistochemical staining for ACTH ( C , ACTH, 200X). Crooke's cell adenoma, with characteristic strongly positive perinuclear CAM5.2 staining ( D and E , CAM5.2, 400X), and a corresponding haloing of perinuclear ACTH positivity ( F , ACTH, 400X). Atypical pituitary adenoma, demonstrating two mitoses (arrowheads) in a high-powered field ( G , H&E, 400X). ACTH, adrenocorticotropic hormone; H&E, hematoxylin and eosin.

Fig. 4

Treatment algorithm for pediatric pituitary adenoma. ACTH, adrenocorticotropic hormone; BAX, bilateral adrenalectomy; CRH, corticotropin releasing hormone; EBRT, external beam radiotherapy; HDDS, high-dose dexamethasone suppression; IPSS, inferior petrosal sinus sampling; MRI, magnetic resonance imaging; PBRT, proton beam radiotherapy; SRS, stereotactic radiosurgery; TSR, transsphenoidal resection.