Giant pituitary adenoma

Giant pituitary adenoma

Epidemiology

Giant pituitary adenomas comprise about 6-10% of all pituitary tumors.

It is estimated that 5% of pituitary adenoma become invasive and may grow to gigantic sizes (>4 cm in diameter).

They are mostly clinically non-functioning adenomas and occur predominantly in males 1)

Types

Clinical

The presenting symptoms are usually secondary to compression of neighboring structures, but also due to partial or total hypopituitarismFunctioning pituitary adenomas give rise to specific symptoms of hormonal hypersecretion.

Treatment

The use of dopamine agonists is considered a first-line treatment in patients with giant macroprolactinomas. Somatostatin analogs can also be used as primary treatment in cases of growth hormone and thyrotropin producing giant adenomas, although remission of the disease is not achieved in the vast majority of these patients.

The intrinsic complexity of these tumors requires the use of different therapies in a combined or sequential way. A multimodal approach and a therapeutic strategy involving a multidisciplinary team of expert professionals form the basis of the therapeutic success in these patients 2).


The main goal of surgical treatment of giant pituitary adenoma is maximum possible tumor extirpation with minimal side effects, which can be achieved by careful preoperative planning of operative approach, based on directions of tumor extensions and invasiveness. Maximal surgical removal of giant adenomas offers best chances to control tumor growth when followed with adjuvant medical and radiation therapies 3).


While the use of endoscopic approaches has become increasingly accepted in the resection of pituitary adenomas, limited evidence exists regarding the success of this technique for patients with large and giant pituitary adenomas.

Major blood supply of giant pituitary adenomas originates from branches of the infraclinoidal portion of the internal carotid artery, different from normal anterior pituitary gland. Surgical route should depend not only on tumor shape and extension but on feeding systems 4).

The main goal of surgical treatment of giant pituitary adenoma is maximum possible tumor extirpation with minimal side effects, which can be achieved by careful preoperative planning of operative approach, based on directions of tumor extensions and invasiveness. Maximal surgical removal of giant adenomas offers best chances to control tumor growth when followed with adjuvant medical and radiation therapies 5).


In cases of progressive enlargement of residual lesions, a second endoscopic debulking of the tumor may be considered for control of the disease 6).

Outcome

Giant pituitary adenomas carry higher surgical risks despite recent advances in microsurgical and/or endoscopic surgery, and postoperative acute catastrophic changes without major vessel disturbance are still extremely difficult to predict, may manifest as postoperative pituitary apoplexy, and are associated with very poor outcomes.

Resection of both large and giant pituitary adenomas by microscopic transsphenoidal surgery may be safe and effective surgical technique with low morbidity and mortality 7).

Case series

References

1) , 2)

Iglesias P, Rodríguez Berrocal V, Díez JJ. Giant pituitary adenoma: histological types, clinical features and therapeutic approaches. Endocrine. 2018 Sep;61(3):407-421. doi: 10.1007/s12020-018-1645-x. Epub 2018 Jun 16. Review. PubMed PMID: 29909598.
3)

Sinha S, Sharma BS. Giant pituitary adenomas–an enigma revisited. Microsurgical treatment strategies and outcome in a series of 250 patients. Br J Neurosurg. 2010 Feb;24(1):31-9. doi: 10.3109/02688690903370305. PubMed PMID: 20158350.
4)

Ogawa Y, Sato K, Matsumoto Y, Tominaga T. Evaluation of Fine Feeding System and Angioarchitecture of Giant Pituitary Adenoma – Implications for Establishment of Surgical Strategy. World Neurosurg. 2015 Oct 5. pii: S1878-8750(15)01255-3. doi: 10.1016/j.wneu.2015.09.087. [Epub ahead of print] PubMed PMID: 26455764.
5)

Sinha S, Sharma BS. Giant pituitary adenomas–an enigma revisited. Microsurgical treatment strategies and outcome in a series of 250 patients. Br J Neurosurg. 2010 Feb;24(1):31-9. doi: 10.3109/02688690903370305. PubMed PMID: 20158350.
6)

Gondim JA, Almeida JP, Albuquerque LA, Gomes EF, Schops M. Giant pituitary adenomas: surgical outcomes of 50 cases operated on by the endonasal endoscopic approach. World Neurosurg. 2014 Jul-Aug;82(1-2):e281-90. doi: 10.1016/j.wneu.2013.08.028. Epub 2013 Aug 29. PubMed PMID: 23994073.
7)

Karki M, Sun J, Yadav CP, Zhao B. Large and giant pituitary adenoma resection by microscopic trans-sphenoidal surgery: Surgical outcomes and complications in 123 consecutive patients. J Clin Neurosci. 2017 Aug 1. pii: S0967-5868(16)30922-5. doi: 10.1016/j.jocn.2017.07.015. [Epub ahead of print] PubMed PMID: 28778803.

Granular cell tumor of the sellar region

Granular cell tumor of the sellar region

AKA (infundibular) granular cell tumor (GCT). WHO grade I. Obsolete terms: choristoma1) granular cell myoblastomapituicytoma (this term is now reserved for a circumscribed glial neoplasm). A circumscribed tumor with nests of large cells has granular, eosinophilic cytoplasm due to copious lysosomes in the cytoplasm.

Epidemiology

While rare, GCTs are the most common primary tumor of the neurohypophysis and pituitary stalk/infundibulum 2) with a predilection for the stalk (these result in suprasellar extension). GCTs have been identified in the gastrointestinal tractgenitourinary tract, the orbital region as well as in other locations of the central nervous system with no connection to the pituitary gland or hypothalamus (e.g. spinal meninges 3)). Female: male ratio ≥ 2:1.

Pathology

Asymptomatic microscopic clusters of granular cells (tumorettes) are more common, with an incidence of up to 17% 4).

Clinical

They usually follow a slow progression with benign behavior. The most common presentation is with visual field deficits due to optic chiasm compression 5). However, any symptom typical of a hormonally inactive sellar mass may occur.

Diagnosis

Imaging: may appear radiographically identical to adenomas. Rarely considered in the differential diagnosis pre-op. Isodense on CT and isointense on T1WI MRI, dense homogeneous enhancement on CT & MRI.

Treatment

If GTC is suspected pre-op, a transcranial approach is preferred over transsphenoidal because of the vascularity which has prevented total resection in 60–70% of reported cases 6)XRT may be considered for subtotal resection 7).

Surgical resection is the standard treatment, more recently with transsphenoidal surgery when indicated. Surgical resection results in optimal outcome for patients 8).

Case reports

Three patients had a diagnosis of GCT of the sellar region occurring over an 18-year period. All three patients were followed postoperatively at our multidisciplinary pituitary center (median follow-up = 30 months; range 12-30 months). Hormonal disturbances, an incidental lesion requiring diagnosis, and neurological symptoms were indications for surgery in these patients. Two patients underwent a craniotomy and one underwent endoscopic transsphenoidal surgery. All three patients were free of tumor recurrence at last follow-up. In one case tested, positive thyroid transcription factor-1 (TTF-1) immunohistochemistry was observed.

GCT is generally a benign tumor of the sellar region. Surgical resection is the standard treatment, more recently with transsphenoidal surgery when indicated. Surgical resection results in optimal outcome for patients 9).


A 70-year-old female presented with progressive vision impairment found to have bitemporal visual field defects. Subsequent magnetic resonance imaging (MRI) revealed a 2.9 cm × 2.5 cm × 2.5 cm parasellar mass with extension into the third ventricle and causing optic tract edema (OTE). Right frontotemporal orbital craniotomy was performed and the tumor was partially removed to decompress optic nerves. Pathology identified the tumor as granular tumor of the sellar region. The patient’s vision improved minimally after the surgery. Follow-up MRI after 3 months and 11 months showed stable left OTE.

GCTs were thought to be benign tumors with slow growth, but they could potentially possess aggressive features and invade into surrounding structures as described in this case. OTE can be a rare MRI finding of GCTs. Only one case of GCT-related OTE has been reported in literature to our best knowledge 10).


A 36-year-old neurologically normal woman with known MEN-1 underwent a screening magnetic resonance imaging (MRI) scan which revealed a 10 mm x 6 mm x 7 mm sellar/suprasellar lesion. She underwent endoscopic endonasal transsphenoidal resection. The subsequent neuropathological analysis was consistent with GCT of the pituitary gland. This is the first report of a GCT of the pituitary gland occurring in a patient with MEN-1 11).

References

1) , 5)

Cohen-Gadol AA, Pichelmann MA, Link MJ, et al. Granular cell tumor of the sellar and suprasellar region: clinicopathologic study of 11 cases and literature review. Mayo Clin Proc. 2003; 78:567–573
2) , 7)

Schaller B, Kirsch E, Tolnay M, et al. Symptomatic granular cell tumor of the pituitary gland: case report and review of the literature. Neurosurgery. 1998; 42:166–70; discussion 170-1
3)

Markesbery WR, Duffy PE, Cowen D. Granular cell tumors of the central nervous system. J Neuropathol Exp Neurol. 1973; 32:92–1093
4)

Fuller GN, Wesseling P, Louis DN, et al. Granular cell tumors of the neurohypophysis. In: WHO classification of tumors of the central nervous system. 4th ed. Lyon: International Agency for Research on Cancer; 2007:241–242
6)

Gueguen B, Merland JJ, Riche MC, et al. Vascular Malformations of the Spinal Cord: Intrathecal Perimedullary Arteriovenous Fistulas Fed by Medullary Arteries. Neurology. 1987; 37:969–979
8) , 9)

Ahmed AK, Dawood HY, Cote DJ, Bale TA, De Girolami U, Laws ER Jr, Smith TR. Surgical resection of granular cell tumor of the sellar region: three indications. Pituitary. 2019 Dec;22(6):633-639. doi: 10.1007/s11102-019-00999-z. PubMed PMID: 31620953.
10)

Dai Y, Hagen M, Andaluz N, Bhabhra R. Aggressive granular cell tumor of the neurohypophysis with optic tract edema and invasion into third ventricle. Surg Neurol Int. 2019 Nov 15;10:217. doi: 10.25259/SNI_356_2019. eCollection 2019. PubMed PMID: 31819811; PubMed Central PMCID: PMC6884947.
11)

Pendharkar AV, Lin CY, Born DE, Hoffman AR, Dodd RL. Granular Cell Pituitary Tumor in a Patient with Multiple Endocrine Neoplasia-1. Cureus. 2019 Apr 25;11(4):e4541. doi: 10.7759/cureus.4541. PubMed PMID: 31275768; PubMed Central PMCID: PMC6592835.

Adamantinomatous Craniopharyngioma

Adamantinomatous Craniopharyngioma

craniopharyngioma with epithelium that forms stellate reticulum, wet keratin, and basal palisades. Up to 95% of cases of this variant shows CTNNB1 mutations and aberrant nuclear expression of beta-catenin 1).

Bimodal age distribution: childhood peak age 5–15 years, adult peak age 45–60 years 2).

The evolving characterization of the biological basis of adamantinomatous craniopharyngioma (ACP) has provided insights critical for novel systemically delivered therapies. While current treatment strategies for ACP are associated with low mortality rates, patients experience severely lowered quality of life due to high recurrence rates and chronic sequelae, presenting a need for novel effective treatment regimens. The identification of various dysregulated pathways that play roles in the pathogenesis of ACP has prompted the investigation of novel treatment options. Aberrations in the CTNNB1 gene lead to the dysregulation of the Wnt signaling pathway and the accumulation of nuclear β-catenin, which may play a role in tumor invasiveness. While Wnt pathway/β-catenin inhibition may be a promising treatment for ACP, potential off-target effects have limited its use in current intervention strategies. Promising evidence of the therapeutic potential of cystic proinflammatory mediators and immunosuppressants has been translated into clinical therapies, including interleukin 6 and IDO-1 inhibition. The dysregulation of the pathways of mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK), epidermal growth factor receptor (EGFR), and programmed cell death protein 1 and its ligand (PD-1/PD-L1) has led to identification of various therapeutic targets that have shown promise as clinical strategies. The Sonic Hedgehog (SHH) pathway is upregulated in ACP and has been implicated in tumorigenesis and tumor growth; however, inhibition of SHH in murine models decreased survival, limiting its therapeutic application. While further preclinical and clinical data are needed, systemically delivered therapies could delay or replace the need for more aggressive definitive treatments. Ongoing preclinical investigations and clinical trials of these prospective pathways promise to advance treatment approaches aimed to increase patients’ quality of life 3).


Early disease onset, clinical manifestation, histomorphology, and increased tendency to relapse distinguish the adamantinomatous craniopharyngioma (adaCP) from the more favorable papillary craniopharyngioma variant (papCP). A molecular hallmark of adaCP is the activated Wnt signaling pathway indicated by nuclear β-catenin accumulation in a subset of tumor cells. A mouse model recently illustrated that these cells are the driving force in tumorigenesis of adaCP. This observation and the peculiar growth pattern points to the existence of a specific tumor stem cell (TSC) population in human CP. Tumor stem cell-like characteristics of β-catenin accumulating cell clusters in adaCP, which may represent a tumor stem cell niche and might contribute to tumor recurrence. The potential impact of these special cell groups in regard to future CP management, including postoperative follow-up and additional treatment remains to be explored 4).

Osteogenic factor Bmp2 may play an important role in the calcification of adamantinomatous craniopharyngioma ACP via autocrine or paracrine mechanisms. Given the presence of osteogenic markers (Runx2 and Osterix), craniopharyngioma cells could differentiate into an osteoblast-like lineage, and the process of craniopharyngioma calcification resembles that which occurs in osteogenesis/odontogenesis 5).

Adamantinomatous and papillary craniopharyngiomas harbor mutations that are mutually exclusive and clonal. These findings have important implications for the diagnosis and treatment of these neoplasms 6).

References

1) , 2)

Louis DN, Ohgaki H, Wiestler OD, et al. WHO classification of tumors of the central nervous system. Lyon, France 2016
3)

Hengartner AC, Prince E, Vijmasi T, Hankinson TC. Adamantinomatous craniopharyngioma: moving toward targeted therapies. Neurosurg Focus. 2020 Jan 1;48(1):E7. doi: 10.3171/2019.10.FOCUS19705. PubMed PMID: 31896087.
4)

Hölsken A, Stache C, Schlaffer SM, Flitsch J, Fahlbusch R, Buchfelder M, Buslei R. Adamantinomatous craniopharyngiomas express tumor stem cell markers in cells with activated Wnt signaling: further evidence for the existence of a tumor stem cell niche? Pituitary. 2013 Dec 20. [Epub ahead of print] PubMed PMID: 24356780.
5)

Song-Tao Q, Xiao-Rong Y, Jun P, Yong-Jian D, Jin L, Guang-Long H, Yun-Tao L, Jian R, Xiang-Zhao L, Jia-Ming X. Does the calcification of adamantinomatous craniopharyngioma resemble the calcium deposition of osteogenesis/odontogenesis? Histopathology. 2013 Jan 31. doi: 10.1111/his.12071. [Epub ahead of print] PubMed PMID: 24387671.
6)

Brastianos PK, Taylor-Weiner A, Manley PE, Jones RT, Dias-Santagata D, Thorner AR, Lawrence MS, Rodriguez FJ, Bernardo LA, Schubert L, Sunkavalli A, Shillingford N, Calicchio ML, Lidov HG, Taha H, Martinez-Lage M, Santi M, Storm PB, Lee JY, Palmer JN, Adappa ND, Scott RM, Dunn IF, Laws ER Jr, Stewart C, Ligon KL, Hoang MP, Van Hummelen P, Hahn WC, Louis DN, Resnick AC, Kieran MW, Getz G, Santagata S. Exome sequencing identifies BRAF mutations in papillary craniopharyngiomas. Nat Genet. 2014 Jan 12. doi: 10.1038/ng.2868. [Epub ahead of print] PubMed PMID: 24413733.
WhatsApp WhatsApp us
%d bloggers like this: