Specific imaging features of sellar atypical teratoid/rhabdoid tumor or the lack of thereof

Abstract

Primary sellar atypical teratoid/rhabdoid tumor (AT/RT) is the most aggressive sellar mass. Although rare, sellar AT/RT exhibits a very relentless clinical course and usually results in death within months to a few years after diagnosis. The best clinical evidence suggests that surgical debulking and timely adjuvant chemoradiation are most effective in prolonging survival. A preoperative radiological diagnosis of sellar AT/RT thus is crucial in informing patients and physicians about this devastating disease. This minireview summaries the imaging features of sellar AT/RT. magnetic resonance imaging features of sellar AT/RT and the much more common sellar mass, pituitary macroadenoma, are similar in most aspects: They are both isointense to brain gray matter on T1 and T2 imaging and enhance upon gadolinium administration. Suprasellar extension and cavernous sinus invasion are present in practically all cases of sellar AT/RT, but are also present in 50%-75% of pituitary macroadenomas, especially in large ones, suggesting that suprasellar extension and cavernous sinus invasion disproportionate to the tumor size may favor sellar AT/RT diagnosis. Since sellar AT/RT grows very rapidly and does not allow significant remodeling of perisellar structures, the imaging features of perisellar structures such as optic chiasm and cavernous sinus may be key for imaging diagnosis of sellar AT/RT although they have not been well described in sellar AT/RT. In limited cases of sellar AT/RT, optic chiasm degeneration and thinning, which are very common in pituitary macroadenoma, are not present, giving hope for using features of perisellar structures to diagnose sellar AT/RT by imaging.

Key Words: Primary sellar atypical teratoid/rhabdoid tumor; Sellar imaging; Sellar mass; Pituitary macroadenoma; Optic chiasm; Cavernous sinus

Core Tip: Primary sellar atypical teratoid/rhabdoid tumor (AT/RT) is the most aggressive sellar malignancy and poses grave clinical consequences. Preoperative diagnosis of sellar AT/RT is important for patients and their families and physicians to understand the unfavorable prognosis and to plan management. The imaging features of sellar AT/RT and pituitary macroadenoma largely overlap so that imaging diagnosis of sellar AT/RT is very challenging. Extensive cavernous sinus invasion disproportionate to tumor size may suggest sellar AT/RT. It remains to be explored whether the absence of imaging evidence of remodeling of perisellar structures such as the optic chiasm and cavernous sinus will lead to the diagnosis of sellar AT/RT.

INTRODUCTION

A sellar mass can be neoplastic, hyperplastic, inflammatory, infiltrative, infectious, or vascular in nature[1]. Pituitary adenoma (also known as pituitary neuroendocrine tumor), however, is the most common sellar mass (> 80%)[2]. Imaging diagnosis of a sellar mass is usually quite straightforward because by probability alone, a sellar mass has a very large chance to be a pituitary adenoma[1,2]. Imaging diagnosis does not perform well in differentiating a non-adenoma sellar mass from a pituitary adenoma, and the error rate can be 38%-61%[3]. Imaging diagnosis performs especially poorly in differentiating a rare sellar malignancy such as primary sellar atypical teratoid/rhabdoid tumor (AT/RT) from a pituitary adenoma[4,5], which is largely due to the radiologist’s cognitive error of not realizing sellar AT/RT as a diagnostic entity, the lack of sufficient clinical information, and the limits of a static imaging[6,7].

In this mini-review, we will discuss the clinicopathological and imaging features of sellar AT/RT and the challenges of imaging diagnosis of this very aggressive tumor.

CLINICOPATHOLOGICAL FEATURES OF SELLAR AT/RT

AT/RT is a malignancy of the central nervous system and can originate from any parts of the central nervous system, including the sellar[7,8]. Primary sellar AT/RT is a distinct type of AT/RT, and is the most aggressive sellar malignancy known[9,10]. Sellar AT/RT is fortunately very rare; there have been so far about 60 definitively diagnosed cases reported in the literature. The vast majority of patients with sellar AT/RT are female[9-11]. The etiology of sellar AT/RT is not clear but presumably due to spontaneous somatic mutations in certain poorly understood primitive cells in the sella.

Molecular pathogenesis of sellar AT/RT

AT/RT is composed of primitive tumor cells of multiple lineages so that molecular pathogenesis of AT/RT likely also involves multiple mechanisms[7,12]. Most commonly, loss of the integrase interactor 1 (INI1) protein expression defines the molecular pathogenesis of AT/RT. The INI1 protein is encoded by the SMARCB1 gene. INI1 is an integral member of a critical chromatin remodeling complex and functions to maintain chromatin structure[13]. In some cases of AT/RT, loss of Brahma-related gene 1 (BRG1) protein expression is the dominant molecular mechanism of AT/RT[7,12]. The BRG1 protein is encoded by the SMARCA4 gene. Like INI1, BRG1 also functions to maintain chromatin structure[14]. Recently, tumor DNA methylation profile has also been studied in AT/RT[15]. Primary sellar AT/RT, as a distinct type of AT/RT, exclusively exhibits loss of INI1, rather than BRG1, and is classified as the MYC sub-group, World Health Organization grade 4, by DNA methylation[9,10,15]. As sellar AT/RT mostly affects adult females, sex hormones may have a permissive role in the pathogenesis[11].

Clinical course of sellar AT/RT

Sellar AT/RT almost always assumes a rapidly progressive course[9,10,16,17]. Typically an adult female would present with headache for about a month and acute visual changes for a week. Brain computed tomography (CT) or magnetic resonance imaging (MRI) would identify a sellar mass. Pituitary MRI would show a large sellar mass with suprasellar extension and cavernous sinus invasion. The radiological diagnosis is usually pituitary macroadenoma with or without intratumoral bleed or apoplexy. Hormonal testing would show deficiency of one or multiple pituitary hormones. The patient would undergo transsphenoidal tumor resection, only to be found to harbor an invasive sellar mass that cannot be removed due to tight adhesion or tendency of bleeding. Some debulking or biopsy would be done and histology would show a poorly differentiated malignancy. After molecular studies of the surgical specimen, sellar AT/RT would be diagnosed. The patient would then undergo repeat surgical exploration or chemo-radiation. The sellar AT/RT would relentlessly progress despite treatment, resulting in deaths within months to a few years after presentation[9,10,16,17].

Patients with sellar AT/RT and family members often are surprised by the rapid deterioration of their health, as they are told by their physicians that they just have a pituitary macroadenoma which is not life-threatening[16,17]. Surgeons are also often surprised by the invasive tumors they encounter intraoperatively[16,17]. It is thus critically important to attempt to diagnose sellar AT/RT preoperatively by imaging, if possible.

Pathological features of sellar AT/RT

Histologically, sellar AT/RT exhibits poorly differentiated, atypical epithelioid-like spindle cells with rhabdoid features (Figure 1)[12,16]. Immunostaining of INI1, SMARCB1 gene sequencing, or fluorescence in situ hybridization of the SMARCB1 locus can be used to make the molecular diagnosis of sellar AT/RT[12,16]. In recent years, tumor DNA methylation becomes the dominant molecular diagnosis tool[15].

Figure 1 Histological features of sellar atypical teratoid/rhabdoid tumor. Hematoxylin and eosin stain (Left). Epithelioid-like spindle cells with pink cytoplasm and prominent nuclei arranged in fascicular pattern, × 20 (Right). Focal tumor cells exhibiting rhabdoid features, × 40. Reproduced from Lev et al[16]. Citation: Lev I, Fan X, Yu R. Sellar Atypical Teratoid/Rhabdoid Tumor: Any Preoperative Diagnostic Clues? AACE Clin Case Rep 2015; 1: e2-e7. Copyright© 2015 Elsevier Inc. Published by Elsevier Inc. This is an open access article with User License: Creative Commons Attribution-NonCommercial-NoDerivs (CC BY-NC-ND 4.0). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

IMAGING DIAGNOSIS OF SELLAR AT/RT

Imaging diagnosis of sellar AT/RT is challenging. First of all, sellar AT/RT is a rare malignancy[9,10]; endocrinologist, surgeons, and radiologists may not be aware of the existence of this sellar entity. Second, there may be only subtle, if at all, differences in the imaging features of sellar AT/RT and the much more common sellar mass, pituitary macroadenoam (to be discussed below). Last, a single static preoperative imaging cannot provide dynamic information such as the tumor growth speed[4-6]. As MRI is the main imaging modality for sellar mass, we will focus our discussion here on sellar (or pituitary) MRI.

Imaging features of sellar AT/RT

Table 1 lists the MRI imaging features of 47 patients with confirmed molecular diagnosis of sellar AT/RT and description of the imaging results[9,10,16-44]. All patients are adults and all but 3 are female. All tumors are larger than 1 cm and most are much larger. All tumors exhibit suprasellar extension. Cavernous sinus involvement is explicitly described in 31 patients and all but 1 patient exhibit unilateral or bilateral cavernous sinus invasion. Although sellar AT/RT as a group exhibits the above common features, these features are not sufficiently specific.

Table 1 Magnetic resonance imaging features of primary sellar atypical teratoid/rhabdoid tumor cases confirmed by molecular studies.

Ref.	Year	Age	Sex	Imaging features
Georgountzos et al[18]	2024	51	F	“Large” with left cavernous sinus invasion
Zamudio-Coronado et al[19]	2023	60	F	1.3 cm with right cavernous sinus invasion
Aldhafeeri et al[20]	2023	32	M	“Large” with right cavernous sinus invasion
Yu[17]	2023	45	F	1.9 cm × 2.2 cm × 1.8 cm with bilateral cavernous sinus invasion
Yu[17]	2023	32	F	2.1 cm with right cavernous sinus invasion
Baiano et al[11]	2022	32	F	“Large” with cavernous sinus invasion
Baiano et al[11]	2022	42	F	“Large” with left cavernous sinus invasion
Baiano et al[11]	2022	41	F	“Large” with left cavernous sinus invasion
Baiano et al[11]	2022	50	F	“Large” with left cavernous sinus invasion
Major et al[10]	2022	70	F	1.8 cm × 2.2 cm × 1.7 cm with right cavernous sinus invasion
Duan et al[21]	2022	47	F	“Large” with bilateral cavernous sinus invasion
Duan et al[21]	2022	52	F	“Large” with bilateral cavernous sinus invasion
Duan et al[21]	2022	47	M	“Large” with right cavernous sinus invasion
Duan et al[21]	2022	46	F	“Large” with left cavernous sinus invasion
Duan et al[21]	2022	45	F	“Large” with bilateral cavernous sinus invasion
Duan et al[21]	2022	73	F	“Large” with right cavernous sinus invasion
Duan et al[21]	2022	41	F	“Large” cavernous sinus invasion was not specified
Fukuda et al[22]	2021	45	F	“Large” with bilateral cavernous sinus invasion
Liu et al[9]	2020	43	F	4.5 cm cavernous sinus invasion was not specified
Liu et al[9]	2020	52	F	2.8 cm cavernous sinus invasion was not specified
Liu et al[9]	2020	50	F	2.7 cm cavernous sinus invasion was not specified
Liu et al[9]	2020	29	F	1.9 cm cavernous sinus invasion was not specified
Liu et al[9]	2020	80	F	2.2 cm with bilateral cavernous sinus invasion
Bokhari et al[23]	2020	40	F	2.9 cm × 1.7 cm × 2.3 cm with right cavernous sinus invasion
Madhavan et al[24]	2020	58	F	2.1 cm with 3.1 cm suprasellar extension
Siddiqui et al[25]	2019	55	F	3.5 cm × 1.7 cm cavernous sinus invasion was not specified
Asmaro et al[26]	2019	62	F	“Large” cavernous sinus invasion was not specified
Lawler and Robertson[27]	2019	27	F	“Large” cavernous sinus invasion was not specified
Su and Su[28]	2018	37	F	2.57 cm × 1.96 cm × 3.63 cm cavernous sinus invasion was not specified
Nishikawa et al[29]	2018	42	F	1.9 cm × 2.0 cm with left cavernous sinus invasion
Barresi et al[30]	2018	59	F	2.3 cm × 1.2 cm with left cavernous sinus invasion
Huq et al[31]	2018	62	F	“Large” cavernous sinus invasion was not specified
Pratt et al[32]	2017	47	F	2.6 cm × 3.9 cm × 3.2 cm with bilateral cavernous sinus invasion
Almalki et al[33]	2017	36	F	“Large” with bilateral cavernous sinus invasion
Elsayad et al[34]	2016	66	M	2.2 cm × 1.6 cm × 1.4 cm cavernous sinus invasion was not specified
Larrán-Escandón et al[35]	2016	43	F	2.0 cm × 2.3 cm cavernous sinus invasion was not specified
Nobusawa et al[36]	2016	69	F	2.8 cm × 1.6 cm with left cavernous sinus invasion
Lev et al[16]	2015	36	F	3.3 cm × 3.2 cm × 2.3 cm with left cavernous sinus invasion
M. Regan et al[37]	2015	45	F	“Large” with left cavernous sinus invasion
Park et al[38]	2014	42	F	“Large” cavernous sinus invasion was not specified
Shitara and Akiyama[39]	2014	44	F	“Large” cavernous sinus invasion was not specified
Moretti et al[40]	2013	60	F	“Large” with left cavernous sinus invasion
Chou et al[41]	2013	43	F	2 cm with left cavernous sinus invasion
Schneiderhan et al[42]	2011	61	F	2 cm with left cavernous sinus invasion
Schneiderhan et al[42]	2011	57	F	2 cm with right cavernous sinus invasion
Arita et al[43]	2008	56	F	2.5 cm with right cavernous sinus invasion
Raisanen et al[44]	2005	31	F	1.6 cm cavernous sinus invasion was not specified
Raisanen et al[44]	2005	20	F	2.0 cm without cavernous sinus invasion

M: Male; F: Female. Note that most cases exhibit suprasellar extension.

Comparison of imaging features of sellar AT/RT and pituitary macroadenoma

As the most common diagnosis of a sellar mass larger than 1 cm is pituitary macroadenoma[2], MRI features of pituitary macroadenoma and sellar AT/RT are compared in Table 2. Both pituitary macroadenoma and sellar AT/RT are isointense to brain gray matter in T1 and T2 imaging, and both enhance after gadolinium contrast administration in T1 imaging[9,16,17]. Although gross suprasellar extension and cavernous sinus invasion are less common in pituitary macroadenoma than in sellar AT/RT[45,46], the difference is not large enough to be diagnostically useful. Representative pituitary macroadenoma and sellar AR/RT MRI images are shown in Figure 2.

Figure 2 Magnetic resonance imaging of pituitary macroadenoma and sellar atypical teratoid/rhabdoid tumor. A-C: A 4.1 cm × 4.4 cm macroprolactinoma of a 19-year-old male; D-F: A 2.2 cm × 1.8-cm sellar atypical teratoid/rhabdoid tumor of a 45-year-old female. T1 imaging without contrast (A and D). T1 imaging after contrast administration (B and E). T2 imaging (C and F). Asterisk, sellar mass. Note the limited cavernous sinus invasion despite large tumor size and the optic chiasm thinning in the patient with macroprolactinoma. Also note the extensive bilateral cavernous sinus invasion but intact optic chiasm in the patient with sellar atypical teratoid/rhabdoid tumor. Panel E is reproduced from Yu[17]. Citation: Yu R. Sellar Mass in 2 Patients With Acute-Onset Headache and Visual Symptoms: Not Your Usual Pituitary Adenoma. AACE Clin Case Rep 2023; 9: 197-200. Copyright © 2015 Elsevier Inc. Published by Elsevier Inc. This is an open access article with User License: Creative Commons Attribution-NonCommercial-NoDerivs (CC BY-NC-ND 4.0). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

Table 2 Magnetic resonance imaging characteristics of pituitary macroadenoma and sellar atypical teratoid/rhabdoid tumor (see text for detail).

	Pituitary macroadenoma	Sellar atypical teratoid/rhabdoid tumor
T1	Isointense to brain gray matter	Isointense to brain gray matter
T1 after contrast	Enhancing	Enhancing
T2	Isointense to brain gray matter	Isointense to brain gray matter
Gross suprasellar extension	50%-75%	Approximately 100%
Gross cavernous sinus invasion	50%-75%	97%
Optic chiasm degeneration (T2 hyperintensity)	56%	Absence in limited cases
Optic chiasm thinning	37%	Absence in limited cases
Cavernous sinus remodeling	Common	Unlikely

While the slow growth of pituitary macroadenoma is known to be associated with remodeling of perisellar structures[47-50], sellar AT/RT grows much faster than pituitary macroadenoma and does not allow ample remodeling of the perisellar structures[16,17]. Features of clearly identifiable perisellar structures such as the optic chiasm may help differentiating sellar AT/RT from pituitary macroadenoma. Optic chiasm degeneration and thinning are found in 55% and 37% of pituitary macroadenomas, respectively[47]. Optic chiasm remodeling in sellar AT/RT has not been systemically addressed. In the 3 cases of sellar AT/RT I have personally taken care of, optic chiasm degeneration or thinning was not present[16,17], suggesting absence of optic chiasm remodeling signs on MRI in a patient with a large sellar mass could suggest sellar AT/RT. Similarly, the sella itself is often expanded with or without destruction in pituitary macroadenoma[49,50]. It remains to be systemically studied whether the sella size is indeed unchanged in sellar AT/RT.

This minireview on sellar AT/RT has certain limitations. The reviewed sample size is relatively small due to the rarity of sellar AT/RT, which may affect the comprehensiveness and reliability of the findings. Additionally, the study mostly focuses on radiological diagnosis of sellar AT/RT but does not address the natural history and treatment outcomes of this tumor.

CONCLUSION

In summary, primary sellar AT/RT is the most aggressive sellar malignancy and poses grave clinical consequences. Preoperative diagnosis of sellar AT/RT is important for patients and their families and physicians to understand the unfavorable prognosis and to plan management. Currently, imaging features of sellar AT/RT and pituitary macroadenoma largely overlap so that imaging diagnosis of sellar AT/RT is very challenging. Extensive cavernous sinus invasion disproportionate to tumor size may suggest sellar AT/RT. It remains to be explored whether the absence of imaging evidence of remodeling of perisellar structures such as the optic chiasm and cavernous sinus will lead to the diagnosis of sellar AT/RT. For future research, multi-center collaborative studies are recommended to increase the sample size and enhance the statistical power of the findings. Furthermore, incorporating advanced imaging techniques such as functional MRI or positron emission tomography-CT could potentially improve diagnostic accuracy of sellar AT/RT.