Cystic lesions in the sellar region encompass a broad gamut of pathologies, which can be challenging to distinguish on imaging, given their variability in clinical presentation and heterogeneity of cyst appearance. The presence of a sellar cyst generates a range of presumptive diagnoses — with pathologies including cystic pituitary adenomas, craniopharyngiomas, Rathke cleft cysts (RCC), arachnoid cysts, epidermoid cysts, dermoid cysts, and xanthogranulomas, among others (1, 2). Although some cystic lesions are benign, incidentally found lesions, others can lead to significant morbidity through disruption of hormonal axes or associated mass effect. Incidentally found lesions such as small pituitary adenoma or RCC may be observed, while surgical resection is indicated for symptomatic lesions or those requiring tissue diagnosis. Clinical and imaging factors are often used to generate a preliminary diagnosis and guide management. This variation in treatment pathways necessitates further study into the features that distinguish these various cystic pathologies, especially the two most common pathologies: RCC and cystic pituitary adenoma. No validated classification system of cystic sellar lesions exists. The localization of the lesion within the sella has been classically used to differentiate lesions originating from the pars intermedia (e.g., RCC) from those originating from the pars distalis (e.g., classic adenomas). Anterior lesions from the pars distalis often exhibit posterior displacement of the infundibulum, and posterior lesions from the pars intermedia often displace the infundibulum anteriorly. For large lesions extending into the suprasellar cisterns, the infundibulum is often hard to identify, and, therefore, this method cannot reliably predict the origin of the lesion. In this study, the classification scheme can be applied to every lesion, regardless of size using the heterogeneity of the cyst wall/contents and presence of a solid component on preoperative magnetic resonance imaging (MRI). We used this a priori classification scheme and applied it to a retrospective cohort of patients.

We retrospectively queried an institutional neurosurgical database from April 2008 to January 2020 for cases with the keywords “cyst” and “cystic” in preoperative radiology reports. Only patients with a final tissue diagnosis after surgical excision and/or cyst drainage were included in the study. Patients with non-sellar cysts, such as pineal cyst or epidermal inclusion cyst, were excluded. This study was approved by our institutional review board for ethical conduct of research and protection of human subjects. Patient consent was not required since no identifying information was used in this article.

Our primary aim was to apply an a priori cyst classification scheme and compare cystic lesion type with final pathologic diagnosis. Pre-operative thin-slice MRI (1.5T or 3T) and clinical and biochemical data were reviewed for each case. T1 pre- and post-gadolinium contrast images were reviewed along with T2-weighted images. The cyst classification scheme was developed based on focused discussions amongst the authors prior to its application to cyst classification in a retrospective fashion. Classification was independently performed by three authors (ST, MPC, and DJC) who were blinded from the final cyst pathology. Agreement by two or more authors was required for final cyst classification. Inter-rater reliability was assessed using Fleiss’ kappa (κ). Confirmed lesion identity was extracted from pathology reports. Fisher’s exact test was used to evaluate the relationship between cystic lesion type and lesion pathology.

The primary objective of the study was to estimate the association between cyst type and pathology, especially as it helped distinguish RCC from cystic pituitary adenomas. Cystic lesions were classified by the heterogeneity of the cyst wall/contents and the presence of a solid component on preoperative MRI ( Figure 1 ). Type 1 cystic lesions were defined by a well-circumscribed regular border and homogeneous contents with no solid component (i.e. containing cyst contents and cyst wall only). Type 2 cystic lesions were defined by a well-circumscribed but irregular border with heterogenous content/septations and a subtle solid, non-cystic component. Type 3 lesions were defined by a well-circumscribed regular boarder and homogenous contents (like Type 1), but with an obvious solid component. Type 4 lesions were defined by irregular borders with heterogenous contents/septations (like Type 2) with multiple cysts, was predominately solid, and sometimes not well-circumscribed ( Figure 2 ). The radiographic classification scheme was consistent and easy to apply. There was unanimous consensus on cyst type for 91% of cases, and 100% agreement between at least 2 of the 3 reviewers (κ=0.86).

We originally queried an institutional database of 1083 transsphenoidal operations in 982 patients for sellar pathology (757 operations for pituitary adenoma) performed by one of the senior authors (ERL) from April 2008 to January 2020. In total, 205 patients were found to have undergone transsphenoidal surgery for cystic sellar pathology. We classified the lesions of these patients (mean age 42 years, range 16-90 years; 68% women) into the four cyst types ( Table 1 ). Type 1 and 2 cysts were the most prevalent (33% and 35%, respectively), with 5% of lesions being classified as Type 3, and 27% as Type 4. In our cohort, RCC and cystic pituitary adenomas comprised the vast majority of cystic lesions (36% and 45%, respectively). Arachnoid cysts (7%) and craniopharyngiomas (6%) were the next most common, with only one patient each having a pathologic diagnosis of chordoma, apoplexy without evident tumor, epidermoid cyst, and colloid cyst. There was a significant association between cyst type and histopathologic diagnosis (p<0.0001; Table 2 ).

The majority of the cystic pituitary adenomas were non-staining tumors (38.7% of adenomas), with prolactin- (31.2%) and ACTH-staining (11.8%) tumors following in prevalence. Approximately 46.2% of pituitary adenomas exhibited evidence of hormone secretion, and the remainder were non-functioning. Among the functioning tumors, 67.4% were prolactinomas, 18.6% presented with Cushing disease and 9.3% were associated with acromegaly. Roughly 30% of patients presented with symptomatic hypopituitarism, and roughly 25% of patients exhibited clinical signs of hyperprolactinemia ( Table 1 ).

Differentiating cystic sellar lesions can be challenging given the heterogeneity of cyst appearance on preoperative imaging and the wide array of cystic pathologies that can present in this region. The initial differential strongly impacts the recommended management, especially in incidentally found lesions. Our proposed classification system is transparent and simple to use with a high interrater reliability. It summarizes key imaging features and may be most helpful when used alongside clinical and biochemical findings to steer management and treatment.

This study presents a novel cyst classification scheme for categorizing cystic sellar lesions based on the heterogeneity of the cyst wall/contents and the presence of a solid component on pre-operative MRI. We suggest that cyst type can be used in conjunction with other pre-operative factors to aid in the differentiating RCC from cystic pituitary adenomas, including cystic prolactinomas.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

ST, MC, and DC were involved in data collection, data analysis, and manuscript writing. XB created figures and provided image formatting. EL provided the idea for the study and the cohort of cases from which the data was derived. All authors were heavily involved in manuscript editing. All authors contributed to the article and approved the submitted version.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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