Secondary vs. primary pituitary xanthogranulomas: which yellow is more mellow?

Abstract

Pituitary xanthogranulomatomas (XG) are a rare pathological entity caused by accumulation of lipid laden macrophages and reactive granuloma formation usually triggered by cystic fluid leakage or hemorrhage. Our aim was to compare clinical characteristics and presenting features of patients with secondary etiology of XG and those with no identifiable founding lesion (primary -“pure” XG) in order to gain new insights into this rare pituitary pathology. In a retrospective review of 714 patients operated for sellar masses, at tertiary center, we identified 16 (2.24%) with histologically confirmed diagnosis of pituitary XG over the period of 7 years (2015–2021). Patients were further analyzed according to XG etiology: “pure”- XG (n = 8) with no identifiable founding lesion were compared to those with histological elements of pituitary tumor or cyst – secondary XG (n = 8). We identified 16 patients (11 male), mean age 44.8 ± 22.3 years, diagnosed with pituitary XG. Secondary forms were associated with Ratke’s cleft cyst (RCC, n = 2) and pituitary adenoma (PA, n = 6). The most common presenting features in both groups were hypopituitarism (75%), headache (68.5%) and visual disturbances (37.5%). Predominance of male sex was noted (males 68.75%, females 31.25%), especially in patients with primary forms. Patients with primary pituitary XG were all males (p = 0.0256) and more frequently affected by panhypopituitarism (87.5% vs. 25%, p = 0.0406) compared to patients with secondary causes. Hyperprolactinemia was noted in pituitary tumor group with secondary etiology only (p = 0.0769). Majority of lesions were solid on magnetic resonance imaging - MRI (81.25%). Distinct clinical phenotype was observed dependent on the etiology of XG.

PITUITARY XANTHOGRANULOMAS (XG) are chronic inflammatory lesions caused by accumulation of lipid laden macrophages and granuloma formation, usually secondary to hemorrhage, infarction or necrosis upon existing neoplasm or cyst. Primary forms have less clear etiology linked to autoimmunity or systemic xanthogranulomatous involvement. Clinical and radiological presentation of these lesions may mimic other more common pathologies like pituitary neuroendocrine tumor (PitNET), Rathke’s cleft cyst (RCC), craniopharyngioma (CP) and pituitary abscess. In this paper we use both new (PitNET) and old (PA) terminology for the same pituitary tumor entity for two reasons 1) in order to relate to previous publications more easily and 2) because our patients were diagnosed with PA in the past.

Pure XG or “cholesterol granuloma” of the sellar region was first reported in 1988 in 4 out of 211 sellar tumors, when it was regarded as a variant of adamantinomatous CP (aCP) [1]. In 1999 Paulus et al. reported 37 XG cases, from their surgical series of CPs, and defined 13 of them as clinically and histologically distinct from aCP, consisting of pure pituitary XG with or without traces of squamous or cuboid epithelium [2]. Interestingly, no papillary CP with secondary xanthogranulomatous alteration was found. As reported by Paulus et al., these sellar XGs occurred preferentially in adolescents and young adults, with typically smaller tumor size and better outcomes, but also with the more severe hypopituitarism at presentation compared to CPs [2]. In 2000 World Health Organization (WHO) added sellar XG as a new entity to brain tumor classification [3]. The latest insights confirm this at the molecular level. Adamantinomatous and papillary CPs harbor mutually exclusive clonal mutations of CTNNB1 gene in 70% and BRAF gene in 86% of cases, respectively [4-6]. In contrast to CPs and similar to RCCs, XG harbor only wild type BRAF and CTNNB1 genes [7]. However, since not all CP harbor these mutations and XG are common component of aCPs, we excluded all patients with diagnosis of CP from our study.

XG arise from an inflammatory reaction leading to granuloma formation containing cholesterol clefts, hemosiderin deposits, foamy macrophages and multinucleated giant cells with fibrotic reaction. Leakage of cystic content from a pituitary cyst or tumor, rupture and hemorrhage are involved in the pathogenesis of secondary forms. However, pathogenesis of primary forms is less straightforward, relaying on several hypothesis. First one is a continuum of inflammatory pituitary lesions with evolution from xanthomatous and xanthogranulomatous hypophysitis to XG formation. Second one, regarding systemic histiocytic involvement caused by activating mutations in Mitogen Activated Protein Kinase (MAPK) pathway genes i.e. BRAF p.V600E in some juvenile forms with systemic, including the very rare pituitary involvement are recognized in the latest 5^th edition of WHO classification of central nervous system tumors from 2022 as juvenile xanthogranuloma (JXG), a non-Langerhans cell hystiocytic disorder in children [8, 9].

The latest 5^th edition of WHO classification of central nervous system tumors from 2022 defines XG as reactive lesions arising from chronic irritation or trauma usually from other tumors [9].

Xanthogranuloma of the sellar region were included in the World Health Organisation (WHO) of the tumors of the central nervous system in 2000 [3], but not in further editions in 2007, and 2016 [10, 11], emphasizing the complexity of its definition. Similarly, “Xanthogranuloma of the Sellar Region” was described as a separate entity by Perry and Brat in “Practical Surgical Neuropathology: A Diagnostic Approach” in 2010 but not in the in Practical Surgical Neuropathlogy: A Diagnostic Approach: A Volume in the Pattern Recognition Series 2^nd Edition published in 2017 [12, 13]. Such information depicts the difficulties and the evolution in the defining of xanthogranuloma, previously being recognized as tumor lesion and currently being understood presumably as reactive inflammatory entity [14].

Based on previous clinical observations that “pure” forms affect younger patients presenting with more severe multiple hormone deficiencies, headache and visual disturbances, we tried to compare the clinical phenotypes of patients with secondary causes of pituitary XG and those with no other identifiable cause. To our knowledge and according to the literature, no such comparison was performed before.

Material and Methods

Patients diagnosed with XG after pituitary surgery in the University Clinical Center of Serbia in Belgrade during 2015–2021 period were included. Relevant data (clinical presentation, hormonal status, pathohistological and MRI reports) was collected from patient electronic medical histories and analyzed retrospectively. The EasyR program was used for statistical data processing. Data obtained after processing with parametric tests were presented as arithmetic mean (x̄) and standard deviation (SD), while data obtained after processing with non-parametric tests were presented as number and percentage (%). ANOVA was used for age comparison, Fisher’s exact test for gender and presenting clinical, hormonal and radiological features. p-value <0.05 was considered as significant.

Results

In our tertiary center diagnosis of XG was histologically confirmed in 16 out of 714 (2.24%) patients, who underwent pituitary surgery over the period of 7 years (2015–2021). Secondary forms were associated with Rathke’s cleft cyst (RCC, n = 2) and pituitary neuroendocrine tumor, (PitNET, n = 6). “Pure” pituitary XG was diagnosed in 8 patients. Most common presenting features in our cohort, were hypopituitarism (75%), headache (68.5%) and visual disturbances (37.5%). Arginine-vasopressin (AVP) deficiency (6.25%), neurologic symptoms (12.5%) and hyperprolactinemia (25%) were less frequent at presentation. In patients with primary forms 87.5% had hypopituitarism and headache. In patients with secondary form 62.5% had hypopituitarism while 50% had headache at presentation. Visual disturbances were equally present in both groups 38%. Presenting features of our patients with XG are depicted in Fig. 1.

Fig. 1

Clinical presentation of patients diagnosed with primary and secondary pituitary xanthogranuloma

We observed male preponderance in primary XG (8 vs. 0), contrary to secondary XG (3 vs. 5). Mean age at presentation was similar in patients with primary XG (40.75 ± 19.87 years) and secondary XG (45.43 ± 20.92 years; p = 0.389). Panhypopituitarism was more common in “pure” forms compared to secondary etiology (87.5% vs. 25%, p = 0.0406). Partial hypopituitarism (18.75%) was found in three patients with secondary etiology due to pituitary tumor. Hyperprolactinemia (25%) was found in 4 patients with pituitary tumors, none with “pure” pituitary XG (p = 0.0769). Comparison of patients with primary and secondary forms of pituitary XG is presented in Table 1.

Table 1

Comparison of patients diagnosed with primary vs. secondary forms of pituitary xanthogranuloma

		Primary form	Secondary form	p value
		%	%
Gender	male	100%	37.5%	0.0256*
	female	0.0%	62.5%
Panhypopituitarism	no	12.5%	75%	0.0406*
	yes	87.5%	25%
Partial hypopituitarism	no	100%	62.5%	0.2
	yes	0.0%	37.5%
AVP deficiency	no	87.5%	100%	>0.999
	yes	12.5%	0.0%
Hyperprolactinemia	no	100%	50%	0.0769
	yes	0%	50%
Headache	no	12.5%	50%	0.282
	yes	87.5%	50%
Visual disturbances	no	62.5%	62.5%	>0.999
	yes	37.5%	37.5%
Solid form	no	12.5%	25%	>0.999
	yes	87.5%	75%
Cystic form	no	87.5%	87.5%	>0.999
	yes	12.5%	12.5%
Mixed form	no	100%	87.5%	>0.999
	yes	0.0%	12.5%

* stands for significant statistical p-value < 0.05

Relevant individual clinical data, including MRI appearance and pathohistology, are presented in Table 2.

Table 2

Individual characteristic and presenting features of patients with pituitary xanthogranuloma (XG)

	Gender, age	Primary/secondary	Symptoms and signs	Hormonal status	Magnetic resonance imaging	Pathohystological finding
1.	Male, 18 years	primary	Short stature, No puberty, Headache	Panhypopituitarism Normal PRL	Intrasellar and suprasellar propagation solid lesion (37 × 23 × 35 mm)	XG Numerous cholesterol clefts surrounded by macrophages (CD68+, CD163+) and necrotic debris. Neither elements of the anterior pituitary (negative stains for Synaptophysin, SF-1, Pit-1 and T-Pit) nor squamous epithelium (negative stain for p63) were observed.
2.	Male, 18 years	primary	Short stature, No puberty, Headache	Panhypopituitarism Normal PRL	Intrasellar and suprasellar solid lesion (19 × 18 × 12 mm)	XG Numerous macrophages (CD68+, CD163+) surrounding cholesterol clefts. Elements of epithelium and anterior pituitary were not observed (CK(AE1/AE3)–, Synaptophysin–).
3.	Male, 36 years	primary	Strabism, Double vision, Headache, Loss of libido, Erectile dysfunction	Panhypopituitarism Normal PRL	Intrasellar and suprasellar with parasellar propagation to cavernous sinuses solid lesion (14 × 15 × 8 mm)	XG Cholesterol clefts surrounded by numerous macrophages and tissue of anterior pituitary infiltrated by T (CD3+) and B (CD20+) lymphocytes. No IgG4 i CD1a positive cells were identified.
4.	Male, 24 years	primary	Headache Erectile dysfunction Fatigue	Panhypopituitarism Normal PRL	Intrasellar and suprasellar cystic lesion	XG Cholesterol clefts surrounded by macrophages, fibrous tissue capsule
5.	Male, 58 years	primary	Bitemporal hemianopsia, Headache	Panhypopituitarism Normal PRL	Intrasellar and, suprasellar solid lesion	XG Cholesterol clefts surrounded by macrophages and foreign body cells
6.	Male, 71 years	primary	Polyuria-polydipsia	AVP deficiency	Intra sellar and suprasellar solid lesion 15 × 12 × 11 mm	XG Numerous macrophages (CD68+) and giant cell of foreign body type with cholesterol clefts in the cytoplasm adjacent to the fragments of anterior pituitary (Synaptophysin+) and non-keratinizing squamous epithelium of unknown origin (squamous metaplasia in Rathkes cyst vs. craniopharyngioma).
7.	Male, 47 years	primary	Loss of libido and body hair, Gynecomastia Headache	Panypopituitarism, normal PRL	Intrasellar and suprasellar solid lesion (16 × 18 × 22 mm)	XG Necrotic tissue and cholesterol crystals surrounded by macrophages
8.	Male, 54 years	primary	Headache Double vision Loss of vision in the right eye	Panhypopituitarism	Instrasellar and suprasellar solid lesion	XG Cholesterol clefts surrounded by macrophages
9.	Female, 8 years	secondary	Divergent strabism, Double vision, Photophobia, Headache	Normal	Intrasellar and suprasellar with propagation to right cavernous sinus solid lesion	XG rupture of RCC Cysts covered by cylindrical epithelium, positive for CK7 and EMA, and scattered p40 positive cells. Cells were negative for S-100, GFAP, TTF-1, synaptophysin and anterior pituitary hormones, and surrounded by cholesterol clefts and macrophages (CD68+, CD163+).
10.	Male, 39 years	secondary	Headache, Fatigue	Panhypopituitarism Normal PRL	Intrasellar with suprasellar propagation cystic lesion	XG rupture of RCC A small fragment of cylindric epithelium (CK (AE1/AE3)+, CK7+, EMA+, Vimentin–, CD68–) surrounded by numerous macrophages (CD68+) and cholesterol clefts.
11.	Female, 40 years	secondary	Amenorrhea, Galactorrhea	Elevated PRL, TSH Partial hypopituitarism, isolated hypogonadism	Intrasellar with suprassellar propagation solid lesion (17 × 25 × 6 mm)	XG PRL+, TSH+ pituitary adenoma Thyrotroph PitNET adjacent to the numerous cholesterol clefts surrounded by macrophages and foreign-body giant cells.
12.	Male, 55 years	secondary	Acral growth	Elevated IGF-1, PRL Partial hypopituitarism, isolated hypogonadism	Intrasellar and supraselar solid lesion (17 mm)—CT scan (MRI was not possible to carry out due to the presence of metal bodies)	XG GH+, PRL+ pituitary adenoma a smaller zone of necrosis with several cholesterol crystals surrounded by several foreign body-type giant cells
13.	Female, 70 years	secondary	Bitemporal hemianopsia, Headache Vertigo	Normal	Intrasellar and suprasellar solid lesion	XG Null-cell pituitary adenoma with zones of cholesterol crystals surrounded by macrophages
14.	Male, 77 years	secondary	Syncope, Vertigo Poor memory	Partial hypopituitarism (low IGF-1, cortisol, LH, FSH, testosterone) Elevated PRL	Intrasellar and suprasellar with infrasellar propagation and sphenoid bone destruction (29 × 28 × 27 mm) solid lesion	XG LH+, FSH+, pituitary adenoma Gonadotroph PitNET adjacent to the numerous cholesterol clefts, zones of hyalinisation and rare macrophages
15.	Female, 67 years	secondary	Bilateral ophtalmoplegia Headache	Panhypopituitarism	Intrasellar and suprasellar solid lesion with small cystic component (31 × 35 × 39 mm)	XG Pit NET apoplexy Cholesterol clefts and macrophages (CD68+, CD163+) embedded in fibrous tissue adjacent to the small fragment of PitNET (Synaptophysin+, CK8/18+, p40–, TTF-1–, Vimentin–). Precise diagnosis of PitNET disabled by the loss of tissue in sections aimed for anterior pituitary transcription factors and hormones.
16.	Female, 45 years	secondary	Galactorrhea	Elevated PRL	Intrasellar solid lesion with suprasellar, parasellar and infrasellar propagation (22 × 17 × 14 mm)	XG Silent ACTH pituitary adenoma and elements of cholesterol clefts macrophages and foreign body type cells

PRL - prolactin, TSH - thyrotropin stimulating hormone, GH - growth hormone, IGF-1-Insulin like growth factor 1, FSH - follicular stimulating hormone, LH - luteinizing hormone, AVP-arginine vasopressin, Pit NET-Pituitary neuroendocrine tumor, RCC-Rathke’s cleft cyst, XG-xanthogranuloma

The most common MRI presentation, regardless of etiology, included solid lesions (81.25%), and suprasellar propagation (Table 1) (Fig. 2). Only three patients (18.75%) had cystic appearance. Suprasellar propagation was absent only in one patient, while three had additional parasellar and one infrasellar propagation.

Fig. 2

MRI presentation of patients diagnosed with pituitary xanthogranuloma

A. B. Apoplectic PitNET with secondary xanthogranuloma formation (Patient 15 in Table 2)

C. D. Ruptured Ratke’s cleft cyst (RCC) with secondary xanthogranuloma formation (Patient 10 in Table 2)

E. F. Primary sellar xanthogranuloma (Patient 6 in Table 2)

Preoperative MRI sequences of a sellar region. (A) Apoplectic Pit NET presenting as lesion with central heterogenous hyperintense signal due to hemorrhage on precontrast T1WI in coronal view (B) with inhomogenous postcontrast enhancement on postcontrast T1WI in coronal view (C) Pituitary xanthogranuloma secondary to RCC rupture presenting as heterogenous hyperintense lesion with suprasellar epicenter on postcontrast T1WI in coronal and (D) sagittal view. (E) Pituitary xanthogranuloma presenting as solid sellar lesion with hyperintense to isointense signal on postcontrast T1WI in coronal view and (F) discreetly inhomogeneous hyperintense signal on postcontrast T1WI in sagittal view.

Pathohistology reports in all patients were consistent with diagnosis of XG depicting cholesterol clefts surrounded by macrophages and giant cell of foreign body type, some fibrous and/or inflammatory reaction. Traces of squamous epithelium were found in one patient with primary sellar XG (Table 2 and Fig. 3, patient 6) suggestive of squamous metaplasia of unknown origin Fig. 3). Additionally, cylindrical epithelium (CK (AE1/AE3)+, CK7+, EMA+, Vimentin–, CD68) surrounded by numerous macrophages (CD68+) and cholesterol clefts was found in two patients with secondary XG due to rupture of RCC (Table 2, patient 9 and 10, Fig. 3, patient 10). In patients with XG secondary to pituitary tumors cholesterol clefts and macrophages (CD68+, CD163+) were typically embedded in fibrous tissue adjacent to a small fragment of PitNET (Table 2, Fig. 3, patient 15).

Fig. 3

Pathohistological finding of patients diagnosed with pituitary xanthogranuloma

A. B. C. Pituitary xanthogranuloma secondary to pituitary tumor apoplexy (Patient 15 in Table 2)

D. E. F. Pituitary xanthogranuloma secondary to rupture of Ratke’s cleft cyst (Patient 10 in Table 2)

G. H. I. Primary pituitary xanthogranuloma (Patient 6 in Table 2)

(A) Xanthogranuloma after the apoplexy of the tumor. The tissue was composed of foamy cells and cholesterol clefts (HE, ×200) (B) Foamy cells are decorated by CD68 (×200) (C) The remnants of neuroendocrine tumor are visualized by stain for Synaptophysin (×200); (D) Xanthogranuloma due to rupture of Ratke’s cleft cyst. Numerous cholesterol crystals surrounded by macrophages (CD68, ×100); (E) A small fragment of cylindric epithelium close to macrophages (arrow) (CD68, ×400) (F) showed CK7 immunopositivity of the fragment, suggesting the origin in the Ratke’s cyst (CK7, ×400); (G) Sellar xanthogranuloma; anterior pituitary (upper left) next to numerous cholesterol clefts (down, right) (HE, ×200); (H) Cholesterol clefts are surrounded by macrophages and giant foreign-body cells, all being CD68 positive (CD68, ×400); (I) A very small fragment of flattened squamous epithelium (HE, ×200; insert p40, ×400).

Discussion

Incidence of pituitary XG in our study was 2.24% similar to 2% reported by Ved et al. who diagnosed 6 patients with XG out of 295 endoscopic endonasal pituitary surgeries performed over the 5 year period [15]. Unlike other case series reporting the female preponderance [7, 15], our study reported male predominance (11 male, 5 female), similar to findings of only one study matching ours in size, by Yang et al. (9 male, 5 female) [16].

Due to rarity of this pathological entity very few small original case series are reported so far, ranging in size from 5–37 patients with different etiology including only “pure” XGP lesions [7, 15, 16], primary and secondary to CP [2, 17], primary and secondary due to RCC [17, 18] and secondary due to PA [19, 20]. However, no previous study compared clinical presentation between groups with different etiology. In order to explore their clinical phenotype, we compared two groups, equal in size, different in etiology of XG (primary n = 8 and secondary n = 8 due to PA n = 6 and RCC n = 2).

Recently a case report with review of the literature analyzed 71 published cases of sellar XG [21]. No differences in gender distribution were found. Mean age was 35 years and 70.4% had hypopituitarism, 64.7% visual disorders, 53.5% headache, 28.7% polyuria-polydipsia [21].

Primary and secondary pituitary XG were equally prevalent in our cohort (50 %). We observed low prevalence of RCC in secondary cases: only two patients (12.5%) with rupture of RCC, compared to studies reporting RCC in 26% to 86% of patients diagnosed with pituitary XG [17, 18]. PA was the leading cause of secondary XG, reported in 6 of 8 (75%) of our secondary XG patients. Nishioka et al. reported PA with XG in 2.2% (5 out of 231 operated patients with PA). Nonfunctioning PitNET was the most prevalent type in other series [20]. In our study 3 patients had functioning and 3 nonfunctioning PitNET. Studies investigating XG in patients with PitNET showed female predominance [19, 20], like our study (4 female, 2 male patients).

As previously reported, intra/suprasellar localization of pituitary lesion is the most prevalent [7]. In our series MRI revealed cystic lesions in only 3 patients (18.75%), one with primary, two with secondary etiology (RCC and PA). This is probably due to very low prevalence of RCC (12.5%) in our series. Majority of patients (81.25%), had solid appearance of pituitary lesion on MRI. In a study yielding 15 reported cases of PitNET with xanthogranulomatous change, tumors usually had a cystic component [19], finding noted in only one of our patients with PitNET apoplexy. Guerrero-Perez reported sellar-suprasellar location in 71.8%, T1W hyperintensity in 76.3%, T2W hypointensity in 38.9% and cystic appearance in 50.7% [21]. Extensive systematic review of MRI features of pituitary XG lesions has been published recently by Lozovanu et al. in 2022 [14].

Polyuria-polydipsia due to AVP deficiency was infrequent at presentation in our series, reported in only one patient (6.25%). Ved et al. reported it in only one of their 6 cases with pituitary XG, while Hernandez-Estrada et al. reported AVP deficiency, at presentation, in 6 out of 27 patients (22.2%) [7, 15]. Our patient who presented with AVP deficiency, was published previously, with review of the literature including 10 cases of sellar XG presenting with AVP deficiency, as an infrequent presenting feature [22].

Prevalence of hypopituitarism at presentation in patients with XG was variable among the studies. Hypopituitarism was observed at presentation in 75 % of our patients. The highest prevalence of hypopituitarism was reported by Amano et al. in 86% (6 out of 7 patients) [18]. Yang et al., reported hypopituitarism in 42.9% of 14 patients [16]. Hernandez-Estrada reported panhypopituitarism in 40.7% of 27 patients [7]. In our study, panhypopituitarism was confirmed in 56.25% of patients, more frequently in male patients (8 males, 1 female), especially those with primary etiology (7 primary, 2 secondary etiology). Observations regarding more severe hypopituitarism, headache, visual disturbances and younger age, previously reported by Paulus et al. in patients with primary pituitary XG are in line with this specific clinical phenotype [2]. From their surgical series Paulus et al. reported smaller size of primary XG compared to CP and superior outcomes regarding recurrence, headache and visual disturbances after surgery, only persistence of irreversible hypopituitarism, suggesting a milder and more favorable clinical phenotype in patients with primary pituitary XG compared to CP group [2].

Our study reported hyperprolactinemia in 4 patients (25%) with pituitary XG (two functioning lactotroph PitNETs, and two with non-functioning PitNET due to stalk compression) compared to study by Ved et al. who reported hyperprolactinemia in 4/6 (66.7%) patients with pituitary XG [15].

Compression symptoms such as headache in 68.5% and neuro-ophthalmic disorders including hemianopsia, diplopia, photophobia, strabismus, ophtalmoplegia and ptosis, were present in 37.5% of our patients (3 patients with primary, 3 with secondary etiology). In study by Yang et al., which included 14 patients, headache was present in 85%, visual disturbances in 71.4% [16]. Amano et al. reported 7 patients with XG, 6 secondary to RCC, with high prevalence of headache 86% and visual disturbances 71%, suggesting a XG as the end stage of RCC undergoing degenerative transformation after leakage, rupture and hemorrhage, due to the finding of cuboid or columnar epithelium in 86% of these patients [18]. High prevalence of headache and hypopituitarism could be explained by the inflammatory and destructive nature in primary and tendency to hemorrhage and apoplexy in some patients with RCC and PA with secondary etiology of XG lesions.

Presence of epithelium in patients with primary forms of XG, lacking the other components of a cystic pituitary lesion or CP, was observed in one of our patients reported previously by us and other authors [2, 17, 22]. The origin of traces of epithelium, which can be found in some patients with primary XG is intriguing and described in <10% of patients [9].

Another important issue, which should not be neglected, is the heterogeneity within pituitary XG lesions affecting the sampling bias. For example, inflammation and hemorrhage associated XG, within other lesions may not be captured by microscopy which could be a potential limitation of this study.

Conclusion

Our study reports 2.24% incidence of pituitary xanthogranulomas in a large series of patients operated for sellar masses. Awareness is raised of this rare yet important pathological entity often misdiagnosed. Regarding distinct etiology of the lesion (pure or secondary to PA or RCC) we report no difference in MRI presentation of typically solid lesion with suprasellar extension. However, we observed differences in gender distribution with male preponderance only in primary lesions as well as in presenting panhypopituitarism, which is 3.5-fold more prevalent with primary lesions. Our findings support the previously reported more severe hypopituitarism with compression symptoms in patients with “pure” forms of XG pituitary lesions. Further research in this field is warranted.

Ethical Approval

This retrospective study involving human participants was in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Acknowledgments

This work was supported by the Serbian Ministry of Science (Project number 200110).

Disclosure

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

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