case_images: PMC10556246_01
case_images: (A) Case 1: Pre-surgical coronal pituitary MRI showing a solid cystic tumor lesion (17 mm x 14 mm). A hyperintense cystic portion and a small hypointense left paramedian eccentric solid mural nodule can be seen on T2. (B) Case 1: Post-surgical coronal MRI exhibiting changes at the sellar and suprasellar level. Minimal hemorrhagic changes, lateralized to the left, without any clearly visible tumor lesion, are seen in T2. (C,D) Case 1: Representative image of XS showing multinucleated giant cells; hemosiderophages (arrow head); and reactive fibroblastic proliferation (*). Morphological details of multinucleated giant cells (D; H/E staining). Scale bar 20 mum. (E,F) Case 1: Microscopical examination of XG showing a solid area composed of a mixture of tumoral/inflammatory cells, and the focus of dystrophic microcalcification associated with clear acicular cholesterol crystals (arrow) immersed in an inflammatory process (E). (F) Details of microcalcification (H/E staining). Scale bar 20 mum. (G) Case 2: Preoperative coronal MRI of sellar lesion measuring 12 mm x 17 mm x 20 mm, faintly hyperintense on T2 with hypointense margins. The lesion is compressing and displacing the chiasm and optic pathways. (H) Case 2: Postoperative coronal MRI revealing a 4 mm remnant in the central sector, hypointense on T2 coronal, and indicative of hemosiderin deposit. Areas in the periphery are suggestive of glandular parenchyma. (I,J) Case 2: Representative images of histopathological and immunohistochemical staining of resected tumoral tissue. Diffuse infiltration of macrophage mononuclear cells with foamy cytoplasm with a xanthomized appearance are seen (I; H/E staining). A strong and diffuse immunolabeling for CD68 is clearly detected in macrophages (J; 3, 3'-diaminobenzidine staining). Scale Bar 100 mum. (K) Case 2: Representative electron micrographs of pituitary tissue depicting numerous epithelial cells containing several secretory granules of different sizes. Next to these cells, the presence of dense connective tissue (*) with a fibrocyte (F) is highlighted. N, nuclei; F, fibrocyte. (L) Case 2: A macrophage (Ma) is immersed in the pituitary parenchyma, exhibiting phagocytic vacuoles (arrowhead) probably containing secretory granules in the process of digestion. N, nuclei; Ma, Macrophage; dense connective tissue (*).
case_images: fnins-17-1227144-g001.jpg
case_images: PMC10556246_02_fnins-17-1227144-g001.jpg
case_images: fig1
case_images: T2 and isointense signal on T1, without any enhancement after intravenous contrast (Figure 1G). The lesion was compressing and displacing the optic chiasm and cephalic tracts. The histopathological analysis showed an extensive xanthogranulomatous chronic inflammatory reaction composed of abundant clumped foamy macrophages (Figure 1I), some multinucleated giant cells, and lymphocytes. The immunohistochemical staining revealed strong and diffuse CD68-positive macrophage staining (Figure 1J). At the electron microscopy level, it was observed that the endocrine cells were intermingled with fibroblasts, abundant collagen fibers, and inflammatory cells (mainly macrophages; Figures 1K,L). Neurohypophysis was not identified (Figure 1H).
case_images: PMC10556246_02
case_images: (A) Case 1: Pre-surgical coronal pituitary MRI showing a solid cystic tumor lesion (17 mm x 14 mm). A hyperintense cystic portion and a small hypointense left paramedian eccentric solid mural nodule can be seen on T2. (B) Case 1: Post-surgical coronal MRI exhibiting changes at the sellar and suprasellar level. Minimal hemorrhagic changes, lateralized to the left, without any clearly visible tumor lesion, are seen in T2. (C,D) Case 1: Representative image of XS showing multinucleated giant cells; hemosiderophages (arrow head); and reactive fibroblastic proliferation (*). Morphological details of multinucleated giant cells (D; H/E staining). Scale bar 20 mum. (E,F) Case 1: Microscopical examination of XG showing a solid area composed of a mixture of tumoral/inflammatory cells, and the focus of dystrophic microcalcification associated with clear acicular cholesterol crystals (arrow) immersed in an inflammatory process (E). (F) Details of microcalcification (H/E staining). Scale bar 20 mum. (G) Case 2: Preoperative coronal MRI of sellar lesion measuring 12 mm x 17 mm x 20 mm, faintly hyperintense on T2 with hypointense margins. The lesion is compressing and displacing the chiasm and optic pathways. (H) Case 2: Postoperative coronal MRI revealing a 4 mm remnant in the central sector, hypointense on T2 coronal, and indicative of hemosiderin deposit. Areas in the periphery are suggestive of glandular parenchyma. (I,J) Case 2: Representative images of histopathological and immunohistochemical staining of resected tumoral tissue. Diffuse infiltration of macrophage mononuclear cells with foamy cytoplasm with a xanthomized appearance are seen (I; H/E staining). A strong and diffuse immunolabeling for CD68 is clearly detected in macrophages (J; 3, 3'-diaminobenzidine staining). Scale Bar 100 mum. (K) Case 2: Representative electron micrographs of pituitary tissue depicting numerous epithelial cells containing several secretory granules of different sizes. Next to these cells, the presence of dense connective tissue (*) with a fibrocyte (F) is highlighted. N, nuclei; F, fibrocyte. (L) Case 2: A macrophage (Ma) is immersed in the pituitary parenchyma, exhibiting phagocytic vacuoles (arrowhead) probably containing secretory granules in the process of digestion. N, nuclei; Ma, Macrophage; dense connective tissue (*).
case_images: fnins-17-1227144-g001.jpg
case_images: PMC10556246_02_fnins-17-1227144-g001.jpg
case_images: fig1
case_images: T2 and isointense signal on T1, without any enhancement after intravenous contrast (Figure 1G). The lesion was compressing and displacing the optic chiasm and cephalic tracts. The histopathological analysis showed an extensive xanthogranulomatous chronic inflammatory reaction composed of abundant clumped foamy macrophages (Figure 1I), some multinucleated giant cells, and lymphocytes. The immunohistochemical staining revealed strong and diffuse CD68-positive macrophage staining (Figure 1J). At the electron microscopy level, it was observed that the endocrine cells were intermingled with fibroblasts, abundant collagen fibers, and inflammatory cells (mainly macrophages; Figures 1K,L). Neurohypophysis was not identified (Figure 1H).
case_images: PMC10556246_03
case_images: (A,B) Case 3: Preoperative coronal and sagittal MRI showing a large, thick-walled, cystic-like lesion (28 mm x 19 mm x 19 mm), hypointense on T1, extended to the suprasellar cistern. Neither the signal corresponding to the neurohypophysis nor the pituitary stalk are identified. (C) Panoramic photomicrograph showing dense connective tissue (dotted circle) and frequent macrophages (dot rectangle; H/E staining). Scale Bar 100 mum. (D) Multinucleated giant cell and hemosiderin-laden macrophages can be detected (arrow head; H/E staining). Scale bar 20 mum. (E) Simple columnar tubular epithelial rest immersed in an inflammatory background (H/E staining). Scale bar 20 mum.
case_images: fnins-17-1227144-g002.jpg
case_images: PMC10556246_03_fnins-17-1227144-g002.jpg
case_images: fig2
case_images: It also caused lysis and remodeling of the sphenoid bone in anterior and posterior directions while compressing both cavernous sinuses in a lateral direction (Figures 2A,B). A histopathological examination revealed an extensive chronic xanthogranulomatous-type inflammatory reaction, represented by abundant foamy macrophages interspersed with multinucleated giant cells, lymphocytes, and neutrophils associated with cholesterol spikes (Figures 2C,D). In addition, signs of recent bleeding and isolated tubular epithelial structures were observed lined by cylindrical epithelium, without atypia, which were closely related to the inflammatory process (Figures 2C-E).
case_images: PMC10556246_04
case_images: (A) Case 4: Pre-surgical coronal MRI showing a solid expansive lesion measuring 39 mm x 31 mm x 32 mm, hypertense on T1 with gadolinium. An eccentric area with a cystic appearance in the right lateral sector is also seen. (B) Post-surgical coronal MRI showing an intrasellar lesion measuring 25 mmx 35 mmx 27 mm with suprasellar growth infiltrating both carvenous sinuses, isointense on T1. An area of intratumoral hemorrhage in the right lateral basal is also detected. (C) Panoramic photomicrograph of surgical specimen revealing leftward neuroendocrine pituitary tumor with signs of ischemia, interstitial hemorrhage, and erythrocyte extravasation. To the right, dense fibroconnective tissue with slits, abundant hemosiderophages, and cell multinucleated giants (arrow). (Insert a) Pituitary neuroendocrine tumor composed of chromophobe cells with interstitial hemorrhage and signs of ischemia. (Insert b) Hemosiderophages and macrophages. (H/E staining). Scale Bar 100 mum. (D,E) Remnants of tumoral tissue showing extensive hemorrhage and macrophage activation (Toluidine blue staining). Scale Bar 100 mum (D); 20 mum (E). (F) Polimorfonuclear immune cells, including eosinophils (Eo), neutrophils (Neu), and erythrocytes (E) are frequently observed as part of the connective tissue forming the sellar xanthogranulomas. In the background, detritus from necrotic cells, including membranes (black arrowhead), nuclei fragments (white arrowhead), and organelles (white cross) can also be seen. (G) At higher magnification, a neutrophil (Neu) is observed engulfing debris material from the microenvironment (arrowhead), which is comprised of collagen fibers (*), granular remains (white cross), and free chromatin (Chr).
case_images: fnins-17-1227144-g003.jpg
case_images: PMC10556246_04_fnins-17-1227144-g003.jpg
case_images: fig3
case_images: The lesion included the left internal carotid in its cavernous course, the third, fourth, and sixth cranial nerves, and the V1-V2 segments of the trigeminal (Figures 3A,B). The campimetry evaluation was normal, but a hormonal evaluation revealed panhypopituitarism with involvement of the thyroid, adrenal, and gonadal axis. A small fragment with fibroblastic proliferation, collagen fiber deposition, mononuclear infiltrate of lymphocytes, some hemosiderophages, and occasional foreign body-type multinucleated giant cells (secondary inflammatory reaction) was detected (Figure 3C). Residual neoplastic epithelial tissue with signs of active bleeding and evidence of macrophage activation was also observed (Figures 3D,E). Abundant inflammatory cells (mainly eosinophils and neutrophils) appeared surrounded by a great deal of cellular detritus, such as membranes, apoptotic bodies, and necrotic cells, together with blood extravasation as revealed by electron microscopy (Figure 3F). Moreover, neutrophils exhibited intense phagocytic activity (Figure 3G).
case_images: PMC10556246_05
case_images: (A,B) Case 5: Pre-surgical MRI coronal and sagittal showing a solid, polylobulated lesion, 35 mm x 27 mm x 38 mm, hyperintense on T2 with some cystic areas. An extension toward the suprasellar cistern, generating a mass effect on the hypothalamus and the optic chiasm is shown invading both cavernous sinuses. (C) Histopathological examination showing xanthogranulomatous inflammatory reaction with abundant cholesterol spikes immersed in the pituitary neuroendocrine tumor. Inset: Chromophobe: monomorphic pituitary tumor cells distributed in a solid pattern are shown. (HE staining) Scale Bar 100 mum. (D) Nuclear immunohistochemical staining of Ki67 in neoplastic cells. (3, 3'-diaminobenzidine staining). Scale Bar 100 mum. (E) Electron microscopy picture depicting a capillary structure (dotted circle) containing erythrocytes (E) and inflammatory cells in the lumen. Lymphocytes (Ly) and mononuclear monocytes/macrophages (Ma) are also seen in the surrounding tissue. (F) Microphotograph showing epithelial secretory cells (EC) alongside extravasated erythrocytes (E). In addition, the connective tissue displays fibroblasts (Fi) and infiltrated macrophages (Ma).
case_images: fnins-17-1227144-g004.jpg
case_images: PMC10556246_05_fnins-17-1227144-g004.jpg
case_images: fig4
case_images: It extended cephalad, obliterating the suprasellar cistern, generating a mass effect on the hypothalamus and the optic chiasm, displacing both optic nerves, invading both cavernous sinuses, and surrounding the internal carotid arteries (Figures 4A,B). Signs of hemorrhage and the foci of an intratumoral xanthogranulomatous reaction were also recognized (Figure 4C). Immunohistochemical assays revealed focal and moderate LH staining, focal and weak FSH labeling, and a Ki67 index of 5% of neoplastic cells (Figure 4D). At the electron microscopy level, several inflammatory cells, including monocytes, lymphocytes, and neutrophils, could be observed, together with fibroblasts and abundant collagen fibers (Figure 4E).