Neoplasms and tumor-like lesions of the sellar region: imaging findings with correlation to pathology and 2021 WHO classification.

The sellar region represents a complex anatomical area, composed of multiple structures of different embryological derivation, including the skull base and the pituitary gland, along with vascular, nervous, and meningeal structures. Masses arising in this region include benign and malignant lesions arising from the pituitary gland itself, but also from vestigial embryological residues or surrounding tissues, that may require different therapeutic approaches. While assessing sellar region masses, the combination of clinical presentation and imaging features is fundamental to define hypotheses about their nature. MR represents the imaging modality of choice, providing information about the site of the lesion, its imaging features, and relation with adjacent structures, while CT is useful to confirm the presence of lesion calcifications or to reveal tumor invasion of bony structures. The aim of this pictorial review is to provide an overview of the common neoplasms and tumor-like conditions of the sellar region, according to the 2021 WHO Classification of Tumors of the Central Nervous System (fifth edition), with an emphasis on the radiologic-pathologic correlation. After a brief introduction on the anatomy of this region and the imaging and pathological techniques currently used, the most relevant MRI characteristics, clinical findings, and pathological data, including histologic and molecular features, will be shown and discussed, with the aim of facilitating an appropriate differential diagnosis among these entities.

An update on the pathology of neuroendocrine tumors.

In this review, we highlight different aspects of a specialized tumor subset, neuroendocrine tumors. We discuss the terminology applied to these tumors, define their precancerous state, diagnostic criteria, immunohistochemical and molecular markers and finally the grading system that is currently applied to these subset of tumors.

Are granular osmiophilic material deposits an epiphenomenon in CADASIL?

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is caused by mutations in the NOTCH3 gene. Pathophysiologically, there seems to be multimerization of the extracellular domain of the protein with a possible gain of function on vascular smooth muscular cells. However, the mechanisms and determinants of NOTCH3 multimerization are not completely understood, and it is not completely elucidated whether NOTCH3 multimerization contributes to the appearance of granular osmiophilic material (GOM) deposits, which are the pathological hallmark of CADASIL. We recently reported a patient with parkinsonism and cognitive impairment and with evidence of diffuse white matter changes on imaging, carrying a NOTCH3 nonsense mutation in exon 3 (c.307C>T), and suggested that such a hypomorphic NOTCH3 mutation was likely to be pathogenic. We further pursued ultrastructural examination of skin vessels in our case, and here we report the results, wishing to make a comment on whether GOM deposits should be considered the pathological hallmark for a definitive diagnosis of CADASIL in those patients whose mutations are predicted in the production of hypomorphic protein products.

Glioblastoma in the elderly: the impact of advanced age on treatment and survival.

OBJECTIVE: To evaluate the effects of combined treatments on the outcome and survival of elderly (≥ 65 years) patients with glioblastoma as compared with younger ones. MATERIAL AND METHODS: Fifty consecutive elderly (≥ 65 years) patients (group A) who underwent complete or subtotal (> 80%) resection of brain glioblastoma followed by irradiation and chemotherapy with temozolomide between 2004 and 2009 were retrospectively reviewed and compared with 50 glioblastoma patients aged < 65 years, treated in the same period (group B). Patient sex, tumor location, size and side, combined treatments, reoperation, progression-free survival, and overall survival were compared in the two groups by using the Kaplan-Meyer method. RESULTS: There were no significant differences between the two groups for tumor location, size and side, and Ki-67 Li. Forty-four of 50 group B patients were treated by the Stupp protocol, whereas all group A patients underwent irradiation and adjuvant temozolomide. Second-line chemotherapy was administrated in 32% of group A and 76% of group B cases, and reoperation was performed in 16% and 36%, respectively. The median survival of the overall series of 100 patients was 15.6 months. Group A patients (≥ 65 years) had a median survival of 14.5 months, significantly lower than group B cases (17 months) (p = 0.02). CONCLUSION: Elderly patients with glioblastoma may benefit from combined treatments, including surgery, radiotherapy, and chemotherapy. Although younger patients do survive longer than older ones, the difference of survival is less significant if several criteria of selection to surgery, such as good Karnofsky performance status (KPS), largely resectable tumor, and no significant comorbidity, are respected.

Recurrences of meningiomas: predictive value of pathological features and hormonal and growth factors.

OBJECTIVE: Recurrence of apparently completely resected benign meningiomas is a rather frequent event, the mechanisms of which are still unclear. The aim of this study is to define the pathological features, proliferation indexes, growth factors and hormone receptor expression in predicting the meningioma recurrence. METHODS: Two groups of 50 completely resected benign WHO I meningiomas, with and without recurrence respectively, have been reviewed. Tumor location, consistency, vascularity, and histological types have been considered. Immunohistological studies include mitotic index (MI), Ki-67 LI, estrogen and progesterone receptors (ER and PR), Vascular Endothelial Growth Factor (VEGF), Epidermal Growth Factor (EGF), and Bcl-2. All these factors have been correlated with the recurrence. RESULTS: The tumor recurrence was not correlated with the patient age, tumor location, consistency, vascularity and histology. There was not difference in the histological pattern between local and diffuse recurrences. M.I. and Ki-67 LI were significantly correlated with the recurrence (P<0.0001). PR negativity had a strong predictive value of recurrence (P<0.0001), whereas the ER status was not relevant. VEGF and EGF-R were not correlated with the recurrence of meningiomas, whereas the Bcl-2 protein positivity showed a tendency to the significativity (P=0.0294). The negative association between Bcl-2 and PR is an interesting finding of our study. CONCLUSIONS: Higher MI and Ki-67 LI and PR negativity are predictive factors of recurrence of benign (WHO I) completely resected meningiomas, particularly when Bcl-2 positivity is associated.

Clinical progression and familial occurrence of cerebral cavernous angiomas: the role of angiogenic and growth factors.

OBJECT: The authors studied the expression of angiogenic and growth factors and various proliferative indices in cavernous angiomas of the brain. The goal was to define whether the often progressive clinical course of both sporadic and familial forms of the lesion is correlated with different expression of these factors. METHODS: Forty-three cavernomas of the brain were investigated with immunohistochemical studies and stained for four growth factors (vascular endothelial growth factor [VEGF], tenascin, transforming growth factor-b [TGFb], and platelet-derived growth factor [PDGF]), and for Ki-67 and bcl-2. The intensity of expression was tested in all cases in the walls of cavernoma vessels, in the perivascular tissue, and in the perilesional brain parenchyma. Among the 43 cavernomas, 32 were stable and sporadic single lesions less than 2 cm in size, whereas 11 were cavernomas larger than 2 cm (up to 6 cm). These larger cavernomas had more aggressive behavior (documented growth in five cases, mass effect in eight, significant hemorrhage in four), familial occurrence (six cases), and/or multiple lesions (five cases). The expression of VEGF, tenascin, and PDGF in cavernomas did not significantly differ in the two groups of patients, whereas TGFb expression was higher in the more aggressive forms of cavernomas. The expression of Ki-67 and bcl-2 was always absent in stable lesions, and it was positive in eight (72.7%) of 11 aggressive lesions. The perilesional brain parenchyma showed a significantly higher expression of TGFb, PDGF, and tenascin in more aggressive cavernomas. CONCLUSIONS: The familial occurrence and more aggressive clinical behavior of cavernous angiomas of the brain are associated with higher expression of Ki-67 and bcl-2 in the cavernoma tissue, as in other proliferative lesions. These features are also associated with higher expression of some growth factors (excluding VEGF) in the perilesional brain parenchyma, suggesting that the neighboring vasculature and glia may be predisposed to and recruited for further growth and progression.