New Advances and Challenges in Sellar and Para-Sellar Pathology

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Causes, Screening and Diagnosis".

Deadline for manuscript submissions: closed (31 August 2021) | Viewed by 16675

Special Issue Editor

Division of Neurosurgery, Azienda Ospedaliero-Universitaria, Consorziale Policlinico, University "Aldo Moro" of Bari, Bari, Italy
Interests: Skull base surgery; vascular neurosurgery; neuro-oncology; eloquent area surgical mapping; pediatric neurosurgery

Special Issue Information

Dear Colleagues,

The sellar and parasellar region is a complex anatomical region that contains many important structures in a relatively small space. As a major consequence, a broad spectrum of lesions can occur in this site, including neoplastic, inflammatory, infectious and vascular conditions. The diagnosis of these lesions can be challenging, since many of them have similar clinical and imaging features. Thus, an accurate diagnosis and consequent treatment requires a multidisciplinary approach. Multimodal treatment approach is important, as many sellar and parasellar tumours require surgery, radiotherapy and medical therapy. Recent years have witnessed several advances in the understanding of the imaging, endocrinological, biological and molecular features and of surgical approaches of sellar and parasellar lesions, allowing for an accurate diagnosis and novel therapeutic approaches. On the other hand, many challenges remain in terms of diagnosis, prognosis and optimal, personalised treatment.

This Special Issue will focus on new advances and the challenges in the pathology, diagnosis, therapeutic approaches, as well as novel biological and molecular features, of the lesions of the sellar and parasellar region. Original research articles and comprehensive up-to-date reviews are encouraged to elucidate and identify the current status and future directions in this topic.

We look forward to your contributions.

Prof. Dr. Francesco Signorelli
Guest Editor

Manuscript Submission Information

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Keywords

  • Primary sellar and parasellar tumors
  • Non-neoplastic sellar and parasellar lesions
  • Metastases to the sellar and parasellar regions
  • Endocrine disease of the pituitary
  • Endocrinological assessment of hypothalamic and pituitary lesions
  • Neuroimaging
  • Surgery
  • Targeted therapies
  • Radiation therapy
  • Molecular biology

Published Papers (6 papers)

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12 pages, 1109 KiB  
Article
Pituitary Imaging Abnormalities and Related Endocrine Disorders in Erdheim–Chester Disease
by Skand Shekhar, Jorge A. Irizarry-Caro, Ninet Sinaii, William A. Gahl, Juvianee I. Estrada-Veras, Rahul H. Dave, Bernadette R. Gochuico, Georgios Z. Papadakis, Nicholas Patronas, Constantine A. Stratakis, Kevin O’Brien and Fady Hannah-Shmouni
Cancers 2021, 13(16), 4126; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13164126 - 17 Aug 2021
Cited by 5 | Viewed by 3119
Abstract
Purpose: We examined abnormal pituitary imaging (API) and associated endocrine dysfunction in subjects with ECD. Methods: A cross-sectional descriptive examination of a natural history cohort study diagnosed with ECD was conducted at a clinical research center. Subjects underwent baseline endocrine tests of anterior [...] Read more.
Purpose: We examined abnormal pituitary imaging (API) and associated endocrine dysfunction in subjects with ECD. Methods: A cross-sectional descriptive examination of a natural history cohort study diagnosed with ECD was conducted at a clinical research center. Subjects underwent baseline endocrine tests of anterior and posterior pituitary function and dedicated pituitary gland MRI scans. We determined the frequency of various pituitary imaging abnormalities in ECD and assessed its relationships with age, sex, body mass index (BMI), BRAF V600E status, high sensitivity C-reactive protein (hsCRP), erythrocyte sedimentation rate (ESR), pituitary hormone deficits and number, diabetes insipidus (DI), and panhypopituitarism. Results: Our cohort included 61 subjects with ECD [age (SD): 54.3 (10.9) y, 46 males/15 females]. API was present in 47.5% (29/61) of ECD subjects. Loss of the posterior pituitary bright spot (36.1%) followed by thickened pituitary stalk (24.6%), abnormal enhancement (18.0%), and pituitary atrophy (14.8%) were the most common abnormalities. DI and panhypopituitarism were more frequent in subjects with API without differences in age, sex distribution, hsCRP, ESR, and BRAF V600E status compared to normal pituitary imaging. Conclusions: We noted a high burden of API and endocrinopathies in ECD. API was highly associated with the presence of panhypopituitarism and DI. Therefore, a thorough assessment of hypothalamic–pituitary integrity should be considered in subjects with ECD. Full article
(This article belongs to the Special Issue New Advances and Challenges in Sellar and Para-Sellar Pathology)
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15 pages, 1283 KiB  
Article
Genetic Profiling of a Cohort of Italian Patients with ACTH-Secreting Pituitary Tumors and Characterization of a Novel USP8 Gene Variant
by Donatella Treppiedi, Anna Maria Barbieri, Genesio Di Muro, Giusy Marra, Federica Mangili, Rosa Catalano, Emanuela Esposito, Emanuele Ferrante, Andreea Liliana Serban, Marco Locatelli, Andrea Gerardo Lania, Anna Spada, Maura Arosio, Erika Peverelli and Giovanna Mantovani
Cancers 2021, 13(16), 4022; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13164022 - 10 Aug 2021
Cited by 13 | Viewed by 2268
Abstract
Cushing’s Disease (CD) is a rare condition characterized by an overproduction of ACTH by an ACTH-secreting pituitary tumor, resulting in an excess of cortisol release by the adrenal glands. Somatic mutations in the deubiquitinases USP8 and USP48, and in BRAF genes, have [...] Read more.
Cushing’s Disease (CD) is a rare condition characterized by an overproduction of ACTH by an ACTH-secreting pituitary tumor, resulting in an excess of cortisol release by the adrenal glands. Somatic mutations in the deubiquitinases USP8 and USP48, and in BRAF genes, have been reported in a subset of patients affected by CD. The aim of this study was to characterize the genetic profile of a cohort of 60 patients with ACTH-secreting tumors, searching for somatic mutations in USP8, USP48, and BRAF hotspot regions. Seven patients were found to carry USP8 somatic mutations in the well-characterized 14-3-3 protein binding motif (n = 5 P720R, n = 1 P720Q, n = 1 S718del); 2 patients were mutated in USP48 (M415I); no mutation was identified in BRAF. In addition, a novel USP8 variant, G664R, located in exon 14, upstream of the 14-3-3 protein binding motif, was identified in 1 patient. Functional characterization of USP8 G664R variant was performed in murine corticotroph tumor AtT-20 cells. Transient transfection with the USP8 G664R variant resulted in a significant increase of ACTH release and cell proliferation (+114.5 ± 53.6% and +28.3 ± 2.6% vs. empty vector transfected cells, p < 0.05, respectively). Notably, USP8 proteolytic cleavage was enhanced in AtT-20 cells transfected with G664R USP8 (1.86 ± 0.58–fold increase of N-terminal USP8 fragment, vs. WT USP8, p < 0.05). Surprisingly, in situ Proximity Ligation Assay (PLA) experiments showed a significant reduction of PLA positive spots, indicating USP8/14-3-3 proteins colocalization, in G664R USP8 transfected cells with respect to WT USP8 transfected cells (−47.9 ± 6.6%, vs. WT USP8, p < 0.001). No significant difference in terms of ACTH secretion, cell proliferation and USP8 proteolytic cleavage, and 14-3-3 proteins interaction was observed between G664R USP8 and S718del USP8 transfected cells. Immunofluorescence experiments showed that, contrary to S718del USP8 but similarly to WT USP8 and other USP8 mutants, G664R USP8 displays an exclusive cytoplasmic localization. In conclusion, somatic mutations were found in USP8 (13.3% vs. 36.5% incidence of all published mutations) and USP48 (3.3% vs. 13.3% incidence) hotspot regions. A novel USP8 variant was identified in a CD patient, and in vitro functional studies in AtT-20 cells suggested that this somatic variant might be clinically relevant in ACTH-secreting tumor pathogenesis, expanding the characterization of USP8 functional domains. Full article
(This article belongs to the Special Issue New Advances and Challenges in Sellar and Para-Sellar Pathology)
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13 pages, 3575 KiB  
Article
Primary Endoscopic Endonasal Management of Giant Pituitary Adenomas: Outcome and Pitfalls from a Large Prospective Multicenter Experience
by Salvatore Chibbaro, Francesco Signorelli, Davide Milani, Helene Cebula, Antonino Scibilia, Maria Teresa Bozzi, Raffaella Messina, Ismail Zaed, Julien Todeschi, Irene Ollivier, Charles Henry Mallereau, Guillaume Dannhoff, Antonio Romano, Francesco Cammarota, Franco Servadei, Raoul Pop, Seyyid Baloglu, Giovanni Battista Lasio, Florina Luca, Bernard Goichot, Francois Proust and Mario Ganauadd Show full author list remove Hide full author list
Cancers 2021, 13(14), 3603; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13143603 - 18 Jul 2021
Cited by 23 | Viewed by 2901
Abstract
Purpose: To evaluate factors influencing clinical and radiological outcome of extended endoscopic endonasal transtuberculum/transplanum approach (EEA-TTP) for giant pituitary adenomas (GPAs). Methods: We recruited prospectively all consecutive GPAs patients undergoing EEA-TTP between 2015 and 2019 in 5 neurosurgical centers. Preoperative clinical and radiologic [...] Read more.
Purpose: To evaluate factors influencing clinical and radiological outcome of extended endoscopic endonasal transtuberculum/transplanum approach (EEA-TTP) for giant pituitary adenomas (GPAs). Methods: We recruited prospectively all consecutive GPAs patients undergoing EEA-TTP between 2015 and 2019 in 5 neurosurgical centers. Preoperative clinical and radiologic features, visual and hormonal outcomes, extent of resection (EoR), complications and recurrence rates were recorded and analyzed. Results: Of 1169 patients treated for pituitary adenoma, 96 (8.2%) had GPAs. Seventy-eight (81.2%) patients had visual impairment, 12 (12.5%) had headaches, 3 (3.1%) had drowsiness due to hydrocephalus, and 53 (55.2%) had anterior pituitary insufficiency. EoR was gross or near-total in 46 (47.9%) and subtotal in 50 (52.1%) patients. Incomplete resection was associated with lateral suprasellar, intraventricular and/or cavernous sinus extension and with firm/fibrous consistence. At the last follow-up, all but one patient (77, 98.7%) with visual deficits improved. Headache improved in 8 (88.9%) and anterior pituitary function recovered in 27 (50.9%) patients. Recurrence rate was 16.7%, with 32 months mean recurrence-free survival. Conclusions: EEA-TTP is a valid option for GPAs and seems to provide better outcomes, lower rate of complications and higher EoR compared to one- or multi-stage microscopic, non-extended endoscopic transsphenoidal, and transcranial resections. Full article
(This article belongs to the Special Issue New Advances and Challenges in Sellar and Para-Sellar Pathology)
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11 pages, 475 KiB  
Article
Robotic Radiosurgery for Persistent Postoperative Acromegaly in Patients with Cavernous Sinus-Invading Pituitary Adenomas—A Multicenter Experience
by Felix Ehret, Markus Kufeld, Christoph Fürweger, Alfred Haidenberger, Paul Windisch, Susanne Fichte, Ralph Lehrke, Carolin Senger, David Kaul, Daniel Rueß, Maximilian Ruge, Christian Schichor, Jörg-Christian Tonn, Günter Stalla and Alexander Muacevic
Cancers 2021, 13(3), 537; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13030537 - 31 Jan 2021
Cited by 2 | Viewed by 2366
Abstract
Background: The rates of incomplete surgical resection for pituitary macroadenomas with cavernous sinus invasion are high. In growth hormone-producing adenomas, there is a considerable risk for persistent acromegaly. Thus, effective treatment options are needed to limit patient morbidity and mortality. This multicenter study [...] Read more.
Background: The rates of incomplete surgical resection for pituitary macroadenomas with cavernous sinus invasion are high. In growth hormone-producing adenomas, there is a considerable risk for persistent acromegaly. Thus, effective treatment options are needed to limit patient morbidity and mortality. This multicenter study assesses the efficacy and safety of robotic radiosurgery (RRS) for patients with cavernous sinus-invading adenomas with persistent acromegaly. Methods: Patients who underwent RRS with CyberKnife for postoperative acromegaly were eligible. Results: Fifty patients were included. At a median follow-up of 57 months, the local control was 100%. The pretreatment insulin-like growth factor 1 (IGF-1) levels and indexes were 381 ng/mL and 1.49, respectively. The median dose and prescription isodose were 18 Gy and 70%, respectively. Six months after RRS, and at the last follow-up, the IGF-1 levels and indexes were 277 ng/mL and 1.14, as well as 196 ng/mL and 0.83, respectively (p = 0.0001 and p = 0.0002). The IGF-1 index was a predictor for biochemical remission (p = 0.04). Nine patients achieved biochemical remission and 24 patients showed biochemical disease control. Three patients developed a new hypopituitarism. Conclusions: RRS is an effective treatment for this challenging patient population. IGF-1 levels are decreasing after treatment and most patients experience biochemical disease control or remission. Full article
(This article belongs to the Special Issue New Advances and Challenges in Sellar and Para-Sellar Pathology)
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14 pages, 1730 KiB  
Article
Delayed Postoperative Hyponatremia Following Endoscopic Transsphenoidal Surgery for Non-Adenomatous Parasellar Tumors
by Hirotaka Hasegawa, Masahiro Shin, Noriko Makita, Yuki Shinya, Kenji Kondo and Nobuhito Saito
Cancers 2020, 12(12), 3849; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers12123849 - 20 Dec 2020
Cited by 4 | Viewed by 1764
Abstract
Little is known about delayed postoperative hyponatremia (DPH) accompanied with transsphenoidal surgery for non-adenomatous skull base tumors (NASBTs). Consecutive data on 30 patients with parasellar NASBT was retrospectively reviewed with detailed analyses on perioperative serial sodium levels. Serological DPH (sodium ≤ 135 mmol/L) [...] Read more.
Little is known about delayed postoperative hyponatremia (DPH) accompanied with transsphenoidal surgery for non-adenomatous skull base tumors (NASBTs). Consecutive data on 30 patients with parasellar NASBT was retrospectively reviewed with detailed analyses on perioperative serial sodium levels. Serological DPH (sodium ≤ 135 mmol/L) was observed in eight (27%), with four (13%) of them being symptomatic. DPH developed on postoperative day 7–12 where the mean sodium levels were 134 mmol/L (a mean of 7 mmol/L drop from the baseline) in asymptomatic and 125 mmol/L (a mean of 17.5 mmol/L drop from the baseline) in symptomatic DPH. Serological DPH was accompanied with “weight loss and hemoconcentration (cerebral salt wasting type)” in four (50%), “weight gain and hemodilution (syndrome of inappropriate antidiuretic hormone secretion type)” in three (38%), and no significant weight change in one. Intraoperative extradural retraction of the pituitary gland was the only significant factor for serological DPH (p = 0.035; odds ratio, 12.25 (95% confidence interval, 1.27–118.36)). DPH should be recognized as one of the significant postsurgical complications associated with TSS for NASBTs. Although the underlying mechanism is still controversial, intraoperative extradural compression of the pituitary gland and subsequent dysregulation of the hypothalamo-hypophyseal axis may be responsible. Full article
(This article belongs to the Special Issue New Advances and Challenges in Sellar and Para-Sellar Pathology)
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19 pages, 13258 KiB  
Systematic Review
Gamma Knife Radiosurgery for Pituitary Tumors: A Systematic Review and Meta-Analysis
by Luigi Albano, Marco Losa, Lina Raffaella Barzaghi, Ajay Niranjan, Zaid Siddiqui, John C. Flickinger, Lawrence Dade Lunsford and Pietro Mortini
Cancers 2021, 13(19), 4998; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13194998 - 05 Oct 2021
Cited by 16 | Viewed by 3221
Abstract
To describe and evaluate outcomes of Gamma Knife radiosurgery (GK) for the treatment of pituitary tumors over the past twenty years, a systematic review and meta-analysis according to PRISMA statement was performed. Articles counting more than 30 patients were included. A weighted random [...] Read more.
To describe and evaluate outcomes of Gamma Knife radiosurgery (GK) for the treatment of pituitary tumors over the past twenty years, a systematic review and meta-analysis according to PRISMA statement was performed. Articles counting more than 30 patients were included. A weighted random effects models was used to calculate pooled outcome estimates. From 459 abstract reviews, 52 retrospective studies were included. Among them, 18 reported on non-functioning pituitary adenomas (NFPA), 13 on growth hormone (GH)-secreting adenomas, six on adrenocorticotropic hormone (ACTH)-secreting adenomas, four on prolactin hormone (PRL)-secreting adenomas, and 11 on craniopharyngiomas. Overall tumor control and five-year progression free survival (PFS) estimate after one GK procedure for NFPA was 93% (95% CI 89–97%) and 95% (95% CI 91–99%), respectively. In case of secreting pituitary adenomas, overall remission (cure without need for medication) estimates were 45% (95% CI 35–54%) for GH-secreting adenomas, 64% (95% CI 0.52–0.75%) for ACTH-secreting adenomas and 34% (95% CI: 19–48%) for PRL-secreting adenomas. The pooled analysis for overall tumor control and five-year PFS estimate after GK for craniopharyngioma was 74% (95% CI 67–81%) and 70% (95% CI: 64–76%), respectively. This meta-analysis confirms and quantifies safety and effectiveness of GK for pituitary tumors. Full article
(This article belongs to the Special Issue New Advances and Challenges in Sellar and Para-Sellar Pathology)
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