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Mazin Elsarrag, Parantap D. Patel, Ajay Chatrath, Davis Taylor and John A. Jane Jr.

OBJECTIVE

Innovations in genomics, epigenomics, and transcriptomics now lay the groundwork for therapeutic interventions against neoplastic disease. In the past 30 years, the molecular pathogenesis of pituitary adenomas has been characterized. This enhanced understanding of the biology of pituitary tumors has potential to impact current treatment paradigms, and there exists significant translational potential for these results. In this review the authors summarize the results of genomics and molecular biology investigations into pituitary adenoma pathogenesis and behavior and discuss opportunities to translate basic science findings into clinical benefit.

METHODS

The authors searched the PubMed and MEDLINE databases by using combinations of the keywords “pituitary adenoma,” “genomics,” “pathogenesis,” and “epigenomics.” From the initial search, additional articles were individually evaluated and selected.

RESULTS

Pituitary adenoma growth is primarily driven by unrestrained cell cycle progression, deregulation of growth and proliferation pathways, and abnormal epigenetic regulation of gene expression. These pathways may be amenable to therapeutic intervention. A significant number of studies have attempted to establish links between gene mutations and tumor progression, but a thorough mechanistic understanding remains elusive.

CONCLUSIONS

Although not currently a prominent aspect in the clinical management of pituitary adenomas, genomics and epigenomic studies may become essential in refining patient care and developing novel pharmacological agents. Future basic science investigations should aim at elucidating mechanistic understandings unique to each pituitary adenoma subtype, which will facilitate rational drug design.

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Sepideh Amin-Hanjani, Nicholas C. Bambakidis, Fred G. Barker II, Bob S Carter, Kevin M. Cockroft, Rose Du, Justin F. Fraser, Mark G. Hamilton, Judy Huang, John A. Jane Jr., Randy L. Jensen, Michael G. Kaplitt, Anthony M. Kaufmann, Julie G. Pilitsis, Howard A. Riina, Michael Schulder, Michael A. Vogelbaum, Lynda J. S. Yang and Gabriel Zada

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Davis G. Taylor, Ajay Chatrath, Panagiotis Mastorakos, Gabriella Paisan, Ching-Jen Chen, Thomas J. Buell and John A. Jane Jr.

OBJECTIVE

Syringogenesis in Chiari malformation type I (CM-I) is thought to occur secondary to impaction of the cerebellar tonsils within the foramen magnum (FM). However, the correlation between the CSF area and syringogenesis has yet to be elucidated. The authors sought to determine whether the diminution in subarachnoid space is associated with syringogenesis. Further, the authors sought to determine if syrinx resolution was associated with the degree of expansion of subarachnoid spaces after surgery.

METHODS

The authors performed a retrospective review of all patients undergoing posterior fossa decompression for CM-I from 2004 to 2016 at the University of Virginia Health System. The subarachnoid spaces at the FM and at the level of the most severe stenosis were measured before and after surgery by manual delineation of the canal and neural tissue area on MRI and verified through automated CSF intensity measurements. Imaging and clinical outcomes were then compared.

RESULTS

Of 68 patients, 26 had a syrinx at presentation. Syrinx patients had significantly less subarachnoid space at the FM (13% vs 19%, p = 0.0070) compared to those without syrinx. Following matching based on degree of tonsillar herniation and age, the subarachnoid space was significantly smaller in patients with a syrinx (12% vs 19%, p = 0.0015). Syrinx resolution was associated with an increase in patients’ subarachnoid space after surgery compared with those patients without resolution (23% vs 10%, p = 0.0323).

CONCLUSIONS

Syrinx development in CM-I patients is correlated with the degree to which the subarachnoid CSF spaces are diminished at the cranial outlet. Successful syrinx reduction is associated with the degree to which the subarachnoid spaces are increased following surgery.

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Sauson Soldozy, Michelle Yeghyayan, Kaan Yağmurlu, Pedro Norat, Davis G. Taylor, M. Yashar S. Kalani, John A. Jane Jr. and Hasan R. Syed

OBJECTIVE

The goal of this study was to systematically review the outcomes of endoscopic endonasal surgery (EES) for pediatric craniopharyngiomas so as to assess its safety and efficacy.

METHODS

A systematic literature review was performed using the PubMed and MEDLINE databases for studies published between 1986 and 2019. All studies assessing outcomes following EES for pediatric craniopharyngiomas were included.

RESULTS

Of the total 48 articles identified in the original literature search, 13 studies were ultimately selected. This includes comparative studies with other surgical approaches, retrospective cohort studies, and case series.

CONCLUSIONS

EES for pediatric craniopharyngiomas is a safe and efficacious alternative to other surgical approaches. Achieving gross-total resection with minimal complications is feasible with EES and is comparable, if not superior in some cases, to traditional means of resection. Ideally, a randomized controlled trial might be implemented in the future to further elucidate the effectiveness of EES for resection of craniopharyngiomas.

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Ali O. Jamshidi, André Beer-Furlan, Daniel M. Prevedello, Ronald Sahyouni, Mohamed A. Elzoghby, Mina G. Safain, Ricardo L. Carrau, John A. Jane Jr. and Edward R. Laws

OBJECTIVE

The endoscopic endonasal approach has been proposed as a primary surgical strategy for select craniopharyngiomas. However, those tumors that arise from the sella have not been classified with the other craniopharyngioma subtypes in terms of surgical nuances, intraoperative findings, and postoperative outcomes. The authors describe their experience with a select subtype of craniopharyngioma arising within the sella subjacent to the diaphragma sellae and refer to these tumors as type 0.

METHODS

After obtaining IRB approval, three institutions retrospectively reviewed their data collected from 2005 to 2017. Patients eligible for inclusion in the study were those who had tumors that originated from the sella inferior to the diaphragma sellae. Demographic, clinical, radiological, surgical, and follow-up data were examined and analyzed.

RESULTS

Twenty-eight patients (average age 19.3 years, range 3–60 years) were included in this study. Sixteen patients (57%) were younger than 18 years of age. All patients had characteristic imaging features of an expanded sella. Seventy-five percent of the patients presented with some form of visual field deficit (89% had radiographic optic apparatus compression) and 39% with hypopituitarism. The average maximal tumor diameter in the axial, coronal, or sagittal plane was 3.1 cm. Gross-total resection was achieved in 82% of the patients. Twenty-one percent of patients experienced an iatrogenic complication, and there were only two cases (7%) of postoperative cerebrospinal fluid (CSF) leakage. Only two patients (7%) required the use of a nasoseptal flap as part of their original reconstruction. Pathology was uniformly the adamantinomatous subtype. Postoperative objective visual outcomes were improved in 71% of the patients with visual symptoms or visual field deficits on presentation and stable in 24%. Mean follow-up was 45.1 months (range 3–120 months) with an 18% recurrence rate at a mean of 44.4 months (range 10–84 months). One patient was lost to follow-up. Thirty-six percent of patients received postoperative radiation to treat recurrence or residual tumor. Endocrine data are also presented.

CONCLUSIONS

Craniopharyngiomas that originate within the sella below the diaphragma sellae are a select subtype characterized by 1) an enlarged sella, 2) an intact diaphragma sellae at surgery, and 3) an adamantinomatous pathology. These tumors can be treated transnasally without the absolute need for neurovascular flap reconstruction, as there is a low risk of CSF leakage.

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Alexandra M. Giantini Larsen, David J. Cote, Hasan A. Zaidi, Wenya Linda Bi, Paul J. Schmitt, J. Bryan Iorgulescu, Michael B. Miller, Timothy R. Smith, M. Beatriz Lopes, John A. Jane Jr. and Edward R. Laws Jr.

OBJECTIVE

The authors report the diagnosis, management, and outcomes of 6 cases of spindle cell oncocytoma (SCO) in an effort to guide clinical diagnosis and management of these uncommon lesions.

METHODS

This study is a retrospective review of cases involving adult patients who underwent resection of pituitary lesions at the authors’ institutions between January 2000 and October 2017. The authors identified patients with histopathological confirmation of SCO and collected clinical data, including preoperative, perioperative, and postoperative management, complications, and outcomes.

RESULTS

Six patients with SCO were identified. Clinical findings at initial presentation included visual disturbances, dizziness, and headache. All patients underwent resection. Four resections were initially performed by the transsphenoidal approach, and 2 resections were performed by craniotomy at an outside institution with subsequent transsphenoidal reoperations. Neither necrosis nor increased mitotic activity was seen in the tumor samples. All samples stained positive for S100 protein and thyroid transcription factor 1 and negative for glial fibrillary acidic protein and pituitary hormones. Five of the samples stained positive for epithelial membrane antigen. The average MIB-1 index was 8.3% (range 2–17). Postoperatively, 3 of the 6 patients received further treatment for progression of residual tumor or for recurrence, 2 have stable residual tumor, and 1 has had no recurrence after gross-total resection. Two patients developed postoperative complications of transient sixth cranial nerve palsy and diplopia. There were no other complications.

CONCLUSIONS

SCO poses both a diagnostic and therapeutic challenge. These tumors are often initially misdiagnosed as nonfunctional pituitary adenomas because of their sellar location and nonspecific symptomatology. Postoperatively, SCO must also be distinguished from other neoplasms of the posterior pituitary gland through histopathological examination. Resection of SCO can be challenging, given its highly vascular and adherent nature. Long-term follow-up is critical, as the tumor is associated with higher recurrence and progression rates compared to other benign neoplasms of the sella.

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Panagiotis Mastorakos, Davis G. Taylor, Ching-Jen Chen, Thomas Buell, Joseph H. Donahue and John A. Jane Jr.

OBJECTIVE

Cavernous sinus invasion (CSI) in Cushing’s disease (CD) negatively affects the probability of complete resection, biochemical cure, and need for adjuvant therapy. However, the prediction of CSI based on MRI findings has been inconsistent and variable. Among macroadenomas, the Knosp classification is the most widely utilized radiographic predictor of CSI, but its accuracy in predicting CSI and the probability of gross-total resection is limited in the setting of microadenomas or Knosp grade 0–2 macroadenomas. The authors noticed that the presence of a triangular shape of adenomas adjacent to the cavernous sinus on coronal MR images is frequently associated with CSI. The authors aimed to determine the correlation of this radiographic finding (“sail sign” [SS]) with CSI.

METHODS

The authors performed a retrospective review of all patients with a pituitary lesion < 20 mm and a biochemical diagnosis of CD treated with endoscopic or microscopic transsphenoidal resection from November 2007 to May 2017. Overall 185 patients with CD were identified: 27 were excluded for negative preoperative imaging, 32 for lacking tumors adjacent to the sinus, 7 for Knosp grade 3 or higher, and 4 for inadequate intraoperative assessment of the CSI. Following application of inclusion and exclusion criteria, 115 cases were available for statistical analysis. Intraoperative CSI was prospectively evaluated at the time of surgery by one of two neurosurgical attending surgeons, and MRI data were evaluated retrospectively by a neurosurgical resident and attending neuroradiologist blinded to the intraoperative results.

RESULTS

A positive SS was identified in 23 patients (20%). Among patients with positive SS, 91% demonstrated CSI compared to 10% without an SS (p < 0.001). Using the SS as a predictor of CSI provided a sensitivity of 0.7 and a specificity of 0.98, with a positive predictive value (PPV) of 0.91 and a negative predictive value of 0.9. Among patients with positive SS, 30% did not achieve immediate postoperative remission, compared to 3.3% of patients without an SS (p < 0.001).

CONCLUSIONS

The presence of a positive SS among Cushing’s adenomas adjacent to the CS provides strong PPV, specificity, and positive likelihood ratio for the prediction of CSI. This can be a useful tool for preoperative planning and for predicting the likelihood of long-term biochemical remission and the need for adjuvant radiosurgery.

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Winson S. Ho and John A. Jane Jr.

Osteogenesis imperfecta (OI) is an inherited connective tissue disorder that causes bone fragility and deformity. Neurological manifestations, including macrocephaly and hydrocephalus, have been reported. Increased vascular fragility or bleeding diathesis also predisposes OI patients to intracranial hemorrhage. The development of chronic subdural fluid collections or hydrocephalus may require CSF diversion. The authors report a previously unrecognized complication of CSF diversion in a patient with OI, that is, a delayed severe cranial deformity, presumably due to over-shunting. In addition to the cosmetic concern, the deformity caused severe headaches and tenderness. The patient underwent craniectomy and titanium mesh cranioplasty, which resulted in the complete resolution of symptoms. This report raises the possibility that over-shunting in patients with OI could predispose to the formation of cranial deformity requiring surgical intervention.

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Davis G. Taylor and John A. Jane Jr.

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Toshihiro Ogiwara, Alhusain Nagm and Kazuhiro Hongo