Guidelines on the Management of Patients with Nonfunctioning Pituitary Adenomas

2. Preoperative Imaging Assessment of Patients with Suspected Nonfunctioning Pituitary Adenomas

download pdf Neurosurgery, 2016

Sponsored by: Congress of Neurological Surgeons (CNS) and the AANS/CNS Tumor Section

Endorsed by: Joint Guidelines Committee of the American Association of Neurological Surgeons (AANS) and the Congress of Neurological Surgeons (CNS)

Clark C. Chen, MD, PhD¹, Bob S. Carter, MD, PhD¹, Renzhi Wang, MD², Kunal S. Patel, BA¹, Christopher Hess, MD, PhD³, Mary E. Bodach, MLIS⁴, Luis M. Tumialan MD⁵, Nelson M. Oyesiku, MD, PhD⁶, Chirag G. Patil, MD⁷, Zachary Litvack, MD⁸, Gabriel Zada, MD⁹, Manish K. Aghi, MD, PhD^{10   1}Center for Theoretical and Applied Neuro-Oncology, Division of Neurosurgery, University of California, San Diego, San Diego, California, USA

²Department of Neurosurgery, Peking Union Medical College Hospital, Beijing, China

³Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California, USA

⁴Guidelines Department, Congress of Neurological Surgeons, Schaumburg, Illinois, USA

⁵Barrow Neurological Institute, Phoenix, Arizona, USA

⁶Department of Neurosurgery, Emory University, Atlanta, Georgia, USA

⁷Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, California, USA

⁸Department of Neurosurgery, George Washington University, Washington, DC, USA

⁹Department of Neurological Surgery, University of Southern California, Los Angeles, California, USA

¹⁰Department of Neurosurgery, University of California, San Francisco, San Francisco, California, USA

Correspondence:

Clark Chen, MD, PhD
Center for Theoretical and Applied Neuro-Oncology
Moores Cancer Center
University of California, San Diego
3855 Health Science Drive #0987
La Jolla, CA 92093-0987
E-mail: clarkchen@ucsd.edu

Abstract

Background: The authors reviewed published articles pertaining to the preoperative imaging evaluation of nonfunctioning pituitary adenomas (NFPAs) and formulated recommendations.

Methods: The MEDLINE database was queried for studies investigating imaging for the preoperative evaluation of pituitary adenomas.

Results: From an initial search of 5598 articles, 122 articles were evaluated in detail and included in this article. Based on analysis of these articles, the recommendations are as follows: 1) High resolution magnetic resonance imaging (Level II) is recommended as the standard for preoperative assessment of NFPAs, but may be supplemented with CT (Level III) and fluoroscopy (Level III). 2) Although there are promising results suggesting the utility of magnetic resonance spectroscopy, magnetic resonance perfusion, positron emission tomography, and single-photon emission computed tomography, there is insufficient evidence to make formal recommendations pertaining to their clinical applications.

Conclusions: The authors identified 122 articles that form the basis of recommendations for preoperative imaging evaluation of NFPAs. Preoperative imaging assessment of NFPAs requires a thoughtful integration of multiple imaging modalities and judicious clinical assessment.

RECOMMENDATIONS

Question
What imaging modality should be carried out in the preoperative diagnosis of NFPAs?
Target population
These recommendations apply to adults with imaging findings, signs, and symptoms suggestive of a nonfunctioning pituitary adenoma.
Recommendation
High-resolution MRI (Level II) is recommended as the standard but may be supplemented with CT (Level III).

Question
What imaging modalities can be used to preoperatively evaluate NFPA histology and characteristics?
Target population
These recommendations apply to adults with imaging findings, signs, and symptoms suggestive of a nonfunctioning pituitary adenoma.
Recommendation 
While promising results are available pertaining to MR spectroscopy, MR perfusion, PET, and SPECT for preoperative assessment of NFPA histology and characteristics, there is insufficient evidence to make a formal recommendation for their use.

Question
What imaging modalities can be used to preoperatively evaluate cavernous sinus invasion?
Target population
These recommendations apply to adults with imaging findings, signs, and symptoms suggestive of a nonfunctioning pituitary adenoma.
Recommendation
While promising results are available pertaining to high-resolution MR and proton density imaging as tools of assessing cavernous sinus invasion, there is insufficient evidence to make a formal recommendation for their use.

Question
What imaging modality can be used to preoperatively evaluate tumor vascularity and hemorrhage?
Target population
These recommendations apply to adults with imaging findings, signs, and symptoms suggestive of a nonfunctioning pituitary adenoma.
Recommendation
While promising results are available pertaining to perfusion and gradient echo imaging as tools for assessing tumor vascularity and hemorrhage, there is insufficient evidence to make a formal recommendation for their use.

INTRODUCTION

Surgical management of nonfunctioning pituitary adenomas (NFPAs) is largely based on imaging evaluation in the context of clinical assessment. To date, information pertaining to the preoperative radiography of pituitary lesions is derived entirely from retrospective series, with little contribution from prospective studies or randomized control trials (RCTs). This review aims to summarize the key studies that impact the clinical utilization of neuroimaging in the preoperative management of NFPAs.

METHODOLOGY

Process Overview
The evidence-based clinical practice guideline task force members and the Tumor Section of the American Association of Neurological Surgeons (AANS) and the Congress of Neurological Surgeons (CNS) conducted a systematic review of the literature relevant to the management of nonfunctioning pituitary adenomas (NFPAs). Additional details of the systematic review are provided below and within the introduction and methodology chapter of the guideline.

Disclaimer of Liability This clinical systematic review and evidence-based guideline was developed by a physician volunteer task force as an educational tool that reflects the current state of knowledge at the time of completion. The presentations are designed to provide an accurate review of the subject matter covered. This guideline is disseminated with the understanding that the recommendations by the authors and consultants who have collaborated in its development are not meant to replace the individualized care and treatment advice from a patient’s physician(s). If medical advice or assistance is required, the services of a physician should be sought. The recommendations contained in this guideline may not be suitable for use in all circumstances. The choice to implement any particular recommendation contained in this guideline must be made by a managing physician in light of the situation in each particular patient and on the basis of existing resources.

Potential Conflicts of Interest
All NFPA Guideline Task Force members were required to disclose all potential conflicts of interest (COIs) prior to beginning work on the guideline, using the COI disclosure form of the AANS/CNS Joint Guidelines Committee. The CNS Guidelines Committee and Guideline Task Force Chair reviewed the disclosures and either approved or disapproved the nomination and participation on the task force. The CNS Guidelines Committee and Guideline Task Force Chair may approve nominations of Task Force Members with possible conflicts and restrict the writing, reviewing and/or voting privileges of that person to topics that are unrelated to the possible COIs.

Literature Search
The Task Force collaborated with a medical librarian to search for articles published from January 1, 1966, to October 1, 2014 in both PubMed and The Cochrane Central Register of Controlled Trials. Strategies for searching electronic databases were constructed by the guideline taskforce members and the medical librarian using previously published search strategies to identify relevant studies (Appendix A).^1-8

RESULTS

Study Selection
An independent reviewer evaluated the initial 5598 citations using the criteria described above. Articles were excluded for the following reasons: 905 articles were not written in English, 82 articles involved only animal studies, 1810 articles were case reports, 1465 articles did not involve NFPAs, 998 articles did not involve imaging, 48 studies described postoperative assessment of NFPAs, and 55 studies described the use of intraoperative MRIs. After these exclusions, 235 articles were evaluated in detail for the purpose of this review. The same eligibility criteria were used for full-text screening of potentially relevant papers. Overall, 122 studies met the eligibility criteria for this systematic review, including 8 studies producing Class II data and 114 studies producing Class III data related to preoperative imaging for NFPAs. Figure 1 outlines the flow of studies through the review process.

Imaging Modalities
Computed Tomography (CT) Imaging
Prior to the advent of MR imaging, CT imaging^9-16 and CT cisternography^17,18 were used as feasible options for the diagnosis of sellar lesions, supported predominantly with Class III data (Table 1). However, the limited soft-tissue resolution of these modalities rendered limited information on NFPAs.^19,20 While MRI has emerged as the gold standard for preoperative imaging diagnosis of sellar/suprasellar lesions, some surgeons prefer to augment MRI with imaging information from thin-cut CT through the sellar/sphenoid region and/or CT angiogram for preoperative planning and intraoperative navigation.²¹ There are 2 reasons underlying this preference, each supported by Class III data. First, the sphenoid septal anatomy is better visualized on high-resolution CT relative to the various MRI sequences.^22-28 Second, inherent magnetic field homogeneity within regions of air-bone density causes image distortion on MRI, rendering the geometric accuracy of the image tenuous.²⁹

Newer modes of CT imaging are now used to provide more detailed imaging information of sellar/suprasellar lesions when MRI is not accessible or is contraindicated. Multidetector-row CT takes advantage of concurrent acquisition of multiple slices in various directions to provide higher resolution imaging. Images acquired through this modality were found to provide sufficient NFPA visualization in a study of 33 patients with Class III data (Table 1).²³ Dual-energy CT is another imaging technique that utilizes high-frequency cycling of high/low voltages to improve the quality of the CT images acquired. Class III data examining this technique suggests that the modality can provide information that discriminates between pituitary adenomas and meningiomas with a sensitivity of 90.9% and specificity of 100%.³⁰

Magnetic Resonance (MR) Imaging
There is no class I data comparing the sensitivity and specificity of CT and MRI in terms of the detection and characterization of pituitary lesions (Table 1 and Table 2). However, the studies with Class II data that compare CT and MRI have shown that MRI can provide more detailed images of sellar/suprasellar lesions relative to CT.^31,32 This conclusion is supported by several studies with Class III data.^25,28,33-35 In this context, MRI has emerged as the gold standard. Typically, dedicated MR images spaced 1-2 mm apart are obtained through the sellar/suprasellar region for imaging assessment. The anterior lobe of the normal pituitary gland is iso-intense to the imaging appearance of the cerebral gray matter on all MR sequences. As this region is one of the circumventricular organs without an intact blood-brain barrier, gadolinium freely perfuses this region, and the region enhances within 30 minutes of infusion.³⁶

Because the sizes of NFPAs that require surgical attention are relatively large, most MR sequences, scanners, and contrast doses yield comparable results, supported by Class II and III data, in terms of lesion identification (Table 2).^25,37-45 This is in stark contrast to microadenoma detection, in which protocols for contrast administration and MR parameters significantly impact the diagnostic yield.⁴⁶ Nevertheless, visualization of fine anatomic details surrounding the tumor, such as cavernous sinus wall involvement, cranial nerve visualization, or the presence of hemorrhage is influenced by the magnetic strength of the scanner (1.5T versus 3T) as well as the type of MR sequence utilized. Pertinent literature on these matters will be reviewed below.

1.5T vs 3T scanners
The field strength of the magnet used for MRI has progressively increased^47,48 since its initial introduction for clinical use in the 1980s. In principle, imaging at higher field strengths should afford increased spatial resolution and improved anatomic visualization. Previous studies producing type III data largely supports this thesis (Table 3).⁴⁹ One means to evaluate this concept is the determination of imaging evidence of cavernous sinus invasion. To this end, Wolfsberger et al compared the sensitivity and specificity of 1.5T and 3T MR imaging in terms of the integrity of the medial cavernous sinus border in 21 patients who underwent surgical resection of pituitary lesions (Class III data).⁵⁰ Intraoperative findings of medial sinus wall integrity were used as a gold standard, and the imaging interpretations were compared to this gold standard. The authors report that, relative to 1.5T imaging, the 3T imaging yielded superior sensitivity (67% versus 83%, respectively) and specificity (58% relative to 84%) in terms of correlation to surgical findings. The authors additionally report that 3T MRI afforded improved resolution of the intracavernous cranial nerve segments as well as improved differentiation of optochiasmatic structures from the sellar lesion.⁵⁰

Magnetic susceptibility effects present a significant obstacle to high-field MRI around the sella and central skull base. Tissue interfaces, especially around air- and bone-containing structures, cause non-uniformity in the otherwise homogeneous main magnetic field within an MRI scanner. The severity of non-uniformity increases with the strength of the main magnetic field and gives rise to geometric distortion and signal loss around these tissue interfaces. These magnetic susceptibility effects also render normal fat-suppression techniques less effective, making it more difficult to assess involvement of the bony structures around the sella.

Because of the increased resolution provided by higher strength MRIs, subtle patient motion related to respiratory effort has also been shown to compromise image quality. In one study with Class III data, volumetric interpolated breath-hold examination (VIBE, see definition below) was shown to improve the diagnostic utility of MR imaging (Table 4).⁵¹ The necessity of these techniques is likely increased with the use of higher-field-strength MRIs.

Specific MR Sequences
In addition to the conventional T1 and T2 weighted sequences, specific MR techniques are used to characterize pituitary tumors in the preoperative setting. In this section we will provide an overview of these sequences and their application pertaining to NFPAs. The specifics of the type of information provided by these MR sequences are reviewed in the tumor characteristics section.

Constructive Interference Steady State (CISS) techniques such as fast imaging employing steady-state acquisition (FIESTA) use flow-compensated, 2- or 3-dimensional gradient echo acquisition to obtain images with contrast that is proportional to the ratio of T2 relation time to T1 relaxation time. Characterized by high signal-to-noise and high spatial resolution, CISS permits exquisite MR cisternography in order to depict boundaries between CSF and soft tissues.⁵² Class III data have shown that signal intensity on CISS sequences is associated with the firmness of NFPAs (Table 4).⁵³

Dynamic imaging during the intravenous administration of gadolinium chelate show the differential enhancement of structures within and around the sella, thereby allowing the temporal separation of enhancement within the normal pituitary gland, NFPA tumor tissue and vascular structures such as the cavernous sinuses. Although most practices employ 2-dimensional techniques for dynamic MRI in the sella, volumetric gradient-echo techniques can be performed using breath-hold techniques such as the volumetric interpolated breath-hold examination (VIBE) sequence.⁵⁴ The inherent advantage of 3D acquisition over 2D techniques lies in the ability to distinguish smaller structures with greater accuracy. Class III data suggest that VIBE sequence may offer superior image resolution of NFPA invasion of the cavernous sinus (Table 4).⁵¹

Proton density weighted imaging is a standard MR technique designed to minimize the effects of longitudinal relaxation time and local magnetic field inhomogeneity (or T2*) to yield images dependent primarily on the density of protons in the imaging volume. Signal intensity with proton density imaging is proportional to the concentration of hydrogen atoms (especially water molecules) in tissue. Class III data has shown that proton density weighted MR imaging is highly sensitive and specific for predicting NFPA invasion of the cavernous sinus (Table 4).⁵⁵ Periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) is a technique that samples the MRI data measurement space using a set of radially directed strips in a rotating fashion. The technique is designed to reduce the sensitivity of MR to various sources of image artifacts, including motion, field inhomogeneity, and eddy current effects.⁵⁶ Class III data suggests this sequence may help to discriminate NFPAs from other sellar/suprasellar pathologies (Table 4).⁵⁷

MR perfusion imaging can be achieved by a number of different techniques, including dynamic susceptibility contrast (DSC) imaging⁵⁸ and arterial spin labeling (ASL).⁵⁹ DSC evaluates the change in signal on T2*-weighted sequences as gadolinium contrast flows through tissue to calculate blood volume and blood flow. ASL magnetically labels water molecules within a fixed volume of blood and then evaluates the transit of labeled molecules through perfused tissue. Class III data has shown MR perfusion may be used for discriminating NFPAs from other sellar/suprasellar pathologies⁶⁰ and from the normal pituitary (Table 4).⁶¹ There is also Class III data suggesting that perfusion studies also provide information regarding vascularity of the NFPA.⁶²

Diffusion weighted imaging (DWI) is an MR imaging technique that correlates the intensity of each voxel in the image space to the rate of water diffusion of that voxel. A Class II study suggests DWI-based sequences may be used for discriminating NFPAs from other sellar/suprasellar pathologies, and Class III studies have used this for assessing tumor firmness (Table 4).^57,63,64

MR spectroscopy is a technique that allows for detection of specific metabolites related to normal cerebral physiology of the tumor proteome. MR spectroscopy may provide information that affords discrimination of NFPAs from other sellar/suprasellar pathologies, including craniopharyngiomas and hypothalamic hamartomas. However, MR spectroscopy is technically challenging within small volumes such as the sella and is very sensitive to magnetic susceptibility effects due to the surrounding bone.

Gradient-echo image is generated by a frequency-encoded gradient that is applied twice in succession and in opposite directions.⁶⁵ Clinically, it is highly sensitive for the detection of intracerebral hemorrhages by compounding the influence of blood products.⁶⁶ GE sequences have been applied for detection of hemorrhagic conversion of NFPAs (Class III data) (Table 4).⁶⁶

Positron Emission Tomography (PET) Imaging
In general, the utility of PET imaging in the assessment of pituitary lesions is limited and is not routinely used in standard practice. On rare occasions, FDG PET diagnoses patients with incidental pituitary lesions. In a retrospective study with Class III data of 40 967 FDG PET performed at a single center, 30 (0.073%) patients were diagnosed with pituitary incidentalomas (Table 5).⁶⁷

Though rarely used clinically in the standard assessment of NFPAs, select studies have examined the sensitivity and specificity of PET imaging as a possible diagnostic test. In 3 independent case series with Class III data utilizing 18(F)-FDG PET, detection of pituitary adenomas can be achieved with a sensitivity of 94%-100% and a sensitivity of 88%-100% (Table 5).^68-70 In these studies, 18(F) FDG PET provided information allowing for discrimination of pituitary adenomas from other sellar pathology like craniopharyngiomas and meningiomas. Furthermore, Class III data suggest [11C]-L-deprenyl PET may facilitate discrimination of meningiomas from NFPAs.⁷¹

Single-Photon Emission Computed Tomography (SPECT) Imaging
Like PET, SPECT is not routinely used during standard preoperative assessment of NFPAs. Nevertheless, select patients may benefit from SPECT imaging. The uses of different compounds in SPECT have been evaluated. SPECT using iodinated dopamine D2 antagonist S(-) iodobenzamide (IBZM) or similar compounds demonstrated that D2 receptors in pituitary adenomas can be visualized using SPECT (Class III data) (Table 6).⁷² Technetium-99m-hexakis-2-methyoxy-isobutyl-isonitrile SPECT can discriminate NFPAs from normal pituitary gland (Class III data).⁷³ 99mTc(V)-DMSA is actively taken up by NFPAs relative to other sellar/suprasellar lesions and has been shown with Class III data that it can be applied to differentiate NFPAs.^74,75 Use of radiolabeled somatostatin or dopamine can potentially differentiate hormone producing from nonfunctioning pituitary adenomas and identify patients who would benefit from pharmacotherapy, although the clinical feasibility of this is unclear (Class III data).^76-84 Similarly, while other radiopharmaceuticals have been shown to bind to NFPAs in studies with Class III data,^85,86 the diagnostic utility these finding remain unclear.

Preoperative Imaging Characterization of NFPAs
Use of Preoperative Imaging to Differentiate NFPAs from Other Pathologies
One of the most challenging aspects in preoperative assessment of NFPAs involves differentiation from the other lesions that occur in this region. Such discrimination affords neurosurgeons an opportunity to tailor the surgical approach for resection or use specific pharmacotherapy.

MR spectroscopy may be helpful in this regard. For instance, both hypothalamic hamartomas and gliomas exhibit decreased N-acetyl asparate (NAA).^87,88 However, hypothalamic hamartomas are characterized by increased myoinositol while hypothalamic gliomas show increased choline accumulation.⁸⁸ Class III data found that pituitary adenomas, on the other hand, often show a choline peak (Table 7).⁸⁹ Craniopharyngiomas and germinomas both show dominant lipid peaks.^90-92 One study with Class III data demonstrated that the integration of spectroscopy data with conventional MRI sequences better enables preoperative assessment of sellar/suprasellar lesions.⁹³

Other imaging techniques also contribute information that affords better preoperative assessment of NFPAs. One study compared MR perfusion images in ⁴¹ patients with sellar tumors to definitive tissue diagnosis and found higher cerebral blood volume values in meningiomas relative to NFPAs (Table 7).⁶⁰ In addition, [99mTc(V)-DMSA] demonstrates active uptake in NFPAs relative to other sellar/suprasellar lesions.^74,75

Preoperative MR imaging appearances of pituitary adenomas have been associated with their hormone secretory status. One study with Class III data reported that the degree of enhancement on T1-weighted sequences correlate with the proportion of hormone-positive cells (Table 7).⁹⁴ Another study with Class III data reported that lowered T1 relaxation rate was associated with NFPAs relative to secreting adenomas.⁹⁵ Finally, there is a series of studies with Class III data demonstrating that increased tumor extension into adjacent anatomic compartments and cavernous sinus invasion are characteristics associated with NFPAs.^96-99

The utility of PET and SPECT for discriminating NFPAs from hormone-secreting macroadenomas are reviewed under the sections on PET and SPECT imaging. Studies with Class III evidence have shown that different histologic subtypes of NFPAs (null cell adenomas, silent corticotroph, or silent gonadotroph adenomas) are also associated with distinct MR appearances. Class III data suggests that multiple microcysts on T2W imaging, cavernous sinus invasion, lobulated appearance, and size >40 mm are associated with silent corticotroph adenomas (Table 7).^100,101 Furthermore, Class II data suggest biochemical properties of the tumors are associated with specific MR characteristics.¹⁰²

Cavernous Sinus Wall Invasion
Assessment of NFPA invasion into the cavernous sinus can facilitate determination of surgical end-point and strategy (Table 8).¹⁰³ The most common MR sequences for evaluation of sinus invasion are thin-cut T1 and T2W studies, with intent for visualizing the medial wall of the cavernous sinus (Class III).^104,105 Recent studies suggest that proton density weighted or VIBE sequences may yield improved detection of cavernous sinus wall invasion.⁵¹ However, no imaging techniques will perfectly predict NFPA sinus invasion because it is not always possible to directly visualize the medial cavernous sinus wall in patients afflicted with NFPAs.

To address this deficiency, various imaging parameters, supported by Class III, have been proposed as criteria for assessing cavernous sinus wall invasion (Table 8).^106,107 The Knosp criteria is a scale that classified NFPAs by the extent of parasellar extension relative to inter-carotid lines drawn through the intra-cavernous carotid on a coronal MRI.¹⁰⁸ High Knosp grades are associated with increased likelihood of sinus invasion. Variations of this scale, evaluated with Class III data, involve quantitating the extent that the tumor encases the intra-cavernous carotid^109-111 or involvement of the different cavernous sinus compartments.^112-114

Higher degree of encasement is associated with higher likelihood of sinus invasion. Detection of normal pituitary between NFPA and the cavernous sinus, sometimes called “rim sign” or “peri-arterial enhancement,” can be helpful to exclude sinus invasion.^40,115 Asymmetric dural enhancement of tentorium along the posterior portion of the cavernous sinus is associated with increased likelihood of sinus invasion and thought to be related to venous congestion secondary to tumor mass (type III).^116,117

Additionally, functional imaging through SPECT and PET facilitate the discrimination of pituitary adenomas varying in invasive tendencies. Retrospective series with Class III data report that the uptake of technetium-99m sestamibi (SPECT) or 201Tl chloride (SPECT) is higher in invasive NFPAs (Table 8).^101,118,119

Vascularity and Hemorrhage
Preoperative assessment of tumor enhancement patterns and vascularity may facilitate strategies for management of intra- and postoperative tumor hemorrhage.^120-123 These studies have been supported by Class III data (Table 9). Retrospective series suggest that ASL and DSC measurements correlate with tumor vascularity. Higher ASL blood flow values correlated with intraoperative findings of NFPA vascularity and risk of postoperative hemorrhage.⁶² Similarly, DSC indicative of increased blood flow correlated with histologic evidence of vascularity for NFPAs. While these initial studies report promising results, the use of these techniques in preoperative imaging assessment of NFPAs remains investigational and have not been incorporated into standard practice.

Detection of intra-tumoral hemorrhage in NFPAs is also of critical importance in terms of clinical management. These events in the context of clinical deterioration warrant emergent neurosurgical intervention. Most acute hemorrhages appear T1 hypo-intense and T2 hyper-intense (Class III data) (Table 9).^124,125 Class III data suggest T2-weighted gradient-echo (GE) imaging can be used to further enhance the sensitivity of hemorrhage detection.^66,126 Lack of a strong choline peak on MR-spectroscopy was also associated with hemorrhage in NFPAs.⁸⁹

Firmness of the Tumor Mass
Firm, fibrous tumors may be more difficult to manipulate intraoperatively.¹²⁷ Preoperative assessment may allow for application of different surgical strategies. Various MRI sequences with both Class II and III data have been used to evaluate the tissue quality of pituitary adenomas, using intraoperative findings as the gold standard (Table 10).^{53,64,128,129} Retrospective series with Class III data demonstrate association between MR findings of homogenous intensity on T1W, T2W, and contrast enhancement studies with fibrous NFPAs.^53,129,130 While several studies have investigated the correlation between DWI findings and the firmness of NFPAs, these studies have yielded conflicting results. Of the 4 published studies, 2 studies with Class III data found no correlation,^63,64 1 study with Class III data showed positive correlation,¹³¹ and another with Class III data showed negative correlation.¹³²

Pituitary Anatomy
Preoperative assessment of NFPAs involves visualization of the NFPA relative to pertinent sellar anatomy, including visualization of the normal pituitary gland, the pituitary stalk, the optic apparatus, and their relation to one another.

Because the pituitary gland is a circumventricular organ without an intact blood-brain barrier, the normal pituitary tissue typically exhibits higher intensity on contrast-enhanced T1W scans relative to NFPAs.¹³³ The normal pituitary gland is most often displaced superiorly and posteriorly by NFPAs.^133,134 Displacement of normal pituitary in other directions can suggest other pathology.^133,134

The normal pituitary stalk is of relatively low intensity but can be bright when compressed by NFPAs and other sellar/suprasellar lesions (Class III data) (Table 11).¹³⁵ However, preoperative imaging findings of stalk compression/deviation or bright stalk are not always associated with elevated prolactin class expected of stalk effect (Class III data).¹³⁶ Nevertheless, there is an association between the imaging finding of “bright stalk” and NFPA size. One study with Class III data found that ectopic location of the bright spot is correlated with tumors larger than 20 mm.¹³⁷ Another study with Class III data showed that a posteriorly displaced “bright stalk” is associated with higher tumor volume (P < .001).¹³⁸ The shape of the NFPA can also be inferred by the location of the “bright stalk.” “Bright stalk” found above the diaphragm was associated with an hourglass-shaped adenoma, whereas those found in the sella were associated with a barrel-shaped adenoma (Class III data).¹³⁹

The relationship between the tumor and the optic apparatus is typically studied using thin-cut T2W images (Class III data) (Table 11).^140,141 While in most cases the optic chiasm is superior to the tumor, it can be found both anteriorly and posteriorly,¹⁴⁰ and detection of this may adjust surgical approach. Visual field loss is significantly correlated with the height of the chiasm and the tumor (Class III data)¹⁴² as well as optic nerve hyperintensity on T2W images (Class II data),¹⁴³ but not with optic tract edema (Class III data).¹⁴⁴

CONCLUSION

A wide range of anatomic and functional imaging modalities is currently available for preoperative assessment of NFPAs. Understanding the benefits and limitations of these modalities should afford opportunities for judicious clinical application, with the goal of optimizing patient care. Overcoming the limitations of current imaging tools will require thoughtful integration of technologic development and clinical validation.

Disclosure of Funding

These evidence-based clinical practice guidelines were funded exclusively by the CNS and the Tumor Section of the CNS and the AANS, which received no funding from outside commercial sources to support the development of this document.

Acknowledgments

The authors acknowledge the CNS Guidelines Committee for their contributions throughout the development of the guideline, the AANS/CNS Joint Guidelines Committee for their review, comments, and suggestions throughout peer review, and Pamela Shaw, MSLIS, MS, for assistance with the literature searches. The authors also acknowledge the following individual peer reviewers for their contributions: Sepideh Amin-Hanjani, MD, Kathryn Holloway, MD, Odette Harris, MD, Brad Zacharia, MD, Daniel Hoh, MD, Isabelle Germano, MD, Martina Stippler, MD, Kimon Bekelis, MD, Christopher Winfree, MD, and William Mack, MD. Lastly, and most significantly, the authors would like to acknowledge Edward Laws, MD, for serving as an advisor on this nonfunctioning adenoma guidelines project and providing comprehensive critical appraisal.

Disclosures

The authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article. 

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APPENDIX A

Search Strategies
PUBMED 
(microadenoma* OR adenoma* OR macroadenoma* OR incidentaloma* OR chromophobe* OR transsphenoidal*[Title/Abstract]) AND (pituitary OR hypophyse* OR sellar OR transsphenoidal[Title/Abstract]) AND (imag* OR MRI OR CT OR spectroscopy* OR proton OR PET* OR SPECT* OR stereota* OR navigation*[Title/Abstract])

COCHRANE LIBRARY

1. MeSH descriptor Pituitary Neoplasms

2. MeSH descriptor Adenoma

3. 1 and 2

4. ((pituitary OR hypophyse* OR sellar) NEAR/4 (microadenoma* OR adenoma* OR macroadenoma* OR incidentaloma* or chromophobe*)):ti,ab,kw 5. 3 or 4 and (asymptomatic* OR nonfunction* OR non-function* OR nonsecret* OR non-secret* OR inactive OR null OR inert OR silent)

© Congress of Neurological Surgeons 2016

Source: Neurosurgery