Prospective evaluation of the characteristics and incidence of adenoma-associated dural invasion in Cushing disease

Clinical article

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Object

Dural invasion by adrenocorticotropic hormone (ACTH)-secreting adenomas is a significant risk factor for incomplete resection and recurrence in Cushing disease (CD). Since ACTH-producing adenomas are often the smallest of the various types of pituitary tumors at the time of resection, examining their invasion provides the best opportunity to identify the precise sites of early dural invasion by pituitary adenomas. To characterize the incidence and anatomical distribution of dural invasion by ACTH-secreting adenomas, the authors prospectively and systematically analyzed features of dural invasion in patients with CD.

Methods

The authors prospectively studied consecutive patients with CD undergoing the systematic removal of ACTH-secreting adenoma and histological analysis of the anterior sella dura as well as other sites of dural invasion that were evident at surgery. Clinical, imaging, histological, and operative findings were analyzed.

Results

Eighty-seven patients with CD (58 females and 29 males) were included in the study. Overall, dural invasion by an ACTH-positive adenoma was histologically confirmed in 30 patients (34%). Eighteen patients (60% of dural invasion cases, 21% of all patients) had evidence of cavernous sinus wall invasion (4 of these patients also had other contiguous sites of invasion), and 12 patients (40% of dural invasion cases) had invasion of the sella dura excluding the cavernous sinus wall. Eleven patients (13% all patients) had invasion of the routinely procured anterior sella dura specimen. Preoperative MR imaging revealed an adenoma in 64 patients (74%) but accurately predicted dural invasion in only 4 patients (22%) with cavernous sinus invasion and none of the patients with non–cavernous sinus invasion. Adenomas associated with dural invasion (mean ± SD, 10.9 ± 7.8 mm, range 2–37 mm) were significantly larger than those not associated with dural invasion (5.7 ± 2.1 mm, range 2.5–12 mm; p = 0.0006, Mann-Whitney test).

Conclusions

Dural invasion by ACTH-producing adenomas preferentially occurs laterally into the wall of the cavernous sinus. Preoperative MR imaging infrequently detects dural invasion, including cavernous sinus invasion. Invasion is directly associated with tumor size. To provide a biochemical cure and avoid recurrence after resection, identification and removal of invaded sella dura, including the medial cavernous sinus wall, are necessary.

Abbreviations used in this paper: ACTH = adrenocorticotropic hormone; CD = Cushing disease.

Article Information

Address correspondence to: Russell R. Lonser, M.D., Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Building 10, Room 3D20, Bethesda, Maryland 20892-1414. email: lonserr@ninds.nih.gov.

Please include this information when citing this paper: published online September 16, 2011; DOI: 10.3171/2011.8.JNS11456.

© AANS, except where prohibited by US copyright law.

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Figures

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    Magnetic resonance imaging and histological findings in a patient with evidence of cavernous sinus invasion during both surgery and histological analysis. A: Coronal postcontrast T1-weighted MR image showing a hypoenhancing pituitary adenoma (1.1 cm, arrow) in the left side of the anterior lobe of the pituitary. B: Photomicrograph of dural specimen demonstrating cellular invasion suggestive of adenoma. C: Photomicrograph showing fibrous dura and loss of normal lobular pituitary architecture in adjacent tissue consistent with adenoma and invasion. D: Photomicrograph confirming invasion of the dura by an ACTH-producing adenoma. H & E (B), reticulin (C), and ACTH immunostaining (D). Original magnification × 10.

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    Magnetic resonance imaging and histological findings in a patient with evidence of anterior dural invasion during both surgery and histological analysis. A: Coronal postcontrast T1-weighted MR image showing a hypoenhancing pituitary adenoma (8 mm, arrow) in the right anterior pituitary gland. B: Sagittal postcontrast T1-weighted MR image showing a hypoenhancing pituitary adenoma (6 mm, arrow) in the anterior pituitary gland, abutting the anterior dura. C: Photomicrograph of anterior dural specimen demonstrating cellular invasion by an adenoma. D: Photomicrograph showing fibrous anterior dura and loss of normal lobular pituitary architecture in adjacent tissue consistent with adenoma and invasion. E: Photomicrograph showing invasion of the anterior dura by an adenoma. H & E (C), reticulin (D), and ACTH immunostaining (E). Original magnification × 20.

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    Graph showing the correlation among adenoma size, adenoma distribution, and dural invasion. Invasive adenomas are classified as invading the cavernous sinus (closed circles), the sella dura (not including cavernous sinus, open circles), and both the cavernous sinus and the sella dura (gray circles). The mean size of adenomas associated with dural invasion (horizontal line, mean 10.9 ± 7.8 mm, range 2–37 mm) was significantly larger than the mean size of adenomas not associated with dural invasion (horizontal line, mean 5.7 ± 2.1 mm, range 2.5–12 mm; p = 0.0006, Mann-Whitney test).

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    Coronal postcontrast MR image (left) demonstrating a hypointense adenoma in the far lateral aspect of the pituitary gland. At surgery, the adenoma was found invading the cavernous sinus wall dura. Illustration (right) depicting the relationship of the tumor to the venous drainage of the pituitary gland, which courses laterally into the cavernous sinuses. The veins draining the pituitary penetrate the pituitary capsule as well as the dura of the medial cavernous sinus wall. These sites of contiguous pituitary capsule and dura penetration provide low resistance corridors for tumor invasion (inset), compared with other regions of the sella dura, including the immediately adjacent anterior sella dura. This anatomical relationship underlies the preferential invasion of tumors into the medial cavernous sinus wall.

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