Development of a histological pseudocapsule and its use as a surgical capsule in the excision of pituitary tumors

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The presence of a histological pseudocapsule around pituitary tumors was noted in the early 1900s. Since that time there has been no emphasis on the sequence of the stages of its development or on the relationship between these stages and the capacity to identify very small pituitary tumors at surgery in patients in whom preoperative imaging has been nondiagnostic. In addition, limited emphasis has been given to the pseudocapsule’s use for selective and complete resection of pituitary adenomas.


The development of the pseudocapsule was examined by performing histological analysis of portions of pituitary glands removed during 805 operations for Cushing disease.

Twenty-five adenomas, each measuring between 0.25 and 4 mm in maximum diameter, were detected in the excised specimens; 17 were adenocorticotropic hormone–positive adenomas and eight were incidental tumors (four prolactin-secreting and four nonsecreting lesions). In 16 tumors the size of the adenoma could be established. The distribution of tumor size in relation to the presence of a histological pseudocapsule indicates a transition from the absence of a reticulin capsule (tumor diameter ≤ 1 mm) through the initial compression of surrounding tissue (tumor diameter 1–2 mm) to the presence of a multilayered reticulin capsule observed when adenomas become larger (tumor diameter 2–3 mm).


The absence of a reticulin capsule in cases of very small tumors may contribute to limited localization of these lesions during surgical exploration of the pituitary gland. In this article the authors describe surgical techniques in which the histological pseudocapsule is used as a surgical capsule during pituitary surgery. In their experience, recognition of this surgical capsule and its use at surgery has contributed to the identification of microadenomas buried in the pituitary gland, aided the recognition of subtle invasion of the pituitary capsule and contiguous dura mater, and enhanced the consistency of complete tumor excision with small and large tumors.

Abbreviations used in this paper: ACTH = adrenocorticotropic hormone; MR = magnetic resonance; PRL = prolactin.

Article Information

Address reprint requests to: Edward H. Oldfield, M.D., Building 10, Room 5D37, National Institutes of Health, Bethesda, Maryland 20892. email:

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    The histological pseudocapsule and the surgical capsule of an 8-mm adenoma in a patient with Cushing disease. Upper: Intraoperative photographs showing the view of the anterior surface of the pituitary provided by the transsphenoidal approach; the 8-mm contained adenoma lies within the left side of the gland. The capsule of the pituitary gland is intact over the gland (left side of left panel) and the adenoma (right side of left panel). The adenoma has been removed by using the histological pseudocapsule as a surgical capsule. Lower Left: Photomicrographs showing the adenoma. When the margin of the intact adenoma is examined in detail, the several layers of compressed reticulin surrounding the margin of the tumor (asterisk) are obvious. H & E (left) and reticulin staining (right), original magnification × 20. Lower Right: Drawings depicting progressive compression of the anterior lobe surrounding an adenoma as the tumor enlarges.

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    Photomicrographs showing reticulin in the normal and abnormal pituitary gland. Upper: In the normal gland surrounding an adenoma in a patient with Cushing disease, reticulin staining reveals enclosure of each acinus within a thin layer of reticulin (left). Cells staining with luteinizing hormone (LH, center) are more uniformly distributed than cells staining for ACTH (right). Center: In the normal gland surrounding the adenoma of a pregnant patient with Cushing disease, lactotroph hyperplasia is evident by the PRL staining (left) and the expanded but intact acinar structure is evident after reticulin staining (right). Lower: An ACTH-producing microadenoma contained entirely within the posterior lobe in a patient with Cushing disease. The interface between the adenoma and the surrounding posterior lobe is evident. H & E (left), ACTH (center), and reticulin staining (right). Because neither the adenoma nor the posterior lobe contains an acinar structure bound by reticulin, there is no histological pseudocapsule of compressed gland at the interface (asterisk) of the adenoma and the surrounding posterior lobe. Original magnification × 10.

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    Photomicrographs showing representative adenomas with each category of development of the histological pseudocapsule based on the reticulin margin. There is no pseudocapsule in a 0.25-mm prolactinoma (upper), a partially developed reticulin margin in a 0.5-mm null cell adenoma (center), and a compressed multilayered reticulin pseudocapsule in a 3-mm ACTH-secreting adenoma (lower). In the lower panels the asterisks signify identical sites. H & E (upper and center left), anti-PRL (upper center), reticulin staining (upper, center, and lower right), and anti-ACTH (lower left). Original magnifications × 2.5 (upper panels in lower), × 10 (center and lower panels in lower), and × 20 (upper).

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    Graph demonstrating the relationship of adenoma size and the presence of a reticulin pseudocapsule. Open circles represent no capsule, gray circles a partial capsule, and black circles a multilayered reticulin capsule.

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    A: Schematic drawings showing exposure of the pituitary. The initial opening of the anterior face of the sella turcica is performed using a drill with a 3- to 4-mm bur. A 2-mm Kerrison ronguer with a thin distal lip (0.75 mm) is used to remove the remaining thin layer of bone of the anterior sella face in small increments. These small pieces of bone can be flushed away with a brief pulse of saline irrigation, which is performed by the assistant, and suctioned away, permitting removal of the pieces without removing instruments from the working region. The bone is removed laterally until at least 2 mm of the most medial aspect of each cavernous sinus is visible. Superiorly bone removal extends to the tuberculum sellae. Inferiorly, a disc dissector is used to separate gently the dura from the bone of the sella floor after the anterior face of the sella has been removed. The sella floor is then removed with a small pituitary rongeur. Oozing bone margins are covered with a thin layer of bone wax and compressed into the bone interstices by using manipulation of a cotton pledget with the forceps tips. Because of the very low pressure in the cavernous sinus and the smaller dural veins draining into it, the same technique, or placement of small pieces of Gelfoam soaked in thrombin, can be used successfully for any site that slowly oozes blood from the layer between the dura and bone at the margins of the bone removal. At this stage the operative field should be bloodless and should expose the entire anterior sella dura and most of the inferior dura covering the pituitary. Much of the success of the surgery depends on achieving a wide and completely bloodless exposure. Inspection of the dura reveals any region of invasion of the anterior or inferior dura and, in cases of small tumors that reach the anterior surface of the pituitary gland, careful examination of the dural surface may provide clues to the site of the tumor, such as a slight local protuberance or a focal region of dark or light color. Because coagulation of the dura tends to glue it to the underlying pituitary capsule (impeding the capacity to open the dura sharply while leaving the pituitary capsule intact) and because it produces a region of white discoloration of the pituitary capsule and the contiguous region of the pituitary gland immediately beneath it (discoloration that may be misleading when searching for a small microadenoma), coagulation of the anterior or inferior dura is avoided during the exposure. All suction from this point is through a 0.5-inch square cotton pledget onto which the suction tip is placed close to the margin. The dura is opened using a No. 15 scalpel with care to take the incision completely through the dura, but not to enter the capsule of the pituitary gland. To achieve the widest available exposure, the superior margins of the incisions are extended laterally to reach the interface of the circular sinus and the medial margin of the cavernous sinus (upper inset). The cavernous sinus is often intentionally entered along the superior and lateral margin of the exposure, where the lateral aspect of the circular sinus meets the medial aspect of the superior portion of the cavernous sinus. Low-pressure venous bleeding from this opening is controlled by simply plugging the opening with a small piece of Gelfoam moistened in thrombin. To achieve a wide exposure laterally and inferiorly, the medial inferior region of the cavernous sinus is frequently opened during the lateral-most extent of the incision and bleeding is controlled in a similar fashion. The dura is gently and cleanly separated from the pituitary capsule by using a disc dissector in the tissue plane between these layers. This exposes the entire anterior surface of the pituitary gland with an intact pituitary capsule in a bloodless field. Similar to the pia mater, the capsule of the pituitary gland (lower inset) is a strong layer despite its translucent nature and, even though it is visible histologically, like the pia mater, the capsule is invisible to the surgeon. It must always be cut sharply; blunt dissection will not open it and will only transfer pressure to the interior of the gland and to the tumor, potentially spilling the partially liquefied center of the tumor prematurely. B and C: The use of the surgical capsule for selective excision of small adenomas that are visible on MR imaging. When dealing with tumors within the gland that are visible on MR images, a curvilinear incision is made through the pituitary capsule just beyond the point at which the most superficial dome of the tumor reaches, or comes closest to reaching, the surface of the gland (B, left). Thus, this initial incision is not made directly into the tumor, as is common practice. This permits a thin layer of normal gland to be passed through before reaching the surgical capsule of the adenoma (left inset), allowing easy identification of the surgical capsule and the creation of a surgical plane of dissection at the margin of the tumor, at the interface of the normal gland and the surgical capsule of the adenoma. This interface between the adenoma and gland is further defined using the tips of the bipolar forceps in a series of movements parallel to the surface of the adenoma and in the crevice between the gland and adenoma (B, right and center and right insets). If the correct tissue plane is used, the dissection is unimpeded and the gray–white surface of the adenoma is spherical and smooth. After this interface has been clearly defined, gentle dissection of the interface between the adenoma and gland is continued following the curvilinear margin of the adenoma, and with further incisions in the capsule of the pituitary gland just beyond the tumor margin to release tension on the tumor as the dissection proceeds. A small Hardy sucker (2-mm tip) on the margin of a cotton pad is used to provide separation of the interface between the gland and the adenoma for dissection and for sponging the small amount of bleeding out of the field of view. Small pieces of Gelfoam soaked in thrombin help preserve the surgical space along the dissected margins while dissection takes place at other sites around the tumor margin (not shown here). After the most superficial portion of the tumor has been defined circumferentially, the deeper adenoma margins are defined and dissected in a similar fashion (C); the posterior margin of the adenoma often requires dissection using a disc dissector and a small and/or medium ring curette (C, left and center inset). This is performed gently; very little pressure is required if the correct tissue plane is being used, and most of the limited pressure that is applied is directed more toward the gland than the adenoma. After the margins of the tumor have been completely dissected, to prevent rupture of the tumor the last remaining connection between the pseudocapsule of the specimen and the pituitary capsule is grasped with a small cup forceps and the tumor is removed (C, right). In cases of tumors 8 to 10 mm or less in diameter, the entire tumor can usually be shelled out of its bed in the anterior lobe as an intact specimen. Successful and complete removal leaves a smoothly lined hemispherical tissue void in the anterior lobe.

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    Macroadenomas with expansion of sellar contents and/or suprasellar extension. Almost all macroadenomas, regardless of their size, are associated with a preserved, but compressed and displaced, anterior pituitary gland at some location along their margin. The compressed anterior lobe can be identified, separated from the tumor by the use of the surgical capsule of the macroadenoma, and preserved during surgery. This is initially accomplished by preserving the capsule of the pituitary gland during the dural opening (A). After the capsule of the anterior lobe has been separated from the dura, a very superficial—a fraction of a millimeter—horizontal incision is made just through the pituitary capsule by using the belly of a No. 15 scalpel (B, right); the site of this incision is usually approximately 2 to 3 mm below the most superior exposure of the intradural sellar contents. This incision is made so that its depth is just to the edge of the surgical capsule of the macroadenoma, permitting the margin of the adenoma to be defined. Dissection, made using the tips of the bipolar forceps (B) as described in the legend to Fig. 5, further separates the gland from the adenoma, and as the dissection proceeds more of the normal gland becomes apparent. Further sharp incision of the pituitary capsule is performed to stay just beyond the margin of the dissected interface, between the compressed gland and the surgical capsule of the macroadenoma. In this fashion the most superficial portion of the macroadenoma is separated from the compressed gland (A and B). When this surgical plane has been carried to a depth of 3 to 4 mm along the superior, lateral, and inferior edges (B, left) of the exposed tumor (usually in that sequence), the anterior face of the adenoma is incised and the central portion of the tumor is removed (B, right). This is performed to reduce the mass of the tumor and to provide the space needed to continue the circumferential dissection of the gland–tumor interface by using the tips of the bipolar forceps and disc dissectors to deeper levels. It is important not to remove too much of the central portion of the tumor during the debulking because the outer layer of the macroadenoma (the shell of the tumor) is easier to work with if a 2- to 3-mm thickness of its capsule is left intact. This leaves enough thickness of the capsule to provide structure to the tumor margin, which enhances the ease of further dissection (C). It is often necessary to dissect the posterior one-third of the tumor margin gently by using ring curettes with gentle pressure, as described in the legend to Fig. 5, so as not to rupture the surgical capsule of the macroadenoma during its excision.

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    Exploration of the pituitary gland in patients with an endocrine-active adenoma whose imaging studies appear normal. The goal of the exploration is to find and identify the distinct encapsulated margin of the adenoma. Success depends on beginning with a widely exposed, bloodless surgical field (A). Coagulation of the anterior and inferior sella dura is avoided during the exposure and dural opening because it would produce a white area on the surface of the underlying gland that may falsely suggest the site of the adenoma. After widely opening the dura, which provides exposure of an intact pituitary capsule covering the anterior surface of the gland, and after exposure of the extreme lateral margins of the anterior surface, the surfaces are carefully inspected for regions of focal discoloration. The adenoma usually appears to be gray–blue or yellow–white, and can be identified against the background of the anterior lobe surface whose color is orange–pink. B: If no tumor is seen, the lateral surfaces of the anterior lobe are then inspected. For this the lateral dural wall of the sella (the medial wall of the cavernous sinus) is separated from the pituitary capsule by gently passing a disc dissector between these two layers from top to bottom. The space produced provides room for dissection of the interface between the lateral pituitary capsule and the dural wall with the closed tips of a fine-tipped bipolar forceps (B). Dissection is initially superficial and then progresses in stages to deeper levels until the posterior sella has been reached. After these two tissues have been separated, small pieces of Gelfoam are packed into the intervening space to rotate the lateral surface anteriorly and to gently displace it medially into the surgeon’s direct view. After both lateral surfaces are exposed and examined in this fashion, the inferior surface of the gland is separated from the dura. (This is the site at which these two layers—the surface of the pituitary and the dura mater—are most tenaciously attached to each other.) If a tumor can be identified from inspection of the surface, it is removed as described in the text and the legend to Fig. 5. If no tumor is identified on inspection of the superficial gland, a series of vertical incisions is then made (B), each of which begins 1 to 2 mm below the superior edge of the pituitary exposure and is directed downward, initially to a depth of only approximately 1 mm, and then in stages deeper through the anterior lobe until either the intermediate lobe or the glistening white anterior surface of the posterior lobe is reached. Because the pituitary blood supply and the delivery of hypothalamic trophic factors to the pituitary is oriented vertically, vertical incisions should be less likely to cause an infarction in a portion of the pituitary or to isolate the gland from its hypothalamic regulation. A distinct tissue capsule is the primary object of the search, with the intent to identify the margin of the tumor before entering it and spilling its contents, by using the surgical capsule of the adenoma (B and C). When the surgical capsule of the adenoma is identified, the tumor is removed using dissection along the interface of the adenoma and the normal gland, as described in Fig. 5 (A and B). In cases of tumors lying in the posterior portion of the anterior lobe, a 2-mm-wide slice of the anterior lobe may be removed to provide space for dissection and removal of the deep microadenoma (not shown).


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