Gliadel

Context.-Resorbable substances used to achieve hemostasis during neurosurgical procedures comprise 3 principal classes based on chemical composition: (1) gelatin sponge, (2) oxidized cellulose, and (3) microfibrillar collagen. Nonresorbable hemostatic aides include various forms of cotton and rayon-based hemostats (cottonoids and kites). Resorbable and nonresorbable hemostatic agents have been reported to cause symptomatic mass lesions, most commonly following intra-abdominal surgery. Histologic examination typically shows a core of degenerating hemostatic agent surrounded by an inflammatory reaction. Each agent exhibits distinctive morphologic features that often permit specific identification. Hemostat-associated mass lesions have been variously referred to as textilomas, gossypibomas, gauzomas, or muslinomas.

Objectives.-The aims of this study were to (1) identify cases of histologically proven cases of textiloma in neurosurgical operations, (2) characterize the specific hemostatic agent associated with textiloma formation, and (3) characterize the preoperative magnetic resonance imaging appearance of textiloma.

Design.-Cases in which a textiloma constituted the sole finding on repeat surgery for recurrent brain tumor, or was a clinically significant component of a radiologically identified mass lesion together with residual tumor, constituted the study set.

Results.-Five textilomas were identified and evaluated. The primary neoplasm was different in each case and included pituitary adenoma, tanycytic ependymoma, anaplastic astrocytoma, gliosarcoma, and oligodendroglioma. In all cases, preoperative magnetic resonance imaging suggested recurrent tumor. Textilomas included all categories of resorbable hemostatic agent. Other foreign bodies were present in some cases; the origin of these foreign bodies was traced to fibers shed from nonresorbable hemostatic material placed temporarily during surgery and removed before closure (cottonoids and kites). Inflammatory reactions included giant cells, granulomas, and fibroblastic proliferation. Microfibrillar collagen (Avitene) textilomas were associated with a striking eosinophil infiltration that was not seen with any other hemostatic agent.

Conclusions.-Hemostatic agents may produce clinically symptomatic, radiologically apparent mass lesions. When considering a mass lesion arising after intracranial surgery, the differential diagnosis should include textiloma along with recurrent tumor and radiation necrosis.

(Arch Pathol Lab Med. 2004;128:749-758)

A variety of hemostatic agents are routinely used to control intraoperative bleeding in many surgical subspecialties, including neurosurgery. Nonresorbable materials include various forms of cotton pledgets and cloth (such as muslin) and synthetic rayon hemostats (cottonoids and kites); these agents are removed prior to surgical closure, except in the case of muslin, which is used to repair or reinforce intracranial aneurysms. In contrast, although not originally intended as permanent implants, in practice bioabsorbable hemostats are often left in the surgical bed to prevent rebleeding after surgical closure. Three classes of resorbable hemostatic agents are currently in widespread use: gelatin foam (Gelfoam), oxidized cellulose (Surgicel, Oxycel), and microfibrillar collagen (Avitene). These agents and other foreign substances that are deliberately introduced into the central nervous system may induce an excessive inflammatory reaction in the vicinity of the surgical site, which produces a clinically symptomatic and/or radiologically apparent mass lesion that is often indistinguishable from recurrent tumor on clinical and neuroimaging studies.1-35

Textiloma (from Latin textile, a woven fabric, plus the suffix oma, meaning swelling or tumor), gossypiboma (from Latin Gossypium, the genus of cotton plants, plus borna, a Kiswahili term meaning place of concealment), gauzoma (from surgical gauze), and muslinoma (from muslin, a woven cotton fabric) are the historical terms that have been given to foreign body-related inflammatory pseudotumors arising from retained nonabsorbable cotton matrix that is either inadvertently or deliberately (as in the case of muslin wrapping of aneurysms) left behind during surgery, together with the associated inflammatory reaction. All of these terms are still currently in use in the technical literature, but appear infrequently or not at all in most medical dictionaries, pathology textbooks, and neurosurgery textbooks.

The hemostatic agents most widely used in contemporary neurosurgical practice include products in the following categories.

Resorbable Hemostatic Agents

Gelfoam (Figure 1, A through C).-Gelfoam (Ethicon, Somerville, NJ), a gelatin sponge introduced in 1945,36 is derived from an animal source and has an amorphous appearance. It is manufactured by beating and whipping lightly formalinized gelatin solution into a foam of uniform porosity. After drying, the gelatin foam is cut and sterilized. Gelfoam can also be produced in microsphere form for use as an embolie agent. By light microscopy, Gelfoam has a very distinctive branching architecture and stains purple with hematoxylin-eosin (H&E). It shows no birefringence.

Surgicel (Figure 1, D through F).-Surgicel (Ethicon) is an oxidized cellulose polymer (the functional unit is polyanhydroglucuronic acid) that is believed to act as a template for coagulation of bleeding vessels. The polymer was introduced into clinical practice more than 50 years ago37 and is formed by dissolving pure [alpha]-cellulose in an alkaline solution. It is then regenerated into continuous fiber, knitted into gauze, and oxidized. Oxycel (Becton Dickinson, Franklin Lakes, NJ; Figure 1, G through I) is another oxidized cellulose polymer product that is similar to Surgicel. Although both are composed of meshes of cellulose polymer fibers, under microscopic examination in teased fiber preparations (Figure 1, F and I) Surgicel and Oxycel can be distinguished; Surgicel is composed of solid fibers with irregular contours on cross-section, whereas Oxycel is composed of hollow "twisted tubule" fibers. Surgicel and Oxycel stain weakly eosinophilic or occasionally light purple with H&E and show no birefringence. Surgicel is more commonly used in current surgical practice. The most characteristic microscopic feature of Surgicel is interlacing bundles of fibers cut in alternating cross-sections and longitudinal sections. Although the fibers are solid in the native state (Figure 1, F), in surgical specimens they often appear as hollow "ghost" fibers surrounded by blood breakdown products and inflammatory reaction (see Figures 2, B and 3, B).

Avitene (Figure 1, J through L).-Avitene (MedChem Products, Woburn, Mass), often referred to generically as microfibrillar collagen, is a partially water-insoluble acid salt of purified bovine corium collagen that is processed into microcrystals of submicron size. Microfibrillar collagen is available in a "flour form" and also in a nonwoven web form that is produced by compression of the flour form.38 In addition to its hemostatic properties, Avitene is also used for embolization of vascular malformations. Microscopically, eosinophilic acellular coarse fibers or amorphous material can be seen. Avitene fibers exhibit the characteristic birefringence of collagen under polarized light, but this physical property is gradually lost during biodegradation and resorption in vivo. By electron microscopy, the ultrastructural appearance of Avitene is unique and distinctive compared to that of all the other hemostatic agents: the collagen microfibers show a characteristic banding periodicity (see Figure 4, I and J).

Nonresorbable Agents

Cottonoids and Kites.-Cottonoids and kites are synthetic strips and pledgets composed of rayon fibers that contain a filament or strip impregnated with radio-opaque barium sulfate, which is visible on plain radiographic examination.

Muslin.-Muslin is a cotton fabric that is used to provide reinforcement of an aneurysmal wall in unclippable or partially clippable intracranial aneurysms.10,12,14,15,17,18 Muslin fibers are generally inconspicuous on routine H&E sections because they appear essentially transparent, but they become strikingly apparent under polarized light.

A wide variety of other synthetic materials may be left in place during intracranial procedures. For example, silicone-coated synthetic sheets (Silastic) are used as a dura mater substitute for the repair of dural defects.22 Of historical interest, Mills and Lininger23 reported a case of intracranial "myospherulosis" after instillation of antibiotic ointment into a posttraumatic brain abscess. Microscopic remnants of cotton gauze of no clinical consequence are often inadvertently left in the surgical field and subsequently identified incidentally on microscopic examination of a specimen obtained at repeat surgery. Other iatrogenically introduced foreign materials that may be encountered in neurosurgical specimens include copolymer chemotherapy wafers (Gliadel wafers) and several types of agents used for embolization of highly vascular tumors (in addition to Gelfoam and Avitene, as mentioned above), such as polyvinyl alcohol particles and tris-acryl gelatin microspheres (Embospheres). Finally, a number of additional materials of diverse nature may elicit an inflammatory foreign body reaction in the central nervous system.28,33

In the general surgical literature, the incidence of textiloma is highest following abdominal surgery, followed by orthopedic procedures. Textilomas have been reported in all major anatomic compartments (eg, chest, retroperitoneum, extremities, head, and neck) and following a broad range of surgical procedures, with case reports noting adverse effects in association with virtually every major body organ, including bowel, breast, heart, kidney, bladder, urethra, uterus, and ovary.39-57 The time interval to clinical presentation ranges from the immediate postoperative period to decades after surgery.30,58-61

Textiloma has been reported significantly less frequently in the neurosurgical literature compared to general surgery. A MEDLINE search of the literature published from 1965 to 2003 produced only 40 intracranial cases1-21,24,25,35 (listed in Table 1) and 24 cases with an intraspinal or paraspinal location26-34 (listed in Table 2). However, it is likely that the incidence is underestimated. The increasing use of magnetic resonance imaging (MRI) monitoring combined with an increasing frequency of repeat surgery in neurosurgery is augmenting the opportunity to study these mass lesions, which often generate a diagnostic dilemma not only for the clinician, but also for the pathologist, especially at the time of intraoperative frozen section consultation. An awareness of the clinical presentation features of this potential pitfall together with familiarity with the microscopic characteristics and physical properties of the different hemostatic materials currently used in neurosurgical practice is important for accurate diagnosis. We present here a series of histologically confirmed intracranial textilomas.

MATERIALS AND METHODS

The tumor bank database was searched for cases of textiloma radiologically identified as a mass lesion with repeat surgery for presumed recurrent brain tumor or radiation necrosis. Five cases were identified. Routine H&E-stained histologie sections and special stains performed for neuropathologic evaluation at the time of diagnosis were reviewed. All cases were reexamined under polarized light and by electron microscopy. Each case was evaluated to identify the specific hemostatic agent(s) present, the nature and composition of the associated inflammatory reaction, and for correlation with the neuroimaging studies.

RESULTS

Clinical and Neuroimaging Findings

The clinical and neuroimaging findings of the 5 patients constituting our study group are summarized in Table 3. all patients had undergone removal of primary intracranial tumors. Patient age ranged from 18 to 47 years (mean, 30 years). Significant neuroimaging abnormalities were identified on MRI studies performed for follow-up 1 to 7 months after surgery. Studies in the first 4 cases showed a central cavity surrounded by ring enhancement, with edema seen in the adjacent brain parenchyma in 2 cases. Solid material partially filling the surgical cavity was observed in cases 1, 2, and 4. Residual neoplasm was present adjacent to, but separate from, the textiloma in case 3. In case 5, soft tissue density was present along the inferolateral portion of the sella, which had previously been opened for the resection of a pituitary adenoma. Based on the clinical and neuroimaging findings, in all 5 patients the clinical impression favored recurrent tumor or tumor progression, and this prompted repeat surgery and re-resection of the mass lesion.

Histopathologic Findings

Case 1.- Sections from the excised mass showed typical features of an Avitene textiloma (Figure 5). On light microscopy, degenerating eosinophilic to pale gray, amorphous hemostatic material was surrounded by a dense zone of palisading macrophages, the appearance of which closely simulated the pseudopalisading necrosis of high-grade glioma. Another characteristic feature of Avitene textilomas, seen in the present case and not seen with the other hemostatic agents, is a prominent infiltrate of eosinophils, reflecting an allergic response to the foreign material. Foreign body-type multinucleated giant cells were also present. Degenerating Avitene material closely resembled gelatin foam on H&E stains; however, ultrastructural examination disclosed the characteristic periodicity of microfibrillar collagen (Figure 5, F).

Case 2.-A mixed Avitene-cotton granuloma was found (Figure 4). On routine H&E examination (Figure 4, H), the degenerating Avitene portion of this mixed textiloma exhibited morphologic features similar to those of gelatin foam, but, as also seen in case 1, the distinctive ultrastructural banding periodicity of microfibrillar collagen was diagnostic (Figure 4, I and J). The surrounding tissue exhibited a dense fibroblastic response and prominent reactive vascular proliferation. In addition, the remnants of cotton fibers were identified by their hollow cylindrical profiles (Figure 4, D) and birefringence under polarized light examination (Figure 4, E). The ultrastructural appearance of cotton fibers is shown in Figure 4, F and G.

Cases 3 and 4.-Both cases showed a Surgicel textiloma, which in case 3 was composed of a nidus of interwoven cylindrical fibers cut in cross-section and longitudinal section, surrounded by necrosis and mixed acute and chronic inflammation (Figure 2, B). The material was not birefringent under polarizing light. In the same case, residual gliosarcoma was also present adjacent to, but separate from, the textiloma. In case 4, the cellulose material of the textiloma was surrounded by dense collagenous tissue and by a chronic inflammatory infiltrate with reactive vascular proliferation that extended into the adjacent neural parenchyma. Foreign body giant cells were not observed in either case.

Case 5.-A Gelfoam textiloma (Figure 3, A and B) was responsible for the soft tissue density observed on MRI. In addition to the characteristic Gelfoam material that stained purple with H&E, scattered polarizable rayon fibers from a cottonoid or kite were also present (Figure 3, C and D). Surrounding tissue showed mixed acute and chronic inflammation with occasional foreign body giant cells present. Ultrastructurally, the gelatin foam material exhibited a characteristic amorphous architecture (Figure 3, E and F) with areas of "moth-eaten" appearance (Figure 3, F [inset]) secondary to degeneration.

COMMENT

Strictly speaking and by etymology, the terms textiloma, gossypiboma, gauzoma, and muslinoma should be reserved for masses produced by retained cotton or woven fabrics, such as muslin. These terms have been used for many years to describe lesions produced by retained cotton surgical sponges accidentally left in the surgical bed. Synthetic resorbable and nonresorbable hemostatic materials have now largely replaced cotton in neurosurgical practice and are often left in situ to prevent rebleeding after surgical closure. The useful term textiloma could reasonably be adapted, as suggested by Van Goethem et al,31 to encompass mass lesions produced by the newer synthetic hemostatic agents. The historical precedence of textiloma in preference to gossypiboma has also been noted.62 Although these arguments for the general adoption of the convenient term textiloma appear reasonable, one distinction must be emphasized between the implications of a diagnosis of textiloma in general surgical practice versus neurosurgical practice. Textiloma in general surgery is in most cases synonymous with "retained sponge" and thus constitutes an iatrogenic mistake in which a nonresorbable hemostat is inadvertently left behind. Such cases have served as the basis for litigation. In contrast, in current neurosurgical practice, textiloma often (but not always) refers to a resorbable hemostatic agent that is intentionally left in place to prevent the potentially disastrous consequences of postoperative intracranial hemorrhage. The vast majority of neurosurgical patients in whom resorbable hemostatic agents are left in place remain asymptomatic (discussed further below).

As mentioned previously, textilomas may present at any time, from immediately postoperatively to several decades after initial surgery.30,58-61 Our 5 neurosurgical patients all presented with new neuroimaging abnormalities in the first 7 months after surgery. The clinical presentation of neurosurgical textilomas within the first 6 months or so after surgery is likely the result of 2 factors: (1) the natural time course of the acute inflammatory response is maximal during this immediate postoperative period, and thus it is logical that those patients in whom an exceptionally robust inflammatory reaction will occur will manifest during this time, and (2) the standard postoperative MRI follow-up is often between 3 and 6 months postoperatively, so even those patients who are clinically asymptomatic may come to attention by virtue of a new contrast-enhancing lesion appearing on routine follow-up scan. The difficulty of ruling out recurrent tumor based on imaging features alone prompted follow-up surgery in each patient in this series. In case 3, residual and/or recurrent gliosarcoma, in addition to textiloma, was confirmed.

Only a few articles have discussed the appearance of textilomas on computed tomography.1,3,9,12,19,31,32 Computed tomographic images can be confusing and misleading, as the fibrillar material may not be radio-opaque. The barium sulfate impregnating cottonoid filaments and kite strips contains very few protons and does not give significant MRI signals either, although it is visible on standard radiographs.32 The presence of an enhancing lesion, in particular a ring-enhancing lesion, in a patient with a history of intracranial (or spinal) surgery suggests, as in our cases, the differential diagnosis of recurrent tumor, radiation necrosis, or abscess. As illustrated in the present series, textilomas commonly present as contrast-enhancing mass lesions and must be considered in the differential diagnosis.

Variable proportions of acute and chronic inflammatory cells, foreign body giant cells, collagen deposition, reactive vascular proliferation, and degenerated foreign material were observed in our cases. The prominent reactive vascular proliferation correlates with the presence of ring enhancement seen on MRI scans. Foreign body giant cells may or may not be seen. All classes of hemostatic agents have been implicated in the production of textilomas, but the histologic descriptions in the previously reported cases mainly focus on the inflammatory infiltrate.

Following placement of a resorbable hemostatic agent, a physiologic inflammatory response develops around the hemostat until complete absorption is achieved.63,64 In the majority of patients this process is asymptomatic. However, an exuberant inflammatory reaction directed against the foreign material sometimes produces a space-occupying mass. An intense local inflammatory response followed by dense fibrosis occurs after muslin wrapping of unclippable intracranial aneurysms; however, neurologic complications only appear in these cases if the inflammatory reaction extends beyond its intended perivascular location.63,64 Such excessive inflammatory reaction may be misdiagnosed as recurrent tumor, radiation necrosis, abscess, resolving infarction or hematoma, or even unrelated primary or metastatic neoplasm, depending on the particular clinical history of each patient.

Morphologic features, together with the physical properties of hemostat materials observed by light-, polarizing-, and electron microscopy in the degenerated material of this series of textilomas, allowed precise identification of the hemostatic agent in each case. Although degenerating microfibrillar collagen (Avitene) resembled gelatin foam on routine H&E-stained tissue sections, the characteristic collagen periodicity was clearly shown by electron microscopy. In addition, microfibrillar collagen was associated with a prominent eosinophilic infiltrate that was not seen with the other hemostatic agents. A similar eosinophilic reaction to Avitene has been reported in colonie serosa55 and as a systemic allergic reaction.54 An additional unique feature of Avitene textilomas is the presence of circumscribed hypocellular foci of degenerating hemostat surrounded by a densely hypercellular ring of responding phagocytic cells. When multinucleated giant cells are not conspicuous, this granulomatous response can closely mimic the classic necrosis with pseudopalisading that is seen in glioblastoma, especially on intraoperative frozen sections. This constitutes a potential diagnostic pitfall when the possibility of recurrent glioblastoma is considered high on the differential diagnosis.

Dense fibrosis and mixed acute and chronic inflammation, but no foreign-body granulomas, were observed around the hemostat material in our 2 cases of Surgicel textiloma and also in the mixed Avitene-cotton textiloma. Both granulomatous and nongranulomatous inflammatory reactions have been described in intracranial Surgicel textilomas,4 as well as in Gelfoam textilomas.1 The gelatin foam material in our case 5 showed focally a characteristic moth-eaten appearance secondary to degeneration on ultrastructural examination. Prominent fibrosis was present at the periphery of the mixed Avitene-cotton textiloma seen in case 2. Cotton fibers were clearly distinguished from the Avitene material by their hollow cylindrical profiles on H&E sections and by their birefringence under polarized light, as has been noted previously.65 The scattered rayon fibers of a cottonoid or kite mixed with Gelfoam material seen in case 5 were also polarizable.

Resorbable hemostatic agents are used in all craniotomies at our institution and are left in situ in most. The pathologic reactions described in this article thus represent a small minority of the large number of patients in whom such materials are left within a resection cavity. Nevertheless, it is important to recognize that the manufacturers of several such agents, including Surgicel and Gelfoam, recommend removal of the material once hemostasis is achieved. Avitene is less likely to provoke a major reaction, but its manufacturer also suggests removing "excess" material before ending the operation. No data are available that compare the relative risks of leaving hemostatic material in a surgical cavity (and thereby provoking a textiloma requiring repeat surgery) versus not leaving hemostatic material behind (and allowing a post-operative hemorrhage, also requiring follow-up surgery). We recommend that such residual materials be kept to a minimum in the intracranial compartment, particularly adjacent to delicate structures like cranial nerves, and that they be avoided altogether within the spinal cord.

Our findings and those reported previously indicate that (1) reaction to hemostatic agents may produce significant space-occupying mass lesions appropriately termed textilomas (also termed gossypibomas, gauzomas, and muslinomas) that are clinically and/or radiologically apparent; (2) textilomas may present with neuroimaging features that mimic recurrent tumor; (3) the morphologic features of the various resorbable and nonresorbable hemostatic agents often permit precise identification; (4) all classes of hemostatic agents may produce textilomas; and (5) 2 unique features may be observed in some microfibrillar collagen (Avitene) textilomas, namely, a robust allergic response with prominent eosinophilic infiltrate and foci of degenerating hemostat surrounded by hypercellular cuffs that mimic the histologie appearance of necrosis, with pseudopalisading seen in high-grade gliomas. In the differential diagnosis of a mass lesion arising after prior intracranial surgery, the possibility of textiloma should be considered along with recurrent tumor, radiation necrosis, and abscess.

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Teresa Ribalta, MD, PhD; Ian E. McCutcheon, MD; Antonio C. Neto, MD; Deepali Gupta, MD; A. J. Kumar, MD; David A. Biddle, MD; Lauren A. Langford, MD, Dr med; Janet M. Bruner, MD; Norman E. Leeds, MD; Gregory N. Fuller, MD, PhD

Accepted for publication March 3, 2004.

From the Department of Pathology, Hospital Clinic, Institut d'lnvestigacions Biomediques August Pi i Suner (IDIBAPS), Universitat de Barcelona, Barcelona, Spain (Dr Ribalta); the Departments of Neurosurgery (Dr McCutcheon), Pathology (Drs Neto, Gupta, Langford, Bruner, and Fuller), and Neuroradiology (Drs Kumar and Leeds), The University of Texas M. D. Anderson Cancer Center, Houston; and the Department of Pathology and Laboratory Medicine, The University of Texas at Houston Medical School (Dr Biddle).

Presented in part at the annual meeting of the United States and Canadian Academy of Pathology, Orlando, Fla, March 1997.

The authors have no relevant financial interest in the products or companies described in this article.

Reprints: Gregory N. Fuller, MD, PhD, Department of Pathology-085, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030 (e-mail: gfuller@mdanderson.org).

Copyright College of American Pathologists Jul 2004
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