Are acoustic neuromas encapsulated tumors? TIMOTHY C. KUO, MD, ROBERT K. JACKLER, MD, KONDI WONG, MD, NIKOLAS H. BLEVINS, MD, and LAWRENCE H. Pil-rs, Mr), San Francisco, California
In articles and chapters on the subject of acoustic neuroma, it is almost invariably stated that they are well-encapsulated tumors. During surgical procedures, blunt mechanical dis-
section defines a natural subsurface cleavage plane that leaves intact a several millimeter thick rind of tumor surface. Occasionally, as a concession to neural integrity, less than complete resection is elected, leaving behind this "capsular" remnant. To clarify the nature ot the surface of acoustic neuromas and to test whether this long held description is indeed correct, a microscopic analysis of 10 surgical specimens was performed. A wedge was harvested from the free surface of the tumor in the mid cerebeilopontine angle that included a large, undisturbed section of the tumor surface. Histologic analysis showed that for most of the tumor surface only an extremely thin (3 to 5 gm) layer of connective tissue envelops the tumor. Neoplastic Schwann cells, which extend essentially to the margin of the tumor, were found to be somewhat flattened and compressed in the vicinity of the surface. Although acoustic neuromas are surrounded by a continuous layer of connective tissue, it is so exceptionally thin (on average less than the diameter of a red blood cell) that its edge cannot be visualized intraoperafively by a surgeon. Because the pathologic definition of a capsule is a thick, enveloping layer of connective tissue that is both micro- and macroscopicaliy evident, it must be concluded that acoustic neuromas are nonencapsulated, at least in the conventional sense of the term. The surface peel observed intraoperatively is surgically produced during tumor debulking by cleaving of the looser central component from the more compressed portion of neoplastic cells that lies immediately beneath the free margin of the lesion. (©tolaryngol Head Neck Surg 1997;] 17:606-9.)
N u m e r o u s reports, including some dating back nearly a century, have described the gross and microscopic histologic appearance of acoustic neuromas] -6 From their earliest descriptions in the literature to the present, acoustic neuromas have typically been described as well-encapsulated benign tumors that produce symptoms because of their mass effect on surrounding structures rather than by infiltration. 7 This widely accepted concept of acoustic neuromas as being encapsulated most likely stems from two characteristics of these tumors: (1) they have a smooth and well demarcated surface and (2) during surgical removal a looser central region can often be demarcated from a more dense superficial rind. The properties of the external surface
From the Departments of Otolaryngology,Pathology, and Neurosurgery, University of California, San Francisco. Presented in part at the Annual Meeting of the AmericanAcademy of Otolaryngology-Headand Neck Surgery, New Orleans, La., Sept. 17-20, 1995. Reprint requests: Robert K. Jackler, MD, 350 Parnassus Ave. #210, San Francisco, CA 94117. Copyright © 1997 by the American Academy of OtolaryngologyHead and Neck Surgery Foundation, Inc. 0194-5998/97/$5.00 + 0 23/1/75135 606
of acoustic neuromas have much clinical relevance. Microdissection of surrounding neurovascular structures from this surface constitutes the primary surgical challenge presented by these tumors. Much recent interest has been directed at the nature of the tumornerve interface. Ultrastructural and immunohistochemical evidence suggests that microinvasion of the auditory and facial nerves is more prominent than formerly believed. 8-N A recent trend toward more conservative resection, leaving in situ tiny surface fragments as a means of improving neural preservation, suggests a need to better understand the histologic nature of the tumor fragment left in place. This study was undertaken to explore the possibility that, contrary to long held conventional wisdom, acoustic neuromas might not actually be encapsulated tumors. Our reason for raising this question was the observation that the tumor surface was similar, in terms of both color and consistency, to more central regions. METHODS
Tumor surface specimens were harvested from 10 unilateral acoustic neuromas the size of which ranged from 1.5 to 3 cm in diameter within the cerebellopon-
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Fig. 1. Reticulin stain of the surface of an acoustic neuroma, The thin layer of connective tissue that envelopes the tumor is only 3 to 5 gm thick. Neoplastic cells, which extend virtually to the external margin of the tumor, become flattened and more tightly packed in this vicinity.
tine angle. A generous wedge (5 to 10 mm wide) was gently cut from the external surface of the tumor with a No. 11 blade. Every effort was made to harvest only undisturbed expanses of the tumor surface that had not been cauterized or otherwise surgically traumatized. After removal, the superficial surface of each specimen was marked by application of india ink and Bouin fixative. The tissue was fixed in 10% buffered formalin and embedded in paraffin. Careful attention was paid during embedding to ensure that tumor surfaces marked with ink could be clearly differentiated from the surgically cut planes. The tissue was sliced into 4 gm thin sections on a microtome in a plane perpendicular to the marked surface. Several levels of each specimen were taken to ensure adequate sampling. The cut sections were then deparaffinized and stained with standard hematoxylin and eosin. To further elucidate the nature of connective tissue observed in proximity to the tumor surface, trichrome and reticulin stains were applied to specimens obtained from five patients. The pathologic features of all the sections were analyzed under both high- and low-power magnification. To adjust for any inhomogeneities in the connective tissue "capsule" of each specimen, measurements of the thickness of tumor surface connective tissue from the center and lateral edges were taken from each section. These values were averaged with those from other sections derived from the same specimen. After analysis of the original 10 specimens, an l l t h specimen was obtained to determine the nature of the
grossly apparent "capsular rind" produced after tumor debulking. A generous segment of this surgically formed 2 to 3 mm thick tumor peel was harvested, fixed, embedded, sectioned, stained, and analyzed in like manner to the earlier obtained tumor surface wedge samples. RESULTS A very thin layer of connective tissue, which averaged 3 to 5 ~m in thickness (one third to two thirds the
diameter of an erythrocyte), was observed to envelope the surface of each acoustic neuroma studied. The tumor stained with both reticulin and trichrome (Fig. 1). Neoplastic Schwann cells extended virtually to the free margin of the tumor in every specimen studied. The organization of tumor cells varied, in terms of both density and alignment, in different regions of the tumor. Central regions tended to be more loosely packed, the Schwann cell arranged rather haphazardly. Nearer to the tumor surface, however, the neoplastic cells became somewhat denser and tended to align along concentric lines tangential to the tumor surface. Within a few millimeters of the surface, increased numbers of capillaries and larger-caliber blood vessels were seen. Some of these vessels also exhibited sparse perivascular lymphocytes. Fibrin deposition and extravasated red blood cells with scant amounts of hemosiderin were sometimes seen. Focal increases in thickness of the surface connective tissue (30 to 40 gm) tended to occur along these vascular channels.
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Fig. 2. Histologic appearance (hematoxylin and eosin) of the surface rind left behind after debulking of the looser central region of the tumor. This purported "capsule" is in fact composed of both tumor cells and connective tissue. Neoplastic Schwann cells abut the undisturbed external surface of the tumor (left).
The specimen obtained from the grossly observable "rind" of the tumor after intracapsular debulking showed a dense band of connective tissue within which lay scattered schwannoma tumor cells. On both the internal and external aspect of this dense band lay more loosely arranged tumor (Fig. 2). DISCUSSION
By strict pathologic definition, a tumor capsule is composed of a complete rim of compressed connective tissue that macroscopically separates tumor from surrounding tissue. The neoplastic component of an encapsulated tumor can be enucleated, leaving behind a nonneoplastic rind thick enough to be seen and felt by a surgeon. The fibrous tissue envelope that has been observed enveloping acoustic neuromas is extremely thin, averaging only 3 to 5 gm in thickness. To give a sense of scale, a red blood cell is approximately 7 gm in diameter. Tumor cells impinge directly on this microscopic layer. Armed with even the most powerful of operating microscopes, the most keen-eyed surgeon is unable to appreciate the edge of such a thin surface connective tissue layer. Thus from a surgical point of view, acoustic neuromas must be considered nonencapsulated tumors. It is interesting to speculate on the origin of the thin
connective tissue membrane that envelopes acoustic neuromas. Hypothetically, it either may be generated by the tumor itself or may arise because of compression of surrounding tissue. A particularly attractive explanation for its origin is draping of arachnoidal sheets, which are present in abundance in the cerebellopontine angle, on the expanding tumor surface. It is conceivable that the rich network of arterioles and venules evident on the tumor surface may derive from the vessels native to this arachnoid layer. The thin enveloping membrane on acoustic neuromas appears to be an ineffective barrier against tumor penetration. In numerous studies of the interface between tumor and nerve (audiovestibular and facial), neoplastic Schwann cells often extend beyond surgically apparent boundaries, s-15 In addition, when en bloc nerve-tumor specimens are viewed histologically, there is frequently neither intervening connective tissue nor a clear cleavage plane between neoplastic cells and nerve. Perhaps the thin surface membrane becomes resorbed when entrapped between tumor and nerve, possibly because of compression atrophy. Surgeons have long assumed that acoustic neuromas are encapsulated tumors, most probably because the lesions are geometrically regular, smooth surfaced, and leave behind a thick rind once the looser central portion
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has b e e n enucleated. T h e surgically f o r m e d surface peel, familiar to all surgeons w h o treat patients with acoustic n e u r o m a , is not a true capsule but represents the m o r e ordered and tightly packed layer of S c h w a n n cells that a p p r o x i m a t e the t u m o r surface. It w o u l d be e r r o n e o u s to call this surgically p r o d u c e d rind a pseudocapsule. A pseudocapsule, by definition, is a c o m p r e s s e d r i m o f p a r e n c h y m a l tissue that surrounds an e x p a n d i n g lesion. In the subsurface r e g i o n o f an acoustic n e u r o m a the S c h w a n n cells b e c o m e aligned in sheets that run parallel to the surface convexity, unlike the m o r e haphazard whorls of the m o r e central c o m p o nent of the tumor. Cellular density also b e c o m e s greater in the vicinity o f the t u m o r surface. T h e clinical r e l e v a n c e of these findings stems f r o m the increasing trend toward i n c o m p l e t e resection o f acoustic n e u r o m a as a c o n c e s s i o n to preservation of neural integrity. In m a n y centers, including ours, a remnant o f the t u m o r surface m a y be left in situ on the facial or audiovestibular nerve. 16,17 This "capsular r e m nant" is typically 1 to 3 m m thick and several m i l l i m e ters in diameter. This strategy does not leave behind m e r e l y a c o n n e c t i v e tissue fragment; nearly the entire r e m n a n t is c o m p o s e d of neoplastic cells. As a practica! matter, an increasing body of e v i d e n c e suggests that such fragments s e l d o m generate t u m o r recurrence, particularly w h e n they are left behind on a neural s e g m e n t in the c e r e b e l l o p o n t i n e angle. 18-% It is p r e s u m e d that When attached solely to a nerve, tumor cells derive insufficient b l o o d supply to generate a recurrence. H o w e v e r , small r e m n a n t s left in better vascularized regions, such as areas in contact with the brain stem or a dural surface, m a y be at risk for regrowth. It has been o b s e r v e d that small remnants left in the distal internal auditory canal, w h e r e an abundant vascular supply exists, h a v e a substantial likelihood o f generating recurrent disease. 24 The authors are grateful to Mr. Alfred Au and Ms. Julianna Cayetano for their expertise in and contributions to preparation of our histologic specimens.
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