Unlike most soft tissue
tumors,
schwannoma is characterized by the presence of distinct linear, frequently duplicated external lamina (EL). Although electron microscopy remains the gold standard for demonstrating this unique feature and distinguishing its morphologic variants from mimickers, the use of two anti-EL
antibodies,
laminin and
type IV collagen, appears to supersede electron microscopy in terms of current practice. To determine whether immunohistochemical expression correlates with ultrastructural findings, 10 cellular
schwannomas, 18 classic
schwannomas, and 3 melanotic
schwannomas were evaluated ultrastructurally and immunohistochemically using
antibodies to
type IV collagen and
laminin. Immunohistochemically, a moderate to strong intensity in more than 50% of
tumor cells was detected using either antibody in most cases of cellular
schwannomas (70%), the Antoni A areas of classic
schwannomas (78%), and melanotic
schwannomas (67%). Ultrastructurally, the presence of diffusely continuous, duplicated EL was observed in 30% of cellular
schwannomas and 56% of classic
schwannomas, while 50% of cellular
schwannomas and 22% of classic
schwannomas showed either continuous simple EL or discontinuous but duplicated EL alone. In addition, two cellular
schwannomas (20%) and four classic
schwannomas (22.2%) had only a simple layer of EL in focal areas. In contrast to the distinct immunostaining surrounding individual cells seen in the former two subtypes, all three melanotic
schwannomas displayed a biphasic-staining pattern of the EL (ie, individual cell and nested), which was confirmed at the ultrastructural level. The authors found a significant difference in intensity between the Antoni A and B areas of classic
schwannomas using both
laminin and
type IV collagen. In addition, the intensities of
laminin and
type IV collagen in the Antoni A areas of classic
schwannomas were significantly stronger compared with those of cellular
schwannomas. Nevertheless, there was no significant difference either between two
antibodies or between cellular and classic variants with regard to the extent of immunoreaction. Only in classic
schwannomas did the extent of immunoreaction against both
laminin and
type IV collagen correlate significantly with the ultrastructural EL distribution pattern (diffusely continuous vs. discontinuous). However, this association was not detected in cases of cellular
schwannomas. On the other hand, the intensities of
laminin and
type IV collagen did not correlate with the ultrastructural thickness of EL, irrespective of the morphologic subtypes. In conclusion, both type
collagen IV and
laminin are still reliable markers of EL in various types of
schwannomas.
Schwannomas exhibiting a monolayered EL are as strong in immunoreaction as those displaying reduplicated/thickened EL, indicating that a single layer of EL is thick enough to be identified by both
antibodies with sufficient sensitivity. The peculiar biphasic EL pattern seen in melanotic
schwannoma remains under-recognized, which may lead to misdiagnosis as
malignant melanomas, especially in limited biopsy specimens.