Immunohistochemical and ultrastructural comparative study of external lamina structure in 31 cases of cellular, classical, and melanotic schwannomas.

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.