Am J Clin Pathol 2006;125:203-208 203
© American Society for Clinical Pathology
Anatomic Pathology / CLAUDIN-1 IN MENINGIOMAS
Immunohistochemical Staining for Claudin-1 Can Help
Distinguish Meningiomas From Histologic Mimics
Hejin P. Hahn, MD, PhD, Elizabeth A. Bundock, MD, PhD, and Jason L. Hornick, MD, PhD
Key Words: Immunohistochemistry; Claudin; Tight junctions; Meningioma; Schwannoma; Solitary fibrous tumor; Hemangiopericytoma; Soft
A b s t r a c t
The histologic distinction between meningiomas
and other tumors of the central nervous system
occasionally can be difficult. Claudin-1 is a tight
junction–associated protein recently shown to be
expressed in anaplastic meningiomas. The purpose of
this study was to determine whether
immunohistochemical staining for claudin-1 could help
distinguish meningiomas from histologic mimics,
compared with commonly used markers. Tissue sections
from 10 meningothelial meningiomas, 20 fibrous
meningiomas, 10 atypical meningiomas, 7 solitary
fibrous tumors of the meninges, 5 meningeal
hemangiopericytomas, and 7 vestibular schwannomas
were stained immunohistochemically for claudin-1,
epithelial membrane antigen, S-100 protein, CD34, and
glial fibrillary acidic protein. In total, 21 (53%) of 40
meningiomas were immunoreactive for claudin-1,
whereas none of the other tumors were positive. In
contrast, there was considerable overlap in the
distribution of the other antibodies evaluated. Claudin-
1 seems to be a specific marker for meningiomas in this
context. Although its sensitivity is relatively low,
claudin-1 may be helpful in a panel of immunostains to
distinguish meningiomas from histologic mimics.
Distinguishing between meningiomas and other tumors
arising in the meninges occasionally can be difficult. In partic-
ular, fibrous meningiomas are morphologically similar to
other spindle cell tumors of the central nervous system,
including meningeal hemangiopericytoma (HPC), solitary
fibrous tumor (SFT) of the meninges, and vestibular schwan-
noma. However, because of differences in prognosis and
patient management, proper diagnosis is critical. For example,
meningeal HPC has a much higher propensity to recur and
metastasize than does fibrous meningioma.1
Although immunohistochemical analysis is helpful for
differentiating among meningeal tumors, there is considerable
overlap in their immunoprofiles. Epithelial membrane antigen
(EMA), a marker commonly used to support the diagnosis of
meningioma, is positive in approximately 30% of meningeal
HPCs2and in a similar fraction of SFTs.3CD34, a marker that
usually is positive in SFTs, is expressed in up to 60% of
fibrous meningiomas.4Finally, S-100 protein, although uni-
formly strongly positive in schwannomas, can be detected in
as many as 80% of fibrous meningiomas as well.4Thus, new
immunohistochemical markers would be beneficial for distin-
guishing among these entities.
Perineuriomas and meningiomas contain numerous cell
junctional complexes.5Claudin-1 is a tight junction–associat-
ed protein that recently has been shown to be expressed in per-
ineuriomas and anaplastic meningiomas.2,6However, the dis-
tribution of claudin-1 in low-grade meningiomas and in other
dural-based spindle cell tumors has not been elucidated fully.
The purpose of this study was to determine whether immuno-
histochemical staining for claudin-1 could help distinguish
meningiomas from potential histologic mimics, in comparison
with markers commonly used in this differential diagnosis.
Am J Clin Pathol 2006;125:203-208
© American Society for Clinical Pathology
Hahn et al / CLAUDIN-1 IN MENINGIOMAS
histologic type and grade were not specified. These authors
also reported negative staining for claudin-1 in all 10 schwan-
nomas they examined, similar to our results. However, our
study is the first to examine claudin-1 expression in SFTs of
the meninges, which can be difficult to distinguish from
meningiomas with spindled morphologic features; all cases
Meningiomas are thought to originate from the cell clusters
capping the arachnoid villi.14In addition to other morphologic
and ultrastructural similarities, meningiomas and arachnoidal
cap cells have numerous cell adhesion structures. However,
although tight junctions are seen in arachnoid cells, the cell
adhesion structures in meningiomas are desmosome-like.
Claudins are understood to be components of tight junctions. So
how can claudin-1 expression in meningiomas be explained?
There is increasing evidence that tumor cells can show aberrant
expression or abnormal cellular localization of claudin-1. For
example, despite the fact that tight junctions are not identified
by electron microscopy in the spindle cell component of bipha-
sic and monophasic synovial sarcomas, claudin-1 and other
tight junction proteins recently have been shown to be
expressed in these areas.15In addition, Schuetz et al16recently
demonstrated staining for claudin-1 and other tight
junction–associated antigens in many cases of Ewing sarco-
ma/primitive neuroectodermal tumor, although well-formed
tight junctions are not detected ultrastructurally in these tumors.
Finally, in colorectal adenocarcinomas, claudin-1 expression
can be found not only at cell-cell boundaries (as anticipated in
epithelial cells) but also in the cytoplasm of tumor cells.17
Claudin-1 seems to be a specific marker for meningiomas
in comparison with other spindle cell tumors arising in the
meninges. Although its sensitivity is relatively low, claudin-1
may be helpful when used in a panel of immunostains to dis-
tinguish meningiomas from histologic mimics.
From the Department of Pathology, Brigham and Women’s
Hospital and Harvard Medical School, Boston, MA.
Presented in part at the 94th annual meeting of the United
States and Canadian Academy of Pathology, San Antonio, TX,
February 26-March 4, 2005.
Address reprint requests to Dr Hornick: Dept of Pathology,
Brigham and Women’s Hospital, 75 Francis St, Boston, MA 02115.
1. Guthrie BL, Ebersold MJ, Scheithauer BW, et al. Meningeal
hemangiopericytoma: histopathological features, treatment,
and long-term follow-up of 44 cases. Neurosurgery. 1989;
2. Rajaram V, Brat DJ, Perry A. Anaplastic meningioma versus
meningeal hemangiopericytoma: immunohistochemical and
genetic markers. Hum Pathol. 2004;35:1413-1418.
3. Fletcher CDM, Unni KK, Mertens F, eds. Pathology and
Genetics of Tumours of Soft Tissue and Bone. Lyon, France:
IARC Press; 2002. World Health Organization Classification of
4. Perry A, Scheithauer BW, Nascimento AG. The
immunophenotypic spectrum of meningeal
hemangiopericytoma: a comparison with fibrous meningioma
and solitary fibrous tumor of meninges. Am J Surg Pathol.
5. Kleihues P, Cavenee WK, eds. Pathology and Genetics of
Tumours of the Nervous System. Lyon, France: IARC Press;
2000. World Health Organization Classification of Tumours.
6. Folpe AL, Billings SD, McKenney JK, et al. Expression of
claudin-1, a recently described tight junction-associated
protein, distinguishes soft tissue perineurioma from potential
mimics. Am J Surg Pathol. 2002;26:1620-1626.
7. Carneiro SS, Scheithauer BW, Nascimento AG, et al. Solitary
fibrous tumor of the meninges: a lesion distinct from fibrous
meningioma: a clinicopathologic and immunohistochemical
study. Am J Clin Pathol. 1996;106:217-224.
8. Meis JM, Ordonez NG, Bruner JM. Meningiomas: an
immunohistochemical study of 50 cases. Arch Pathol Lab Med.
9. Theaker JM, Gatter KC, Esiri MM, et al. Epithelial membrane
antigen and cytokeratin expression by meningiomas: an
immunohistological study. J Clin Pathol. 1986;39:435-439.
10. Winek RR, Scheithauer BW, Wick MR. Meningioma,
meningeal hemangiopericytoma (angioblastic meningioma),
peripheral hemangiopericytoma, and acoustic schwannoma: a
comparative immunohistochemical study. Am J Surg Pathol.
11. Artlich A, Schmidt D. Immunohistochemical profile of
meningiomas and their histological subtypes. Hum Pathol.
12. Suzuki SO, Fukui M, Nishio S, et al. Clinicopathological
features of solitary fibrous tumor of the meninges: an
immunohistochemical reappraisal of cases previously
diagnosed to be fibrous meningioma or hemangiopericytoma.
Pathol Int. 2000;50:808-817.
13. Bhattacharjee M, Adesina AM, Goodman C, et al. Claudin-1
expression in meningiomas and schwannomas: possible role in
differential diagnosis [abstract]. J Neuropathol Exp Neurol.
14. Yamashima T. On arachnoid villi and meningiomas:
functional implication of ultrastructure, cell adhesion
mechanisms, and extracellular matrix composition. Pathol
Oncol Res. 1996;2:144-149.
15. Billings SD, Walsh SV, Fisher C, et al. Aberrant expression of
tight-junction related proteins ZO-1, claudin-1, and occludin
in synovial sarcoma: an immunohistochemical study with
ultrastructural correlation. Mod Pathol. 2004;17:141-149.
16. Schuetz AN, Rubin BP, Goldblum JR, et al. Intercellular
junctions in Ewing sarcoma/primitive neuroectodermal tumor:
additional evidence of epithelial differentiation. Mod Pathol.
17. Miwa N, Furuse M, Tsukita S. Involvement of claudin-1 in the
beta-catenin/Tcf signaling pathway and its frequent
upregulation in human colorectal cancers. Oncol Res.