A clinicopathologic study of 11 rosette-forming meningiomas: a rare and potentially confusing pattern

Abstract

described in experimental studies of subarachnoid epineph-rine injection in dogs [12], have only since been reported twice. One case report describes a secretory meningioma with rosette formation associated with Moyamoya disease [10]. This feature was also briefly mentioned and illustrated in the 1982 monograph by Dr. John Kepes [5]. However, to date, no studies have examined the spectrum or signifi-cance of rosette formation in meningiomas. Herein, we present our experience with meningiomas showing rosette formation.A total of 11 rosette-forming meningiomas were identi-fied from 11 patients from the authors’ files. Information regarding neuroimaging features and clinical presentation was obtained from the medical records at the institutions from which the cases originated. All cases were classified and graded utilizing the 2007 World Health Organization (WHO) scheme [6] (Fig. 1).Histochemical and immunohistochemical stains per-formed as part of the diagnostic workup or as part of a con-sult workup included EMA, progesterone receptor (PR), vimentin, reticulin, trichrome, GFAP, CD99, CAM 5.2, Ki-67, CD34, collagen IV, and synaptophysin.The clinical details are highlighted in Supplemen-tary Table 1, with patients ranging in age from 18 to 86 (median: 60) years and a F:M ratio of 1.8. Imaging studies were available in all 11 cases and showed features indis-tinguishable from those of conventional meningioma. All tumors were intracranial, single masses, ranging from 3.2 to 6.2 cm in greatest dimension.Histologic, histochemical, and immunohistochemical features are summarized in Table 1 and Supplementary Table 2. All but one case showed rosettes with central vari-ably collagenized eosinophilic structures, while gland-like lumens (i.e., “true rosettes) were also seen in 4 cases (in one it was the only form of rosette and in another it was Meningiomas are amongst the most common intracranial neoplasms and display a remarkable morphologic diversity, which may prove diagnostically challenging in some cases. Rosette formation is an exceptionally rare and mostly an unappreciated feature in meningiomas, other than the ependymoma-like perivascular pseudorosettes encountered in papillary meningioma [7, 11] and rarely, in non-papillary counterparts [9]. Although these perivascular structures should perhaps be termed ‘meningothelial pseudorosettes’ and may coexist with other rosette forms, these were not the focus of the current study.In tumor pathology, rosette formation is usually con-sidered as evidence of either neuronal or ependymal dif-ferentiation, but has also been described in rare examples of osteosarcoma, lymphoma and melanoma [2, 3, 8]. To our knowledge, meningothelial rosettes, which were first

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Acta Neuropathol
DOI 10.1007/s00401-015-1456-6
CORRESPONDENCE
A clinicopathologic study of 11 rosette‑forming meningiomas:
a rare and potentially confusing pattern
Christopher Liverman1 · Manuela Mafra2 · Shih‑Sung Chuang3 · Aditya Shivane4 ·
Arundhati Chakrabarty5 · Robin Highley6 · David A. Hilton4 · Nicholas P. Byrne7 ·
Pieter Wesseling8,9 · Arie Perry1
Received: 3 June 2015 / Revised: 17 June 2015 / Accepted: 17 June 2015
© Springer-Verlag Berlin Heidelberg 2015
described in experimental studies of subarachnoid epineph-
rine injection in dogs [12], have only since been reported
twice. One case report describes a secretory meningioma
with rosette formation associated with Moyamoya disease
[10]. This feature was also briefly mentioned and illustrated
in the 1982 monograph by Dr. John Kepes [5]. However,
to date, no studies have examined the spectrum or signifi-
cance of rosette formation in meningiomas. Herein, we
present our experience with meningiomas showing rosette
formation.
A total of 11 rosette-forming meningiomas were identi-
fied from 11 patients from the authors’ files. Information
regarding neuroimaging features and clinical presentation
was obtained from the medical records at the institutions
from which the cases originated. All cases were classified
and graded utilizing the 2007 World Health Organization
(WHO) scheme [6] (Fig. 1).
Histochemical and immunohistochemical stains per-
formed as part of the diagnostic workup or as part of a con-
sult workup included EMA, progesterone receptor (PR),
vimentin, reticulin, trichrome, GFAP, CD99, CAM 5.2,
Ki-67, CD34, collagen IV, and synaptophysin.
The clinical details are highlighted in Supplemen-
tary Table 1, with patients ranging in age from 18 to 86
(median: 60) years and a F:M ratio of 1.8. Imaging studies
were available in all 11 cases and showed features indis-
tinguishable from those of conventional meningioma. All
tumors were intracranial, single masses, ranging from 3.2
to 6.2 cm in greatest dimension.
Histologic, histochemical, and immunohistochemical
features are summarized in Table 1 and Supplementary
Table 2. All but one case showed rosettes with central vari-
ably collagenized eosinophilic structures, while gland-like
lumens (i.e., “true rosettes) were also seen in 4 cases (in
one it was the only form of rosette and in another it was
Meningiomas are amongst the most common intracranial
neoplasms and display a remarkable morphologic diversity,
which may prove diagnostically challenging in some cases.
Rosette formation is an exceptionally rare and mostly
an unappreciated feature in meningiomas, other than the
ependymoma-like perivascular pseudorosettes encountered
in papillary meningioma [7, 11] and rarely, in non-papillary
counterparts [9]. Although these perivascular structures
should perhaps be termed ‘meningothelial pseudorosettes’
and may coexist with other rosette forms, these were not
the focus of the current study.
In tumor pathology, rosette formation is usually con-
sidered as evidence of either neuronal or ependymal dif-
ferentiation, but has also been described in rare examples
of osteosarcoma, lymphoma and melanoma [2, 3, 8]. To
our knowledge, meningothelial rosettes, which were first
Electronic supplementary material The online version of this
article (doi:10.1007/s00401-015-1456-6) contains supplementary
material, which is available to authorized users.
* Arie Perry
Arie.Perry@ucsf.edu
1 UCSF Medical Center, San Francisco, CA, USA
2 Centro Hospitalar Lisboa Central, Lisbon, Portugal
3 Chi-Mei Medical Center, Tainan, Taiwan
4 Derriford Hospital, Plymouth, Devon, UK
5 St James University Hospital, Leeds, UK
6 Hull Royal Infirmary, Hull, UK
7 John Muir Medical Center, Walnut Creek, CA, USA
8 VU University Medical Center, Amsterdam, The Netherlands
9 Radboud University Medical Center, Nijmegen, The
Netherlands

Acta Neuropathol
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the predominant pattern). Rosette formation was diffuse
in 4 cases and therefore predominated over more classic
meningothelial features (Table 1). Meningothelial perivas-
cular pseudorosettes were also encountered rarely, but this
was not a prominent feature in any of our cases. Classifica-
tion of non-rosetted areas revealed 5 of the 13 recognized
variant histologies, along with 5, 5, and 1 WHO grade I, II,
and III malignancy assignments, respectively. In addition to
rosette formation, nuclear palisading resembling Verocay
bodies was prominent in one case.
EMA was at least focally positive in all but one case,
demonstrating membrane and cytoplasmic staining, but not
a dot-like pattern as one might expect in ependymal tumors.
PR was variably positive in 8 cases and negative in 3 cases.
CD99 expression was seen in 5 tumors, although only one
showed prominent membrane and basally located dot-like
staining in the rosettes. All cases stained strongly and dif-
fusely for vimentin and were negative for synaptophysin and
GFAP. The Ki-67 labeling index ranged from 1 to 26.7 %
(median: 8.0 %) and generally correlated with tumor grade.
Electron microscopy was performed in two cases and
showed ultrastructural features compatible with meningi-
oma, including desmosomes, interdigitating cell processes,
and intermediate filaments. In one case, giant amianthoid-
type collagen fibrils (450–600 nm) were seen.
Our data suggest that meningothelial rosettes may be
seen non-specifically in many, if not all histologic variants.
Additionally, any grade may be encountered. Thus, we con-
clude that rosette-forming meningiomas do not represent
a clinicopathologically distinct meningioma variant, but
rather a histologic pattern that may rarely pose diagnostic
challenges, particularly when encountered in poorly dif-
ferentiated examples. The main differential diagnosis for
the latter would include Homer Wright rosettes, as encoun-
tered in primitive neuroectodermal tumors (PNETs), neu-
roblastomas, medulloblastomas, and pineoblastomas or
Fig. 1 Histological and immunohistochemical features of rosette-
forming meningiomas. a, b Meningothelial rosettes with central
nuclear-free zone containing fibrillar eosinophilic cytoplasmic pro-
cesses. c Meningothelial ‘true’ rosettes with gland-like lumens were
also present in some cases. d In this PNET-like WHO grade III men-
ingioma, foci resembled Homer Wright rosettes and true ependymal
rosettes. e Meningothelial rosettes containing central collections of
dense, brightly eosinophilic collagen. f Vimentin staining of central
cytoplasmic processes, g EMA immunoreactivity highlights tumor
membranes at periphery of rosettes and lightly stains a few central
processes. h Scattered reticulin fibers are seen within a meningothe-
lial rosette. i A trichrome stain highlights the dense central collagen
within a meningothelial rosette (same case as panel e)

Acta Neuropathol
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true rosettes as seen in ependymal neoplasms or the glan-
dular spaces of metastatic adenocarcinoma. In particular,
peripheral-type PNETs arising in the dura or skull are per-
haps the greatest, albeit quite rare diagnostic pitfall [1, 4].
Nonetheless, the majority of our cases showed foci of clas-
sic meningothelial histology and immunohistochemistry
quickly excluded other diagnostic considerations.
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Table 1 Pathologic features
For meningioma subtypes with multiple variant histologies, they are listed in order of prominence
ND not done
a Cases that include true rosettes, including case 10 where it was the only form of rosette encountered
Case # Grade Subtype Rosettes Mitoses
per 10
HPF
Invasion
(other than
dural)
Other features Electron microscopy
1 I Angiomatous Focal 0 None Verocay-like areas, marked hyalinization,
macronucleoli, focal clear cells
ND
2 II Meningothelial Focal 4 Soft tissue Focal small cells, sheeting, necrosis,
macronucleoli, focally chordoid, mel-
anocytic colonization
ND
3 II Transitional/papillary Focal 2 None Hypercellular, focal small cells, sheeting ND
4 II Meningothelial/papil-
lary/angiomatous
Focala2 None Necrosis, small cells, macronucleoli ND
5 III Transitional/papillary Diffusea14 None Necrosis, hypercellularity, sheeting, focal
small cells
ND
6 I Meningothelial Focal 0 None Macronucleoli ND
7 II Transitional/rhabdoid Focal 5 None Necrosis, sheeting, small cells, macronu-
cleoli
Processes, glycogen,
little collagen
8 II Meningothelial/angi-
omatous
Focal 4 Brain,
focal
ND
9 I Transitional Diffusea0 None ND
10 I Meningothelial Diffusea0 None ND
11 I Angiomatous Diffuse 0 None Giant amianthoid
collagen fibrils,
450–600 nm in width