Open Journal of Pathology, 2013, 3, 170-173
Published Online October 2013 (http://www.scirp.org/journal/ojpathology)
http://dx.doi.org/10.4236/ojpathology.2013.34031
Case Report: An Unusual Osseous Lesion
Benjamin Riviere1, Thérèse Rousset1, Luc Bauchet1,2, Nicolas Menjot de Champfleur3,
Vanessa Szablewski1, Valérie Costes1, Valérie Rigau1
1Department of Histopathology, Saint Eloi-Gui de Chauliac Hospital, University Medical Center, Montpellier, France; 2Department
of Neurosurgery and INSERM U1051, Saint Eloi-Gui de Chauliac Hospital, University Medical Center, Montpellier, France;
3Department of Radiology, Saint Eloi-Gui de Chauliac Hospital, University Medical Center, Montpellier, France.
Received March 18th, 2013; revised April 18th, 2013; accepted April 28th, 2013
Copyright © 2013 Benjamin Riviere et al. This is an open access a rticle di stribute d under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
ABSTRACT
The intraosseous benign notochordal cell tumor (BNCT) is an intravertebral lesion derived from notochordal tissue. The
notochord develop s in humans during the third week of embryo nic life and persists in adults as the nu cleus pulposus of
the vertebral disks. The most common locations of such tumors are the saccrococcygeal region and the skull base. Most
tumors are asymptomatic and small. Magnetic resonance imaging is useful in their detection and precise localization.
Histologically, these lesions consist of sheets of adipocyte-like vacuolated or less vacuolated eosinophilic tumor cells
with eccentrically located round nuclei without myxoid matrix. The tumor cells express the epithelial markers, vimentin
and S100 protein. Main differential diagnosis is chordoma. Intraosseous BNCT do not require any surgical management
and should be recognized by pathologists to prevent unnecessary radical surgery. These lesions should be followed-up
with convention a l MRI.
Keywords: Intraosseous Benign Notochordal Cell Tumor; Osseous Tumor; Histopathology
1. Case Report
We present a fifty-two year old woman with a personal
medical history of fibromyalgia and breast cancer and
family history of colorectal cancer. A random medical
check up revealed the presence of a monoclonal gam-
mopathy suggesting an underlying immunoproliferative
disorder. Subsequent radiological workup demonstrated
an anomaly of the third sacral vertebrae. Magnetic reso-
nance imaging of the spine showed a 2 cm intraosseous
lesion hypointense on T1-weighted imaging, hyperin-
tense on T2-weighted images, enhanced after contrast
infusion and slightly hyperdense on non enhanced CT
scan (Figure 1(a)). There was no expansive soft tissue
mass nor osteolysis.
A surgical biopsy was taken with a clinical diagnosis
of possible myeloma.
2. Pathological Findings
A histological assessment of the specimen revealed nor-
mal trabecular bone. The intertrabecular marrow was
dominated by the proliferation of large clear cells (Fig-
ure 1(g)). These adipocyte-like cells had clear vacuo-
lated cytoplasm and eccentrically or centrally located
round nuclei (Figure 1(h)). No mitotic figures, aniso-
karyosis or cytonuclear atypia were recognized. Alcian
Blue and PAS staining did not demonstrate intracyto-
plasmic glycogen granules. There was no myxoid matrix.
Immunohistochemistry showed positive staining of the
cells for vimentin, S100 protein, EMA (epithelial mem-
brane antigen) and cytokeratin AE1/AE3 (Figures 1(i)
and (j)). KI 67 (MIB-1) was <1% and CD10 was nega-
tive. The radiological and pathological findings suggested
a diagnosis of intraosseous benign notochordal cell tumor.
The monoclonal gammopathy in the blood was finally
considered to be an incidental observation and had no
later implications.
3. Follow Up and Course
Based on these pathological and radiological observa-
tions, simple clinical and radiological follow-up was pro-
posed. Four years later the lesion was radiologically un-
changed (Figures 1(b) to (f)). The patient is presently
followed annually by lumbosacral magnetic resonance
(MR) images, computed tomography (CT) scans, and os-
seous scintigraphy.

Case Report: An Unusual Osseous Lesion 171
Figure 1. MRI of the spine (a) showed signal abnormalities
at the level of S3 (white arrowhead), S4, S5, Co1 and Co2 on
STIR sequences. Four years ((b) to (f)) follow-up showed no
extent of this signal abnormality, appearing hyperdense on
non-enha nced CT scan (b), hype rintense on T2-w eighted im-
ages (c), hyperintense on STIR seque nce (d), hy pointense on
T1-weighted images (e), with slight enhancement after con-
trast infusion (f). Replacement of the inter-trabecular mar-
row by a proliferation of clear and large cells (HES × 200)
(g). Physaliphorous cells: proliferation of adipocyte-like va-
cuolated cells with eccentrically small nuclei without aniso-
caryosis (HES × 400) (h). Immunohistochemistry: strong
cellular reactivity for S100 protein (i) and cytokeratin AE1/
AE3 (IHC × 400) (j).
4. Discussion
The notochord is developed in humans during the third
week of embryonic life and has a role in the formation of
the vertebral column and the neural plate [1]. During
subsequent development of the embryo, the notochord
regresses in the region of the vertebral bodies and per-
sists as the nucleus pulposus of the intervertebral disks
[1,2]. Notochordal remnants can be found in the inter-
vertebral disks, as “rests” or “vestiges”, and disappear by
the age of 1 to 3 years [3]. Ectopic notochordal rests can
occur along the midline of the craniospinal axis, fro m the
dorsum sella to the coccyx, mainly at the base of the
skull [4].
About 160 years ago, these lesions were first described
by Luschka and named ecchondrosis/ecchordosis phy-
saliphora spheno-occipitalis [5,6]. Later Muller and Rib-
bert found that the lesion derived from notochordal tissue
[7]. Intravertebral notochordal remnants were first de-
scribed in 1982 and called ecchordosis physaliphora ver-
tebralis. These observation were made at autopsy [1].
Since then, a number of such microscopic remnants have
been found incidentally at autopsy, generally less than 1
cm [1,8]. More recently, larger intravertebral notochordal
lesion seen radiologically have been described. In 1996,
Darby et al. described the first “giant notochordal rest”,
comparable to remnants found in the intervertebral disk
and ecchordosis physaliphora [1]. It has been argued that
these lesions are histologically different from vestiges
and notochordal rests [9]. As such, terms like “benign
chordoma” or “giant notochordal hamartoma of intraos-
seous origin” have been suggested [1]. Finally, the term
intraosseous benign notochordal cell tumor (BNCT) was
recently adopted, including both small lesions found in-
cidentally and larger lesions that have become detectable
on radiological images or have been symptomatic [1,9,
10].
Benign notochordal cell tumors are intraosseous le-
sions which can occur along the midline of the cranio-
spinal axis, particularly in the saccrococcygeal or sphe-
nooccipital region [8,10]. A recent autopsy series found
BNCTs in 20% of 100 cadavers, with a mean age of 63
years (7 to 82 years), with a distribution of 12% in sac-
crococcygeal vertebrae, 11.5% in the clival region, 5% in
cervical vertebrae, 2% in lumbar vertebrae and none in
the thoracic vertebrae [8].
Benign notochordal cell tumors are usually asympto-
matic [10]. When they do give symptoms, the most pro-
minent is back pain [1,3]. Other symptoms related to the
location of the lesion have been reported (coccydynia,
limitation of movement, numbness, pain of fingers, neck,
buttock and shoulder stiffness) [1] . Radiol ogically, B NCTs
appears hypointense on T1-weighted and hyperintense on
T2-weighted MR images [1,3,10,12]. There is no contrast
enhancement after injection of gadolinium [10-12]. On
CT scans the lesions are often sclerotic [10,12]. These
lesions are well circumscribed. The smaller BNCTs are
not seen radiologically and are incidental microscopic
findings.
Histologically, BNCT is an unencapsulated lesion fill-
ing the intertrabecular spaces and consisting of nests or
sheets of clear cells resembling adipose tissue on low
magnification, [1,3]. They have clear cytoplasm and ec-
centrically located round or oval nuclei [1,9]. Smaller
granular cells are seen with eosinophilic g lobules of con-
densed cytoplasm. These cells show centrally located en-
larged nuclei with rare small nucleoli [1,3,9]. The phy-
saliphorous cells are “bubbly” cells containing multiple
clear cytoplasmic vacuoles [1]. In some cases, cystic spaces
are present and contains eo sinophilic colloidlike material
being positive for Alcian blue and periodic acid-Schiff
[1,9]. There is no intercellular stroma or myxoid matrix
[1,3]. The cell pr oliferatio n is rela tive l y unifo r m [1]. There
are no mitoses, atypia or nuclear pleomorphism, no fi-
brous bands, lobulation or necrosis [1,3,9]. Surrounding
bone trabeculae are often sclerotic [3,9]. The lesion can

Case Report: An Unusual Osseous Lesion 172
harbour some residual islands of normal haematopoietic
marrow cells [1].
Immunohistochemically, the tumor cells stain for vi-
mentine, S100 protein and epithelial markers like epi-
thelial marker antigen (EMA) or cytokeratins (AE1AE3)
[1,10]. They show a low (<1%) KI-67 (MIB-1) prolifera-
tion index [1]. The same immunopro file is found in non-
tumor notochordal tissue and chordomas [1].
The evolution of BNCTs is indolent, with a benign
behaviour and appears to be relatively frequent compared
to chordomas [1].
BNCTs can be observed with no particular treatment,
but do need a long-term follow-up [1]. The follow-up
program is based on CT scans and MR images, and
should be focused on exclud ing osteolysis or ex tens ion to
soft tissue. Such transformations are indicators of chor-
doma development [3]. If symptomatic, surgery can be
an option [ 1].
The histologic similarity o f the noto chordal v estiges of
intervertebral discs, ecchordosis physaliphora, BNCTs
and chordomas are important. Intervertebral vestiges are
persisting notochords within the intervertebral disks in
adults [1]. The main difference is their location because
vestiges are present in the center of the intervertebral
disk as opposed to the vertebral body for BNCT [1]. Ves-
tiges are described as a cysticlike space in the annulus
fibrosus [1]. Histologically, they are composed of cords
or strands of notochordal cells embedded in a myxoid
matrix [1]. The presence of this intercellu lar myxoid ma-
trix differenciates them from BNCTs.
Ecchordosis physaliphora are extraosseous, ectopic
notochordal lesions of embryologic origin, similar to
notochordal vestiges of the intervertebral disk [1,5,6].
They are often located intracranially, on the dorsum of
the clivus and in the prepontine cisterna [13]. They can
be found at any level from the dorsum sellae to the sac-
crococcygeal region and are usually present extradurally
[13]. Ecchordoses grow slowly and in most cases are
clinically asymptomatic [7]. Some rare cases do become
symptomatic trough tumour expansion, brain compres-
sion or haemorrhage [13]. Because of their location, the
differential diagno sis with BNCTs is easy [1]. In contrast
to chordoma, ecchordosis physaliphora is small (<3.5
cm), shows no contrast enhancement on MR images and
are similar histologically to intervertebral notochordal
rests with the same immunohistochemical profile as the
other notoch or dal lesions [1,4,13].
The main differential diagnosis to BNCT is chordoma,
a low grade malignant neoplasm of notochordal origin.
Chordomas can occu r anywhere in the axial skeleton and
common locations are the base of skull and saccrococ-
cygeal vertebrae [8,10]. Chordomas are aggressive neo-
plasms characterized by slow growth with local destruc-
tion of bone [1]. These tumors are larger, ranging in size
from 50 mm or more and can involve more than one ver-
tebral body [1]. Symptoms frequently include pain and
neurological deficits. Distant metastases have been re-
ported in up to 43% of patients and the overall median
survival time with chordoma has been estimated to be
approximately 6 years [1].
Radiologically, chordomas also appear hypointense on
T1-weighted and hyperintense on T2-weighted MR im-
ages but demonstrate heterogeneous and marked contrast
enhancement after injection of gadolinium [3,4,10,12].
There is often extensive lytic bone destruction, presence
of an expansive soft tissue mass and intratumoral calci-
fication on CT scans [3,10,12].
Macroscopically, chordomas present as a gelatinous
lesion with hemorrhagic areas and bone destruction [1].
Microscopically, a chordoma is composed of irregular
strands or cords of atypical chordoid cells in an intercel-
lular myxoid matrix [1,3,10]. On low magnification mi-
croscopy, the lesion has a lobularity with fibrous septae
[1]. The cells can be large with pale cytoplasm and in-
tracytoplasmic septations or abundant eosinophilic cyto-
plasm [1,3,10]. There are atypical hyperchromatic nuclei,
necrosis can be seen, and mitotic figures are found [1,3].
Destruction of adjacent bone is present [1]. An immuno-
profile equivalent to BNCT is found (EMA, protein S100
and vimentine positivity). However, p53 overexpression
and increased KI-67 (MIB-1) indicate the increased pro-
liferative activity [1,10]. Recent studies have demon-
strated that brachyur y is a u sefu l marker for the d iagnosis
of chordomas. Brachyury is a key transcription factor
involved in the early specification of the posterior meso-
derm for development of the notochord [14]. A microar-
ray analysis of gene expression showed that axial chor-
domas express high levels of brachyury, and this was
supported by immunohistochemical studies demonstrat-
ing brachyury as a sens itive an d specific marker fo r cho r-
domas [14,15]. Treatment of these tumors is based on ra-
dical surgery combined with radiation therapy. Although
treated aggressively, these tumours have a high degree of
local recurrence [3].
Other lesions that can be confused with BNCT are
metastatic carcinomas, particularly originating from clear
cell carcinoma of the kidney [1,10].
Considering their common origin as well as histologi-
cal, immunohistochemical and ultrastructural similarities,
BNCTs are tho ught to be the benign coun terpart to chor-
domas [3,10,11]. It is not known however, whether
BNCTs can be a chordoma precur sors [1,11]. On e report
from 2002, do describe a chordoma observed adjacent to
a benign notoch ordal lesion in the coccyx occurring con-
comitant with two BNCTs in the sacrum [1]. In 2005, a
report was published describing two cases with BNCTs
associated with miniature chordomas (incipient chordo-
mas) [16]. Finally, one study (2007) identified BNCTs in

Case Report: An Unusual Osseous Lesion 173
7.3% (6 of 82) of sacral/coccygeal resections performed
for chordoma [11]. Recently, Kikuchi et al. reported two
cases of pulmonary tumor with notochordal differentia-
tion, suggestive of benign notochordal cell tumor of ex-
traosseous origin [14]. These two cases suggest a new
explanation for the histogenesis of extra-axial chordomas,
indeed BNCTs may be a precursor lesion of not only
convention al axial chordo ma but also of extra-axial ch or-
doma [14]. It is therefore important to consider the pos-
sible evolution of BNCT into chordomas.
5. Conclusion
The intraosseous benign notochordal cell tumor (BNCT)
is a benign lesion from notochordal origin. Important
histopathological observations, such as absence of cyto-
nuclear atypia, mitosis or myxoid background, may help
to distinguish BNCTs from the malignant chordoma. In
addition, the clinical presentation and radiological imag-
ing are important contributors to the correct diagnosis.
To distinguish BNCTs from chordoma is important for
treatment decisions and in predicting outcome, as the
indolent nature of BNCTs only requires surveillance and
has a good prognosis. Malignant transformation to chor-
domas is an undecided possibility.
REFERENCES
[1] H. Amer and M. Hameed, “Intraosseous Benign Noto-
chordal Cell Tumor,” Archives of Pathology & Labora-
tory Medicine, Vol. 134, No. 2, 2010, pp. 283-288.
[2] W. L. Wang, J. H. Abramson, A. Ganguly and A. E.
Rosenberg, “The Surgical Pathology of Notochordal Re-
mnants in Adult Intervertebral Disks: A Report of 3
Cases,” American Journal of Surgical Pathology, Vol. 32,
No. 8, 2008, pp. 1123-1129.
http://dx.doi.org/10.1097/PAS.0b013e3181757954
[3] A. Chauvel, F. Taillat, O. Gille, et al., “Giant Vertebral
Notochordal Rest: A Newentity Distinct from Chordo-
ma,” Histopathology, Vol. 47, No. 6, 2005, pp. 646-649.
http://dx.doi.org/10.1111/j.1365-2559.2005.02168.x
[4] F. Mehnert, R. Beschorner, W. Küker, U. Hahn and T.
Nägele, “Retroclival Ecchordosisphysaliphora: MR Imag-
ing and Review of the Literature,” American Journal of
Neuroradiology, Vol. 25, No. 10, 2004, pp. 1851-1855.
[5] H. Luschka, “Die Altersveräenderungen der Zwischen-
wirbelknorpel,” Virchows Archiv A, Pathological Anato-
my and Histology, Vol. 9, No. 3, 1856, pp. 311-327.
http://dx.doi.org/10.1007/BF01879395
[6] R. Virchow, “Untersuchungen ueber die Entwicklung des
Schaedelgrundes,” G. Rimer, Berlin, 1857, p. 47.
[7] H. Ribbert and H. Steiner, “Uber die Ecchondrosis Phy-
salifora Sphenooccipitalis,” Zentralbl Allg Pathol Anat,
Vol. 5, 1894, pp. 457-461.
[8] T. Yamaguchi, S. Suzuki, H. Ishiiwa and Y. Ueda, “Intra-
osseous Benign Notochordalcell Tumours: Overlooked
Precursors of Classic Chordomas?” Histopathology, Vol.
44, No. 6, 2004, pp. 597-602.
http://dx.doi.org/10.1111/j.1365-2559.2004.01877.x
[9] T. Yamaguchi, S. Suzuki, H. Ishiiwa, K. Shimizu and Y.
Ueda, “Benign Notochordalcell Tumors: A Comparative
Histological Study of Benign Notochordal Cell Tumors,
Classic Chordomas, and Notochordal Vestiges of Fetal
Intervertebral Disks,” American Journal of Surgical Pa-
thology, Vol. 28, No. 6, 2004, pp. 756-761.
http://dx.doi.org/10.1097/01.pas.0000126058.18669.5d
[10] T. Yamaguchi, J. Iwata, S. Sugihara, et al., “Distin-
guishing Benign Notochordalcell Tumors from Vertebral
Chordoma,” Skeletal Radiology, Vol. 37, No. 4, 2008, pp.
291-299. http://dx.doi.org/10.1007/s00256-007-0435-y
[11] V. Deshpande, G. P. Nielsen, D. I. Rosenthal and A. E.
Rosenberg, “Intraosseous Benign Notochord Cell Tumors
(BNCT): Further Evidence Supporting a Relationship To-
chordoma,” American Journal of Surgical Pathology, Vol.
31, No. 10, 2007, pp. 1573-1577.
http://dx.doi.org/10.1097/PAS.0b013e31805c9967
[12] T. Nishiguchi, K. Mochizuki, M. Ohsawa, T. Inoue, K.
Kageyama, A. Suzuki, T. Takami and Y. Miki, “Dif-
ferentiating Benign Notochordal Cell Tumors from Chor-
domas: Radiographic Features on MRI, CT, and Tomo-
graphy,” American Journal of Roentgenology, Vol. 196,
No. 3, 2011, pp. 644-650.
http://dx.doi.org/10.2214/AJR.10.4460
[13] S. H. Ng, S. F. Ko, Y. L. Wan, L. M. Tang and Y. S. Ho,
“Cervical Ecchordosis Physaliphora: CT and MR Fea-
tures,” British Journal of Radiology, Vol. 71, No. 843,
1998, pp. 329-331.
[14] Y. Kikuchi, T. Yamaguchi, H. Kishi, K. Azuhata, G.
Kimizuka, K. Hiroshima and Y. Nakatani, “Pulmonary
Tumor with Notochordal Differentiation: Report of Two
Cases Suggestive of Benign Notochordal Cell Tumor of
Extraosseous Origin,” American Journal of Surgical Pa-
thology, Vol. 35, No. 8, 2011, pp. 1158-1164.
http://dx.doi.org/10.1097/PAS.0b013e318220e085
[15] R. Tirabosco, D. C. Mangham, A. E. Rosenberg, et al.,
“Brachyury Expression in Extra-Axial Skeletal and Soft
Tissue Chordomas: A Marker That Distinguishes Chor-
doma from Mixed Tumor/Myoepithelioma/Parachordoma
in Soft Tissue,” American Journal of Surgical Pathology,
Vol. 32, No. 4, 2008, pp. 572-580.
http://dx.doi.org/10.1097/PAS.0b013e31815b693a
[16] T. Yamaguchi, H. Watanabe-Ishiiwa, S. Suzuki, Y. Iga-
rashi and Y. Ueda, “Incipientchordoma: A Report of Two
Cases of Early-Stage Chordoma Arising from Benign
Notochordal Cell Tumors,” Modern Pathology, Vol. 18,
No. 7, 2005, pp. 1005-1010.
http://dx.doi.org/10.1038/modpathol.3800378