Keywords chordoma - CT - cystic - extradural - MRI - transdural
Introduction
A clival cystic chordoma is an extremely rare entity and represents a radiological
challenge. If this already rare entity deviates from the classic computed tomography
(CT) and magnetic resonance imaging (MRI) appearances of chordomas due to the disproportion
between the large extraosseous soft tissue component and the moderate bone involvement,
and also it deviates from the few reported cases of cystic intracranial chordoma due
to the extradural location, an inappropriate differential pathway may be led down.
We present a case of clival chordoma with CT and MRI unconventional appearances, such
as cystic aspect, extradural location, and poor bone involvement.
Case Report
A 10-year-old girl was admitted to our institution after the radiological diagnosis
of a mass of the clival region. The clinical history started several months before
the admission with headache, pain on the right side of the head mainly raised by physical
activity (especially sport). Because of this persisting symptom and because of the
appearance of right palpebral spasms, the young girl underwent an ophthalmological
evaluation with diagnosis of right eye strabismus (esophoria). After the surgical
correction of the strabismus, the headache improved but not disappeared. A right neurosensorial
hypoacusia, present since the infancy, showed a worsening instead, hence an MRI was
performed. The physical examination at the admission did not point out deficits except
for a mild weakness of the left lower limb. The girl was attending normal school and
showed normal cognitive and psychomotor development on specific test administered
at the admission. Noncontrast-enhanced CT scan showed a centrally located retroclival
large mass, extending to the sellar region, with a tooth-shaped calcification floating
in the posterior part and a sequestration of destroyed bone in the upper part, resembling
the sella, and elevating the pituitary gland. Despite the large dimension of the mass,
only a slight bone erosion of the clivus was present ([Fig. 1 ]). MRI better delineated location and extent of the lesion, along the dorsal aspect
of the clivus in the extradural space, extending from the foramen magnum to the sellar
region. Sagittal T2-weighted imaging (T2-WI) disclosed transdural transgression and
invasion of prepontine and right cerebellopontine (CP) angle cistern, with compression
and “indention” of the pons, and elevation of the pituitary gland. Axial images showed
invasion of both cavernous sinus and Meckel's caves and lateral displacement of cavernous
internal carotid arteries. The mass showed low signal intensity on T1-weighted imaging
(T1-WI) and very hyperintense signal on T2-WI ([Fig. 1 ]), without evidence of intralesional septa. Two intralesional foci of increased signal
on T1-WI and decreased signal on T2-WI and susceptibility-weighted images (SWI) corresponded
to calcifications on CT. Diffusion-weighted images (DWI) demonstrated moderate high
signal intensity of the lesion, due to “T2 shine through” (apparent diffusion coefficient
[ADC]: 1,400 × 10−6 mm2 /s in average). After administration of gadolinium-based contrast medium, the mass
did not demonstrate any contrast enhancement. A two-step surgical removal of the tumor
mass was planned. As first step, the young girl underwent a gross debulking of the
tumor through a retrosigmoid approach (craniotomy) to the right CP angle. The operation
was performed under general anesthesia and with electrophysiological intraoperative
monitoring. At surgery, the tumor appeared as a gelatinous mass, plastically growing
into the CP angle cistern and extending into the adjacent cisterns. A marked encasement
of the vessels and the cranial nerves by the tumor was evident. However, the dissection
of the tumor from the neurovascular structures was facilitated by its soft aspect
and by the absence of a significant peritumoral inflammatory reaction. The neoplasm
was removed by a microsurgical technique and by suction. The neoplasm was followed
and removed up to the junction between the posterior and the middle cranial fossae,
where a detachment and perforation of the skull base dura mater was evident as well
as the tumor passing from the middle to the posterior fossa. The postoperative course
was uneventful. The mild motor deficit of the left lower limb quickly disappeared.
The patient was readmitted 3 months after the first operation to allow her to finish
the school time. No symptoms occurred in this period, and she was neurologically intact
at the admission. MRI showed stable residual mass. The girl underwent a second surgery
for the removal of the component of the tumor involving the anterior skull base though
an endoscopic endonasal transsphenoidal approach. As expected, the tumor was extradural
and occupied the retroclival space. The macroscopic appearance was the same as the
previous operation. The postoperative course was uneventful. The patient is now receiving
proton radiotherapy on the residual tumor. On histopathological examination, the neurosurgical
specimens were composed of mucinous material containing epithelial appearing tumor
cells, with monomorphic relatively small round nuclei ([Fig. 2A, B ]); the cells were focally arranged in cords and clusters. Focally, a small fragment
of mature bone tissue within the mucinous stroma was observed. The cells showed expression
of vimentin, pan-cytokeratin, and S100 ([Fig. 2C ]–[E ], respectively). The INI1 nuclear expression was retained (not shown). The cells
did not display significant mitotic and/or proliferative activity (MIB1 immunostaining)
(not shown).
Fig. 1 (A–D ) Sagittal reformatted CT (A ) and sagittal T2-WI (B ) an expansile retroclival mass. On T2-WI, mass appeared in the extradural space,
with transdural passage and intradural component indenting the pons. On CT (A ), bone invasion was relatively light, sella turcica, and pituitary gland were elevated
by the mass, and a tooth-shaped calcification was floating in the posterior part of
the chordoma. Chordoma had a cystic appearance, hyperintense on T2-WI (B ), and moderate hyperintense on DWI (C ). On T1-WI after gadolinium (D ), there was no evidence of contrast enhancement. CT, computed tomography; DWI, diffusion-weighted
imaging; T1-WI, T1-weighted imaging; T2-WI, T2-weighted imaging.
Fig. 2 (A –E ) Histopathological features of cystic chordoma. The histopathological examination
revealed mucinous material containing monomorphic epithelial tumor cells with small-rounded
nuclei and large clear cytoplasm, focally arranged in cords and clusters (A, B ). The cells showed expression of vimentin (C ), pan-CK (D ), and S100 (E ). (A, B ) Routine H and E staining; (C ): immunostaining with monoclonal mouse antihuman vimentin, clone V9, Dako-Agilent,
Cernusco sul Naviglio, Italy; (D ): immunostaining with monoclonal mouse antihuman CK antibody, clone AE1/AE3, Dako-Agilent;
(E ): immunostaining with polyclonal rabbit antibody antihuman S100, Dako-Agilent; all
immunohistochemistry performed on Dako-Omnis staining system, Dako. CK, cytokeratin.
Discussion
Chordomas are rare and locally invasive malignant tumors that represent 1% of intracranial
tumors and 4% of all primary bone tumors; they most commonly affect adults in their
fourth and fifth decades of life, with male and whites predilection, while they are
rare among children.[1 ] Arising from embryonic remnants of the primitive notochord, chordomas can develop
along the cranial (32%), spinal (32.8%), and sacral (29.2%) portions of the craniovertebral
axis.[1 ] Spheno-occipital synchondrosis is the most common site of origin of intracranial
chordomas, arising from the upper third or along the caudal margin of the clivus.[1 ] Occasionally, the extrusion of the notochord during the ossification can occur in
aberrant locations, and notochord rests may persist into the extradural or intradural
spaces. This would allow the chordomas to grow without bony involvement.[2 ] There are three histological variants of chordoma: classical, chondroid chordomas,
containing hyaline cartilage,[1 ] and dedifferentiated chordoma. Dedifferentiated chordoma comprise <5% of all chordoma
subtypes, and they are a particularly aggressive tumor with a predilection for the
pediatric population with a much poorer prognosis.[3 ] Chondroid variant often shows a less aggressive clinical behavior than classical
chordoma.[4 ]
Also, the degree of bone invasion and the integrity of dural are independent risk
factors for the clinical prognosis of skull base chordoma patients.[4 ] Recently, Wu et al[5 ] classified clivus chordoma as endophytic (Type I) or exophytic (Type II) based on
the degree of skull base bone invasion, and exploring the mechanisms of such bone
invasion, they confirmed that the expression level of PTEN (phosphatase and tensin
homolog) gene is associated with the degree of bone invasion, and the regulatory molecule
transforming growth factor beta 1 may play an important role in bone invasion (Experimental
Study on Differences in Clivus Chordoma Bone Invasion: An iTRAQ-Based Quantitative
Proteomic Analysis). The classic appearance of intracranial chordoma at MRI is a well-circumscribed,
expansile soft tissue mass, with high signal intensity on T2-WI, intermediate to low
signal intensity on T1-WI, moderate to marked contrast enhancement. Variable intralesional
dark areas on SWI (susceptibility weighted imaging) or GRE (gradient echo sequences)
images are present due to intratumoral hemorrhages or calcifications; however, calcifications
(bone sequestra or dystrophic calcifications) are better depicted by CT scan.[6 ]
This clival chordoma did not conform to the typical CT and MRI appearances of intracranial
chordoma, first due to the completely cystic appearance of the mass and the poor bone
involvement in the face of a voluminous extrabone component.
Based on cystic appearance, differential diagnosis included epidermoid cyst (EC),
ecchordosis physaliphora (EP), and benign notochordal cell tumors (BNCTs), but considering
also the location of the lesion, none of these lesions corresponded to our case ([Table 1 ]).[7 ] Although some MRI features were compatible with EC, such as T1 and T2 signal intensity
and no contrast enhancement, ECs usually show restricted diffusion on DWI (bright
hyperintensity), and they are usually intradural lesions (75%),[8 ] which are not consistent with our case. EP is a congenital, often asymptomatic,
benign lesion derived from intradural notochord remnants, usually located in the midline,
such as in the dorsum of the clivus.[9 ] However, EP usually arises from the intradural space, on the contrary, our case
seems to be an extradural mass with secondary intradural invasion, a growth behavior
that belongs to chordomas.[10 ] Whether intradural chordomas arise from EP is still under debate; in literature,
rare cases of symptomatic EP are described and malignant transformation to chordoma
is also contemplated,[11 ] but EP remains relatively small in size (2–3 cm) and only few cases of EP >3 cm
have been reported in the literature, considering that “giant EP” is defined >6 cm3 in size.[9 ]
[11 ] The substantially larger dimensions do not support the hypothesis that it could
be a degenerated EP.
Table 1
Imaging characteristics of our case and differential diagnosis
T1-WI
T2-WI
DWI/ADC
Contrast enhancement
Bone erosion
Location
Our case
Low
High
No restriction (ADC: 1,400 × 10−6 mm2 /s)
No
Mildly
Extradural, secondary intradural
EC
Low
High
Restriction
No
No
Intradural
EP
Low
High
No restriction
No
No
Intradural
BNCTs
Low
High
No restriction
No
No
Intraosseous
Chondrosarcoma of the skull base
Low/intermediate
High
No restriction (> mean ADC value: 2,051 ± 261 × 10−6 mm2 /s)[1 ]
Yes
Yes “ring-and-arc” calcification
Extradural off midline
Abbreviations: ADC, apparent diffusion coefficient; BNCTs, benign notochordal cell
tumors; DWI, diffusion-weighted imaging; EC, epidermoid cyst; EP, ecchordosis physaliphora;
T1-WI, T1-weighted imaging; T2-WI, T2-weighted imaging.
BNCTs are benign intraosseous lesions of notochordal cell origin reported to be found
in 20% of autopsy series in the midline of clivus and vertebral bodies, with increasing
frequency of their identification on MRI studies.[12 ] BNCTs appear as well-defined intraosseous lesion, and as for EC and EP, signal intensity
is low on T1-WI and high on T2-WI, without contrast enhancement, diffusion restriction,
or soft tissue extension, but the location is extradural.[12 ] We considered the hypothesis of cystic intracranial chordomas, but based on a review
of the cases reported in the literature, while the lack of severe bone involvement
resulted as a typical feature, the extradural location was never reported. Most of
the intracranial cystic chordomas were intradural, in one case, the lesion was located
in the right cavernous sinus and in another case, the authors were not completely
sure of the location, which nevertheless seemed to be extradural ([Table 2 ]).[13 ]
[14 ]
[15 ]
[16 ]
[17 ]
[18 ]
[19 ]
[20 ]
[21 ]
[22 ]
[23 ] Also, the patients' age was not conclusive, only 4/11 patients were child or teenagers.
Chondrosarcoma could be another possible differential diagnosis for midline chordomas
with dural invasion in the presence of intratumoral calcification, but the absence
of contrast enhancement did not support completely this hypothesis.[24 ] Chondrosarcoma arises in the petroclival fissure, and therefore, it is usually located
off midline.[24 ] CT may show calcification of the tumor, often in characteristic “rings and arcs”
(chondroid matrix mineralization).[24 ] Furthermore, recent studies demonstrate that DWI may be helpful in the differential
diagnosis between chordoma and chondrosarcoma, with chondrosarcoma having a higher
average ADC than chordoma.[7 ]
Table 2
Case reports of cystic chordomas reported in literature
Authors (year)
Age/sex
T1-WI
T2-WI
DWI
CE
Bone erosion
Location
Niida et al (1994)[13 ]
5/M
Hypo
Hyper
–
No (CT)
No
Retroc. Intrad.
Nishigaya et al (1998)[14 ]
56/M
Hypo
Hyper
–
Mild
No
Retroc. Intrad.
Seung and Kim (2004)[15 ]
12/F
Hypo
Hyper
Hyper
No
Mild
Retroc. Intrad.
Ciarpaglini et al (2009)[16 ]
60/M
Hypo
Hyper
–
No
No
Retroc. Intrad.
Cho et al (2012)[17 ]
32/M
Hypo
Hyper
Slightly hyper
Small foci
No
Retroc. Intrad.
Hashim et al (2014)[18 ]
15/F
Hypo (+foci of hemo.)
Hyper
–
No
No
Retroc. Intrad.
AlOtaibi et al (2014)[19 ]
51/M
Hypo
Hyper
–
Mild
No
Retroc. Intrad.
Ozek et al (2018)[20 ]
35/F
Hypo
Hyper
Hyper
No
No
Retroc. Intrad.
Vinke et al (2016)[21 ]
11/M
Hypo
Hyper
–
Mild
No
Retroc. Intrad.
Kim et al, 2018[22 ]
27/M
Hypo
Hyper
Hyper
No
No
Retroc. Intrad.
Sathe et al (2019)[23 ]
26/M
Hypo
Hyper
No RD
No
Mild
Cavernous sinus
Abbreviations: CE, contrast enhancement; CT, computed tomography; hemo., hemosiderin;
Hyper, hyperintense; Hypo, hypointense; Intrad., intradural; RD, restricted diffusion;
Retroc., retroclival; T1-WI, T1-weighted imaging; T2-WI, T2-weighted imaging.
Conclusion
Cystic chordoma is an extremely rare entity that should be considered in the differential
diagnosis of cystic lesions of the clival region. But in our case, cystic chordoma
not only demonstrated unconventional appearance on CT and MRI with respect to intracranial
chordoma, and yet it did not conform to reported radiological appearance of intracranial
cystic chordoma.
