Keywords calcifying pseudoneoplasms of the neuraxis - CAPNON - Meckel's cave - Cyst
Introduction
Calcifying pseudoneoplasms of the neuraxis (CAPNON) are rare, non-neoplastic, calcified
lesions that were first described by Rhodes and Davis in 1978 as an unusual fibro-osseous
component in intracranial lesions.[1 ] They can occur anywhere in the central nervous system, including the brain and spine.
These tumors can be either intra-axial or extra-axial. The clinical symptoms, including
seizures, headache, and focal neurological deficits, are attributed to the local compression
or irritation of adjacent tissue.[2 ] The etiology of CAPNON remains unclear, but it has been suggested that CAPNON may
develop as a healing response to multiple triggering factors, such as trauma, infection,
or inflammation.[3 ] Although there are no standard guidelines for its management, complete resection
of the lesion can achieve a good prognosis without recurrence. We present a case of
CAPNON of the Meckel cave involving the trigeminal nerve with a cyst extending into
the cerebellopontine cistern, which recurred after resection of the cystic component.
Case Presentation
A 48-year-old man presented with a 4-year history of right-sided ptosis. He also had
right facial numbness, and the transient right facial spasm resolved for several months.
Magnetic resonance imaging (MRI) revealed a calcified mass in the right Meckel cave
with a cyst extending to the right cerebellopontine cistern, compressing the midbrain
and upper pons ([Fig. 1A ]). The calcified mass in Meckel's cave was 15 × 15 mm in diameter ([Fig. 1B ]), with mixed intensity signals on T1- and T2-weighted images with peripheral enhancement
([Fig. 1C ]). The cystic lesion of the cerebellopontine cistern was 10 × 13 mm in diameter with
high-intensity signals on T2-weighted images without enhancement. Based on radiological
examinations, the differential diagnoses included meningioma, trigeminal schwannoma,
and fibro-osseous tumor.
Fig. 1 (A ) Axial T2-weighted MRI demonstrates a low-intensity mass in the right of Meckel's
cave (arrow ) connected to a cystic lesion in the cerebellopontine cistern (arrowhead ). (B ) Plain coronal CT demonstrating a calcified mass in the right of Meckel's cave. (C ) Axial T1-weighted image with contrast enhancement demonstrating irregular rim enhancement
of the mass in the right of Meckel's cave.
An attempt was initially made to resolve the patient's ptosis by excising the cystic
lesion located in the right cerebellopontine cistern, while the calcified mass in
Meckel's cave was left untouched. Through right lateral suboccipital craniotomy, excision
of the cystic lesion attached to the right trigeminal nerve and decompression of the
oculomotor nerve could be achieved ([Fig. 2A, B ]). The patient had an uneventful postoperative course and his right ptosis improved.
A histopathological examination revealed connective tissue without any signs of a
neoplasm. Postoperative MRI showed that the cystic lesion in the right cerebellopontine
cistern was fully removed ([Fig. 3A ]). However, within the next 23 months, the cystic lesion grew back to its preoperative
level ([Fig. 3B ]). The patient had a recurrence of right ptosis and right trigeminal neuralgia affecting
the V1 and V2 territories. Resection of the lesion, including the calcified mass in
the right Meckel cave and the cystic lesion extending to the right cerebellopontine
cistern, was planned through a right extradural subtemporal approach 27 months after
the initial surgery. The calcified mass in Meckel's cave could be extirpated with
the preservation of the compressed right trigeminal nerve. The tentorial incisura
([Fig. 3C, D ]) was cut to remove the cystic lesion connecting to the calcified mass in Meckel's
cave. The patient's postoperative course was uneventful, and his right ptosis and
trigeminal neuralgia resolved. Postoperative MRI showed complete resection of both
the calcified mass and the cystic lesion ([Fig. 3C ]), with no recurrence at 10 months after the procedure.
Fig. 2 (A ) Operative view in the first operation demonstrating the cystic lesion in the right
cerebellopontine cistern attaching with the trigeminal nerve. (B ) Operative view of the first operation after extirpation of the cystic mass. The
arrowhead indicates the right trigeminal nerve. The double arrow indicates the cochlear nerve. The arrow indicates the basilar artery. (C ) Operative view in the second operation demonstrating a calcified mass in the right
Meckel cave (arrow ) through a right extradural subtemporal approach. (D ) Operative view in the second operation demonstrating total extirpation of the calcified
mass in the right of Meckel's cave and a cystic lesion in the cerebellopontine cistern
with preservation of the trigeminal nerve (arrow ).
Fig. 3 (A ) T2-weighted MRI obtained after the initial operation shows that the cystic lesion
in the right cerebellopontine cistern was removed, while the low-intensity mass in
the Meckel cave remained. (B ) T2-weighted MRI obtained 23 months after the initial operation demonstrating recurrence
of the cystic lesion in the right cerebellopontine cistern (arrow ) with a low-intensity mass in Meckel's cave (arrowhead ). (C ) T2-weighted MR image obtained after the second operation demonstrating removal of
both the low-intensity mass in Meckel's cave and the cystic lesion in the right cerebellopontine
cistern with preservation of the trigeminal nerve (arrow ).
Histopathological Findings
The histopathological examination found calcified fibrillary material cores, which
were surrounded by spindled epithelioid cells and fibrovascular tissue containing
lymphocytes. Calcified material was often arranged in a linear pattern and contiguous
with spindled cells and fibrous connective tissue ([Fig. 4A ]). Immunohistochemical staining revealed focally scattered epithelial membrane antigen
(EMA) positive peripheral spindled epithelioid cells ([Fig. 4B ]).
Fig. 4 (A ) Hematoxylin and eosin staining demonstrating cores of calcified, fibrillary materials
surrounded by spindled to epithelioid cells and fibrovascular tissue containing lymphocytes.
(B ) Some peripheral spindled to epithelioid cells demonstrating positive epithelial
membrane antigen (EMA) immunostaining.
Discussion
CAPNON are non-neoplastic and uncommon, can occur throughout the neuraxis, and affect
both children and adults aged 2 to 90 years.[4 ] Intracranial CAPNON is associated with a relatively higher incidence of intra-axial
and supratentorial lesions.[5 ]
[6 ] The lesions seem to be slow growing, and the presenting symptoms tend to be related
to local compression or irritation of adjacent tissues. Seizures, followed by headaches,
are the most common symptoms of intracranial CAPNON.[2 ] When CAPNON are located in the skull base, cranial neuropathy may also be present
as a result of compression and involvement.[7 ]
[8 ]
[9 ]
[10 ]
[11 ]
[12 ]
[13 ]
[14 ]
[15 ] Yang et al[13 ] reviewed 24 CAPNON cases located at the skull base and identified a high incidence
(45.8%) of cranial neuropathy, likely due to the adherence of CAPNON to the cranial
nerves. Garen et al[7 ] reported a case of CAPNON in Meckel's cave presenting with a 6-year history of atypical
right facial pain that resolved following resection of the lesion.
Radiological findings are nonspecific and reflect heavy calcifications. CT shows solid
attenuated calcifications, and MRI often shows a well-demarcated lesion that is uniformly
hypointense on both T1- and T2-weighted images.[2 ]
[3 ] Contrast enhancement often shows minimal internal or rim enhancement but can be
more prominent in the setting of inflammatory changes and aggressive growth.[16 ] Surrounding brain edema has been reported in some cases[2 ]
[17 ]
[18 ]
[19 ] but is usually absent. Contiguous cystic lesions with calcified lesions have been
reported in some cases.[17 ]
[19 ]
[20 ]
[21 ] Intracranial CAPNON should be differentiated from calcified meningiomas, chordoma,
chordosarcoma, schwannoma, cavernous malformation, and other inflammatory lesions.[3 ]
[22 ]
[23 ] Meningiomas typically show isointensity on T1-weighted images and have mixed hypo-
and hyperintensity on T2-weighted images of MRI, and have homogeneous gadolinium enhancement.
Chordoma, chordosarcoma, and schwannoma typically show very high signal on T2-weighted
images. CAPNON typically have heavily calcified lesions that show uniform hypointensity
on T1- and T2-weighted images of MRI, and minimal linear rim or serpiginous internal
enhancement with or without minimal surrounding edema. Despite these characteristic
imaging features, radiological diagnoses of CAPNON are not always easy to make without
surgical specimen.
The “classic” histopathological features of CAPNON include a distinctive set of common
elements: (1) a chondromyxoid matrix with a nodular pattern; (2) palisading spindles
to epithelioid cells; (3) varying amounts of fibrous stroma; (4) calcification, osseous
metaplasia, and scattered psammoma bodies; and (5) foreign body reaction with giant
cells.[24 ] Although not all cases of CAPNON exhibit these histopathological features, the combination
of their presence can lead to a diagnosis of CAPNON. An immunohistochemical analysis
is useful for diagnosing CAPNON. Palisading cells are usually positive for EMA and
vimentin but are negative for glial fibrillary acid protein (GFAP), S-100 protein,
and smooth muscle actin.[25 ] EMA is the most effective way to distinguish CAPNON from calcified psammomatous
and metaplastic meningioma. Meningiomas are widely positive for the expression of
EMA, whereas the expression of EMA is limited in CAPNON. This is confirmed linearly
to the periphery of the chondromyxoid matrix.[26 ] It has been speculated that CAPNON expresses EMA only when the meninges are involved
and that EMA positivity is limited to meningeal cells entrapped in CAPNON lesions.[13 ]
Although the etiology of CAPNON remains unclear, it has been speculated that they
may form as part of a reactive process related to inflammation or injury, and some
studies support this theory.[4 ]
[16 ] Yang et al[25 ] revealed evidence for this theory, including the aggregation of a neurofilament
light chain protein (NF-L), a marker of axonal injury, in all lesion cores, and variable
infiltration of CD8+ T cells with a decreased CD4+ /CD8+ T-cell ratio in cellular areas. Thus, the cores of CAPNON might be formed by the
aggregation of tissue debris containing NF-L from damaged axons, which would then
calcify or ossify over time and attract a chronic reactive outer layer consisting
of various cells, such as spindled fibroblasts, with variable fibrosis and activated
macrophages, including multinucleated giant cells.[25 ]
The treatment of CAPNON depends on factors such as the location, size, and presentation
of the signs and symptoms. Asymptomatic lesions can be conservatively managed. In
cases of symptomatic or growing lesions, total resection is considered the standard
of care if technically feasible. Surgical resection has been attempted in most cases
for symptomatic lesions in the skull base, but the extent of resection may be limited
by the firm, calcified nature and its adherence to cranial nerves.[9 ]
[10 ]
[13 ]
[22 ] It has been suggested that cranial neuropathies may not completely resolve, even
after gross total resection.[13 ] Five cases of recurrent intracranial CAPNON have been reported.[4 ]
[8 ]
[18 ]
[21 ]
[27 ] Four patients experienced recurrence after subtotal resection, whereas one patient
experienced recurrence after gross total resection.[27 ] In all cases, recurrent CAPNON developed in the original location. The clinical
course of the present case may be unique. The cystic component extending to the cerebellopontine
cistern recurred 23 months after the initial surgery, which resected only the cystic
part. Subsequent total resection of the lesion including the calcified mass in Meckel's
cave and the cystic component extending to the cerebellopontine cistern through a
single surgical corridor could achieve good clinical course without recurrence. As
the cystic component might be a reactive substance of the core of CAPNON in Meckel's
cave, recurrence of the lesion might be unavoidable without resection of the core
of CAPNON. Resecting both the calcified mass and the cystic lesion should be mandatory.
Conclusion
The authors reported a case of CAPNON in Meckel's cave with a unique clinical course
in which the recurrence of a cystic lesion in the cerebellopontine cistern following
the first operation was resolved by the second operation, resecting both the calcified
mass and the cystic lesion.
