Calcifying Pseudoneoplasms of the Neuraxis- A Rare Case and Review of Its Literature
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.304118
Source of Support: None, Conflict of Interest: None
Calcifying pseudoneoplasm of the neuraxis (CAPNON) are rare, non-neoplastic, calcified lesions of the central nervous system (CNS) believed to be reactive in nature. Since their first description by Rhodes and Davis in 1978, less than 50 cases have been reported in the literature. Little is known about the etiology, natural history and course.
Here, we report a case of right thalamic CAPNON which we are managing expectantly. To our knowledge, none have previously been reported in the thalamic region. Additionally, this article provides a review of the current CAPNON literature. It is important to distinguish these benign lesions from the more common calcified vascular, neoplastic, or non-neoplastic differential diagnoses, as complete resection is curative.
A 10-year-old boy presented with a history of abnormal movements and weakness of left upper and lower limbs since 5 years of age. The movements were repetitive, but constantly varying involuntary movements of the limbs. The movements were sometimes violent. They were continuous and random and more when the child was active. With relaxation comes a decrease in movements. Sometimes he had twisting and writhing movements of the left upper and lower limbs. He had difficulty walking as he could not run and walk fast and also had difficulty in using the left hand. On examination, he had left-sided hemiparesis with mixed movement disorder with hemiballism, choreoathetosis and dystonia. He was evaluated with an MRI brain (done two years ago) which showed a 2.7 Õ 2.0 Õ 3.3 cm non-enhancing T1w hyperintense and T2w iso to hypointense lesion without diffusion restriction involving the right thalamus without any perilesional edema [Figure 1]. Features were suggestive of a CAPNON. He was advised biopsy at elsewhere hospital, but parents brought the child to our hospital. We evaluated the child with a repeat MRI brain, which showed no interval change in the size of the lesion. As the lesion was in the eloquent region of the brain and size of the lesion remained the same for the past two years, he was started on Tetrabenazine for the movement disorder, physiotherapy and advised regular follow up with a repeat MRI brain after a year.
Here, we present a brief review of the literature of this rare entity in the following headings.
There is no clear age predominance as patient age ranged from 6 to 68 years with a mean age of 44.2 years. However, a male predominance (1.92:1) was noted. Calcifying pseudoneoplasm are encountered both intracranially and spinally with a virtually equal prevalence. They are seen in all segments of the spine from the foramen magnum to the lumbar spine and generally located in the epidural space (84.21%). However, Smith et al. and Özdemir et al. each reported a case with an extramedullary intradural location. Chang et al. presented a patient with a CAPNON arising intraosseously from the body, dens, and laminae of the axis. In the case of intracranial CAPNON, there is a relatively higher incidence of intra-axial lesions when compared to extra-axial (63.4% vs 36.4%).
The etiology and natural history of CAPNON are unclear and thought to result from a reactive process. This is suggested by associated granulomatous inflammation typically surrounding the calcified mass.
Rodriguez et al. support this theory in their description of an unusual case of co-existing CAPNON and a low-grade cerebellar ependymoma associated with marked piloid gliosis on histology. The authors conclude that CAPNON is a result of a tumefactive reaction rather than metaplasia.
In a study by Aiken et al., it has been suggested but not proven that CAPNON may develop as a healing response to an array of inciting factors. This can account for the variations in histopathologic features. The causal factors are not yet understood, but the response to possible trauma, infection or inflammation has been proposed.
The clinical presentation of patients with CAPNON is heterogeneous and generally depends on the location and size of the lesion. Symptoms are related to local compression or irritation of the adjacent tissue. In spinal affections, the predominant cause of presentation was pain in 94.7% of the patients [local neck or back pain (57.9%), radiating pain (26.3%), and other pain (10.5%)]. In contrast, seizures (36.4%) were the most common symptom of intracranial CAPNON, followed by headache in 22.7% of the patients. In a few cases, it was an incidental finding.
Dense calcifications are consistently found as uniform radiological characteristic of CAPNON in plain radiographs, CT, and MRI studies [Figure 2]
Appear as high density lesions (100%).,,,,
Appears as hyperdense lesions (100%).,,,,,,,,
Usually appears heterogeneous.,,,,,,,
Spinal CAPNON usually appears hypointense on T1 and T2WI, sometimes isointense on both T1 and T2WI. Intracranial CAPNON usually appears hypointense on both T1 and T2WI. In the case reported by Montibeller et al., a discrepancy between T1-WI (isointense) and T2-WI (hypointense) was noted. Overall, after contrast administration, most lesions showed rim or inhomogeneous internal linear enhancement (66.7%). In a few cases, (17.6%) there was no enhancement at all,, and in one case a homogeneous enhancement was observed.
Histopathology [Figure 3]
Typically, CAPNONs are characterized by a peculiar acellular basophilic chondroid-myxoid matrix in a lobular to a focal nodular pattern. This matrix is often surrounded by palisading spindle to epitheloid cells reminiscent of a granuloma, and contains variable amounts of calcium deposits, osseous metaplasia, and scattered psammoma bodies. Furthermore, variable amounts of the fibrovascular stroma are also seen.,,, These characteristic findings are to different extents expressed and evident in individual lesions and may be partly absent in some cases. Mitoses are usually absent. In one report, Ki-67 immunostaining nuclei have been noted predominantly in stromal cells. Immunostaining of the surrounding palisading to epitheloid cells reveals reactivity to vimentin and epithelial membrane antigen (EMA), and spindle cells in the fibrous matrix have been found to have immunoreactivity to osteocalcin.,, Notably, Smith et al. exclusively found positive immunoreactions to glial fibrillary acidic protein (GFAP) and S-100 protein in their report of an “unusual fibro-osseous lesion”.
When considering the differential for calcifying intra-axial or extra-axial lesions, the uniform T1 and T2 hypointensity without solid enhancement is a key distinguishing feature.
Primary brain tumors may present with calcifications - oligodendrogliomas, choroid plexus papillomas, ependymomas and astrocytomas.
Vascular pathologies such as (giant) aneurysms, arteriovenous or cavernous malformations
Infectious lesions such as tuberculomas with calcifications.
Intracranial extra-axial lesions (at the skull base), meningiomas constitute the most important differential diagnosis, whereas chordomas, chondrosarcomas, and vestibular schwannomas have also been considered previously. Craniopharyngiomas and pituitary stones may also be calcified; however, their typical location and clinical appearance make them more easily distinguishable from CAPNON.
Among intraspinal lesions, herniated disc fragments, synovial cysts, neurinomas, and psammomatous meningiomas should be primarily considered. In addition, epidural abscesses and old calcified hematomas should also be taken into account. On the basis of the imaging features described in most of the CAPNONs (solid hyperdensity in CT scans and uniform hypointensity on T1-WI and T2-WI without surrounding edema and usually only linear or rim contrast enhancement in MRI studies), CAPNONs are often definable from further differential diagnoses. Nonetheless, the evidence of surrounding edema and solid enhancement does not rule out CAPNON., Solid contrast enhancement in calcified lesions is characteristic of meningioma, chordoma, chondrosarcoma, and vestibular schwannoma, whereas significant surrounding edema is characteristic for gliomas. For the histopathological workup, chordomas, chondroblastomas, chondrosarcomas, and infectious granulomatous diseases are the main histological differential diagnoses. The lobular pattern and the chondromatous appearance are shared elements in CAPNON and chordomas; however, the lack of ribbon-like cells (arranged in an abundant extracellular matrix) and absence of a vacuolated pattern of the cytoplasm make chordomas unlikely. Chondrosarcomas and chondroblastomas may be considered because of the cartilaginous aura and because of the calcifications and the epitheloid cells. They can be distinguished by lacking evidence of nodular or confluent granulomatous configuration. Moreover, the absence of cellular elements in proliferation emphasizes the benign nature of CAPNON. Lastly, the absence of lymphocytes and Langhans giant cells rules out tuberculoma and bacterial etiopathogenesis.
Once the diagnosis of a symptomatic and/or growing CAPNON is suspected on the basis of the clinical presentation and imaging studies, complete surgical resection should be attempted, if technically feasible. If complete resection is impossible (e.g., eloquent/difficult anatomical location), partial resection should be attempted to render histopathological diagnosis possible. There is widespread acceptance that while surgical resection may provide symptom relief, histological diagnosis, and prevention of recurrence, it does not come without risk.
An analysis by Stienen et al. revealed a significantly higher recurrence rate in cases with incomplete resection. However, in two cases of partial resection, recurrence and local progression of the pre-existing lesions occurred, complicating the postoperative course: Jun et al. and Smith et al. each reported one case where the lesions showed progression within a period of 4-8 years. Calcifying pseudoneoplasm thus bear the potential of slow but progressive growth. Still, until today, there are no recommendations concerning adjuvant therapy or the frequency and length of the radiological follow-up. On the basis of the reported slow progression of residual tumor cells, Stienen et al. proposed a follow-up program analogous to that of patients with a low-grade meningioma. Analysis of the literature did not reveal any deaths directly associated with CAPNON.
Calcifying pseudoneoplasm are rare benign lesions of the CNS of yet unknown origin. Due to the increasing number of reports, this clinical entity should be taken into consideration in the differential diagnosis of intracranial and intraspinal calcified lesions. They should be included in the differential diagnosis of a calcified mass with marked T1 and T2 hypointensity and no enhancement. The decision to proceed with surgical intervention must be influenced by the clinical presentation. The type of approach (e.g. biopsy versus total resection) should be discussed at a multidisciplinary level to mitigate the inherent risks of surgical intervention.
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There are no conflicts of interest.
[Figure 1], [Figure 2], [Figure 3]