Calcifying pseudoneoplasm of the neuraxis (CAPNON) is a rare benign lesion that can mimic malignant neoplasms.
Case presentationA 19-year-old woman presented with long-standing seizures and severe headache. Magnetic resonance imaging revealed a giant intra-axial mass (8.3cm) in the right hemisphere with calcifications and mass effect, suggestive of a high-grade glioma. Complete surgical resection was performed. Histopathological examination showed a fibrillary stroma with abundant dystrophic calcifications, without atypia or mitotic figures. Immunohistochemistry demonstrated positivity for GFAP and S100 and negativity for EMA in the lesion, with a low proliferative index (Ki-67 <1%), confirming CAPNON.
ConclusionCAPNON is an important differential diagnosis of calcified lesions. Although its radiological appearance may be aggressive, it is a benign lesion, and complete surgical resection is usually curative.
La pseudoneoplasia calcificante del neuroeje (CAPNON) es una lesión benigna rara que puede simular neoplasias malignas.
Presentación del casoMujer de 19 años con crisis convulsivas de larga evolución y cefalea intensa. La resonancia magnética mostró una masa intraaxial gigante (8,3cm) en el hemisferio derecho, con calcificaciones y efecto de masa, sugiriendo un glioma de alto grado. Se realizó resección quirúrgica completa. El estudio histopatológico reveló un estroma fibrilar con abundantes calcificaciones distróficas, sin atipia ni mitosis. La inmunohistoquímica mostró positividad para GFAP y S100 y negatividad para EMA en la lesión, con un índice de proliferación celular bajo (Ki-67 <1%), confirmando CAPNON.
ConclusiónEl CAPNON constituye un importante diagnóstico diferencial de lesiones calcificadas. Aunque su apariencia radiológica pueda ser agresiva, se trata de una lesión benigna y la resección quirúrgica completa suele ser curativa.
Calcifying pseudoneoplasms of the neuraxis (CAPNONs) are rare, non-neoplastic lesions with benign behaviour that may occur anywhere within the central nervous system.1 They were initially described by Miller in 1922, who mistakenly interpreted them as fibro-osseous lesions.2 Despite advances in neuroimaging and neuropathology, the pathogenesis of this entity remains poorly understood; it has been proposed that it represents a reactive process secondary to various factors, including injuries, infections, metabolic disturbances, and neoplasms.3
CAPNONs may affect patients of any age and sex, and their clinical presentation is variable, depending primarily on lesion location, size, and mass effect.1,3 The most frequent clinical manifestations include headache, seizures, and focal neurological deficits, contributing to the ability of these lesions to mimic multiple neoplastic and infectious conditions of the central nervous system.2–4
From a radiological perspective, CAPNONs represent a considerable diagnostic challenge. On computed tomography, they usually appear as calcified intracranial masses, whereas on magnetic resonance imaging they are characterised by hypointensity on both T1- and T2-weighted sequences, with little or minimal contrast enhancement.4 Nevertheless, these findings are non-specific and frequently lead to incorrect preoperative diagnoses, particularly of glial neoplasms.7,8
The definitive diagnosis of CAPNON is established by histopathological examination, which reveals distinctive, although variable, morphological features together with a non-specific immunohistochemical profile.2,4,8,9 Owing to the rarity of this entity and its capacity to mimic neoplastic lesions, accurate recognition of its clinical, radiological, and histopathological characteristics is essential to avoid unnecessarily aggressive treatments. The relevance of the present case lies in the occurrence of a calcifying pseudoneoplasm of the neuraxis with an intra-axial location and unusually large size, which clinically and radiologically mimicked a high-grade glioma, thereby constituting a significant diagnostic challenge. This type of presentation is uncommon and highlights the importance of considering this entity in the differential diagnosis of calcified cerebral lesions.
Case reportA 19-year-old female patient, with no relevant past medical history, presented with a clinical course of approximately four years characterised by episodes of focal seizures originating in the right hemibody, associated with postural instability, emesis, fixed gaze without lateralisation, and rigidity, without loss of sphincter control. She received pharmacological treatment with lamotrigine 25mg every 12h, with an adequate initial response.
Over the last three months, the patient experienced worsening of her clinical condition, with the onset of severe throbbing headache in the left parietal region (10/10), exacerbated by Valsalva manoeuvres. Neurological examination revealed a Glasgow Coma Scale score of 15/15, without motor or sensory deficits, with right papilloedema and left homonymous hemianopia as the only pathological findings.
Magnetic resonance imaging with contrast administration demonstrated a large heterogeneous intra-axial lesion in the right cerebral hemisphere, measuring 8.3cm×7cm×3cm, with areas of haemorrhage and central dystrophic calcifications, mild vasogenic oedema, and minimal contrast enhancement. The lesion exerted mass effect on the ventricular system, corpus callosum, and brainstem, particularly the midbrain, without midline shift (Fig. 1). Based on these findings, a high-grade glioma was considered the principal diagnostic impression.
A craniotomy with complete resection of the lesion was performed, and the specimen was submitted for histopathological examination. Macroscopically, the specimen consisted of an irregular fragment of cerebral parenchyma measuring 6cm×5cm×4cm and weighing 163g, with diffuse haemorrhagic areas and a gritty consistency on sectioning (Fig. 2).
Histological examination with haematoxylin and eosin staining revealed a heterogeneous lesion composed of a fibrillary and fibrous stroma formed by monotonous elongated cells without cytological atypia, associated with abundant large amorphous dystrophic calcifications, both isolated and confluent, without evidence of mitotic activity, necrosis, or atypia. Likewise, no significant inflammatory process, spindle cell proliferation, or prominent vascularisation was identified (Fig. 3).
Immunohistochemical analysis demonstrated positivity for GFAP and S100, with negativity for EMA and progesterone receptor in the lesional component, which showed almost no cellular proliferative activity, as indicated by a Ki-67 index of less than 1% (Fig. 4). Markers such as CD3, CD20, and CD68 were not performed because of the scant accompanying inflammatory process and the absence of histiocytes or multinucleated giant cells. These findings were consistent with a calcifying pseudoneoplasm of the neuraxis (CAPNON).
Discussion
Calcifying pseudoneoplasms of the neuraxis (CAPNON) are rare, non-neoplastic, benign lesions that can present at any age, showing no clear sex or anatomical location predilection.1,3 Although most reported cases are located in supratentorial regions, lesions have also been described in the cerebellum, spinal cord, and cranial nerves.4–6 The pathogenesis of this entity remains uncertain; however, it has been proposed to represent a reactive process secondary to various stimuli, such as injuries, infection, or pre-existing neoplasms.3,8
The clinical presentation of CAPNON depends primarily on the size and mass effect of the lesion, rather than its histological nature. The most frequently reported symptoms include headache, seizures, and focal neurological deficits.2–4 In the case reported, the patient developed long-standing focal epilepsy and a visual field defect, findings that are consistent with what is described in the literature for large supratentorial lesions.2,7
From a radiological perspective, CAPNONs represent a major diagnostic challenge. On computed tomography (CT), they are usually observed as well-circumscribed calcified intracranial masses, whereas on magnetic resonance imaging (MRI), they are typically described as hypointense lesions on T1- and T2-weighted sequences, with scarce or minimal enhancement following contrast administration.4,8 However, these features are non-specific and can mimic various entities, including meningiomas, cavernomas, and calcified infectious conditions, which frequently leads to preoperative misdiagnoses.8,9 In the present case, a high-grade glial lesion was considered among the diagnostic options due to the clinical presentation, unusually large tumour size, mass effect, presence of perilesional oedema, and haemorrhagic areas, despite the scarce enhancement following contrast administration. This highlights a radiological–pathological discordance, reflecting the diagnostic difficulty of this condition.
The definitive diagnosis of CAPNON is established through histopathological examination. The morphological characteristics can vary, but the classic features include abundant amorphous dystrophic calcifications, occasional lamellar bone formation, a chondromyxoid matrix, fibrous stroma, and, in some cases, a foreign-body reaction with multinucleated giant cells.4,8,9 A wide variety of immunohistochemical stains have been used to characterise CAPNON. Most recent reports have focused on S100 protein, EMA, and GFAP, showing variable expression; a minority of cases are immunoreactive for S100, negative for EMA, and positive for GFAP.10
In our case, large amorphous dystrophic calcifications predominated. GFAP and S100 highlighted the surrounding glial parenchyma, whereas the lesional component was negative for EMA and progesterone receptor and showed a Ki-67 labelling index of less than 1%. Although some cases report a chronic inflammatory infiltrate with multinucleated giant cells, its absence does not exclude the diagnosis; therefore, the use of markers such as CD3, CD20, or CD68 was not considered, as no elements suggestive of an inflammatory or histiocytic condition were identified to justify their application, suggesting variability in the tissue response of this entity. Furthermore, these markers are not part of the routine panel for the differential diagnosis of this case, which was substantiated by the characteristic morphological findings and appropriate clinical–radiological correlation.10
The possibility of CAPNON presenting as a collision tumour in association with other neoplasms has been described, which poses an additional diagnostic challenge. In the present case, no evidence of a second neoplastic component was identified in the extensively sampled material.11
Within the differential diagnosis, various entities were considered. Solitary fibrous tumour can present as a well-circumscribed lesion with a fibrous component; however, it lacks the extensive characteristic calcifications observed in this case, and exhibits a haemangiopericytoma-like vascular pattern and a distinctive immunohistochemical profile. Meningioma, especially the psammomatous variant, can show small calcifications, though it typically presents in an extra-axial location. Oligodendroglioma can be associated with calcifications and a cortical location, but it displays a characteristic neoplastic cellularity that was not evidenced here. Likewise, low-grade gliomas may show scarce enhancement, but they differ in their histological architecture. Taken together with the observed morphology, these findings favoured the diagnosis of CAPNON.11,12
The management of CAPNON depends on location, size, and symptoms. Asymptomatic lesions can be managed conservatively, whereas in symptomatic cases complete surgical resection is the treatment of choice and is usually curative, with a low recurrence rate.2,5,13 In our patient, total resection of the lesion was associated with a favourable clinical outcome.
ConclusionAccurate diagnosis of CAPNON requires a careful and comprehensive histopathological examination, with appropriate clinical–radiological correlation, given that immunohistochemical findings are variable and non-specific.2,4,8,9 Timely recognition of this entity is essential to establish appropriate management.
In symptomatic cases, complete surgical resection is the treatment of choice and is usually curative, with an excellent prognosis and a low recurrence rate.2,5,11 The present case highlights the importance of considering CAPNON within the differential diagnosis of calcified intracranial lesions, particularly in young patients, in order to avoid unnecessarily aggressive therapeutic interventions and optimise clinical outcomes. The presented case stands out due to its unusually large size (8.3cm) and the discordance between the scarce enhancement and the suspicion of a high-grade lesion, thereby expanding the known radiological spectrum of CAPNON.
ORCID IDWilliam David Cardales Arizal: 0009-0003-8943-0137
Brandon Steve Gómez Gil: 0009-0007-6556-1860
Nancy Mejía Vargas: 0009-0009-3202-1694
Ethics committeeApproved and endorsed.
Informed consentUnderstood, accepted, and signed by the patient.
FundingThis study did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Conflict of interestThe authors declare that they have no affiliations with or involvement in any organisation or entity with any financial interest in the subject matter discussed in this manuscript.
The authors thank Dr. Edwin Carrascal for his contribution as consultant pathologist.
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The Spanish text of this article is available as supplementary material in Appendix 1.
