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Mesenchymal non-meningothelial tumors of the central nervous system: a literature review and diagnostic update of novelties and emerging entities
Acta Neuropathologica Communications volume 11, Article number: 22 (2023)
The fifth edition of the World Health Organization Classification of Tumors of the Central Nervous System (CNS) now includes mesenchymal tumors that occur uniquely or frequently in the CNS. Moreover, this version has aligned the terminology of mesenchymal tumors with their soft tissue counterparts. New tumor types have been added, such as the “intracranial mesenchymal tumor, FET-CREB fusion-positive”, the “CIC-rearranged sarcoma”, and the “Primary intracranial sarcoma, DICER1-mutant”. Other entities (such as rhabdomyosarcoma) have remained in the current WHO classification because these tumor types may present specificities in the CNS as compared to their soft tissue counterparts. Based on an extensive literature review, herein, we will discuss these newly recognized entities in terms of clinical observation, radiology, histopathology, genetics and outcome, and consider strategies for an accurate diagnosis. In light of this literature analysis, we will also introduce some potentially novel tumor types.
Mesenchymal non-meningothelial tumors have always been included in the World Health Organization Classification of Tumors of the Central Nervous System (WHO CNS5). The WHO CNS5 is based on the cell of origin (fibroblastic, endothelial, muscular, cartilaginous, notochoral or undetermined) and the advances of genetic and epigenetic data. The WHO CNS5 considerably modified the section on mesenchymal, non-meningothelial tumors. Indeed, this new version covers only tumor types that have special histopathological or molecular features, and occur uniquely in the CNS, or because they are relatively common in the CNS as compared to other tissues. On the one hand, many tumor types, which are common in soft tissue and only exceptionally found in the CNS (such as lipoma, angiolipoma, hibernoma, liposarcoma, osteoma, osteosarcoma, osteochondroma, epithelioid haemangioendothelioma, angiosarcoma, leiomyoma, leiomyosarcoma, fibrosarcoma, desmoid-type fibromatosis, myofibroblastoma, and inflammatory myofibroblastic tumor), and have been present since 2000, have been removed from the current classification. On the other hand, new histomolecular entities have been added, like the intracranial mesenchymal tumor, FET::CREB fusion–positive, CIC-rearranged sarcoma, and primary intracranial sarcoma, DICER1-mutant. Despite this increase in histomolecular deciphering, and because of this modified nosological organization within the classification, the proportion of mesenchymal, non-meningothelial tumors in the spectrum of all CNS tumors has artificially decreased (Fig. 1). Reflecting this tendency, a specific paragraph dedicated to mesenchymal tumors was written in the review presenting the novel entities of the WHO CNS5 . Based on an extensive literature review, the aims of this discussion are to present the clinical, radiological, histopathological and molecular findings of the newly introduced mesenchymal tumor types found in the classification and novelties of previously recognized entities (Fig. 2). The last part of this review concerns potentially novel subgroups described in the recent literature.
Newly introduced mesenchymal tumors in the last WHO classification
Intracranial mesenchymal tumor (IMT), FET::CREB fusion-positive
Clinical and radiological characteristics
IMT, FET::CREB fusion-positive tumors develop predominantly in supratentorial sites (78% of reported cases) [2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29] but can also be located in infratentorial sites (17% of reported cases) [2, 23, 25, 30,31,32,33] and in the spine (5% of reported cases) [11, 23, 34]. They are extra-axial, attached to the meninges or dura [23, 25], or are intraventricular [2, 6, 15, 23, 25, 26, 28]. Presenting symptoms depend on the tumor’s location. Most cases occur in children or young adults with a median age of 19 at diagnosis (ranging from 4 to 79 years) [2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36]. They predominantly affect females (representing 62% of reported cases) [2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36]. In 21% of reported cases, a previous history of cancer (lymphoma or carcinoma) has been reported [2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36]. Radiologically, tumors are hypointense on T1-weighted sequences and are variably intense on T2-weighted images . Lesions present an enhanced tissular portion, and lobulated contours with frequent cystic components . Contrary to meningiomas, a dural tail is rarely observed . The clinical behavior of these tumors seems to be heterogeneous: a subset of cases have aggressive outcomes with local recurrences [6, 13, 21,22,23, 25, 28, 29, 33], metastases [11, 18, 23, 36] and 8% of reported patients have died from the disease [18, 23, 36] (Fig. 3).
Histopathology and cellular origin
These tumors are multinodular and well-circumscribed from the brain parenchyma, frequently surrounded by a fibrous pseudocapsule. Dense lymphoplasmacytic cuffing at the tumor periphery or intratumoral lymphoplasmacytic infiltrates are typically observed. The stroma may be collagenous (with amianthoid fibers), myxoid or mucin-poor (Fig. 4A, B) [22, 23, 25]. The cellular density is variable and different patterns have been reported (from syncytial or sheet-like growth to reticular cord-like structures) [22, 23, 25]. Tumor cell morphology varies from epithelioid/rhabdoid cells to stellate/spindle cells or monotonous round cells (Fig. 4A, B) [22, 23, 25]. Mitotic activity is generally low but cases with high proliferative indexes have been described at diagnosis or during recurrence [23, 25, 36]. Morphological features reminiscent to meningiomas (such as intranuclear cytoplasmic inclusions and whorls) have been noted [22, 23, 25]. Calcifications (but no psammoma bodies), osseous metaplasia and a pseudochondroid matrix may be exceptionally observed . Using immunohistochemistry, CD99, CD68, desmin and EMA are frequently expressed in various ways (focal to diffuse) (Fig. 4C) [22, 23, 25]. SSTR2a is not stained or only focally on tumor cells [23, 25]. Ultrastructural analyses revealed, in one study, the presence of junction-type desmosomes, zonula occludens, zonula adherens, suggesting an arachnoidal origin for tumor cells . These results and DNA-methylation profiling analyses have demonstrated that IMT, FET::CREB fusion-positive are distinct from angiomatoid fibrous histiocytomas of soft tissue [23, 25]. Therefore, the proposed terminology of the WHO classification is provisional and has to be improved.
The molecular hallmark of IMT is represented by a fusion of a FET gene with genes from the CREB (cAMP response element) family genes. In the FET family genes, fusions reported in IMT encompass mostly EWSR1 (97% of reported cases) [2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24, 26,27,28,29,30,31,32,33,34,35] while FUS was only reported in one case  and no fusion implicating TAF15 gene has been reported to date. These data make the fluorescence in situ hybridization for EWSR1 a potentially useful diagnostic tool when histology is in line with a diagnosis of IMT (Fig. 4D). From the CREB family genes, CREB1, CREM and ATF1 are equally distributed (representing 31, 36 and 33% of partner genes respectively) in fusions encountered in IMT [2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36], contrary to other extra-CNS tumors with FET::CREB fusion (like angiomatoid fibrous histiocytomas of the soft tissue having more than 80% of reported cases described with an EWSR1::CREB1 fusion). Whereas no methylation class exists in the DKFZ classifier of CNS tumors (v12.5), two recent studies have shown that IMT, FET::CREB fusion-positive are characterized by a distinct epigenetic profile from other tumors of the CNS, but do not represent an homogeneous methylation class [23, 25]. One of them suggests that they are subdivided into two methylation groups (A and B) . Further studies are needed to clearly delineate the epigenetic boundaries of IMT and their clinical or prognosis implications.
The WHO CNS5 established the following essential diagnostic criteria for IMT, FET::CREB fusion-positive: 1/ primary intracranial location; 2/ variable morphological features including spindle cells, mucin-rich stroma, haemangioma-like vasculature, or epithelioid cells in a mucin-poor collagenous stroma; 3/ demonstration of a FET::CREB family fusion.
Most CIC-rearranged sarcomas of the CNS occur in supratentorial sites (85% of reported cases) [37,38,39,40,41,42,43,44,45,46] whereas spinal presentation accounts for 15% of reported cases [42, 46,47,48]. Presenting symptoms depend on the tumor’s location [37, 39, 44, 46]. There is a wide age range at presentation, from children to elderly adults (ranging from 0 to 71) [37,38,39,40,41,42,43,44,45,46,47,48]. However, there is a striking predilection for children and young adults (median age: 10 years), and 68% of cases are found in the pediatric age group [37,38,39,40,41,42,43,44,45,46,47,48]. There is no gender predisposition (sex ratio male/female of 1.2) [37,38,39,40,41,42,43,44,45,46,47,48]. Radiological data are scarce in the literature and limited to case reports [37,38,39, 43, 44, 47,48,49]. Tumors seem to manifest as a parenchymal hematoma (50% of reported cases) [37, 39, 44, 49] or as a solid and cystic mass (38% of reported cases) [38, 43, 47]. Like their soft tissue counterparts, most tumors follow an aggressive course with frequent recurrences (61% of reported cases), most commonly local [37,38,39,40,41, 43,44,45,46,47,48], resulting in death (38% of reported cases) [37,38,39,40,41,42,43,44,45, 47,48,49].
Histopathology and cellular origin
These tumors are well-circumscribed from the brain parenchyma. They are mainly composed of diffuse sheets or lobules of undifferentiated round cells, epithelioid or even rhabdoid cells [37, 39, 41, 42, 44, 46,47,48,49]. Divergent differentiations (chondroid, glioneuronal with neuropil) have been described, which explain why some tumors were initially diagnosed as pleomorphic xanthoastrocytomas or gangliogliomas [38, 40, 44]. Similar glial/glioneuronal differentiation has not been reported to date in soft tissue counterparts with CIC-fusions [1,2,3,4,5,6,7,8,9,10]. A collagenous stroma or focal myxoid changes may be present in the tumor (Fig. 4E–H) [39, 43, 44, 46,47,48,49]. Necrosis is common and mitotic activity is brisk [37, 42, 44, 46, 47, 49]. When evaluated by immunohistochemistry, CIC-rearranged sarcomas may express, only focally or in a subset of tumor cells, markers of various differentiations (such as GFAP, CD56, synaptophysin, neurofilament, CKAE1/AE3, PS100, desmin, smooth muscle actin) [37, 38, 40, 44, 46,47,48]. A CD99 immunoexpression, which is frequently observed in their soft tissue counterparts, is focal or absent in CNS cases [37, 39, 46,47,48]. As in soft tissue [50, 51], WT1 and ETV4 are frequently positive and represent useful ancillary markers (Fig. 4H) [37, 39, 47, 49] and one recent study has shown its high sensitivity and specificity in the CNS compared to its other potential differential diagnoses . Sarcomas with CIC::NUTM1 fusions express NUT protein [42, 45]. The main differential diagnosis in the CNS is represented by the atypical teratoid and rhabdoid tumor which is easily ruled out by using immunohistochemistry staining for INI1 and BRG1. Although the cell of origin of CIC-rearranged sarcomas is still unknown, the fact that soft tissue and CNS tumors share the same DNA-methylation profiling is suggestive of a common mesenchymal origin .
Whereas CIC::DUX4 fusion is encountered in 95% of CIC-rearranged sarcomas of the soft tissue, the molecular spectrum of CNS cases seems to be larger with different fusion partners: CIC::LEUTX (29%) [38, 40, 48], CIC::NUTM1 (29%)[42, 45], CIC::DUX4 (18%) [37, 46, 47], ATXN1::DUX4 (12%) [43, 49], ATXN1::NUTM1 (6%) , and a frameshift deletion of the CIC gene (6%) . Whereas CIC::LEUTX and CIC::NUTM1 have also been reported in a subset of CIC-rearranged sarcomas [42, 53], fusions implicating the ATXN1 gene seem to be only encountered in CNS tumors. Whatever the type of fusion, a recent study has evidenced that CIC-rearranged sarcomas and ATXN1-rearranged sarcomas of the CNS share the same DNA-methylation signature and are not distinct from their soft tissue counterparts . However, further series comparing CNS (particularly those showing glial/glioneuronal differentiation) and soft tissue tumors are needed to confirm these data.
The WHO CNS5 listed the following essential diagnostic criteria: 1/ evidence of a CIC gene fusion; 2/ predominant round cell phenotype; 3/ mild nuclear pleomorphism; 4/ variable admixture of epithelioid and/or spindle cells; 4/variably myxoid stroma; 5/ variable CD99 and frequent ETV4 and WT1 expression. The DNA-methylation profile for CIC-rearranged sarcoma is a desirable diagnostic criterion.
Primary intracranial sarcoma, DICER1-mutant
As its name suggests, the primary intracranial sarcoma, DICER1-mutant is almost exclusively encountered in supratentorial sites (92% of reported cases) [54,55,56,57,58,59,60,61,62,63]. However, exceptional infratentorial and spinal cases have been reported [54, 56, 58, 64]. Presenting symptoms depend on the tumor’s location. There is a wide age range at presentation, from children to elderly adults (ranging from 0 to 76) [54,55,56,57,58,59,60,61,62,63,64]. However, there is a striking predilection for children and young adults (median age: 6 years), and 87% of cases occur in the pediatric age group [54,55,56,57,58,59,60,61,62,63,64]. The gender distribution is almost equal (sex ratio female/male of 1.3) [54,55,56,57,58,59,60,61,62,63,64]. Radiological data are scarce in the literature and limited to case reports [57, 59,60,61,62,63]. The primary intracranial sarcoma, DICER1-mutant seems to present as a solid and cystic mass, with hemorrhage and leptomeningeal attachment, hypointensity on T1-weighted sequences, hyperintensity on T2-weighted images and a heterogeneous enhancement after gadolinium injection. Further series, including a radiological description of proven primary intracranial sarcoma, DICER1-mutant is needed to confirm these features. While the prognosis for patients with DICER1-mutant primary intracranial sarcoma remains to be determined, the literature data (36 cases) showed that 33% of patients presented local recurrences and that 86% of them are alive at the end of follow-up [54,55,56,57, 59,60,61,62,63,64]. A recent study has evidenced that a combination of surgery, chemotherapy, and radiotherapy seems to be beneficial in the treatment of this sarcoma subtype .
DICER1-mutant primary intracranial sarcomas are mainly well-circumscribed tumors from the brain parenchyma and may present a leptomeningeal component. Histopathologically, they are pleomorphic or composed of spindle cells arranged in fascicules or a patternless growth [54, 55, 57,58,59,60,61,62,63, 65, 66]. A rhabdoid morphology or a myogenic differentiation (evidenced using desmin and/or myogenin markers) is frequently observed (Fig. 4I–L) [54, 55, 57,58,59,60, 62, 63, 65, 66]. The stroma may be myxoid and/or chondroid [54, 55, 57, 58, 62, 63, 65, 66]. Cytoplasmic eosinophilic globules PAS-positive are often present [54, 57, 59, 62, 63]. Using immunohistochemistry, they frequently express myogenic markers (desmin, smooth muscle actin, and occasionally myogenin), with variable intensity (focal or patchy) [54, 55, 57,58,59,60,61,62,63,64]. Because of the expression of S100 proteins, synaptophysin and neurofilament and the wide variety of differentiation (including lipomatous and pseudo-meissnerian components), a potential neural crest lineage has been suggested [63, 64]. A subset of reported cases has evidenced a p53 overexpression and a loss of ATRX expression [59, 61, 64]. GFAP, Olig2, and cytokeratins are not expressed [54, 55, 59,60,61,62,63]. DICER1-mutant primary intracranial sarcomas may present a complete or mosaic loss of H3K27me3 . TLE1 immunopositivity has been suggested as a potential diagnostic surrogate , but the sensitivity and specificity of this biomarker needs to be studied in CNS tumors. Neoplasms from other organs showing a myogenic differentiation and harboring DICER1 alterations have been reported in the literature (pleuropulmonary blastoma-like peritoneal sarcomas, DICER1 renal sarcomas and rhabdomyosarcomas of the urogenital tract with DICER1 mutations) [67,68,69], but their relationship (including epigenetic data) has to be elucidated before suggesting a potential unified terminology [70, 71].
A DICER1 alteration is encountered in 98% of reported case [54,55,56,57,58,59,60,61,62,63,64] (only two cases proven by DNA-methylation profiling failed to reveal any mutation [56, 58]). DICER1-mutant primary intracranial sarcomas are characterized by a biallelic alteration of the DICER1 gene combining a hotspot missense mutation on one allele and a truncating mutation (frameshift, nonsense, or splice-site) on the other . Some tumors (5% of reported cases) harbor a single mutation accompanied by loss of heterozygosity eliminating the remaining wildtype allele [59, 63, 66]. A part of reported patients (26% of reported cases with available constitutional data) have a germline alteration of DICER1, as part of DICER1 syndrome, and rare cases have been reported with a familial history of cancers (gynecological cancers) [55, 57, 58, 60, 64, 65, 72]. Primary intracranial sarcomas, DICER1-mutant present a high level of tumor mutational burden. Indeed, associated with DICER1 alterations, recurrent mutations in the MAP-kinase pathway (mainly KRAS, NF1 and NRAS genes) and TP53 gene have been reported in 64% [54, 56,57,58,59, 63, 64, 72] and 60% of reported cases [54, 56,57,58,59, 62, 63, 72]. DICER1-mutant primary intracranial sarcoma harbors a distinct DNA methylation profile in the v12.5 version of the CNS tumor classification . However, an epigenetic overlap with extracranial sarcomas harboring DICER1 mutation remains undetermined.
The current WHO classification has listed the following essential diagnostic criteria: 1/ primary intracranial sarcoma; 2/ pathogenic DICER1 mutation (either germline or somatic). For unresolved lesions, the DNA-methylation profile for primary intracranial sarcoma, DICER1-mutant is mandatory.
New insights for well-known tumors
Very few CNS cases in the literature have detailed histopathological and molecular characterizations. As reported in soft tissue, primary CNS alveolar rhabdomyosarcomas present fusions implicating PAX3 and FOXO1 genes (Fig. 4M–P) [73,74,75,76]. It has been evidenced that these fusions induce Olig2 expression by tumor cells, making this diagnosis challenging in the CNS (Fig. 4O) [75, 76]. Primary CNS alveolar rhabdomyosarcomas with proven FOXO1 or PAX3 fusions typically concern children and young adults with a pineal (3 cases) or a posterior fossa mass (1 case) [73,74,75,76]. In the pineal location, differential diagnoses of pediatric tumors with myogenic differentiation include atypical rhabdoid and teratoid tumors, medulloblastoma with divergent differentiations (particularly medullomyoblastoma), teratomas with a rhabdomyosarcomatous component, pineal anlage tumors and pineoblastomas with rhabdomyoblastic differentiation. These diagnoses may be obtained using clinical data, histopathology and immunohistochemistry. Data concerning the outcomes of cases proven molecularly are scarce and further reports are needed. The WHO CNS5 has listed the following essential diagnostic criteria: 1/ a malignant primitive tumour with at least focal immunohistochemical demonstration of skeletal muscle lineage; 2/ absence of non-rhabdomyosarcomatous components. The confirmation of a FOXO1 gene fusion in diagnostically difficult cases is needed.
Chordomas have reappeared as a specific taxonomic category in the current WHO classification . This nosology clearly distinguishes four clinicopathological forms of chordomas: conventional, chondroid, dedifferentiated (which have historically represented the pejorative evolution of a classical chordoma following radiation therapy) and the poorly differentiated chordoma, SMARCB1-deficient. This last subtype mainly concerns children (86% of reported cases) with a median age of 7 (varying from 1 to 42 years-old) [77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93]. There is a slight female predominance (female to male ratio: 1.5) [77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93]. They are mainly located in the skull base (64% of reported cases) but may be encountered in the sacroccygeal region (27% of reported cases) or more rarely in the mobile vertebral column (9% of reported cases) [77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93]. Histopathologically, they are composed of cohesive sheets of epithelioid or spindle cells without chondromyxoid stroma and without physaliphorous cells (Fig. 4Q–R) [77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93]. A subset of cases having a classical morphology and INI1 loss have been reported and it remains uncertain if they represent the same clinicopathological type as the poorly differentiated form [77, 78, 93]. A diagnosis is made using the combination of a brachyury expression and the loss of INI1 protein immunoreactivity (Fig. 4S–T). It has been evidenced that poorly differentiated chordomas, SMARCB1-deficient are associated with a poor outcome with high rates of metastases (30% of reported cases) and death (43% of reported cases) [77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93]. To date, no distinct methylation class exists in the current version of the DKFZ classifier (v12.5). However, recent work that studied a cohort of CNS tumors with SMARCB1 deficiency showed that poorly differentiated chordomas, SMARCB1-deficient constitute a different cluster . The WHO CNS5 listed the following essential diagnostic criteria: 1/ a midline axial bone tumor; 2/ Lobules of cohesive and physaliphorous cells in a myxoid or chondroid matrix; 3/ Brachyury immunopositivity. In the case of epithelioid/solid forms, a loss of SMARCB1 (INI1) expression to confirm the diagnosis of poorly differentiated chordoma is mandatory.
Angioleiomyomas are well-known in the soft tissue and are classified within pericytic (perivascular) tumors in the WHO CNS5 (Fig. 5A–D) . In the literature, dural presentations of a cavernous subtype of angioleiomyomas have been reported and a recent study performed a comprehensive clinicoradiologic and molecular characterization of a series . Dural angioleiomyomas present clinical (affecting adults between the fourth and the sixth decades), and radiological similarities to soft tissue angioleiomyomas (such as hyperintensity on T2-weighted images and a strong enhancement after contrast injection) . A subset presented the same p.Gly41Cys GJA4 mutation, recently reported in other vascular lesions from different organs (liver, skin, orbit, soft tissue) [96,97,98]. Moreover, DNA methylation profiles indicate that dural angioleiomyomas grouped together and formed a distinct epigenetic group, separating them from the clusters of soft tissue angioleiomyomas, other vascular tumors, inflammatory myofibroblastic tumors and meningiomas. The extensive literature review identified several cases similar to these lesions, with a wide variety of denominations (mainly named as cavernous hemangiomas and veinous hemangiomas). Because of its dural location and distinct methylome profile, a potential terminology to designate this benign tumor could be “dural angioleiomyoma”. Further studies are needed to confirm its inclusion in a future version of the WHO classification of CNS tumors.
Spindle cell neoplasms, NTRK-rearranged
NTRK gene fusions have been described in a wide variety of CNS and soft tissue tumors, including the provisional tumor type “spindle cell neoplasm, NTRK-rearranged” (SCN-NTRK), added to the 2020 WHO Classification of Soft Tissue Tumors. Because of histopathological and molecular overlaps with other soft tissue entities, controversy remains concerning the lineage and terminology of SCN-NTRK. Rare CNS primary presentations of SCN-NTRK have been reported in the literature [99,100,101]. A recent series including soft tissue and CNS cases revealed similar histopathological, immunophenotypical, and molecular (spindle cell tumors with coexpression of CD34 and S100 and a CDKN2A homozygous deletion) features and formed a unique and new methylation cluster (Fig. 5E–H) . These tumors are predominately found in children and young adults [99,100,101]. While a recent study evidenced that SCN-NTRK share similar features in all locations, SCN-NTRK are probably underdiagnosed, and further cases of CNS SCN-NTRK are needed to confirm or not their place in the next WHO Classification of CNS tumors.
Several mesenchymal non-meningothelial tumors have now been defined by specific molecular alterations, with some being exclusive to the CNS. In this respect, the WHO CNS5 represents an extension of the changes first introduced by the former edition. The increased precision in decipherment was achieved by novel genetic and DNA-methylation diagnostic technologies. The utility of this last methodology is particularly interesting for mesenchymal tumors because of the existence of two different classifiers (one for brain tumors and one for soft tissue tumors). This increased complexity reflects our current understanding of biological features of CNS tumors. However, great effort is now necessary to 1/ compare them to their extra-CNS counterparts; 2/ to more precisely characterize the clinical and radiological aspects and outcomes of these new tumor types, and eventually 3/ to determine a grading (no grade is currently associated with these novel tumor types) to adapt therapeutic approaches in the future.
Louis DN, Perry A, Wesseling P, Brat DJ, Cree IA, Figarella-Branger D et al (2021) The 2021 WHO classification of tumors of the Central Nervous System: a summary. Neuro-Oncol 23:1231–1251
Bale TA, Oviedo A, Kozakewich H, Giannini C, Davineni PK, Ligon K et al (2018) Intracranial myxoid mesenchymal tumors with EWSR1-CREB family gene fusions: myxoid variant of angiomatoid fibrous histiocytoma or novel entity? Brain Pathol Zurich Switz 28:183–191
Ballester LY, Meis JM, Lazar AJ, Prabhu SS, Hoang KB, Leeds NE et al (2020) Intracranial myxoid mesenchymal tumor with EWSR1-ATF1 Fusion. J Neuropathol Exp Neurol 79:347–351
Bin Abdulqader S, Altuhaini K, Tallab R, AlTurkistani A, Alhussinan M, Alghamdi S et al (2020) Primary intracranial angiomatoid fibrous histiocytoma: two case reports and literature review. World Neurosurg 143:398–404
Choy B, Pytel P (2016) Primary intracranial myoepithelial neoplasm: a potential Mimic of Meningioma. Int J Surg Pathol 24:243–247
De Los Santos Y, Shin D, Malnik S, Rivera-Zengotita M, Tran D, Ghiaseddin A et al (2021) Intracranial myxoid mesenchymal neoplasms with EWSR1 gene rearrangement: report of 2 midline cases with one demonstrating durable response to MET inhibitor monotherapy. Neuro-Oncol Adv 3:vdab016
Dunham C, Hussong J, Seiff M, Pfeifer J, Perry A (2008) Primary intracerebral angiomatoid fibrous histiocytoma: report of a case with a t(12;22)(q13;q12) causing type 1 fusion of the EWS and ATF-1 genes. Am J Surg Pathol 32:478–484
Ghanbari N, Lam A, Wycoco V, Lee G (2019) Intracranial myxoid variant of angiomatoid fibrous histiocytoma: a case report and literature review. Cureus 11:e4261
Hansen JM, Larsen VA, Scheie D, Perry A, Skjøth-Rasmussen J (2015) Primary intracranial angiomatoid fibrous histiocytoma presenting with anaemia and migraine-like headaches and aura as early clinical features. Cephalalgia Int J Headache 35:1334–1336
Kao Y-C, Sung Y-S, Zhang L, Chen C-L, Vaiyapuri S, Rosenblum MK et al (2017) EWSR1 fusions with CREB family transcription factors define a novel myxoid mesenchymal tumor with predilection for intracranial location. Am J Surg Pathol 41:482–490
Kim NR, Kim S-I, Park JW, Park C-K, Chung CK, Choi S-H et al (2022) Brain parenchymal angiomatoid fibrous histiocytoma and spinal myxoid mesenchymal tumor with FET: CREB fusion, a spectrum of the same tumor type. Neuropathol Off J Jpn Soc Neuropathol 5:796
Komatsu M, Yoshida A, Tanaka K, Matsuo K, Sasayama T, Kojita Y et al (2020) Intracranial myxoid mesenchymal tumor with EWSR1-CREB1 gene fusion: a case report and literature review. Brain Tumor Pathol 37:76–80
Konstantinidis A, Cheesman E, O’Sullivan J, Pavaine J, Avula S, Pizer B et al (2019) Intracranial angiomatoid fibrous histiocytoma with EWSR1-CREB family fusions: a report of 2 Pediatric cases. World Neurosurg 126:113–119
Lemnos L, Salle H, Caire F, Duchesne M (2022) Angiomatoid fibrous histiocytoma: an atypical brain location newly described as intracranial mesenchymal tumor FET-CREB fusion-positive. Acta Neurol Belg 8:745
Levy AS, Sakellakis A, Luther E, Morell AA, Rosenberg A, Saad AG et al (2022) Concurrent intraventricular intracranial myxoid mesenchymal tumor and ependymoma in a long-term ewing sarcoma survivor. Neuropathol Off J Jpn Soc Neuropathol 5:960
Libbrecht S, Van Der Meulen J, Mondelaers V, Baert E, Vande Walle C, Van Dorpe J et al (2020) Intracranial myxoid mesenchymal tumor with EWSR1-CREB1 fusion. Pathol Res Pract 216:153239
Liu C, Liu Y, Zhao Y, Wei J, Ma Y, Liu Y et al (2020) Primary intracranial mesenchymal tumor with EWSR1-CREM gene fusion: a case report and literature review. World Neurosurg 142:318–324
Ochalski PG, Edinger JT, Horowitz MB, Stetler WR, Murdoch GH, Kassam AB et al (2010) Intracranial angiomatoid fibrous histiocytoma presenting as recurrent multifocal intraparenchymal hemorrhage. J Neurosurg 112:978–982
Poyuran R, Shah SP, Kesavapisharady K, Chandrasekharan K, Narasimhaiah D (2022) Intracranial mesenchymal tumour with EWSR1 gene rearrangement: the first report of intracranial mesenchymal tumour with FET-CREB fusion from India. Pathology (Phila). 31:3025
Sasaki M, Hirono S, Gao Y, Suda I, Matsutani T, Ota M et al (2022) Clinicopathological and genomic features of Pediatric Intracranial Myxoid Mesenchymal Tumor with both of EWSR1-CREM Gene Fusion and MAP3K13 Mutation: a case report and comparison with adult cases in the literature. NMC Case Rep J 9:101–109
Sciot R, Jacobs S, Calenbergh FV, Demaerel P, Wozniak A, Debiec-Rychter M (2018) Primary myxoid mesenchymal tumour with intracranial location: report of a case with a EWSR1-ATF1 fusion. Histopathology 72:880–883
Sloan EA, Chiang J, Villanueva-Meyer JE, Alexandrescu S, Eschbacher JM, Wang W et al (2020) Intracranial mesenchymal tumor with FET-CREB fusion-a unifying diagnosis for the spectrum of intracranial myxoid mesenchymal tumors and angiomatoid fibrous histiocytoma-like neoplasms. Brain Pathol Zurich Switz 8
Sloan EA, Gupta R, Koelsche C, Chiang J, Villanueva-Meyer JE, Alexandrescu S et al (2021) Intracranial mesenchymal tumors with FET-CREB fusion are composed of at least two epigenetic subgroups distinct from meningioma and extracranial sarcomas. Brain Pathol Zurich Switz 7
Tan NJH, Pratiseyo PD, Wahjoepramono EJ, Kuick CH, Goh JY, Chang KTE et al (2021) Intracranial myxoid angiomatoid fibrous histiocytoma with “classic” histology and EWSR1:CREM fusion providing insight for reconciliation with intracranial myxoid mesenchymal tumors. Neuropathol Off J Jpn Soc Neuropathol 41:306–314
Tauziède-Espariat A, Sievers P, Larousserie F, Benzakoun J, Guillemot D, Pierron G et al (2022) An integrative histopathological and epigenetic characterization of primary intracranial mesenchymal tumors, FET:CREB-fused broadening the spectrum of tumor entities in comparison with their soft tissue counterparts. Brain Pathol Zurich Switz 32:e13010
Valente Aguiar P, Pinheiro J, Lima J, Vaz R, Linhares P (2021) Myxoid mesenchymal intraventricular brain tumour with EWSR1-CREB1 gene fusion in an adult woman. Virchows Arch Int J Pathol 478:1019–1024
Vizcaino MA, Giannini C, Chang HT, Kipp BR, Fritchie K, Vaubel R (2021) Intracranial angiomatoid fibrous histiocytoma with rhabdoid features: a mimic of rhabdoid meningioma. Brain Tumor Pathol 38:138–144
Ward B, Wang CP, Macaulay RJB, Liu JKC (2020) Adult intracranial myxoid mesenchymal tumor with EWSR1-ATF1 Gene Fusion. World Neurosurg 143:91–96
White MD, McDowell MM, Pearce TM, Bukowinski AJ, Greene S (2019) Intracranial myxoid mesenchymal tumor with rare EWSR1-CREM translocation. Pediatr Neurosurg 54:347–353
Alshareef MA, Almadidy Z, Baker T, Perry A, Welsh CT, Vandergrift WA (2016) Intracranial angiomatoid fibrous histiocytoma: case report and literature review. World Neurosurg 96:403–409
Hojo K, Furuta T, Komaki S, Yoshikane Y, Kikuchi J, Nakamura H et al (2022) Systemic inflammation caused by an intracranial mesenchymal tumor with a EWSR1::CREM fusion presenting associated with IL-6/STAT3 signaling. Neuropathol Off J Jpn Soc Neuropathol 2:187
Kambe A, Kuwamoto S, Shimizu T, Amisaki H, Sakamoto M, Inagaki H et al (2021) A case of intracranial myxoid mesenchymal tumor with EWSR1:CREM fusion in an adult female: extensive immunohistochemical evaluation. Neuropathol Off J Jpn Soc Neuropathol 41:315–323
Velz J, Agaimy A, Frontzek K, Neidert MC, Bozinov O, Wagner U et al (2018) Molecular and clinicopathologic heterogeneity of intracranial tumors mimicking Extraskeletal Myxoid Chondrosarcoma. J Neuropathol Exp Neurol 77:727–735
Tauziède-Espariat A, Pierron G, Guillemot D, Benevello C, Pallud J, Benzakoun J et al (2022) An extracranial CNS presentation of the emerging “intracranial” mesenchymal tumor, FET: CREB-fusion positive. Brain Tumor Pathol 5:174
Shaikh ST, Hajra D, Singh S, Nagaraju S, El-Maghraby H (2022) Intracranial myxoid mesenchymal tumour with EWSR1-ATF1 fusion sans myxoid stroma-report of a newer entity with brief review of literature. Neurol India 70:1639–1642
Tauziède-Espariat A, Pierron G, Guillemot D, Sievers P, Cazals-Hatem D, Faillot T et al (2021) A novel SMARCA2-CREM fusion: expanding the molecular spectrum of intracranial mesenchymal tumors beyond the FET genes. Acta Neuropathol Commun 9:174
Bielle F, Zanello M, Guillemot D, Gil-Delgado M, Bertrand A, Boch A-L et al (2014) Unusual primary cerebral localization of a CIC-DUX4 translocation tumor of the ewing sarcoma family. Acta Neuropathol (Berl) 128:309–311
Hu W, Wang J, Yuan L, Zhang X, Ji Y, Song C et al (2020) Case report: a unique case of pediatric central nervous system embryonal tumor harboring the CIC-LEUTX fusion, germline NBN variant and somatic TSC2 mutation: expanding the spectrum of CIC-rearranged neoplasia. Front Oncol 10:598970
Ito M, Ishikawa M, Kitajima M, Narita J, Hattori S, Endo O et al (2016) A case report of CIC-rearranged undifferentiated small round cell sarcoma in the cerebrum. Diagn Cytopathol 44:828–832
Lake JA, Donson AM, Prince E, Davies KD, Nellan A, Green AL et al (2020) Targeted fusion analysis can aid in the classification and treatment of pediatric glioma, ependymoma, and glioneuronal tumors. Pediatr Blood Cancer 67:e28028
Łastowska M, Trubicka J, Sobocińska A, Wojtas B, Niemira M, Szałkowska A et al (2020) Molecular identification of CNS NB-FOXR2, CNS EFT-CIC, CNS HGNET-MN1 and CNS HGNET-BCOR pediatric brain tumors using tumor-specific signature genes. Acta Neuropathol Commun 8:105
Le Loarer F, Pissaloux D, Watson S, Godfraind C, Galmiche-Rolland L, Silva K et al (2019) Clinicopathologic features of CIC-NUTM1 Sarcomas, a new molecular variant of the family of CIC-Fused Sarcomas. Am J Surg Pathol 43:268–276
Pratt D, Kumar-Sinha C, Cieślik M, Mehra R, Xiao H, Shao L et al (2021) A novel ATXN1-DUX4 fusion expands the spectrum of “CIC-rearranged sarcoma” of the CNS to include non-CIC alterations. Acta Neuropathol (Berl) 141:619–622
Siegfried A, Masliah-Planchon J, Roux F-E, Larrieu-Ciron D, Pierron G, Nicaise Y et al (2019) Brain tumor with an ATXN1-NUTM1 fusion gene expands the histologic spectrum of NUTM1-rearranged neoplasia. Acta Neuropathol Commun 7:220
Sturm D, Orr BA, Toprak UH, Hovestadt V, Jones DTW, Capper D et al (2016) New brain tumor entities emerge from molecular classification of CNS-PNETs. Cell 164:1060–1072
Yamada S, Muto J, De Leon JCA, Kumai T, Ito K, Murayama K et al (2020) Primary spinal intramedullary ewing-like sarcoma harboring CIC-DUX4 translocation: a similar cytological appearance as its soft tissue counterpart but no lobulation in association with desmoplastic stroma. Brain Tumor Pathol 37:111–117
Donahue JE, Yakirevich E, Zhong S, Treaba DO, Lakis NS, Ali SM et al (2018) Primary spinal epidural CIC-DUX4 undifferentiated sarcoma in a child. Pediatr Dev Pathol Off J Soc Pediatr Pathol Paediatr Pathol Soc 21:411–417
Song K, Huang Y, Xia C-D, Zhu H-Q, Wang J (2022) A case of CIC-rearranged sarcoma with CIC-LEUTX gene fusion in spinal cord. Neuropathol Off J Jpn Soc Neuropathol 2:179
Satomi K, Ohno M, Kubo T, Honda-Kitahara M, Matsushita Y, Ichimura K et al (2022) Central nervous system sarcoma with ATXN1::DUX4 fusion expands the concept of CIC-rearranged sarcoma. Genes Chromosomes Cancer 61:683–688
Hung YP, Fletcher CD, Hornick JL (2016) Evaluation of ETV4 and WT1 expression in CIC-rearranged sarcomas and histologic mimics. Mod Pathol Off J U S Can Acad Pathol Inc 29:1324–1334
Le Guellec S, Velasco V, Pérot G, Watson S, Tirode F, Coindre J-M (2016) ETV4 is a useful marker for the diagnosis of CIC-rearranged undifferentiated round-cell sarcomas: a study of 127 cases including mimicking lesions. Mod Pathol Off J U S Can Acad Pathol Inc 29:1523–1531
Ouvrard C, Métais A, Brigot E, Berthaud C, Pucelle N, Lacombe J et al (2022) ETV4 immunohistostaining is a sensitive and specific diagnostic biomarker for CIC-rearranged sarcoma of the central nervous system. Histopathology 81:852–855
Huang S-C, Zhang L, Sung Y-S, Chen C-L, Kao Y-C, Agaram NP et al (2016) Recurrent CIC Gene Abnormalities in Angiosarcomas: a molecular study of 120 cases with concurrent investigation of PLCG1, KDR, MYC, and FLT4 gene alterations. Am J Surg Pathol 40:645–655
Alexandrescu S, Meredith DM, Lidov HG, Alaggio R, Novello M, Ligon KL et al (2020) Loss of histone H3 trimethylation on lysine 27 and nuclear expression of transducin-like enhancer 1 in primary intracranial sarcoma, DICER1-mutant. Histopathology 2:104
Das A, Roy P, Modi SK, Achari RB, Sen S, Singh A et al (2019) Germline DICER1-mutant intracranial sarcoma with dual chondroid and spindle cell morphology and pulmonary metastases treated with multimodal therapy. Pediatr Blood Cancer 66:e27744
Diaz Coronado RY, Mynarek M, Koelsche C, Mora Alferez P, Casavilca Zambrano S, Wachtel Aptowitzer A et al (2022) Primary central nervous system sarcoma with DICER1 mutation-treatment results of a novel molecular entity in pediatric peruvian patients. Cancer 128:697–707
Kamihara J, Paulson V, Breen MA, Laetsch TW, Rakheja D, Shulman DS et al (2020) DICER1-associated central nervous system sarcoma in children: comprehensive clinicopathologic and genetic analysis of a newly described rare tumor. Mod Pathol Off J U S Can Acad Pathol Inc 33:1910–1921
Koelsche C, Mynarek M, Schrimpf D, Bertero L, Serrano J, Sahm F et al (2018) Primary intracranial spindle cell sarcoma with rhabdomyosarcoma-like features share a highly distinct methylation profile and DICER1 mutations. Acta Neuropathol (Berl) 136:327–337
Lee JC, Villanueva-Meyer JE, Ferris SP, Sloan EA, Hofmann JW, Hattab EM et al (2019) Primary intracranial sarcomas with DICER1 mutation often contain prominent eosinophilic cytoplasmic globules and can occur in the setting of neurofibromatosis type 1. Acta Neuropathol (Berl) 137:521–525
Leelatian N, Goss J, Pastakia D, Dewan MC, Snuderl M, Mobley BC (2022) Primary intracranial sarcoma, DICER1-mutant presenting as a pineal region tumor mimicking pineoblastoma: case report and review of the literature. J Neuropathol Exp Neurol 81:762–764
Nejo T, Takayanagi S, Tanaka S, Shinozaki-Ushiku A, Kohsaka S, Nagata K et al (2022) Primary intracranial spindle cell sarcoma, DICER1-Mutant, with MDM2 amplification diagnosed on the basis of extensive molecular profiling. Clin Med Insights Case Rep 15:11795476221131188
Sakaguchi M, Nakano Y, Honda-Kitahara M, Kinoshita M, Tanaka S, Oishi M et al (2019) Two cases of primary supratentorial intracranial rhabdomyosarcoma with DICER1 mutation which may belong to a “spindle cell sarcoma with rhabdomyosarcoma-like feature, DICER1 mutant”. Brain Tumor Pathol 36:174–182
Yao K, Duan Z, Feng J, Yan C, Qi X (2022) DICER1-associated central nervous system sarcoma with neural lineage differentiation: a case report. Diagn Pathol 17:72
Schweizer L, Hartmann W, Koch A, Nunninger M, Thomale U-W, Pennacchietti V et al (2022) Evidence of neural crest cell origin of a DICER1 mutant CNS sarcoma in a child with DICER1 syndrome and NRAS-mutant neurocutaneous melanosis. Neuropathol Appl Neurobiol 48:e12830
Roy A, Kumar V, Zorman B, Fang E, Haines KM, Doddapaneni H et al (2015) Recurrent internal tandem duplications of BCOR in clear cell sarcoma of the kidney. Nat Commun 6:8891
Warren M, Hiemenz MC, Schmidt R, Shows J, Cotter J, Toll S et al (2020) Expanding the spectrum of dicer1-associated sarcomas. Mod Pathol Off J U S Can Acad Pathol Inc 33:164–174
Bennett JA, Ordulu Z, Young RH, Pinto A, Van de Vijver K, Burandt E et al (2021) Embryonal rhabdomyosarcoma of the uterine corpus: a clinicopathological and molecular analysis of 21 cases highlighting a frequent association with DICER1 mutations. Mod Pathol Off J U S Can Acad Pathol Inc 34:1750–1762
Dehner LP, Schultz KA, Hill DA (2022) Anaplastic sarcoma of kidney and DICER1. Pediatr Dev Pathol Off J Soc Pediatr Pathol Paediatr Pathol Soc 25:574
Schultz KAP, Nelson A, Harris AK, Finch M, Field A, Jarzembowski JA et al (2020) Pleuropulmonary blastoma-like peritoneal sarcoma: a newly described malignancy associated with biallelic DICER1 pathogenic variation. Mod Pathol Off J U S Can Acad Pathol Inc 33:1922–1929
Kommoss FKF, Stichel D, Mora J, Esteller M, Jones DTW, Pfister SM et al (2021) Clinicopathologic and molecular analysis of embryonal rhabdomyosarcoma of the genitourinary tract: evidence for a distinct DICER1-associated subgroup. Mod Pathol Off J U S Can Acad Pathol Inc 34:1558–1569
McCluggage WG, Foulkes WD (2021) DICER1-associated sarcomas: towards a unified nomenclature. Mod Pathol Off J U S Can Acad Pathol Inc 34:1226–1228
Yang K, Wang J, Kanwar N, Villani A, Ajani O, Fleming A et al (2022) A primary DICER1-sarcoma with KRAS and TP53 mutations in a child with suspected ECCL. Brain Tumor Pathol 39:225–231
Jour G, Serrano J, Koelsche C, Jones DTW, von Deimling A, Allen J et al (2019) Primary CNS alveolar Rhabdomyosarcoma: importance of epigenetic and transcriptomic assays for Accurate diagnosis. J Neuropathol Exp Neurol 78:1073–1075
Tanaka R, Inoue K, Yamada Y, Yoshida M, Shima H, Ito J et al (2021) A case of primary CNS embryonal rhabdomyosarcoma with PAX3-NCOA2 fusion and systematic meta-review. J Neurooncol 154:247–256
Tauziède-Espariat A, Beccaria K, Pierron G, Guillemot D, Hasty L, Abbou S et al (2021) Pineal alveolar rhabdomyosarcoma with PAX3:NCOA2 fusion inducing OLIG2 expression, a potential pitfall in the central nervous system. Histopathology 79:437–439
Xie L, Wang W, Zhou H, Han Z, Xu J, Xu Z et al (2022) Adult primary pineal alveolar Rhabdomyosarcoma with FOXO1 gene rearrangement and OLIG2 expression: a rare case report and literature review. Int J Surg Pathol 30:769–775
Antonelli M, Raso A, Mascelli S, Gessi M, Nozza P, Coli A et al (2017) SMARCB1/INI1 involvement in pediatric chordoma: a mutational and immunohistochemical analysis. Am J Surg Pathol 41:56–61
Beccaria K, Tauziède-Espariat A, Monnien F, Adle-Biassette H, Masliah-Planchon J, Pierron G et al (2018) Pediatric chordomas: results of a multicentric study of 40 children and proposal for a histopathological prognostic grading system and new therapeutic strategies. J Neuropathol Exp Neurol 77:207–215
Buccoliero AM, Caporalini C, Scagnet M, Baroni G, Moscardi S, Mussa F et al (2019) Appl Immunohistochem Mol Morphol AIMM 27:147–154
Cha YJ, Hong C-K, Kim D-S, Lee S-K, Park HJ, Kim SH (2017) Poorly differentiated chordoma with loss of SMARCB1/INI1 expression in pediatric patients: a report of two cases and review of the literature. Neuropathol Off J Jpn Soc Neuropathol 2:89
Chavez JA, Din NU, Memon A, Perry A (2014) Anaplastic chordoma with loss of INI1 and brachyury expression in a 2-year-old girl. Clin Neuropathol 33:418–420
Gounder MM, Zhu G, Roshal L, Lis E, Daigle SR, Blakemore SJ et al (2019) Immunologic correlates of the abscopal effect in a SMARCB1/INI1-negative poorly differentiated chordoma after EZH2 inhibition and radiotherapy. Clin Cancer Res Off J Am Assoc Cancer Res 25:2064–2071
Hasselblatt M, Thomas C, Hovestadt V, Schrimpf D, Johann P, Bens S et al (2016) Poorly differentiated chordoma with SMARCB1/INI1 loss: a distinct molecular entity with dismal prognosis. Acta Neuropathol (Berl) 132:149–151
Huang S-M, Chen C-C, Chiu P-C, Lai P-H, Ho J-T, Tseng H-H (2003) Unusual presentation of posterior mediastinal chordoma in a 2-year-old boy. J Pediatr Hematol Oncol 25:743–746
Jaber OI, Ashhab MA (2019) Metastatic poorly differentiated chordoma: the eyes do not see what the mind does not know. Autopsy Case Rep 9:e2019120
Miyahara H, Nodomi S, Umeda K, Itasaka S, Waki K, Imai T (2020) Chemoradiotherapy for unresectable INI1-negative chordoma in a child. J Pediatr Hematol Oncol 42:65–68
Mobley BC, McKenney JK, Bangs CD, Callahan K, Yeom KW, Schneppenheim R et al (2010) Loss of SMARCB1/INI1 expression in poorly differentiated chordomas. Acta Neuropathol (Berl) 120:745–753
Owosho AA, Zhang L, Rosenblum MK, Antonescu CR (2018) High sensitivity of FISH analysis in detecting homozygous SMARCB1 deletions in poorly differentiated chordoma: a clinicopathologic and molecular study of nine cases. Genes Chromosomes Cancer 57:89–95
Rekhi B, Michal M, Ergen FB, Roy P, Puls F, Haugland HK et al (2021) Poorly differentiated chordoma showing loss of SMARCB1/INI1: clinicopathological and radiological spectrum of nine cases, including uncommon features of a relatively under-recognized entity. Ann Diagn Pathol 55:151809
Renard C, Pissaloux D, Decouvelaere AV, Bourdeaut F, Ranchère D (2014) Non-rhabdoid pediatric SMARCB1-deficient tumors: overlap between chordomas and malignant rhabdoid tumors? Cancer Genet 207:384–389
Shih AR, Chebib I, Deshpande V, Dickson BC, Iafrate AJ, Nielsen GP (2019) Molecular characteristics of poorly differentiated chordoma. Genes Chromosomes Cancer 58:804–808
Tsitouras V, Wang S, Dirks P, Drake J, Bouffet E, Hawkins C et al (2016) Management and outcome of chordomas in the pediatric population: the hospital for Sick Children experience and review of the literature. J Clin Neurosci Off J Neurosurg Soc Australas 34:169–176
Yadav R, Sharma MC, Malgulwar PB, Pathak P, Sigamani E, Suri V et al (2014) Prognostic value of MIB-1, p53, epidermal growth factor receptor, and INI1 in childhood chordomas. Neuro-Oncol 16:372–381
Hasselblatt M, Thomas C, Federico A, Bens S, Hellström M, Casar-Borota O et al (2022) Low-grade diffusely infiltrative tumour (LGDIT), SMARCB1-mutant: a clinical and histopathological distinct entity showing epigenetic similarity with ATRT-MYC. Neuropathol Appl Neurobiol 48:e12797
Kallen ME, Hornick JL (2021) The 2020 WHO classification: what’s new in soft tissue tumor pathology? Am J Surg Pathol 45:e1-23
Tauziède-Espariat A, Pierre T, Wassef M, Castel D, Riant F, Grill J et al (2022) The dural angioleiomyoma harbors frequent GJA4 mutation and a distinct DNA methylation profile. Acta Neuropathol Commun 10:81
Hongo H, Miyawaki S, Teranishi Y, Mitsui J, Katoh H, Komura D et al (2022) Somatic GJA4 gain-of-function mutation in orbital cavernous venous malformations. Angiogenesis 5:796
Ugwu N, Atzmony L, Ellis KT, Panse G, Jain D, Ko CJ et al (2021) Cutaneous and hepatic vascular lesions due to a recurrent somatic GJA4 mutation reveal a pathway for vascular malformation. HGG Adv 2:871
Gong H, Gao K, Mao P, Ma S, Zhao D, Bian Y et al (2022) A rare case of spindle cell neoplasm with NTRK-fusion in central nervous system. Pathol Int 5:61
Kang J, Park JW, Won J-K, Bae JM, Koh J, Yim J et al (2020) Clinicopathological findings of pediatric NTRK fusion mesenchymal tumors. Diagn Pathol 15:114
Tauziède-Espariat A, Duchesne M, Baud J, Le Quang M, Bochaton D, Azmani R et al (2022) NTRK-rearranged spindle cell neoplasms are ubiquitous tumors of myofibroblastic lineage with a distinct methylation class. Histopathology 9:73
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Tauziède-Espariat, A., Hasty, L., Métais, A. et al. Mesenchymal non-meningothelial tumors of the central nervous system: a literature review and diagnostic update of novelties and emerging entities. acta neuropathol commun 11, 22 (2023). https://doi.org/10.1186/s40478-023-01522-z
- DNA-methylation profiling
- Central nervous system