A Low-Grade Angiomyxofibromatous Tumor of the Falx Cerebelli: A Mimic of Fourth Ventricular Tumors

Abstract

Low-grade fibromyxoid tumors are very uncommon in children. A tumor of this type has never been reported in the posterior fossa to date. Such lesions may mimic more common lesions of the posterior fossa. Awareness of this entity and its subsequent behavior may guide better management and outcomes. We describe the case of a previously unreported low-grade angiomyxofibromatous tumor of the falx cerebelli in a 10-year-old female, whose presentation mimicked cystic lesions of the posterior fossa causing obstructive hydrocephalus. Microscopic examination revealed stellate cells set in myxoid and edematous stroma, along with a plexiform vasculature pattern. The tumor cells were diffusely immunopositive for vimentin and focally positive for S-100 protein, but negative for epithelial membrane antigen, CD34, MIC2, Bcl-2, glial fibrillary acidic protein, cytokeratin, CAM 5.2, desmin, and smooth muscle actin. This lesion could not be categorized according to the current World Health Organization classification of tumors of the nervous system. Therefore, there is a need for a better understanding of the central nervous system (CNS) myxoid neoplasms and a reassessment of the classification of CNS tumors.

 

MissingLinkText

Keywords

angiomyxofibromatous - falx - mimic - obstructive hydrocephalus - posterior fossa

Introduction

Fourth ventricular tumors are a common neurosurgical pathology. However, cystic space-occupying lesions inside the fourth ventricle are very rare, with only a handful of cases reported so far.[1] Myxoid tumors comprise a heterogeneous group of lesions having a common feature, that is, an abundance of mucopolysaccharide matrix. However, central nervous system (CNS) myxoid tumors are very rare. There have been only four reported cases of angiomyxofibromatous tumors of the falx cerebri that do not fit into any category of existing well-recognized classification of CNS tumors or soft tissue tumors.[2] [3] [4] [5] The case reported here is, to our knowledge, the first reported case mimicking a space-occupying lesion of the fourth ventricle and originating from the falx cerebellum.

 

MissingLinkText

Case Description

A 13-year-old female patient presented with complaints of headache, dizziness, and blurring of vision for 3 months, with insidious onset and progressive in nature. The patient had no significant past medical history. Physical examination did not show any other neurological deficits. Noncontrast computed tomography scan of head showed a space-occupying lesion in the fourth ventricle ([Fig. 1]). Magnetic resonance imaging (MRI) of the brain showed a well-defined cystic lesion in the fourth ventricle, measuring approximately 5.0 (craniocaudal) × 4.0 (anteroposterior) × 4.3 (width) cm in size. The lesion was hyperintense on T2-weighted imaging ([Fig. 2]), with calcification inferiorly on the left side and a few thin, nonenhancing septations. It was associated with moderate obstructive dilatation of the bilateral lateral and third ventricles, along with mild periventricular edema ([Figs. 2] [3] [4]). Based on image findings, a probable diagnosis of benign cystic lesion of the fourth ventricle leading to obstructive hydrocephalus was considered.

Fig. 1 Computed tomography (CT) scan—axial.

Fig. 2 Sagittal T2-weighted image—lesion encircled.

Fig. 3 Axial T2-weighted image.

Fig. 4 Axial T1-weighted image.

A midline suboccipital craniotomy was performed, and a gross total resection (GTR) was achieved. Intraoperatively, it was found to have a thin pedicle-like attachment to the falx cerebelli. Gross total tumor excision was performed via the telovelar approach. Macroscopic examination showed a creamish-white soft tissue structure. Routine formalin-fixed, hematoxylin-eosin staining showed stellate cells set in myxoid and edematous stroma, along with plexiform vasculature pattern. The blood vessels did not show a thick wall. Inflammatory cells were conspicuously absent. No increased cellularity or whorl formations were noted. Focal epithelial-lined structures were embedded within the lesion, and calcification was also seen ([Fig. 5]). The stellate cells showed no atypia, and mitotic activity was not observed ([Fig. 6]). Immunohistochemical stains were performed on formalin-fixed, paraffin-embedded tissue using the streptavidin-biotin peroxidase complex method and monoclonal antibodies. The tumor cells were diffusely immunopositive for vimentin and focally immunopositive for S-100 protein, but were negative for all other antigens tested, that is, epithelial membrane antigen (EMA), Bcl-2, glial fibrillary acidic protein (GFAP), and CD34. Based on the histopathological and immunohistochemistry findings, the final diagnosis of angiomyxofibromatous tumor of the falx was made.

Fig. 5 Low-power field slide—hypocellular myxoid stroma with columnar epithelial lining and thin-walled blood vessels showing plexiform pattern.

Fig. 6 High-power field slide—stellate cells in myxoid and edematous stroma without atypia.

The patient was discharged from the hospital 1 week postoperation. After operation, patient showed improvement in symptoms. And at 20-month follow-up, patient is relatively asymptomatic with no neurological deficits and the prognosis is good. MRI scan also shows no evidence of recurrence.

 

MissingLinkText

Discussion

Myxoid neoplasms consist of a group of neoplasms for which no widely accepted classification scheme is available. Myxoid glioneuronal tumor has been identified in the 2021 World Health Organization (WHO) classification of the CNS. It is characterized by a proliferation of oligodendrocyte-like tumor cells embedded in a prominent myxoid stroma, often containing floating neurons, neurocytic rosettes, and perivascular neuropil. This tumor is caused by a dinucleotide mutation in the PDGFRA gene.[6] However, the tumor in this case cannot be classified using existing nomenclature. The differential diagnosis would have included fourth ventricular arachnoid cyst, neurocysticercosis, and pilocytic astrocytoma.

Intracranial myxomas are very rare, with only three cases described in the literature. Myxomas are benign tumors of primitive mesenchymal tissue and are usually found in the heart, bones, genitourinary system, and soft tissues. These tumors may be primary or embolic from an underlying cardiac myxoma. There are only a few cases concerning primary intracranial myxomas that have been published in the literature. Primary CNS myxoma is less common than metastatic brain myxoma.[7] Histological examination of myxomas shows characteristic hypocellular areas of sparse strands of cells suspended in a rich myxoid matrix, which stains strongly positive with Alcian blue. Myxomas do not evidence malignant features such as nuclear pleomorphism, hyperchromasia, and mitotic activity. Immunohistochemical analysis characteristically shows immunoreactivity for vimentin but no expression of S-100 protein and EMA.[8] The diagnosis of pure myxoma was dismissed due to the presence of a vascular component described herein. Angiomyxofibromatous tumor of falx cerebri is a very rare entity, with only four case reports in the literature.[2] [3] [4] [5] All four of these cases were supratentorial with attachment to falx. This case was unique in the form of its presentation and location. Medeiros et al reported a case of a 48-year-old female with a tumor composed of bland-appearing spindle and stellate cells in a myxoid matrix with prominent vascularity.[2] Tsuji et al reported a case of an 8-year-old male with a tumor composed of bland-appearing spindle and stellate cells in a myxoid matrix with sparsely proliferating small and dilated vessels.[3] Sugita et al reported a case of a 55-year-old female with a tumor composed of bland-appearing spindle and stellate cells with abundant myxoid matrix and prominent proliferation of capillary-sized vessels.[4] Tauziede-Espariat et al reported a case of a 50-year-old male with a tumor composed of mast cells, spindle cells, and fibroblasts intertwined with lymphocytes in an abundant myxoid matrix and proliferation of small vessels. Mast cells were immunopositive for EMA and S-100 protein. Fibroblasts and endothelial cells were immunopositive for CD34.[5]

Based on the immunohistochemical analysis of all reported cases of angiomyxofibromatous tumor ([Table 1]), including our case, the findings suggest that these tumors are diffusely immunopositive for vimentin, suggesting a mesenchymal origin, and exhibit variable immunopositivity for S-100 and PgR (progesterone receptor). Consistently, it has been shown to be negative for GFAP, SMA, cytokeratin, and CD34. Sugita et al reported a case with distinct immunohistochemical features, including diffuse immunopositivity for desmin and focal immunopositivity for EMA.[4] Additionally, two studies demonstrated a low K_i-67 labeling index, and one study showed no nuclear expression of β-catenin in tumor cells, reinforcing the benign nature of angiomyxofibromatous tumor.[3] [5] Two studies performed fluorescent in situ hybridization to detect underlying genetic abnormalities in this type of tumor but did not identify any specific gene mutations.[3] [4]

Table 1 Molecular characteristics of tumor reported in different case reports

	Immunohistochemistry			Fluorescence in situ hybridization (FISH)
	Diffusely positive	Focally positive	Negative
Medeiros et al2	Vimentin	S-100	EMA MIC2 GFAP Cytokeratin Desmin SMA CD34 Bcl-2
Tsuji et al3	Vimentin S-100	PgR	EMA GFAP Cytokeratin Desmin SMA CD34 Bcl-2 Factor 8 Mucin 4 CD31 STAT6 CD10 NSE Myoglobin Myogenin MyoD1 p63 HMB45 MelanA Collagen IV β-catenin (no nuclear expression) Ki-67 labeling index ∼ 2%	EWSR1–4% CREB – 2% ATF – 0% (out of 50 nuclei, cutoff 10%)
Sugita et al4	Vimentin Desmin Rb	S-100 EMA PgR	Cytokeratin SMA CD34 STAT6 ER Muscle-specific actin HHF35	HMGA2–0% NCOA2–0% 13q14 deletion – 8% (out of 50 nuclei, cutoff 20%)
Tauziede-Espariat et al5			S-100 PgR EMA GFAP Cytokeratin Desmin SMA CD34 MIB-1 (inferior to 1%) HMGA2

Abbreviations: Bcl-2, B-cell lymphoma 2; CREB, cAMP response element binding protein; EMA, epithelial membrane antigen; ER, estrogen receptor; EWSR1, Ewing sarcoma breakpoint region 1; GFAP, glial fibrillary acid protein; HMB45, human melanoma black 45; MyoD1, myogenic differentiation 1; NSE, neuron-specific enolase; PgR, progesterone receptor ; Rb, retinoblastoma; SMA, smooth muscle actin; STAT6, signal transducer and activator of transcription 6.

GTR, when feasible, is considered the optimal treatment for primary intracranial myxomas.[9] In all reported cases, including our own, GTR of the tumor was achieved without any signs or symptoms of recurrence, with the longest follow-up period being 6 years, as reported by Medeiros et al.[2] [3] [4] [5] This approach may also be applicable to angiomyxofibromatous tumors; however, due to their tendency to recur following incomplete resection, close postoperative follow-up is essential. This suggests that adequate surgical resection of the tumor, followed by regular follow-up, may suffice without the need for chemoradiotherapy intervention.

 

MissingLinkText

Conclusion

In summary, we have described an unusual angiomyxofibromatous lesion arising in the falx cerebellum, a tumor not accommodated in the current WHO classification or other histopathologic classifications of CNS or soft tissue tumors. The classification and understanding of the pathogenesis of myxoid tumors remain to be established. Given the favorable, essentially curative outcome with surgery alone, awareness of its presentation and behavior is important.

 

MissingLinkText

 

MissingLinkText

Conflict of Interest

None declared.

Authors' Contributions

P.P.M. and P.P. conducted the literature review. The initial draft was prepared by V.R. and P.P., while P.P.M., V.R., and U.K. contributed to reviewing and editing the manuscript.

• References

• 1 Nadkarni T, Hande A, Nagpal R. Arachnoid cyst within the fourth ventricle–a case report. Br J Neurosurg 1995; 9 (05) 675-678
• 2 Medeiros F, Scheithauer BW, Oliveira AM, Gregory RS. Angiomyxofibromatous tumor of the falx cerebri. Am J Surg Pathol 2006; 30 (04) 545-547
• 3 Tsuji K, Nakaya T, Ashizawa K. et al. Pediatric angiomyxofibromatous tumor of the falx cerebri with locally destructive growth into the cranial bone. Pathol Int 2020; 70 (02) 123-125
• 4 Sugita S, Obata M, Takebayashi S, Kikuchi T, Hasegawa T. Angiomyxomatous tumor of the falx cerebri. Pathol Int 2016; 66 (01) 50-51
• 5 Tauziede-Espariat A, Adle-Biassette H, Simonneau A, Guinebretiere JM, Polivka M. 50-year-old man with a falcine mass. Brain Pathol 2017; 27 (03) 403-404
• 6 Louis DN, Perry A, Wesseling P. et al. The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. Neuro-oncol 2021; 23 (08) 1231-1251
• 7 Graham JF, Loo SYT, Matoba A. Primary brain myxoma, an unusual tumor of meningeal origin: case report. Neurosurgery 1999; 45 (01) 166-169 , discussion 169–170
• 8 Rawlinson NJ, West WW, Nelson M, Bridge JA. Aggressive angiomyxoma with t(12;21) and HMGA2 rearrangement: report of a case and review of the literature. Cancer Genet Cytogenet 2008; 181 (02) 119-124
• 9 Weng JC, Song LR, Li D. et al. Surgical management and prognostic factors for primary intracranial myxoma: a single-institute experience with a systematic review. J Neurosurg 2018; 131 (04) 1115-1125

Publication History

Article published online:
26 May 2025