A Rare Case of Primary Central Nervous System Histiocytic Sarcoma Harboring a Novel ARHGAP45::BRAF Fusion: a Case Report and Literature Review

Overview

Journal Brain Tumor Pathol

Specialties Neurology
Oncology
Pathology

Date 2023 Dec 15

PMID 38100030

Authors

Luyi Zhang

Gang Zhang

Han Zheng

Bin Jiang

Yongzhi Ju

Qianqian Duan

Lu An

Hangyu Shi

Affiliations

Soon will be listed here.

Abstract

Introduction: Patients with histiocytic sarcoma occurring in the central nervous system (CNS) are rare and have a very poor prognosis. The increased use of molecular diagnostic approaches in solid tumors has brought more opportunities for the diagnosis and treatment of central nervous system histiocytic sarcoma (CNSHS).

Case Description: A 9-year-old girl was admitted to the hospital with pain in her head and neck, as well as vomiting. Imaging scans showed a prominent abnormality in the anterior falciform region, and histopathology revealed the presence of CD68 (+) and CD163 (+) cells, leading to a preliminary diagnosis of primary intracerebral CNSHS. Molecular profiling tests identified a new variant of ARHGAP45::BRAF fusion in this case, which has not been reported in any other tumor. The patient underwent surgical removal of the tumor and will require long-term monitoring.

Conclusion: The presence of the BRAF point mutation, predominantly BRAF p.V600E, has been documented in prior literature of CNSHS. This is the first case of pediatric histiocytic sarcoma in the anterior falciform region who has a unique ARHGAP45::BRAF fusion. The findings of our study indicate that a broader range of molecular assays should be employed in the diagnosis of CNSHS and opens up new possibilities for the treatment of the patient.

Citing Articles

Clinicopathological and molecular characterization of astrocytoma.

Wu X, Peng W, Zhang X, Tang T, Deng L, Xu Y Front Mol Neurosci. 2025; 18:1483833.

PMID: 39963393 PMC: 11830656. DOI: 10.3389/fnmol.2025.1483833.

Novel :: Gene Fusion in Infantile Fibrosarcoma: A Case Report and Review of Literature.

Gonzalez-Lopez J, Rubio-Martinez L, Atares M, Amaya J, Huart M, Mayordomo-Aranda E Int J Mol Sci. 2025; 26(3).

PMID: 39940949 PMC: 11818928. DOI: 10.3390/ijms26031182.

Case report: Treatment of a rare primary cerebellum histiocytic sarcoma with surgery and radiotherapy.

Yanchu L, Li Z, Qiongwen Z, Jiayu D, Feng W Front Oncol. 2025; 14:1398350.

PMID: 39759133 PMC: 11695375. DOI: 10.3389/fonc.2024.1398350.

A 55-year-old man with a cerebral mass.

Ammendola S, Ricciardi G, Barresi V Brain Pathol. 2024; 34(6):e13310.

PMID: 39362771 PMC: 11483508. DOI: 10.1111/bpa.13310.

Primary CNS histiocytic sarcoma: Two case reports highlighting a novel MIGA2::BRAF gene fusion and genome-wide DNA methylation profiling results.

Cecchi R, Guptil D, Haslett N, Hristov A, Bledsoe J, Tsai H J Neuropathol Exp Neurol. 2024; 83(10):882-886.

PMID: 38879442 PMC: 11413427. DOI: 10.1093/jnen/nlae061.

References

Kommalapati A, Tella S, Durkin M, Go R, Goyal G . Histiocytic sarcoma: a population-based analysis of incidence, demographic disparities, and long-term outcomes. Blood. 2017; 131(2):265-268. PMC: 5757688. DOI: 10.1182/blood-2017-10-812495. View

Hung Y, Qian X . Histiocytic Sarcoma. Arch Pathol Lab Med. 2019; 144(5):650-654. DOI: 10.5858/arpa.2018-0349-RS. View

Kim Y, Yie G, Kim N, Jeon I, Cho H, Seok J . Pediatric intracerebral histiocytic sarcoma with rhabdoid features: Case report and literature review. Neuropathology. 2017; 37(6):560-568. DOI: 10.1111/neup.12396. View

May J, Waddle M, Miller D, Stross W, Kaleem T, May B . Primary histiocytic sarcoma of the central nervous system: a case report with platelet derived growth factor receptor mutation and PD-L1/PD-L2 expression and literature review. Radiat Oncol. 2018; 13(1):167. PMC: 6126020. DOI: 10.1186/s13014-018-1115-x. View

Gounder M, Desai V, Kuk D, Agaram N, Arcila M, Durham B . Impact of surgery, radiation and systemic therapy on the outcomes of patients with dendritic cell and histiocytic sarcomas. Eur J Cancer. 2015; 51(16):2413-22. PMC: 5087129. DOI: 10.1016/j.ejca.2015.06.109. View

Geerlinks A, Abla O . Treatment of Langerhans Cell Histiocytosis and Histiocytic Disorders: A Focus on MAPK Pathway Inhibitors. Paediatr Drugs. 2023; 25(4):399-409. DOI: 10.1007/s40272-023-00569-8. View

Talloa D, Triarico S, Agresti P, Mastrangelo S, Attina G, Romano A . and MEK Targeted Therapies in Pediatric Central Nervous System Tumors. Cancers (Basel). 2022; 14(17). PMC: 9454417. DOI: 10.3390/cancers14174264. View

Louis D, Perry A, Wesseling P, Brat D, Cree I, Figarella-Branger D . The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. Neuro Oncol. 2021; 23(8):1231-1251. PMC: 8328013. DOI: 10.1093/neuonc/noab106. View

Almefty R, Tyree T, Fusco D, Coons S, Nakaji P . Primary histiocytic sarcoma of the brain mimicking cerebral abscess. J Neurosurg Pediatr. 2013; 12(3):251-7. DOI: 10.3171/2013.6.PEDS12533. View

10.

Wu W, Tanrivermis Sayit A, Vinters H, Pope W, Mirsadraei L, Said J . Primary central nervous system histiocytic sarcoma presenting as a postradiation sarcoma: case report and literature review. Hum Pathol. 2013; 44(6):1177-83. DOI: 10.1016/j.humpath.2012.11.002. View

11.

Chalasani S, Hennick M, Hocking W, Shaw G, Lawler B . Unusual presentation of a rare cancer: histiocytic sarcoma in the brain 16 years after treatment for acute lymphoblastic leukemia. Clin Med Res. 2012; 11(1):31-5. PMC: 3573091. DOI: 10.3121/cmr.2012.1092. View

12.

Perez-Ruiz E, Delgado M, Sanz A, Gil A, Dominguez A . Primary leptomeningeal histiocytic sarcoma in a patient with a good outcome: a case report and review of the literature. J Med Case Rep. 2013; 7:127. PMC: 3663802. DOI: 10.1186/1752-1947-7-127. View

13.

Laviv Y, Zagzag D, Fichman-Horn S, Michowitz S . Primary central nervous system histiocytic sarcoma. Brain Tumor Pathol. 2012; 30(3):192-5. DOI: 10.1007/s10014-012-0123-z. View

14.

Idbaih A, Mokhtari K, Emile J, Galanaud D, Belaid H, de Bernard S . Dramatic response of a BRAF V600E-mutated primary CNS histiocytic sarcoma to vemurafenib. Neurology. 2014; 83(16):1478-80. DOI: 10.1212/WNL.0000000000000880. View

15.

Moulignier A, Mikol J, Heran F, Galicier L . Isolated III cranial nerve palsies may point to primary histiocytic sarcoma. BMJ Case Rep. 2014; 2014. PMC: 4139573. DOI: 10.1136/bcr-2014-204663. View

16.

Bai J, Li G, Shen M, Sui D, Lin S . Primary central nervous system histiocytic sarcoma mimicking glioma. Neurol India. 2015; 62(6):684-5. DOI: 10.4103/0028-3886.149409. View

17.

Chen C, Williams E, McAneney T, Williams B, Mandell J, Shaffrey M . Histiocytic sarcoma of the cavernous sinus: case report and literature review. Brain Tumor Pathol. 2014; 32(1):66-71. DOI: 10.1007/s10014-014-0191-3. View

18.

Foster M, Kamaly-Asl I, Stivaros S, Kelsey A, Gattamenini R, Kilday J . Primary cerebral histiocytic sarcoma in childhood: a case report of protracted survival and review of the literature. Childs Nerv Syst. 2015; 31(12):2363-8. DOI: 10.1007/s00381-015-2815-2. View

19.

Brown A, Fan H, Floyd J, Henry J, Higgins R . Primary Central Nervous System Histiocytic Sarcoma Arising After Precursor B-Cell Acute Lymphoblastic Leukemia. J Neuropathol Exp Neurol. 2015; 74(12):1120-6. DOI: 10.1097/NEN.0000000000000258. View

20.

Nieuwenhuis M, van der Salm S, Verhoeff J, van der Kooi A, Slavujecvic-Letic I, Pals S . A 43-Year-Old Female with Multifocal Cerebral Lesions. Histiocytic Sarcoma. Brain Pathol. 2015; 25(3):371-2. PMC: 8029443. DOI: 10.1111/bpa.12260. View