Neurosurgery notes/Tumours/Haematolymphoid and histiocytic tumours/Histiocytic tumour/Histiocytic sarcoma

Histiocytic sarcoma

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Histiocytic tumour

Definition

  • A rare, aggressive, malignant neoplasm with the histological and immunophenotypic characteristics of mature histiocytes
  • It exhibits no other lines of differentiation.

Diagnostic Criteria

  • Essential:
    • A population of malignant cells expressing histiocytic antigens.
    • Exclusion of other lines of differentiation (glial, meningothelial, epithelial, melanocytic, lymphocytic, muscular, vascular, etc.).
  • Desirable: None specified in the sources.

Numbers

  • Mean age 52 years
  • Fewer than 100 cases have been reported, most of them in adults.

WHO Grade

  • No grading but it is a malignancy.

Localisation

  • Brain parenchyma
  • Meninges
  • Cavernous sinus

Histopathology

Macroscopic

  • Histiocytic sarcomas are destructive, soft, fleshy, white masses.
  • They may have occasional yellow necrotic foci.

Microscopic

  • Characterized by highly cellular, non-cohesive infiltrates of large, moderately pleomorphic, mitotically active histiocytes.
  • Tumour cells have abundant eosinophilic cytoplasm, variably indented to irregular nuclei, and often prominent nucleoli.
  • Occasional multinucleated or spindled forms are common.
  • A background reactive inflammation is commonly present.
Fig. 14.06 Histiocytic sarcoma. A Large, highly pleomorphic histiocytic tumour cells with irregular nuclei and prominent nucleoli. B The lineage-specific marker CD163 was diagnostic in this high-grade neoplasm.
Histiocytic sarcoma. (A) Large, highly pleomorphic histiocytic tumour cells with irregular nuclei and prominent nucleoli. (B) The lineage-specific marker CD163 was diagnostic in this high-grade neoplasm.

Immunophenotype

  • +
    • Histiocytic markers (e.g. CD68, CD163, lysozyme, CD11c, and CD14)
  • -
    • Myeloid antigens
    • Dendritic antigens
    • CD30
    • ALK
    • Other lymphoid markers
    • Glial Ag
    • Epithelial Ag
    • Melanocytic Ag
    • Follicular dendritic cell antigens CD23 and CD35
      • Follicular dendritic cell sarcoma expressing these antigens may primarily arise in the brain and must be differentiated from histiocytic sarcoma
    • BRAF p.V600E expression is rare, despite common MAPK alterations.
  • Variably
    • CD34

Aetiology

  • Radiation

Genetic features

  • A study reported RAS/MAPK pathway gene alterations in 16 of 28 cases (57%); these commonly affected MAP2K1, KRAS, and BRAF, but also NRAS, PTPN11, NF1, and CBL.
  • PI3K/AKT/mTOR pathway gene alterations were found in 6 cases (21%); these affected PTEN, MTOR, PIK3B1, and PIK3CA.
  • Alterations in both pathways were not mutually exclusive.
  • CDKN2A and/or CDKN2B were altered in 13 cases (46%), half of which showed homozygous deletions.
  • Single reported cases featured KRAS, NRAS, or CSF1R mutations, or BRAF fusion.
  • Lack IGH or T-cell receptor gene Clonality

Clinical Features

  • Neurological symptoms are related to tumour location.
  • Progress rapidly due to disseminated disease

Radiological Features

  • Neuroimaging typically mimics a malignant primary CNS tumour.
  • Shinohara 2025:
    • On MRI, shows low-to-intermediate T1 signal, heterogeneous high T2 signal; demonstrates diffuse homogeneous or heterogeneous contrast enhancement.
    • Ultrasonography reveals multilobulated hypoechoic masses with internal vascularity on color Doppler.
    • Non-specific features mimic lymphoma, sarcoma, or carcinoma; biopsy with IHC essential for differentiation.

Management

  • Rare so no standardised protocols
  • Localised Disease
    • Shinohara 2025: Surgical resection (R0 margins) is mainstay for unifocal HS; adjuvant radiotherapy added for close margins to curb local recurrence.
  • Advanced Disease
    • Shinohara 2025: CHOP (± etoposide as CHOEP) is common first-line chemotherapy for multifocal/metastatic HS, though relapses frequent.
  • Consolidation & Targeted
    • Shinohara 2025:
      • Hematopoietic Stem Cell Transplantation (autologous/allogeneic) consolidates responses in eligible patients, with some long-term remissions.
      • Targeted options include BRAF/MEK inhibitors (vemurafenib, trametinib) for MAPK mutations, mTOR inhibitors (sirolimus) for PI3K pathway, and PD-1 inhibitors (pembrolizumab) for PD-L1+ tumors.

Prognosis

  • Survival time has been less than 12 months after initial presentation in most reported patients.