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Review Open Access

Histomorphological and molecular characteristics of liposarcoma (Review)

  • Authors:
    • Ery Kus Dwianingsih
    • Rheza Gandi Bawono
    • Ade Saputri
    • Rusdy Ghazali Malueka
    • Yuni Artha Prabowo Putro
    • Sumadi Lukman Anwar
    • Irianiwati Widodo
  • View Affiliations / Copyright

    Affiliations: Department of Anatomical Pathology, Faculty of Medicine, Public Health and Nursing, Gadjah Mada University, Dr Sardjito General Hospital, Yogyakarta 55281, Indonesia, Department of Neurology, Faculty of Medicine, Public Health and Nursing, Gadjah Mada University, Dr Sardjito General Hospital, Yogyakarta 55281, Indonesia, Orthopedic Division, Department of Surgery, Faculty of Medicine, Public Health and Nursing, Gadjah Mada University, Dr Sardjito General Hospital, Yogyakarta 55281, Indonesia, Surgical Oncology Division, Department of Surgery, Faculty of Medicine, Public Health and Nursing, Gadjah Mada University, Dr Sardjito General Hospital, Yogyakarta 55281, Indonesia
    Copyright: © Dwianingsih et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 454
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    Published online on: July 21, 2025
       https://doi.org/10.3892/ol.2025.15200
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Abstract

Liposarcomas represent the most prevalent subtype of soft‑tissue sarcomas, comprising 15‑20% of all documented cases. However, sarcomas demonstrate notable clinical and pathological variability, which complicates the processes of diagnosis and treatment. Histomorphological analysis can produce inconsistent results due to inter‑examiner variability, which highlights the need for more reliable biomarkers. Genetic and epigenetic alterations may delineate the biological behavior of liposarcomas and assist in the prediction of liposarcoma prognosis. The present review highlights the related genomic alterations in sarcoma and their associations with relevant histomorphology, predilection, targeted therapy and prognosis. Well‑differentiated and dedifferentiated liposarcomas exhibit amplified genes, MDM2 proto‑oncogene and cyclin‑dependent kinase 4, which are potential targets for therapy. Myxoid liposarcoma, characterized by the chromosomal translocations t(12;16) with fused in liposarcoma‑DNA damage‑inducible transcript 3 protein (DDIT3) fusion and t(12;22) with Ewing sarcoma RNA‑binding protein 1‑DDIT3 fusion, demonstrate a favorable response to treatment; however, myxoid liposarcoma displays elevated recurrence rates. Moreover, the complex karyotype and lack of specificity in pleomorphic liposarcoma are associated with poor treatment outcomes and increased recurrence rates. Integration of morphological features with molecular biomarkers may potentially enhance diagnosis, facilitate targeted therapies and improve sarcoma prognosis in the future.
View Figures

Figure 1

Histopathological images of WDL. (A)
WDL tumor exhibiting mature adipocytes along with atypical stromal
cells and (B) a small number of lipoblasts. Hematoxylin and eosin
staining; magnification, ×100 and ×400, respectively. WDL,
well-differentiated liposarcoma.

Figure 2

Histopathological images of DDL. (A)
DDL including a well-differentiated adipose tissue component mixed
with non-lipogenic elements, such as (B) a fibrosarcomatous
component. Hematoxylin and eosin staining; magnification, ×100 and
×400, respectively. DDL, dedifferentiated liposarcoma.

Figure 3

MDM2 and CDK4 involvement in the
pathogenesis of liposarcoma. CDK4 gene amplification results in
increased expression of the CDK4 protein, which promotes RB
phosphorylation, thereby driving cell-cycle progression. MDM2
negatively regulates p53 through various mechanisms, inhibiting p53
transcription and facilitating p53 degradation by ubiquitination.
MDM2, murine double minute 2; RB, retinoblastoma; CDK4,
cyclin-dependent kinase 4; P, phosphorus.

Figure 4

Histopathological images of ML. (A)
ML comprising non-lipogenic mesenchymal cells with distinct myxoid
background and a chicken wire vasculature, and (B) a high-grade ML,
exhibiting a >5% round cell component alongside necrotic areas.
Hematoxylin and eosin staining; magnification, ×100 and ×400,
respectively. ML, myxoid liposarcoma.

Figure 5

The pathogenesis of ML. ML
pathogenesis involves the upregulation and activation of RTKs,
including MET, RET and VEGFRs, leading to enhanced PI3K pathway
activity. Growth factors that bind to RTKs, such as IGF-IR,
activate PI3K, transforming PIP2 into PIP3 and triggering AKT
signaling and phosphorylating downstream targets. PTEN inhibits
PI3K signaling by conversion of PIP3 back to PIP2. Moreover, RTKs
activate genes linked to angiogenesis, proliferation and survival
by Ras and the PI3K/AKT pathway. ML is associated with AKT
activation and PIK3CA and PTEN alterations. The oncogenic circuit
includes FUS-DDIT3, the IGF-IR/PI3K/AKT pathway and the Hippo/YAP1
axis. FUS-DDIT3 induces IGF-2 expression, forming an autocrine
IGF-II/IGF-IR signaling loop that activates the IGF-IR/PI3K/AKT
pathway. Signals from IGF-IR and PI3K inhibit Hippo kinase LATS1,
enabling nuclear accumulation of YAP1. FUS-DDIT3 interacts with
YAP1/TEAD in the nucleus, regulating oncogenic gene programs
involved in apoptosis, adipogenesis, the cell cycle and
proliferation. ML, myxoid liposarcoma; RTK, receptor tyrosine
kinase; MET, MET proto-oncogene receptor tyrosine kinase; RET, ret
proto-oncogene; PIP2, phosphatidylinositol 4,5-bisphosphate; PIP3,
phosphatidylinositol (3–5)-trisphosphate; PIK3CA,
phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α;
IGF, insulin-like growth factor; IGF-IR, IGF-1 receptor; FUS-DDIT3,
fused in liposarcoma-DNA damage-inducible transcript 3; YAP1,
Yes-associated protein 1; LATS1, large tumor suppressor kinase 1;
TEAD, transcriptional enhanced associate domain; HGF, hepatocyte
growth factor; GDNF, glial cell line-derived neurotrophic
factor.

Figure 6

Histopathological images of PL. PL
demonstrating (A) spindle to epitheloid pleomorphic cells, (B)
pleomorphic lipoblasts with vacuolated cytoplasm and (C) other
features of pleomorphic lipoblasts. Hematoxylin and eosin staining;
magnification, ×100, ×400 and ×400, respectively.
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Copy and paste a formatted citation
Spandidos Publications style
Dwianingsih EK, Bawono RG, Saputri A, Malueka RG, Putro YA, Anwar SL and Widodo I: Histomorphological and molecular characteristics of liposarcoma (Review). Oncol Lett 30: 454, 2025.
APA
Dwianingsih, E.K., Bawono, R.G., Saputri, A., Malueka, R.G., Putro, Y.A., Anwar, S.L., & Widodo, I. (2025). Histomorphological and molecular characteristics of liposarcoma (Review). Oncology Letters, 30, 454. https://doi.org/10.3892/ol.2025.15200
MLA
Dwianingsih, E. K., Bawono, R. G., Saputri, A., Malueka, R. G., Putro, Y. A., Anwar, S. L., Widodo, I."Histomorphological and molecular characteristics of liposarcoma (Review)". Oncology Letters 30.4 (2025): 454.
Chicago
Dwianingsih, E. K., Bawono, R. G., Saputri, A., Malueka, R. G., Putro, Y. A., Anwar, S. L., Widodo, I."Histomorphological and molecular characteristics of liposarcoma (Review)". Oncology Letters 30, no. 4 (2025): 454. https://doi.org/10.3892/ol.2025.15200
Copy and paste a formatted citation
x
Spandidos Publications style
Dwianingsih EK, Bawono RG, Saputri A, Malueka RG, Putro YA, Anwar SL and Widodo I: Histomorphological and molecular characteristics of liposarcoma (Review). Oncol Lett 30: 454, 2025.
APA
Dwianingsih, E.K., Bawono, R.G., Saputri, A., Malueka, R.G., Putro, Y.A., Anwar, S.L., & Widodo, I. (2025). Histomorphological and molecular characteristics of liposarcoma (Review). Oncology Letters, 30, 454. https://doi.org/10.3892/ol.2025.15200
MLA
Dwianingsih, E. K., Bawono, R. G., Saputri, A., Malueka, R. G., Putro, Y. A., Anwar, S. L., Widodo, I."Histomorphological and molecular characteristics of liposarcoma (Review)". Oncology Letters 30.4 (2025): 454.
Chicago
Dwianingsih, E. K., Bawono, R. G., Saputri, A., Malueka, R. G., Putro, Y. A., Anwar, S. L., Widodo, I."Histomorphological and molecular characteristics of liposarcoma (Review)". Oncology Letters 30, no. 4 (2025): 454. https://doi.org/10.3892/ol.2025.15200
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