How can lipoma be differentiated from liposarcoma on cytologic examination?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: February 10, 2026 • View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

Cytologic Differentiation of Lipoma from Liposarcoma

The definitive cytologic feature distinguishing liposarcoma from lipoma is the presence of atypical multivacuolated lipoblasts with characteristically scalloped or indented hyperchromatic nuclei, which must occur in the appropriate cellular background. 1

Key Cytomorphologic Features

Diagnostic Lipoblasts (Hallmark of Liposarcoma)

  • Lipoblasts diagnostic of liposarcoma have an eccentric, hyperchromatic nucleus that is indented or scalloped by one or more fat vacuoles. 2
  • These cells must be identified using strict criteria and must occur in the appropriate histologic/cytologic milieu, as similar-appearing cells can be seen in non-lipomatous lesions (e.g., silicone reactions). 2
  • Failure to apply strict criteria for identifying lipoblasts and noting their cellular context leads to overdiagnosis of liposarcoma. 2

Benign Lipoma Cytology

  • Lipomas show mature adipocytes without nuclear atypia or pleomorphism. 1
  • The cytologic appearance is bland, with uniform fat cells and no atypical features. 1

Liposarcoma Subtypes and Their Cytologic Appearances

Well-Differentiated Liposarcoma:

  • Contains mature fat interlaced with atypical hyperchromatic cells and rare lipoblasts. 2
  • Shows multivacuolated lipoblasts and atypical lipocytes. 3
  • May demonstrate CDK4 and MDM2 immunoreactivity on cell blocks. 3

Myxoid Liposarcoma:

  • Characterized by lipoblasts within a myxoid background. 1
  • Alcian blue staining at varying pH levels can help characterize glycosaminoglycan content, distinguishing myxoid liposarcomas from myxoid chondromatous tumors and chordomas. 1

Dedifferentiated Liposarcoma:

  • High-grade tumor cells display marked nuclear irregularity, enlargement, size variation, with macronucleoli and multinucleation. 3
  • May show both well-differentiated lipomatous components and high-grade (dedifferentiated) tumor cells in the same specimen. 3

Round Cell and Pleomorphic Liposarcoma:

  • The main criterion remains the presence of atypical multivacuolated lipoblasts with scalloped nuclei, though the background cellular features vary with histologic type. 1

Ancillary Testing on Cytology Specimens

Immunocytochemistry

  • CDK4 and MDM2 immunoreactivity can be successfully demonstrated on cell blocks from cytology specimens. 3
  • These markers help confirm the diagnosis when lipoblasts are identified. 3

Molecular Testing

  • MDM2 amplification by fluorescence in-situ hybridization (FISH) can be performed on cytology specimens. 3
  • This definitively distinguishes benign lipoma from atypical lipomatous tumor/well-differentiated liposarcoma. 4
  • Chromosomal rearrangements of 12q15 are characteristic of liposarcomas. 5

Optimal Staining Methods

  • May-Grünwald-Giemsa staining is the most useful staining method for cytologic diagnosis of lipomatous tumors. 1
  • Fat staining is of limited or no value in the cytologic diagnosis of lipomatous tumors. 1

Critical Pitfalls to Avoid

Benign Lesions That Mimic Liposarcoma

  • Regressively changed lipoma, intramuscular lipoma, angiolipoma, hibernoma, and lipoblastoma may contain cells that mimic lipoblasts and lead to erroneous diagnosis of liposarcoma. 1
  • These benign variants require recognition of their specific cytologic patterns to avoid overdiagnosis. 1

Context-Dependent Interpretation

  • Lipoblast-like cells can appear in non-lipomatous conditions, making contextual interpretation essential. 2
  • The cellular background and overall cytologic pattern must support the diagnosis before calling cells "diagnostic lipoblasts." 2

Role of Exfoliative Cytology

  • Lipomatous and dedifferentiated components can be successfully sampled and cytomorphologically identified in effusion fluids from liposarcomas. 3
  • Effusion cytology provides sufficient cellularity for immunocytochemistry and molecular testing. 3
  • Both well-differentiated and dedifferentiated components may be identified in the same effusion specimen. 3

References

2
Research

Lipomatous tumors.

Monographs in pathology, 1996

4
Guideline

Atypical Lipomatous Tumor and Well-Differentiated Liposarcoma Management

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

5
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Related Questions

Can a lipoma develop suddenly?
What causes a lipoma?
What is the management of a 4.2 cm subcutaneous soft tissue mass along the posterolateral aspect of the proximal left thigh, with multiple smaller subcutaneous nodules, to rule out soft tissue sarcoma, such as myxoid liposarcoma, versus benign entities like lipoma variant or angiolipomata (angioliopmatic lesions)?
Do lipomas (fatty tumors) show up on x-rays (radiographs)?
What is the best course of treatment for a patient presenting with a painful mass in the left gluteus, suspected to be either a muscle knot or a lipoma, with a palpable deep small mass in the area?
What empiric antibiotic regimen, dosing, and duration should be used for hospital‑acquired pneumonia, including anti‑pseudomonal β‑lactam and MRSA coverage, with adjustments for renal impairment or β‑lactam allergy?
What criteria should prompt initiation of intraperitoneal (IP) antibiotics in suspected peritoneal dialysis (PD) peritonitis?
What preventive measures can be implemented on a general ward to reduce hospital‑acquired pneumonia (HAP) in adult patients, especially older adults, those with limited mobility, dementia, or chronic lung disease?
For an adult with severe cellulitis containing necrotic tissue, what is the recommended intravenous meropenem dose and duration of therapy, including adjustments for renal impairment?
What is the recommended dosing and administration of midazolam for refractory status epilepticus in an adult patient after adequate benzodiazepine and fast‑acting antiepileptic drug loading?
How should a 9‑mm asymptomatic left parotid gland lesion be managed, including evaluation of cervical lymph nodes, when pleomorphic adenoma cannot be excluded?

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.

Ask Question