Definition/General
Introduction:
Endometrial liposarcoma is an extremely rare malignant adipocytic tumor of the uterus
It represents less than 1% of all uterine sarcomas
It shows lipoblastic differentiation with malignant features
It can occur as pure liposarcoma or as part of heterologous sarcoma.
Origin:
Arises from endometrial mesenchymal cells with adipocytic differentiation
May develop from pre-existing lipomatous lesions
Can occur in the context of adenosarcoma with heterologous elements
Rarely occurs as primary pure liposarcoma.
Classification:
Classified as heterologous sarcoma by WHO classification
Well-differentiated and dedifferentiated types most common
Myxoid/round cell type rare in uterus
Pleomorphic type extremely rare
May be component of mixed sarcoma.
Epidemiology:
Extremely rare tumor
Peak incidence in 5th-6th decades
Postmenopausal women predominantly affected
No clear ethnic predilection
Associated with previous pelvic radiation
May be linked to genetic syndromes.
Clinical Features
Presentation:
Abnormal uterine bleeding (most common)
Enlarging pelvic mass
Postmenopausal bleeding
Pelvic pressure symptoms
Abdominal distension
Weight loss in advanced cases.
Symptoms:
Heavy menstrual bleeding
Intermenstrual bleeding
Pelvic pain
Urinary frequency
Constipation
Abdominal fullness
Fatigue and weakness
Early satiety.
Risk Factors:
Age >50 years
Previous pelvic radiation
Genetic predisposition (Li-Fraumeni syndrome)
Retinoblastoma survivors
Previous chemotherapy
Family history of sarcomas
Obesity (possible association).
Screening:
No specific screening recommendations
High suspicion for large pelvic masses
Imaging studies for evaluation
Tissue sampling essential for diagnosis
Genetic counseling for familial cases.
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Gross Description
Appearance:
Large, lobulated mass with yellow, fatty cut surface
Soft, greasy consistency
Areas of myxoid change
Gelatinous appearance in some areas
May show necrosis and hemorrhage.
Characteristics:
Size ranges from 5-20 cm
Well-circumscribed to infiltrative margins
Cut surface shows yellow adipose tissue
Myxoid areas appear translucent
Solid areas may be present
Heterogeneous appearance.
Size Location:
Usually large at presentation
Mean size 8-12 cm
Involves uterine corpus
May extend to parametrium
Retroperitoneal extension possible
Extrauterine spread in advanced cases.
Multifocality:
Usually unifocal presentation
Multinodular growth pattern possible
May show satellite nodules
Local recurrence common
Distant metastases to lung.
Microscopic Description
Histological Features:
Malignant adipocytes with nuclear atypia
Lipoblasts with scalloped nuclei
Signet-ring lipoblasts
Increased cellularity
Mitotic activity variable
Areas of myxoid stroma
Dedifferentiated areas may be present.
Cellular Characteristics:
Atypical adipocytes with enlarged nuclei
Multivacuolated lipoblasts
Scalloped nuclear contours
Prominent nucleoli
Pleomorphic cells in high-grade areas
Multinucleated cells.
Architectural Patterns:
Lobular growth pattern
Myxoid matrix with branching capillaries
Solid areas with spindle cells
Chicken-wire vasculature in myxoid areas
Dedifferentiated high-grade areas.
Grading Criteria:
Well-differentiated: Low mitotic rate, minimal atypia
Dedifferentiated: High-grade areas present
Myxoid: Round cell component determines grade
Pleomorphic: High-grade by definition.
Immunohistochemistry
Positive Markers:
S-100 (positive in lipoblasts)
Vimentin
FABP4 (fatty acid binding protein)
Perilipin (specific for adipocytes)
C/EBPα (adipocyte marker)
Adipophilin.
Negative Markers:
Cytokeratins (negative)
Desmin (negative)
Smooth muscle actin (negative)
CD34 (negative in tumor cells)
CD117 (negative)
MyoD1 (negative).
Diagnostic Utility:
S-100 positivity in lipoblasts confirms diagnosis
FABP4 and Perilipin specific for adipocytic differentiation
Negative muscle markers exclude other sarcomas
MDM2 and CDK4 positive in well-differentiated/dedifferentiated types.
Molecular Subtypes:
MDM2 amplification (well-differentiated/dedifferentiated)
FUS-DDIT3 fusion (myxoid type)
Complex karyotype (pleomorphic type)
12q13-15 amplification.
Molecular/Genetic
Genetic Mutations:
MDM2 amplification (well-differentiated/dedifferentiated types)
CDK4 amplification
FUS-DDIT3 fusion (myxoid type)
TP53 mutations (pleomorphic type)
RB1 alterations.
Molecular Markers:
MDM2 overexpression
CDK4 overexpression
p16 loss
High Ki-67 in high-grade areas
DDIT3 rearrangement (myxoid type).
Prognostic Significance:
Histological type determines prognosis
Well-differentiated has best prognosis
Dedifferentiated has intermediate prognosis
Round cell component >5% indicates poor prognosis
Size >10 cm indicates poor outcome.
Therapeutic Targets:
MDM2 antagonists (AMG 232)
CDK4/6 inhibitors
mTOR inhibitors
Anti-angiogenic agents
Immunotherapy (investigational)
Combination chemotherapy.
Differential Diagnosis
Similar Entities:
Lipoma (benign adipocytic tumor)
Atypical lipomatous tumor (well-differentiated liposarcoma)
Leiomyosarcoma (smooth muscle differentiation)
Carcinosarcoma (epithelial component)
Adenosarcoma with heterologous elements.
Distinguishing Features:
Lipoma: Mature adipocytes, no atypia
Atypical lipomatous tumor: MDM2 positive, minimal atypia
Leiomyosarcoma: Smooth muscle markers positive
Liposarcoma: Lipoblasts present
Liposarcoma: S-100 positive in fat cells.
Diagnostic Challenges:
Distinguishing well-differentiated from atypical lipomatous tumor
Recognizing lipoblasts vs reactive changes
Identifying dedifferentiated areas
Excluding metastatic liposarcoma
Molecular studies may be helpful.
Rare Variants:
Well-differentiated liposarcoma
Dedifferentiated liposarcoma
Myxoid liposarcoma
Round cell liposarcoma
Pleomorphic liposarcoma.
Sample Pathology Report
Template Format
Sample Pathology Report
Complete Report: This is an example of how the final pathology report should be structured for this condition.
Specimen Information
[specimen type], measuring [size] cm, fatty/myxoid consistency
Diagnosis
Liposarcoma of the endometrium
Classification
WHO Classification: [Well-differentiated/Dedifferentiated/Myxoid/Pleomorphic] liposarcoma
Histological Features
Malignant adipocytic tumor with lipoblasts, mitoses: [count]/10 HPF
Subtype
Subtype: [specify], grade: [low/intermediate/high]
Dedifferentiation
Dedifferentiated areas: [present/absent], [percentage if present]%
Immunohistochemistry
Adipocytic markers: S-100 [+/-], FABP4 [+/-]
MDM2 [+/-], CDK4 [+/-]
Ki-67: [percentage]%
Molecular Studies
MDM2 amplification: [detected/not detected/not performed]
Final Diagnosis
[Subtype] liposarcoma of endometrium, [grade]