Definition/General
Introduction:
Endometrial osteosarcoma is an extremely rare malignant bone-forming tumor of the uterus
It represents less than 1% of all uterine sarcomas
It shows osteoblastic differentiation with malignant osteoid production
It typically occurs as part of heterologous carcinosarcoma or adenosarcoma.
Origin:
Arises from endometrial mesenchymal cells with osteoblastic differentiation
May develop from pluripotent stromal cells
Can occur in the context of carcinosarcoma or adenosarcoma
Rarely occurs as pure osteosarcoma.
Classification:
Classified as heterologous sarcoma by WHO classification
Osteoblastic, chondroblastic, and fibroblastic subtypes
Usually part of mixed heterologous sarcoma
High-grade malignant neoplasm.
Epidemiology:
Extremely rare tumor
Peak incidence in 6th-7th decades
Postmenopausal women predominantly affected
Associated with previous pelvic radiation
May be linked to genetic predisposition.
Clinical Features
Presentation:
Abnormal uterine bleeding (most common)
Rapidly enlarging uterine mass
Postmenopausal bleeding
Pelvic pain and pressure
Hard, irregular mass on examination.
Symptoms:
Heavy bleeding
Pelvic pain
Abdominal distension
Weight loss
Urinary symptoms
Constipation
Back pain (possible bone metastases).
Risk Factors:
Previous pelvic radiation
Age >60 years
Genetic predisposition (Li-Fraumeni syndrome, hereditary retinoblastoma)
Previous chemotherapy
Paget disease (rare association).
Screening:
No specific screening recommendations
High suspicion for hard pelvic masses
Imaging studies show calcifications
Tissue sampling essential for diagnosis.
Master Osteosarcoma Pathology with RxDx
Access 100+ pathology videos and expert guidance with the RxDx app
Gross Description
Appearance:
Hard, gritty mass with calcifications
Gray-white cut surface with bone formation
Firm consistency
Areas of hemorrhage and necrosis
May show cartilaginous areas.
Characteristics:
Size ranges from 3-15 cm
Irregular margins
Cut surface shows chalky white areas
Gritty texture on cutting
Calcifications evident grossly.
Size Location:
Variable size at presentation
Mean size 7-10 cm
Involves uterine corpus
May extend to parametrium
Extrauterine spread common.
Multifocality:
Usually unifocal presentation
Infiltrative growth
May show satellite nodules
Bone metastases common
Lung metastases frequent.
Microscopic Description
Histological Features:
Malignant osteoblasts producing osteoid
Lace-like osteoid pattern
Pleomorphic cells with hyperchromatic nuclei
High mitotic activity
Atypical mitoses
Areas of necrosis.
Cellular Characteristics:
Large, pleomorphic osteoblasts
Prominent nucleoli
Increased nuclear-to-cytoplasmic ratio
Bizarre multinucleated cells
Osteoid production by malignant cells.
Architectural Patterns:
Osteoblastic pattern with osteoid formation
Chondroblastic pattern with cartilage
Fibroblastic pattern
Mixed patterns common
Areas of bone formation.
Grading Criteria:
All cases considered high-grade by definition
Mitotic count >10/10 HPF
Marked nuclear atypia
Necrosis present
Osteoid production confirms diagnosis.
Immunohistochemistry
Positive Markers:
Osteocalcin (specific for osteoblasts)
Osteonectin (SPARC)
Alkaline phosphatase
Vimentin
Runx2 (osteoblast transcription factor)
Osterix.
Negative Markers:
Cytokeratins (negative)
Desmin (negative)
Smooth muscle actin (negative)
S-100 (negative unless chondroid areas)
CD117 (negative).
Diagnostic Utility:
Osteocalcin positivity confirms osteoblastic differentiation
Alkaline phosphatase supports bone formation
Negative epithelial markers exclude carcinoma
Runx2 specific for osteoblasts.
Molecular Subtypes:
TP53 mutations common
RB1 alterations
MYC amplification
CDKN2A deletions
Complex chromosomal abnormalities.
Molecular/Genetic
Genetic Mutations:
TP53 mutations (80-90% cases)
RB1 mutations (40-50%)
CDKN2A deletions
MYC amplification
MDM2 amplification
PTEN loss.
Molecular Markers:
p53 overexpression
Loss of RB expression
p16 loss
High Ki-67 index (>50%)
Chromosomal instability.
Prognostic Significance:
TP53 mutations indicate poor prognosis
High-grade histology correlates with poor outcome
Size >5 cm indicates poor prognosis
Metastatic disease at presentation common.
Therapeutic Targets:
mTOR inhibitors
Multi-kinase inhibitors
Immunotherapy
Combination chemotherapy (doxorubicin-based)
Targeted bone agents.
Differential Diagnosis
Similar Entities:
Chondrosarcoma (cartilage formation)
Leiomyosarcoma (smooth muscle differentiation)
Carcinosarcoma (epithelial component)
Metastatic osteosarcoma
Ossifying fibroid (benign).
Distinguishing Features:
Chondrosarcoma: Cartilage matrix
Leiomyosarcoma: Smooth muscle markers positive
Osteosarcoma: Osteocalcin positive
Osteosarcoma: Malignant osteoid
Metastatic: Primary site evident.
Diagnostic Challenges:
Distinguishing from reactive bone formation
Identifying malignant osteoid
Excluding metastatic disease
Recognizing in mixed tumors
Immunohistochemistry essential.
Rare Variants:
Osteoblastic osteosarcoma
Chondroblastic osteosarcoma
Fibroblastic osteosarcoma
Small cell osteosarcoma
Telangiectatic osteosarcoma.
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, hard/gritty consistency
Diagnosis
Osteosarcoma of the endometrium
Classification
WHO Classification: [Osteoblastic/Chondroblastic/Fibroblastic] osteosarcoma
Histological Features
Malignant bone-forming tumor with osteoid production, mitoses: [count]/10 HPF
Osteoid Formation
Malignant osteoid: [present], pattern: [lace-like/other]
Grade
Grade: High-grade sarcoma
Immunohistochemistry
Osteoblastic markers: Osteocalcin [+/-], Alkaline phosphatase [+/-]
Negative: Cytokeratins, Desmin, SMA
Ki-67: [percentage]%
Final Diagnosis
[Subtype] osteosarcoma of endometrium, high-grade