Definition/General
Introduction:
Endometrial chondrosarcoma is an extremely rare malignant cartilage-forming tumor of the uterus
It represents less than 1% of all uterine sarcomas
It shows chondroblastic differentiation with malignant cartilage production
It typically occurs as part of heterologous carcinosarcoma or adenosarcoma.
Origin:
Arises from endometrial mesenchymal cells with chondroblastic differentiation
May develop from pluripotent stromal cells
Can occur in the context of carcinosarcoma or adenosarcoma
Rarely occurs as pure chondrosarcoma.
Classification:
Classified as heterologous sarcoma by WHO classification
Conventional, dedifferentiated, and mesenchymal subtypes
Usually part of mixed heterologous sarcoma
Grade I-III based on cellularity and atypia.
Epidemiology:
Extremely rare tumor
Peak incidence in 5th-6th decades
Postmenopausal women predominantly affected
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
Firm mass on examination.
Symptoms:
Heavy menstrual bleeding
Pelvic pain
Abdominal distension
Weight loss
Urinary frequency
Constipation
Back pain.
Risk Factors:
Previous pelvic radiation
Age >50 years
Genetic predisposition (multiple hereditary exostoses, Ollier disease)
Previous chemotherapy
Maffucci syndrome.
Screening:
No specific screening recommendations
High suspicion for firm pelvic masses
Imaging studies may show calcifications
Tissue sampling essential for diagnosis.
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Gross Description
Appearance:
Firm, lobulated mass with translucent areas
Gray-blue cut surface with cartilaginous appearance
Gelatinous consistency in areas
May show calcifications.
Characteristics:
Size ranges from 4-12 cm
Well-demarcated to infiltrative margins
Cut surface shows hyaline cartilage
Translucent, pearly appearance
Areas of myxoid change.
Size Location:
Variable size at presentation
Mean size 6-9 cm
Involves uterine corpus
May extend to cervix
Parametrial extension possible.
Multifocality:
Usually unifocal presentation
Lobular growth pattern
May show satellite nodules
Local recurrence common
Distant metastases late.
Microscopic Description
Histological Features:
Malignant chondrocytes in cartilaginous matrix
Lacunar pattern with cells in spaces
Hyaline cartilage matrix
Increased cellularity
Nuclear atypia and pleomorphism
Variable mitotic activity.
Cellular Characteristics:
Enlarged chondrocytes with hyperchromatic nuclei
Binucleated cells common
Prominent nucleoli
Myxoid cytoplasm
Bizarre multinucleated cells in high-grade areas.
Architectural Patterns:
Lobular architecture
Hyaline cartilage matrix
Myxoid areas
Calcifications and ossification
Dedifferentiated areas (high-grade spindle cells).
Grading Criteria:
Grade I: Low cellularity, minimal atypia
Grade II: Moderate cellularity and atypia
Grade III: High cellularity, marked atypia, mitoses >5/10 HPF.
Immunohistochemistry
Positive Markers:
S-100 (positive in chondrocytes)
Vimentin
Collagen type II
Sox9 (chondrocyte transcription factor)
Aggrecan
Cartilage oligomeric matrix protein.
Negative Markers:
Cytokeratins (negative)
Desmin (negative)
Smooth muscle actin (negative)
CD117 (negative)
Osteocalcin (negative).
Diagnostic Utility:
S-100 positivity confirms chondrocytic differentiation
Sox9 specific for chondroblasts
Negative epithelial markers exclude carcinoma
Collagen type II specific for cartilage.
Molecular Subtypes:
IDH1/2 mutations (conventional type)
COL2A1 mutations
TP53 mutations (dedifferentiated areas)
CDKN2A deletions.
Molecular/Genetic
Genetic Mutations:
IDH1/2 mutations (conventional chondrosarcoma)
COL2A1 mutations
TP53 mutations (high-grade/dedifferentiated)
CDKN2A deletions
RB1 alterations.
Molecular Markers:
IDH1 R132H mutation (50-60% cases)
2-hydroxyglutarate accumulation
p53 overexpression (high-grade)
Loss of p16 expression.
Prognostic Significance:
Histological grade most important prognostic factor
Grade I has excellent prognosis
Grade III has poor prognosis
Size >8 cm indicates poor outcome
Dedifferentiation indicates aggressive behavior.
Therapeutic Targets:
IDH inhibitors (ivosidenib for IDH1 mutants)
mTOR inhibitors
Multi-kinase inhibitors
Immunotherapy
Conventional chemotherapy limited efficacy.
Differential Diagnosis
Similar Entities:
Osteosarcoma (bone formation)
Leiomyosarcoma (smooth muscle differentiation)
Chondroma (benign cartilage tumor)
Carcinosarcoma (epithelial component)
Metastatic chondrosarcoma.
Distinguishing Features:
Osteosarcoma: Osteoid formation
Leiomyosarcoma: Smooth muscle markers positive
Chondroma: Benign chondrocytes
Chondrosarcoma: S-100 positive
Chondrosarcoma: Malignant cartilage matrix.
Diagnostic Challenges:
Distinguishing from benign cartilage
Grading based on cellularity and atypia
Identifying dedifferentiated areas
Excluding metastatic disease
IDH mutation testing helpful.
Rare Variants:
Conventional chondrosarcoma
Dedifferentiated chondrosarcoma
Mesenchymal chondrosarcoma
Clear cell chondrosarcoma
Myxoid chondrosarcoma.
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, firm/cartilaginous consistency
Diagnosis
Chondrosarcoma of the endometrium
Classification
WHO Classification: [Conventional/Dedifferentiated/Mesenchymal] chondrosarcoma
Grade
Grade: [I/II/III], mitoses: [count]/10 HPF
Histological Features
Malignant cartilage-forming tumor with [cellularity] and [atypia level]
Cartilage Matrix
Cartilaginous matrix: [hyaline/myxoid/mixed], calcifications [present/absent]
Dedifferentiation
Dedifferentiated areas: [present/absent], [percentage if present]%
Immunohistochemistry
Chondrocytic markers: S-100 [+/-], Sox9 [+/-]
Negative: Cytokeratins, Desmin, SMA
Ki-67: [percentage]%
Molecular Studies
IDH1/2 mutation: [detected/not detected/not performed]
Final Diagnosis
[Subtype] chondrosarcoma of endometrium, Grade [I/II/III]