Definition/General
Introduction:
Primary ovarian sarcomas are rare mesenchymal malignancies comprising 1-2% of ovarian cancers
Include leiomyosarcoma (most common), fibrosarcoma, rhabdomyosarcoma, and undifferentiated sarcoma
Must be distinguished from carcinosarcoma (mixed epithelial-mesenchymal tumor) and metastatic sarcomas.
Origin:
Arise from ovarian stromal tissue, smooth muscle of ovarian vessels, or undifferentiated mesenchymal cells
Leiomyosarcoma arises from smooth muscle elements
Fibrosarcoma from fibrous connective tissue
Rhabdomyosarcoma from primitive mesenchymal cells with skeletal muscle differentiation
De novo development or transformation of benign tumors.
Classification:
WHO 2020 classification: Leiomyosarcoma (40% of ovarian sarcomas)
Fibrosarcoma (20%)
Rhabdomyosarcoma (15% - mostly pediatric)
Liposarcoma (rare)
Angiosarcoma (rare)
Undifferentiated sarcoma (15%)
Other sarcoma types (10%)
Grading: Low, intermediate, high-grade based on differentiation, necrosis, mitotic activity.
Epidemiology:
Peak incidence in 5th-6th decades except rhabdomyosarcoma (pediatric/young adults)
Unilateral in 85% cases (bilateral suggests metastatic disease)
Poor prognosis - 5-year survival 20-40%
Stage at diagnosis most important prognostic factor
Indian population - similar incidence to global rates
Rare in children except rhabdomyosarcoma.
Clinical Features
Presentation:
Rapidly enlarging pelvic mass (90% cases)
Abdominal pain and distension (75% cases)
Constitutional symptoms common due to aggressive nature
Tumor rupture may cause acute abdomen
Large size at presentation (average 15-20 cm)
Unilateral mass typically
Ascites less common than epithelial cancers.
Symptoms:
Pelvic/abdominal pain (80% cases)
Abdominal distension and bloating (70% cases)
Constitutional symptoms: weight loss (40%), fatigue (50%)
Menstrual irregularities (40% premenopausal)
Urinary symptoms from pelvic pressure (30%)
GI symptoms - early satiety, nausea (25%)
Acute pain if tumor rupture occurs.
Risk Factors:
Previous pelvic radiation (secondary sarcomas)
Genetic syndromes - Li-Fraumeni syndrome (p53 mutations), neurofibromatosis
Retinoblastoma gene mutations
Chemical exposure - alkylating agents
Prior malignancy with chemotherapy
Age 40-60 years (except rhabdomyosarcoma)
No specific hormonal associations.
Screening:
No specific screening for ovarian sarcomas
High-risk patients (genetic syndromes, post-radiation) need regular monitoring
Tumor markers usually normal (unlike epithelial cancers)
LDH may be elevated
Imaging shows solid mass with necrosis
MRI helpful for characterization
PET-CT for staging if high-grade.
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Gross Description
Appearance:
Large, solid, lobulated masses with hemorrhagic and necrotic areas
Leiomyosarcoma: white-gray, firm, whorled cut surface
Fibrosarcoma: firm, white-gray with fish-flesh appearance
Rhabdomyosarcoma: soft, gray-pink with gelatinous areas
Surface involvement with tumor nodules
Capsular invasion common.
Characteristics:
Firm to soft consistency depending on type
White-gray to pink-tan cut surface
Extensive necrosis (30-50% of tumor)
Hemorrhagic areas prominent
Myxoid degeneration in some cases
Cystic changes secondary to necrosis
Calcifications rare.
Size Location:
Large size at presentation (15-30 cm, average 20 cm)
Unilateral involvement in 85% cases
Any part of ovary can be affected
Surface involvement with rupture risk
Adherent to surrounding structures
Bilateral suggests metastatic disease.
Multifocality:
Usually solitary when primary
Multiple nodules suggest metastatic disease
Peritoneal implants rare compared to carcinomas
Lymph node involvement uncommon at presentation
Hematogenous spread to lungs, liver common in advanced cases.
Microscopic Description
Histological Features:
Leiomyosarcoma: fascicular growth pattern, spindle cells with eosinophilic cytoplasm
Fibrosarcoma: herringbone pattern, collagen production
Rhabdomyosarcoma: primitive mesenchymal cells, cross-striations (skeletal muscle)
High mitotic activity (>10/10 HPF)
Tumor necrosis present
Nuclear pleomorphism marked.
Cellular Characteristics:
Pleomorphic spindle cells with elongated nuclei
Hyperchromatic nuclei with coarse chromatin
Prominent nucleoli
Abundant eosinophilic cytoplasm (leiomyosarcoma)
Bizarre giant cells may be present
Atypical mitoses common
High nuclear-to-cytoplasmic ratio.
Architectural Patterns:
Fascicular pattern (leiomyosarcoma)
Herringbone pattern (fibrosarcoma)
Storiform pattern (undifferentiated)
Solid sheets with geographic necrosis
Pseudocapsule formation
Vascular invasion common
Infiltrative growth at periphery.
Grading Criteria:
FNCLCC grading system: differentiation score + mitotic count + necrosis score
Grade 1: well-differentiated, <10 mitoses/10 HPF, no necrosis
Grade 2: moderately differentiated, 10-19 mitoses, <50% necrosis
Grade 3: poorly differentiated, >20 mitoses, >50% necrosis
Grade correlates with prognosis.
Immunohistochemistry
Positive Markers:
Leiomyosarcoma: SMA (90%), desmin (70%), h-caldesmon (85%), calponin (80%)
Fibrosarcoma: vimentin (100%), CD34 (variable)
Rhabdomyosarcoma: desmin (95%), myogenin (90%), MyoD1 (85%)
All types: vimentin positive
Ki-67 high proliferation index (>50%).
Negative Markers:
Cytokeratins (negative - distinguishes from carcinosarcoma)
EMA (negative)
PAX8 (negative - excludes Müllerian origin)
WT1 (negative)
Inhibin (negative - excludes sex cord tumors)
S-100 (negative except in nerve sheath tumors)
CD117 (negative - excludes GIST).
Diagnostic Utility:
Muscle markers essential for leiomyosarcoma diagnosis
Myogenin/MyoD1 confirm rhabdomyosarcoma
Negative epithelial markers exclude carcinosarcoma
CD34 helps identify fibrosarcoma
High Ki-67 supports diagnosis
Panel approach necessary for accurate subtyping.
Molecular Subtypes:
Leiomyosarcoma: RB1 loss (60%), p53 mutations (50%)
Rhabdomyosarcoma: PAX3/PAX7-FOXO1 fusions (alveolar type)
Fibrosarcoma: complex karyotype
Undifferentiated: variable molecular profile
p53 overexpression correlates with poor prognosis.
Molecular/Genetic
Genetic Mutations:
TP53 mutations (60% of cases)
RB1 pathway alterations (40% leiomyosarcomas)
PTEN loss (30%)
MDM2 amplification (20%)
Rhabdomyosarcoma: PAX3-FOXO1 (alveolar), PAX7-FOXO1 fusions
Complex chromosomal aberrations
ATRX mutations (15%)
PIK3CA mutations (10%).
Molecular Markers:
p53 overexpression (mutant pattern)
Ki-67 proliferation index (typically >50%)
MDM2 amplification status
ATRX loss (nuclear staining)
Rb protein expression
PTEN expression
mTOR pathway activation
VEGF expression (angiogenesis).
Prognostic Significance:
Grade most important prognostic factor
Size >10 cm poor prognosis
p53 mutations associated with aggressive behavior
High Ki-67 (>50%) poor prognosis
Tumor necrosis negative prognostic factor
Age >60 years worse outcome
Stage at diagnosis critical.
Therapeutic Targets:
MDM2 inhibitors (nutlin-3) for MDM2-amplified cases
mTOR inhibitors (sirolimus)
Anti-angiogenic agents: bevacizumab, pazopanib
PARP inhibitors for DNA repair defects
Immune checkpoint inhibitors under investigation
CDK4/6 inhibitors for RB-deficient tumors.
Differential Diagnosis
Similar Entities:
Carcinosarcoma (malignant mixed Müllerian tumor)
Metastatic sarcoma (uterine leiomyosarcoma)
Fibrothecoma (benign stromal tumor)
Cellular fibroma
GIST (gastrointestinal stromal tumor)
Malignant peripheral nerve sheath tumor
Dedifferentiated liposarcoma.
Distinguishing Features:
Ovarian sarcoma: cytokeratin negative, pure mesenchymal
Carcinosarcoma: biphasic tumor, epithelial component
Metastatic: clinical history, bilateral, smaller
Fibrothecoma: bland spindle cells, no atypia
GIST: CD117+, DOG1+, GI tract origin
MPNST: S-100+, nerve association.
Diagnostic Challenges:
Distinguishing primary from metastatic sarcoma
Carcinosarcoma vs pure sarcoma
Cellular fibroma vs fibrosarcoma
Sampling adequacy in large necrotic tumors
Subtyping poorly differentiated sarcomas
Frozen section interpretation.
Rare Variants:
Angiosarcoma (vascular differentiation, CD31+)
Liposarcoma (adipocytic differentiation)
Chondrosarcoma (cartilaginous matrix)
Osteosarcoma (osteoid production)
Rhabdoid tumor (INI1 loss)
Undifferentiated pleomorphic sarcoma.
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
[Laterality] salpingo-oophorectomy, measuring [size] cm
Diagnosis
[Type] sarcoma of ovary
Classification and Grade
[Histological type], FNCLCC Grade [1/2/3]
Histological Features
Shows [fascicular/herringbone/storiform] pattern with pleomorphic spindle cells, mitotic count [X]/10 HPF, necrosis [X]%
Size and Extent
Tumor size: [X] cm, [confined to ovary/extraovarian extension], stage [I/II/III/IV]
Surgical Margins
Surgical margins: [clear/involved/close <1mm]
Lymphovascular Invasion
Lymphovascular invasion: [present/absent]
Lymph Node Status
Lymph nodes: [X] examined, [X] positive
Special Studies
IHC: [Muscle markers as appropriate for type], vimentin (+), cytokeratins (-), Ki-67 [X]%
Molecular: [p53, other markers if performed]
Grade: FNCLCC Grade [1/2/3] based on differentiation, mitoses, necrosis
Prognostic Factors
Type: [Histological type]; Grade: [FNCLCC grade]; Size: [X] cm; Stage: [stage]; Necrosis: [X]%
Final Diagnosis
[Type] sarcoma of [laterality] ovary, FNCLCC Grade [grade], Stage [stage]