Definition/General
Introduction:
Ovarian carcinosarcoma (malignant mixed Müllerian tumor) is a rare biphasic tumor containing both carcinomatous and sarcomatous elements
Accounts for 1-2% of ovarian malignancies
Previously called malignant mixed mesodermal tumor
Aggressive tumor with poor prognosis.
Origin:
Arises from ovarian surface epithelium or fallopian tube
Monoclonal origin - both components arise from common stem cell
Metaplastic theory - carcinoma undergoes sarcomatous transformation
Epithelial-mesenchymal transition (EMT) plays crucial role
p53 mutations drive tumor development.
Classification:
WHO 2020 classification: Homologous carcinosarcoma - sarcomatous elements native to ovary (fibrosarcoma, leiomyosarcoma)
Heterologous carcinosarcoma - elements foreign to ovary (chondrosarcoma, osteosarcoma, rhabdomyosarcoma)
Epithelial component usually high-grade serous or endometrioid
FIGO staging applies.
Epidemiology:
Peak incidence in 6th-7th decades
Postmenopausal women predominantly affected
Unilateral in 75% cases
Poor prognosis - 5-year survival 20-30%
Indian population - similar age distribution
Associated with Lynch syndrome occasionally.
Clinical Features
Presentation:
Rapidly enlarging pelvic mass (90% cases)
Abdominal distension with ascites (70% cases)
Pelvic/abdominal pain (80% cases)
Postmenopausal bleeding (30% cases)
Constitutional symptoms common due to aggressive nature
Advanced stage at presentation (70% stage III-IV).
Symptoms:
Abdominal pain and distension (85% cases)
Pelvic pressure and fullness (70% cases)
Postmenopausal bleeding (30% cases)
Weight loss and fatigue (40% cases)
Urinary symptoms from pelvic pressure (25% cases)
Bowel symptoms - constipation, early satiety (20% cases).
Risk Factors:
Postmenopausal status
Age >60 years
Prior radiation therapy (pelvic radiation)
Lynch syndrome (MSI-high tumors)
Previous chemotherapy with alkylating agents
Nulliparity
Family history of gynecological cancers.
Screening:
No specific screening available
CA-125 elevated in 80% cases
LDH may be elevated
Imaging shows solid-cystic mass with necrosis
MRI helpful for characterization
PET-CT for staging
Tissue diagnosis essential.
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Gross Description
Appearance:
Large, solid-cystic masses with variegated cut surface
Gray-white areas (carcinomatous) and fleshy areas (sarcomatous)
Extensive necrosis and hemorrhage common
Friable consistency
Papillary projections may be present
Surface involvement with tumor rupture.
Characteristics:
Firm to soft consistency
Variegated appearance - solid and cystic areas
Gray-white to tan-pink coloration
Extensive necrosis (>50% in many cases)
Hemorrhagic areas prominent
Calcifications may be present (chondrosarcomatous areas).
Size Location:
Large size at presentation (10-30 cm, average 15-20 cm)
Unilateral involvement in 75% cases
Bilateral suggests advanced disease
Surface involvement common
Adherent to surrounding structures
Peritoneal implants frequent.
Multifocality:
Usually solitary when confined to ovary
Peritoneal carcinomatosis common at presentation
Omental involvement frequent
Lymph node metastases (30% cases)
Hematogenous spread to lungs, liver
Both components can metastasize.
Microscopic Description
Histological Features:
Biphasic tumor with distinct carcinomatous and sarcomatous areas
Carcinomatous component: high-grade serous, endometrioid, or clear cell morphology
Sarcomatous component: homologous (fibrosarcoma, leiomyosarcoma) or heterologous (chondrosarcoma, osteosarcoma, rhabdomyosarcoma)
Abrupt transition between components.
Cellular Characteristics:
Carcinomatous areas: malignant epithelial cells with pleomorphic nuclei, prominent nucleoli
Sarcomatous areas: spindle cells with elongated nuclei, variable differentiation
High mitotic activity in both components (>10/10 HPF)
Bizarre giant cells may be present.
Architectural Patterns:
Carcinomatous pattern: glandular, papillary, or solid growth
Sarcomatous pattern: fascicular (leiomyosarcoma), storiform (fibrosarcoma), cartilaginous (chondrosarcoma)
Mixed pattern: intimate admixture of both components
Geographic necrosis prominent.
Grading Criteria:
High-grade tumor by definition
Carcinomatous component graded as per standard criteria
Sarcomatous component graded by FNCLCC system
Overall grade determined by higher-grade component
Mitotic count important prognostic factor.
Immunohistochemistry
Positive Markers:
Carcinomatous component: cytokeratins (AE1/AE3, CAM5.2), PAX8 (Müllerian origin), WT1 (serous), ER/PR (variable)
Sarcomatous component: vimentin (100%), specific markers based on differentiation (SMA - leiomyosarcoma, S-100 - chondrosarcoma, desmin - rhabdomyosarcoma).
Negative Markers:
Carcinomatous areas: vimentin (usually negative), muscle markers (negative)
Sarcomatous areas: cytokeratins (negative), PAX8 (negative), WT1 (negative)
Both components: inhibin (negative), calretinin (negative).
Diagnostic Utility:
Cytokeratins essential to identify carcinomatous component
PAX8 positivity confirms Müllerian origin
Muscle markers identify leiomyosarcomatous differentiation
S-100 for chondrosarcomatous areas
p53 usually overexpressed in both components
Ki-67 high in both (>50%).
Molecular Subtypes:
p53-mutated type (most common)
MSI-high type (Lynch syndrome-associated)
BRCA-associated (rare)
Both components show similar molecular profile supporting monoclonal origin.
Molecular/Genetic
Genetic Mutations:
TP53 mutations (90% of cases)
BRCA1/2 mutations (10-15%)
PIK3CA mutations (30%)
PTEN loss (25%)
MSI-high (Lynch syndrome cases - 5%)
KRAS mutations (20%)
ARID1A mutations (25%).
Molecular Markers:
p53 overexpression (mutant pattern)
Ki-67 high proliferation (>70%)
PTEN loss (IHC)
MMR protein loss (MSI-high cases)
ARID1A loss
β-catenin (nuclear in endometrioid areas)
HER2 amplification (rare).
Prognostic Significance:
Stage most important prognostic factor
Size >10 cm poor prognosis
Heterologous elements worse prognosis than homologous
p53 mutations universal but not prognostic
MSI-high may predict immunotherapy response
Residual disease after surgery critical.
Therapeutic Targets:
Carboplatin/paclitaxel standard first-line therapy
PD-1/PD-L1 inhibitors for MSI-high tumors
PARP inhibitors for BRCA-mutated cases
mTOR inhibitors for PI3K pathway alterations
Anti-angiogenic agents: bevacizumab
CDK4/6 inhibitors under investigation.
Differential Diagnosis
Similar Entities:
High-grade serous carcinoma with spindle cell metaplasia
Endometrioid carcinoma with squamous differentiation
Clear cell carcinoma with solid areas
Pure sarcoma of ovary
Metastatic carcinosarcoma (uterine origin)
Immature teratoma with malignant transformation.
Distinguishing Features:
Carcinosarcoma: distinct biphasic morphology, cytokeratin+ and vimentin+ areas
Serous carcinoma: pure epithelial, no true sarcoma
Endometrioid: squamous not sarcomatous
Pure sarcoma: no epithelial component
Metastatic: uterine primary, bilateral
Teratoma: immature neural elements, younger age.
Diagnostic Challenges:
Distinguishing true carcinosarcoma from carcinoma with spindle cell metaplasia
Extensive sampling needed to demonstrate both components
Primary vs metastatic (uterine carcinosarcoma)
Frozen section interpretation challenging
Heterologous elements identification.
Rare Variants:
Adenosarcoma with malignant transformation
Carcinosarcoma with neuroendocrine differentiation
Carcinosarcoma with germ cell elements
Serous carcinosarcoma (most common epithelial type)
Endometrioid carcinosarcoma.
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 with omentum, measuring [size] cm
Diagnosis
Carcinosarcoma (malignant mixed Müllerian tumor)
Classification and Components
Carcinosarcoma with [carcinomatous type] and [sarcomatous type] components
Histological Features
Shows biphasic tumor with malignant epithelial ([type]) and sarcomatous ([homologous/heterologous]) components
Size and Extent
Tumor size: [X] cm, FIGO Stage: [stage], [surface involvement status]
Surgical Margins
Surgical margins: [clear/involved]
Lymphovascular Invasion
Lymphovascular invasion: [present/absent] in [carcinomatous/sarcomatous/both] component(s)
Lymph Node Status
Lymph nodes: [X] positive out of [X] examined
Special Studies
IHC: Carcinoma areas: cytokeratin (+), PAX8 (+); Sarcoma areas: vimentin (+), [specific markers based on type]
Molecular: p53 [result], MSI status [result] if performed
Both components show similar molecular profile supporting monoclonal origin
Prognostic Factors
Components: [carcinoma type] + [sarcoma type]; Grade: high-grade; Stage: [FIGO stage]; Size: [X] cm
Final Diagnosis
Carcinosarcoma of [laterality] ovary, FIGO Stage [stage]