Definition/General
Introduction:
Ovarian metaplastic carcinoma is an extremely rare malignant tumor containing both epithelial and mesenchymal components
It represents less than 0.5% of all ovarian malignancies
Also known as carcinosarcoma or malignant mixed müllerian tumor (MMMT)
Contains carcinomatous and sarcomatous elements
Shows biphasic morphology with distinct epithelial and mesenchymal differentiation.
Origin:
Arises from surface epithelium or inclusion cysts of the ovary
Results from epithelial-mesenchymal transition (EMT)
May arise from pre-existing adenocarcinoma with sarcomatous transformation
Monoclonal origin demonstrated by molecular studies
Represents dedifferentiation of epithelial carcinoma with acquisition of mesenchymal features.
Classification:
Classified under WHO 2020 as mixed epithelial and mesenchymal tumor
Homologous type: mesenchymal elements native to müllerian tract
Heterologous type: foreign mesenchymal elements (cartilage, bone, striated muscle)
High-grade tumor by definition
FIGO staging follows standard ovarian cancer protocols.
Epidemiology:
Peak incidence in 6th-7th decades (55-70 years)
Postmenopausal women predominantly affected (>90%)
Advanced stage at presentation (70% cases Stage III-IV)
Aggressive behavior with poor prognosis
Indian population shows similar demographics
Associated with prior radiation therapy or chemotherapy in some cases.
Clinical Features
Presentation:
Large pelvic mass (most common presentation in 90% cases)
Abdominal distension and bloating
Rapid tumor growth with increasing abdominal girth
Advanced stage at presentation (70% Stage III-IV)
Bilateral involvement in 30-40% cases
Often presents with metastatic disease.
Symptoms:
Abdominal pain and discomfort (80% cases)
Abdominal distension due to large tumor mass
Weight loss and constitutional symptoms
Early satiety and nausea
Bowel obstruction symptoms (advanced cases)
Shortness of breath due to ascites or pleural effusion.
Risk Factors:
Age >55 years (primary risk factor)
Prior radiation therapy to pelvis
Previous chemotherapy exposure
Nulliparity or low parity
Late menopause (>52 years)
Family history of ovarian/breast cancer
Lynch syndrome (rare association).
Screening:
Transvaginal ultrasound shows complex solid-cystic mass
CA-125 markedly elevated (>500 U/mL typically)
CT/MRI abdomen-pelvis for staging
PET-CT to assess metastatic disease
Tissue biopsy required for definitive diagnosis
Genetic counseling for hereditary cancer syndromes.
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Gross Description
Appearance:
Large, bulky tumor with solid and cystic areas
Variegated cut surface with areas of hemorrhage and necrosis
Firm to hard consistency depending on mesenchymal components
May show gritty areas if cartilage or bone present
Gray-white to tan cut surface with focal hemorrhage.
Characteristics:
Mixed solid-cystic architecture on cut surface
Extensive necrosis (50-70% of cases)
Hemorrhagic areas common
Friable consistency in some areas
Hard, gritty areas if heterologous elements present
Surface involvement common (60-70% cases).
Size Location:
Size ranges from 8-25 cm (median 12 cm)
Unilateral involvement more common (60-70%)
Can arise from any part of ovary
Surface involvement frequent
Bilateral disease in 30-40% cases
Often adherent to adjacent structures.
Multifocality:
Unifocal presentation typically
Bilateral involvement in 30-40% cases
Peritoneal implants common at presentation (60% cases)
Lymph node metastases frequent (40-50%)
Omental involvement common (70% advanced cases)
Ascites present in 50-60% cases.
Microscopic Description
Histological Features:
Biphasic tumor with distinct epithelial and mesenchymal components
Carcinomatous component: high-grade adenocarcinoma (serous, endometrioid, or undifferentiated)
Sarcomatous component: fibrosarcoma, leiomyosarcoma, or undifferentiated sarcoma
Sharp transition between components
Extensive necrosis and hemorrhage common.
Cellular Characteristics:
Epithelial component: high-grade nuclear features, prominent nucleoli, high mitotic activity
Mesenchymal component: spindle cells with pleomorphic nuclei, high nuclear-to-cytoplasmic ratio
Atypical mitoses frequent in both components
Necrosis present in >50% cases.
Architectural Patterns:
Epithelial areas: glandular, papillary, or solid patterns
Mesenchymal areas: fascicular, storiform, or disorganized growth
Homologous elements: smooth muscle, endometrial stroma, fibrous tissue
Heterologous elements: cartilage, bone, skeletal muscle (when present)
Transition zones between epithelial and mesenchymal areas.
Grading Criteria:
High-grade tumor by definition
Both components are high-grade malignant
Mitotic activity >10/10 HPF in both components
Nuclear pleomorphism marked in both areas
Necrosis present in majority of cases
No grading system applicable (all considered high-grade).
Immunohistochemistry
Positive Markers:
Epithelial component: CK7 (90-95%), PAX8 (85-90%), WT1 (70-80%), CA125 (60-70%), p53 (abnormal pattern 70-80%)
Mesenchymal component: Vimentin (95-100%), SMA (30-40% if smooth muscle), Desmin (20-30% if smooth muscle), p63 (60-70%).
Negative Markers:
Epithelial areas: CK20, CDX2, TTF1, Mammaglobin, GCDFP15
Mesenchymal areas: CK7, CK20, EMA (focal positivity may occur), PAX8 (negative in sarcomatous areas)
Both components: Inhibin, Calretinin (excludes sex cord stromal tumor).
Diagnostic Utility:
Dual staining pattern confirms biphasic nature
PAX8 positivity in epithelial areas confirms ovarian origin
p63 positivity in mesenchymal areas supports carcinosarcoma
Cytokeratin negativity in sarcomatous areas important
p53 pattern may be abnormal in both components.
Molecular Subtypes:
High-grade serous-like molecular profile in epithelial component
TP53 mutations common in both components (monoclonal origin)
Homologous recombination deficiency (HRD) may be present
High tumor mutational burden in some cases
Epithelial-mesenchymal transition markers positive.
Molecular/Genetic
Genetic Mutations:
TP53 mutations (80-90% cases - found in both components)
BRCA1/2 mutations (15-20% hereditary cases)
PIK3CA mutations (20-25% cases)
PTEN mutations (15-20% cases)
RB1 mutations (10-15% cases)
CDKN2A deletions (20-30% cases).
Molecular Markers:
p53 abnormal expression in both components (80-90%)
High Ki-67 proliferation index (>50% typically)
Loss of RB expression (30-40% cases)
PTEN loss (20-30% cases)
Homologous recombination deficiency (HRD) score elevated
Tumor mutational burden variable.
Prognostic Significance:
Poor prognosis compared to pure epithelial carcinomas
Stage at presentation most important prognostic factor
Sarcomatous component predicts worse outcome
Heterologous elements associated with poor prognosis
5-year survival: Stage I-II (40-60%), Stage III-IV (10-20%)
BRCA mutations may predict better response to platinum therapy.
Therapeutic Targets:
Platinum-based chemotherapy (standard first-line)
PARP inhibitors for BRCA-mutated or HRD-positive cases
Anti-angiogenic agents (bevacizumab)
Immunotherapy (checkpoint inhibitors in MSI-high cases)
mTOR inhibitors (investigational)
CDK4/6 inhibitors (limited efficacy).
Differential Diagnosis
Similar Entities:
High-grade serous carcinoma with spindle cell areas
Endometrioid adenocarcinoma with squamous differentiation
Clear cell carcinoma with solid areas
Undifferentiated carcinoma
Primary ovarian sarcoma
Metastatic carcinosarcoma (uterine origin).
Distinguishing Features:
vs Serous carcinoma: Lacks biphasic morphology
No mesenchymal markers in spindle areas
vs Endometrioid: Squamous differentiation benign
No high-grade sarcomatous areas
vs Clear cell: Lacks hobnail morphology
vs Sarcoma: No epithelial component
Cytokeratin negative
vs Uterine primary: Clinical correlation essential.
Diagnostic Challenges:
Sampling issues may miss biphasic nature
Poorly differentiated areas difficult to classify
Distinction from uterine primary challenging
Small biopsy samples may be inadequate
Immunohistochemistry essential for accurate diagnosis
Molecular studies may be helpful.
Rare Variants:
Adenosarcoma with malignant transformation
Carcinosarcoma with neuroendocrine differentiation
Mixed epithelial-mesenchymal tumor with sex cord elements
Carcinosarcoma with primitive neuroectodermal elements
Each variant requires specialized immunohistochemical workup.
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
Right/Left ovary and fallopian tube, measuring [X x Y x Z] cm and weighing [X] grams. Omentum and peritoneal biopsies as indicated.
Gross Description
The ovary shows a [X] cm solid-cystic mass with variegated cut surface, areas of necrosis and hemorrhage. Surface [involved/uninvolved]. Fallopian tube appears [normal/abnormal].
Microscopic Description
Biphasic tumor with epithelial component showing [features] and mesenchymal component with [features]. [Homologous/Heterologous] elements present.
Immunohistochemistry
Epithelial areas: CK7 Positive, PAX8 Positive, p53 [pattern]. Mesenchymal areas: Vimentin Positive, p63 Positive, Cytokeratins Negative.
Diagnosis
Ovarian Metaplastic Carcinoma (Carcinosarcoma), [Homologous/Heterologous], FIGO Stage [stage]
Staging (FIGO 2014)
T[X]N[X]M[X], Stage [I/II/III/IV] with detailed staging criteria
Final Diagnosis
Right/Left Ovarian Metaplastic Carcinoma (Carcinosarcoma), [Homologous/Heterologous], FIGO Stage [X], with detailed prognostic factors