Definition/General
Introduction:
Adenosarcoma is a rare biphasic malignant tumor of the uterus
It consists of benign epithelial and malignant mesenchymal components
It represents 5-10% of all uterine sarcomas
It typically has a better prognosis than other uterine sarcomas
It was first described by Clement and Scully in 1974.
Origin:
Arises from the endometrial stroma with surface epithelial involvement
The epithelial component is benign endometrial glands
The stromal component undergoes malignant transformation
May arise from adenofibroma with stromal overgrowth
Can develop in endometriosis or adenomyosis.
Classification:
Classified as mixed epithelial-mesenchymal tumor by WHO
Low-grade sarcoma with biphasic pattern
Distinguished from carcinosarcoma by benign epithelial component
Variants include adenosarcoma with sarcomatous overgrowth
May show heterologous elements.
Epidemiology:
Peak incidence in 6th decade (mean age 58 years)
Accounts for 2-5% of all uterine malignancies
Lower incidence than carcinosarcoma
Associated with unopposed estrogen exposure
Tamoxifen therapy increases risk
Prior pelvic radiation may be a risk factor.
Clinical Features
Presentation:
Abnormal uterine bleeding (80-90% cases)
Polypoid mass protruding through cervix
Enlarged, boggy uterus
Pelvic pressure symptoms
Postmenopausal bleeding most common
Rapidly growing uterine mass.
Symptoms:
Menorrhagia in premenopausal women
Postmenopausal bleeding
Pelvic pain and pressure
Urinary frequency
Passage of tissue per vaginum
Abdominal distension
Weight loss (advanced cases).
Risk Factors:
Unopposed estrogen exposure
Tamoxifen therapy
Obesity
Nulliparity
Late menopause
Previous pelvic radiation
Endometriosis
Lynch syndrome (possible association).
Screening:
No specific screening guidelines
High index of suspicion for polypoid lesions
Imaging studies for pelvic masses
Endometrial sampling may be diagnostic
Hysteroscopy for direct visualization.
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Gross Description
Appearance:
Polypoid, fleshy mass with smooth or lobulated surface
Gray-tan to pink cut surface
May show cystic spaces
Soft to firm consistency
Surface may be ulcerated or hemorrhagic.
Characteristics:
Size ranges from 2-15 cm
Polypoid or pedunculated configuration
Cut surface shows solid and cystic areas
May contain cartilage or bone
Leaf-like architecture may be evident
Hemorrhage and necrosis variable.
Size Location:
Mean size 5-8 cm
Primarily involves uterine corpus
May extend to lower uterine segment
Cervical involvement in 20-30% cases
Extrauterine spread uncommon at presentation.
Multifocality:
Usually unifocal at presentation
May be multiple polypoid masses
Deep myometrial invasion in advanced cases
Superficial spread more common than deep invasion
Extrauterine extension rare.
Microscopic Description
Histological Features:
Biphasic tumor with benign glands and malignant stroma
Leaf-like architecture with glands surrounded by cellular stroma
Periglandular stromal condensation
Stromal cells with mild to moderate atypia
Mitotic activity in stromal component (>2/10 HPF).
Cellular Characteristics:
Benign epithelial glands lined by endometrial-type epithelium
Stromal cells are spindle-shaped with elongated nuclei
Mild to moderate nuclear atypia in stroma
Increased stromal cellularity around glands
Mitotic figures predominantly in stromal component.
Architectural Patterns:
Intracanalicular growth pattern similar to phyllodes tumor
Cleft-like spaces lined by benign epithelium
Stromal condensation around glands
Papillary projections into glandular lumens
May show heterologous elements (cartilage, bone, skeletal muscle).
Grading Criteria:
Grading based on stromal mitotic activity
Low-grade: 2-4 mitoses/10 HPF
High-grade: >5 mitoses/10 HPF
Sarcomatous overgrowth: >25% pure sarcoma
Nuclear atypia assessment
Necrosis indicates higher grade.
Immunohistochemistry
Positive Markers:
Epithelial component: Cytokeratins (CK7, CK20)
EMA
ER and PR (usually positive)
Stromal component: Vimentin
CD10 (often positive)
ER and PR (variable)
Smooth muscle actin (focally positive).
Negative Markers:
Stromal component: Desmin (usually negative)
Caldesmon (negative)
CD117 (negative)
S-100 (negative unless neural differentiation)
Cytokeratins (negative in stroma).
Diagnostic Utility:
Cytokeratins confirm epithelial nature of glands
CD10 positivity supports endometrial stromal origin
ER/PR status guides therapy
Smooth muscle markers help exclude leiomyosarcoma
p53 usually wild-type pattern.
Molecular Subtypes:
No established molecular subtypes
Hormone receptor status important for treatment
Mismatch repair proteins should be assessed
p53 mutation rare
PTEN loss may be present.
Molecular/Genetic
Genetic Mutations:
PTEN mutations (30-40% cases)
PIK3CA mutations (20-30%)
KRAS mutations (15-20%)
CTNNB1 mutations (10-15%)
TP53 mutations rare in classic adenosarcoma
Microsatellite instability uncommon.
Molecular Markers:
ER/PR expression in both components
p53 usually wild-type pattern
p16 variable expression
PTEN loss by immunohistochemistry
β-catenin nuclear expression with CTNNB1 mutations.
Prognostic Significance:
Sarcomatous overgrowth indicates poor prognosis
Deep myometrial invasion associated with recurrence
ER/PR negativity may indicate aggressive behavior
p53 overexpression suggests transformation
High Ki-67 correlates with grade.
Therapeutic Targets:
Hormone therapy for ER/PR positive cases
mTOR inhibitors for PTEN-deficient tumors
PI3K/AKT pathway inhibitors
Immunotherapy for mismatch repair deficient cases
Anti-angiogenic agents.
Differential Diagnosis
Similar Entities:
Carcinosarcoma (malignant epithelial component)
Adenofibroma (benign stromal component)
Endometrial polyp with atypia
Adenomyoma with stromal atypia
Low-grade endometrial stromal sarcoma.
Distinguishing Features:
Carcinosarcoma: Malignant epithelial component
Carcinosarcoma: High-grade nuclear atypia
Adenofibroma: Benign stromal component
Adenofibroma: Low mitotic rate
Endometrial polyp: Benign stroma
ESS: Uniform stromal cells
Adenosarcoma: Periglandular stromal condensation.
Diagnostic Challenges:
Distinguishing from atypical adenofibroma
Recognizing sarcomatous overgrowth
Differentiating from endometrial polyp with atypia
Identifying heterologous elements
Adequate sampling essential for diagnosis.
Rare Variants:
Adenosarcoma with sarcomatous overgrowth (>25% pure sarcoma)
Heterologous adenosarcoma (cartilage, bone, skeletal muscle)
Sex cord-like adenosarcoma
Adenosarcoma with rhabdomyosarcomatous differentiation.
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, [polypoid/sessile] configuration
Diagnosis
Adenosarcoma of the uterus
Classification
WHO Classification: Mixed epithelial-mesenchymal tumor, [grade]
Histological Features
Biphasic tumor with benign glands and malignant stroma, stromal mitoses: [count]/10 HPF
Sarcomatous Overgrowth
Sarcomatous overgrowth: [present/absent], [percentage if present]%
Myometrial Invasion
Myometrial invasion: [depth] mm, [percentage]% of wall thickness
Heterologous Elements
Heterologous elements: [present/absent], [type if present]
Immunohistochemistry
Epithelial component: CK7+, ER [result], PR [result]
Stromal component: Vimentin+, CD10 [result], SMA [result]
p53: [wild-type/overexpressed]
Final Diagnosis
Adenosarcoma, [grade], [with/without sarcomatous overgrowth]