Definition/General
Introduction:
Ovarian adenosquamous carcinoma is a rare variant of epithelial ovarian cancer containing both glandular and squamous components
It constitutes less than 1% of all ovarian carcinomas
The tumor demonstrates both adenocarcinomatous and squamous differentiation within the same lesion
It requires at least 10% squamous component for diagnosis
The prognosis is generally poor due to high-grade features.
Origin:
Arises from surface epithelium of the ovary or inclusion cysts
May develop from metaplastic transformation of conventional adenocarcinoma
The squamous component arises through squamous metaplasia of glandular epithelium
Associated with HPV infection in some cases
The pathogenesis involves dual differentiation pathways.
Classification:
WHO 2020 classifies as adenosquamous carcinoma under surface epithelial tumors
Requires both glandular and squamous components to be malignant
Graded using FIGO grading system
Most cases are high-grade (Grade 3)
Staged according to FIGO staging system.
Epidemiology:
Peak incidence in 6th-7th decades (55-65 years)
More common in postmenopausal women
Risk factors include nulliparity
Family history of ovarian/breast cancer
BRCA1/2 mutations (rare)
In Indian population, associated with late presentation and advanced stage.
Clinical Features
Presentation:
Most patients present with advanced stage disease (Stage III-IV in 70-80% cases)
Palpable adnexal mass (90% of cases)
Abdominal distension due to ascites (60-70%)
Pelvic pain or discomfort (50-60%)
Constitutional symptoms like weight loss and fatigue
Early satiety and bloating (40-50%).
Symptoms:
Abdominal pain (70-80% cases)
Pelvic pressure or fullness
Ascites with abdominal distension (60%)
Urinary symptoms (frequency, urgency) in 30%
Bowel symptoms (obstruction in advanced cases)
Vaginal bleeding (rare, <10%)
Paraneoplastic symptoms (hypercalcemia, thromboembolism).
Risk Factors:
Age >50 years (peak 55-65 years)
Nulliparity or low parity
Late menopause (>52 years)
Family history of ovarian/breast cancer
BRCA1/2 mutations (5-10% cases)
Personal history of breast/endometrial cancer
Infertility and ovulation induction drugs.
Screening:
No effective screening for general population
High-risk patients: CA-125 and transvaginal ultrasound
Pelvic examination and imaging (CT/MRI)
Genetic counseling for BRCA carriers
Consider prophylactic bilateral salpingo-oophorectomy in high-risk patients.
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Gross Description
Appearance:
Large, solid-cystic mass with irregular surface
Cut surface shows variegated appearance with solid and cystic areas
Gray-white solid areas representing adenocarcinomatous component
Yellow-tan areas with keratinization representing squamous component
Areas of necrosis and hemorrhage are common
Surface may show papillary excrescences.
Characteristics:
Size ranges from 8-25 cm (median 12-15 cm)
Firm to hard consistency in solid areas
Cystic areas contain serous to mucinous fluid
Cut surface shows heterogeneous appearance
Friable areas with necrosis and hemorrhage
May show calcifications or keratin pearls grossly.
Size Location:
Most tumors are large at presentation (>10 cm in 80% cases)
Can involve unilateral or bilateral ovaries (bilateral in 30-40%)
Usually involves the entire ovarian parenchyma
May show surface involvement with implants
Extension to surrounding structures common in advanced cases.
Multifocality:
Bilateral involvement in 30-40% of cases
Peritoneal implants common (60-70% at presentation)
Omental involvement frequent (omental cake formation)
May involve pelvic organs (uterus, bladder, rectum)
Lymph node metastases to pelvic and para-aortic nodes
Distant metastases to liver, lung, and bone.
Microscopic Description
Histological Features:
Tumor shows both glandular and squamous components
Adenocarcinomatous areas show irregular glands lined by atypical epithelial cells
Squamous component shows solid nests with varying degrees of keratinization
Transition zones between the two components are often present
High-grade nuclear features in both components
Abundant mitotic figures and atypical mitoses.
Cellular Characteristics:
Glandular component: cuboidal to columnar cells with enlarged, hyperchromatic nuclei
Prominent nucleoli and increased nuclear-cytoplasmic ratio
Squamous component: polygonal cells with abundant eosinophilic cytoplasm
Intercellular bridges and keratinization
Nuclear pleomorphism in both components
High mitotic rate (>10 mitoses/10 HPF).
Architectural Patterns:
Glandular pattern: Irregular, infiltrating glands with cribriform or solid areas
Squamous pattern: Solid nests with central keratinization or keratin pearls
Mixed pattern: Intimate admixture of both components
Invasive growth with stromal desmoplasia
Lymphovascular invasion frequently present.
Grading Criteria:
Most cases are high-grade (Grade 3) by definition
Grading based on FIGO system
Grade determined by worst component
Criteria include glandular architecture (<25% glands = Grade 3)
Nuclear pleomorphism (marked = Grade 3)
Mitotic count (>15/10 HPF = Grade 3).
Immunohistochemistry
Positive Markers:
Glandular component: CK7 positive (90-95%)
PAX8 positive (85-90%)
WT1 positive (variable, 40-60%)
CA-125 positive (80-85%)
Squamous component: p63 positive (95-100%)
CK5/6 positive (90-95%)
p40 positive (95-100%)
Both components: p53 positive (70-80%, often mutant pattern).
Negative Markers:
Glandular component: CK20 negative (helps exclude metastatic colorectal)
TTF-1 negative (excludes lung primary)
CDX2 negative (excludes GI primary)
Squamous component: CK7 negative or weak
PAX8 negative in squamous areas
Estrogen receptor usually negative or weak.
Diagnostic Utility:
IHC confirms dual differentiation
p63/p40 positivity essential for squamous component
PAX8/WT1 support ovarian origin of glandular component
p53 pattern helps determine molecular subtype
Mismatch repair proteins for hereditary cancer screening
Panel: CK7, CK20, PAX8, p63, p53, WT1.
Molecular Subtypes:
Most cases show p53 abnormal pattern (high-grade serous-like)
Homologous recombination deficiency in some cases
Microsatellite instability rare (<5%)
BRCA1/2 mutations in hereditary cases
May show copy number variations similar to high-grade serous carcinoma.
Molecular/Genetic
Genetic Mutations:
TP53 mutations in 70-80% of cases (similar to high-grade serous)
BRCA1/2 mutations in 10-15% (hereditary cases)
PIK3CA mutations in 20-25%
PTEN loss in 15-20%
RB1 mutations in squamous component
CDKN2A/p16 alterations
MYC amplification in aggressive cases.
Molecular Markers:
p53 accumulation (mutant pattern in 70-80%)
High Ki-67 proliferation index (>50%)
Loss of BRCA1 expression (germline/somatic)
Homologous recombination deficiency score
Tumor mutational burden variable
Microsatellite instability rare (<5%).
Prognostic Significance:
Poor prognosis compared to conventional serous carcinoma
5-year survival 20-30% for advanced stage
Younger age associated with better outcome
BRCA mutations predict platinum sensitivity
High tumor grade correlates with aggressive behavior
Stage at presentation most important prognostic factor.
Therapeutic Targets:
BRCA-mutated cases: PARP inhibitors (olaparib, niraparib)
Platinum-based chemotherapy (carboplatin + paclitaxel)
Anti-angiogenic therapy: bevacizumab
Immunotherapy: limited efficacy (PD-L1 rarely expressed)
PIK3CA-mutated cases: PI3K inhibitors (investigational).
Differential Diagnosis
Similar Entities:
Metastatic adenosquamous carcinoma from cervix, lung, or uterus
High-grade serous carcinoma with squamous metaplasia
Endometrioid carcinoma with squamous differentiation
Mucinous carcinoma with squamous areas
Squamous cell carcinoma of ovary (pure)
Mature teratoma with malignant transformation.
Distinguishing Features:
Metastatic cervical: HPV positive, p16 positive, smaller size
Primary ovarian: larger size, bilateral involvement common
Serous with metaplasia: focal squamous areas (<10%)
Adenosquamous: extensive squamous component (>10%)
Endometrioid: ER/PR positive, benign squamous metaplasia
Pure squamous: absence of glandular component
Teratoma: immature elements, younger age.
Diagnostic Challenges:
Distinguishing primary versus metastatic adenosquamous carcinoma
Determining percentage of squamous component for diagnosis
Recognizing transition areas between components
Excluding collision tumors (two separate primaries)
Identifying minimal glandular component in predominantly squamous tumors.
Rare Variants:
Adenosquamous with clear cell features
Adenosquamous with neuroendocrine differentiation
Microinvasive adenosquamous carcinoma arising in endometriosis
Adenosquamous with sarcomatoid features
HPV-associated adenosquamous carcinoma (rare in ovary).
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 salpingo-oophorectomy specimen measuring [X x Y x Z] cm, weighing [X] grams
Gross Description
Ovary replaced by solid-cystic mass measuring [X] cm. Cut surface shows variegated appearance with gray-white solid areas and cystic spaces containing [serous/mucinous] fluid. Areas of necrosis and hemorrhage present. Surface [smooth/nodular/ruptured]
Diagnosis
Adenosquamous Carcinoma, High-grade
Microscopic Description
Tumor shows admixture of glandular ([X]%) and squamous ([X]%) components. Glandular areas show irregular, infiltrating architecture with high-grade nuclear features. Squamous component demonstrates solid nests with keratinization and intercellular bridges. High mitotic rate present
Immunohistochemistry
CK7: Positive (glandular), Negative (squamous)\np63: Positive (squamous), Negative (glandular)\nPAX8: Positive (glandular)\np53: [Normal/Abnormal pattern]\nKi-67: [X]% proliferation index
Staging Information
Tumor size: [X] cm\nSurface involvement: [Present/Absent]\nCapsular rupture: [Present/Absent]\nLymphovascular invasion: [Present/Absent]\nFIGO Stage: [Stage]
Final Diagnosis
Ovarian Adenosquamous Carcinoma, High-grade, FIGO Stage [X]