Definition/General
Introduction:
Cervical adenosquamous carcinoma is a rare type of cervical cancer containing both glandular (adenocarcinoma) and squamous cell carcinoma components
It represents 3-5% of all cervical cancers and typically shows more aggressive behavior than pure adenocarcinoma or squamous cell carcinoma.
Origin:
Arises from transformation zone containing both squamous and glandular epithelium
Develops through HPV-mediated transformation affecting both epithelial types
Strong association with high-risk HPV types.
Classification:
WHO Classification recognizes adenosquamous carcinoma as a distinct entity
Requires both glandular and squamous components to be malignant
Both components must be intimately admixed.
Epidemiology:
Peak incidence 40-50 years
Represents 3-5% of cervical cancers
Strong association with HPV 16 and 18
More aggressive than pure histologic types
Higher stage at presentation.
Clinical Features
Presentation:
Abnormal vaginal bleeding (most common)
Abnormal Pap smear showing mixed cell types
Visible cervical lesion
Often presents at higher stage than pure types.
Symptoms:
Vaginal bleeding (intermenstrual, postcoital, postmenopausal)
Vaginal discharge (watery, bloody, foul-smelling)
Pelvic pain more common
Constitutional symptoms in advanced disease.
Risk Factors:
High-risk HPV infection (major risk factor)
Multiple sexual partners
Early sexual activity
Immunosuppression
Smoking
Long-term oral contraceptive use.
Screening:
Pap smear may show mixed cell population
HPV testing important
Colposcopy with directed biopsy
Endocervical curettage may be needed for full assessment.
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Gross Description
Appearance:
Exophytic, ulcerative, or infiltrative lesion
May show mixed texture areas
Friable and easily bleeding
Variable consistency from soft to firm.
Characteristics:
Size variable (1-8 cm)
Mixed consistency reflecting dual components
Irregular surface
Gray-white to tan coloration
May involve entire cervix.
Size Location:
Usually arises from transformation zone
May extend extensively into parametrium
Can involve vaginal fornices and lower uterine segment
Often larger at presentation.
Multifocality:
May be multifocal within cervix
Both components usually present throughout tumor
Field effect with mixed precursor lesions possible.
Microscopic Description
Histological Features:
Intimate admixture of malignant glandular and squamous components
Both components must be invasive
Transition zones between components
Variable proportions of each component.
Cellular Characteristics:
Glandular areas: Enlarged nuclei, loss of polarity
Squamous areas: Polygonal cells, keratinization variable
Both components show malignant cytology.
Architectural Patterns:
Glandular component: Irregular glands, back-to-back arrangement
Squamous component: Nests, cords, solid areas
Stromal invasion by both components.
Grading Criteria:
Grade based on worst component
Usually moderately to poorly differentiated
High nuclear grade common
High mitotic activity in both components.
Immunohistochemistry
Positive Markers:
p16 diffuse positive (HPV-associated)
CK7 positive in glandular areas
p63 positive in squamous areas
CEA may be positive
PAX8 variable.
Negative Markers:
CK20 usually negative
TTF-1 negative
CDX2 negative
WT1 negative
Neuroendocrine markers negative.
Diagnostic Utility:
p16 confirms HPV association
p63 highlights squamous component
CK7 marks glandular areas
CEA supports glandular differentiation.
Molecular Subtypes:
HPV-associated mixed carcinoma
Usually shows high-risk HPV integration in both components.
Molecular/Genetic
Genetic Mutations:
HPV integration affects both components
E6 and E7 oncoproteins
PIK3CA mutations
KRAS mutations possible
TP53 pathway inactivation.
Molecular Markers:
HPV DNA detection in both components
p16 overexpression
High Ki-67 in both areas
Loss of p53 and Rb function.
Prognostic Significance:
Generally worse prognosis than pure types
Higher stage at presentation
Increased lymph node metastasis
Resistance to treatment.
Therapeutic Targets:
HPV-targeted immunotherapy
Immune checkpoint inhibitors
Bevacizumab for recurrent disease
Combination chemotherapy regimens.
Differential Diagnosis
Similar Entities:
Collision tumor (separate adenocarcinoma and squamous carcinoma)
Adenocarcinoma with squamous metaplasia
Squamous carcinoma with glandular differentiation
Mixed CIN/AIS lesions.
Distinguishing Features:
Adenosquamous: Intimate admixture, both invasive
Collision: Separate tumor areas
Metaplasia: Benign squamous areas, single malignant component.
Diagnostic Challenges:
Distinguishing from collision tumors
Assessment of invasion in both components
Small biopsy interpretation
Quantification of components.
Rare Variants:
Adenosquamous with neuroendocrine differentiation
Glassy cell variant
Adenosquamous with sarcomatoid features.
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 in greatest dimension
Diagnosis
[diagnosis name]
Classification
Classification: [classification system] [grade/type]
Histological Features
Shows [architectural pattern] with [nuclear features] and [mitotic activity]
Size and Extent
Size: [X] cm, extent: [local/regional/metastatic]
Margins
Margins are [involved/uninvolved] with closest margin [X] mm
Lymphovascular Invasion
Lymphovascular invasion: [present/absent]
Lymph Node Status
Lymph nodes: [X] positive out of [X] examined
Special Studies
IHC: [marker]: [result]
Molecular: [test]: [result]
[other study]: [result]
Prognostic Factors
Prognostic factors: [list factors]
Final Diagnosis
Final diagnosis: [complete diagnosis]