Definition/General
Introduction:
Cervical adenocarcinoma represents 15-20% of cervical cancers, arising from the glandular epithelium of the endocervical canal
Unlike squamous cell carcinoma, adenocarcinoma shows increasing incidence and presents unique diagnostic challenges.
Origin:
Arises from endocervical glandular epithelium
Develops through progression from normal glands to adenocarcinoma in situ (AIS) to invasive adenocarcinoma
Strong association with high-risk HPV types.
Classification:
WHO Classification recognizes multiple subtypes: usual type, mucinous variants, clear cell, endometrioid, serous, and rare types
HPV-associated and HPV-independent variants.
Epidemiology:
Peak incidence 35-45 years (younger than squamous)
Increasing relative incidence
Strong association with HPV 18 and 45
More difficult to detect by screening.
Clinical Features
Presentation:
Abnormal vaginal bleeding
Watery vaginal discharge
Abnormal Pap smear
May be asymptomatic in early stages
Often presents at higher stage than squamous carcinoma.
Symptoms:
Vaginal bleeding (intermenstrual, postcoital)
Profuse watery discharge
Pelvic pain in advanced cases
May have minimal symptoms early
Abnormal cervical cytology.
Risk Factors:
High-risk HPV infection (especially HPV 18, 45)
Oral contraceptive use
DES exposure
Immunosuppression
Early sexual activity
Multiple sexual partners.
Screening:
Pap smear less sensitive than for squamous lesions
HPV testing important
Endocervical curettage may be needed
Colposcopy with endocervical assessment.
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Gross Description
Appearance:
May appear as normal cervix or show subtle changes
Endophytic growth pattern common
May present as cervical enlargement
Barrel-shaped cervix possible.
Characteristics:
Often not visible on visual inspection
Firm consistency
May show focal areas of hemorrhage or necrosis
Size variable at presentation.
Size Location:
Arises from endocervical canal
May extend into lower uterine segment
Can involve parametrium
Often difficult to assess size grossly.
Multifocality:
May be multifocal within endocervical canal
Skip lesions possible
Field effect with multiple abnormal glands.
Microscopic Description
Histological Features:
Invasive glandular structures showing varying degrees of differentiation
Loss of normal glandular architecture
Infiltrative growth pattern with stromal reaction.
Cellular Characteristics:
Enlarged, pleomorphic nuclei with prominent nucleoli
Increased nuclear-cytoplasmic ratio
Loss of nuclear polarity
Mitotic figures including atypical forms.
Architectural Patterns:
Complex glandular pattern
Back-to-back glands
Cribriform architecture
Solid areas in high-grade tumors
Stromal desmoplasia.
Grading Criteria:
Grade 1: Well-differentiated glands
Grade 2: Moderately differentiated
Grade 3: Poorly differentiated with solid areas
Silva pattern classification also used.
Immunohistochemistry
Positive Markers:
p16 diffuse positive in HPV-associated tumors
CEA positive
CK7 positive
PAX8 may be positive
Mucin stains positive.
Negative Markers:
CK20 negative
p63 negative
CK5/6 negative
TTF-1 negative
CDX2 negative (usually).
Diagnostic Utility:
p16 helps identify HPV-associated tumors
CEA and CK7 support glandular differentiation
Negative squamous markers help exclude adenosquamous carcinoma.
Molecular Subtypes:
HPV-associated usual type
HPV-independent types (clear cell, serous, mesonephric)
Gastric-type adenocarcinoma (HPV-independent).
Molecular/Genetic
Genetic Mutations:
HPV integration in HPV-associated types
STK11 mutations in gastric-type
KRAS mutations in mucinous types
TP53 mutations in serous type.
Molecular Markers:
HPV DNA detection
p16 overexpression in HPV-positive tumors
High Ki-67 in poorly differentiated tumors
Loss of STK11 in gastric-type.
Prognostic Significance:
HPV status affects prognosis
Silva pattern system predicts lymph node metastasis
Grade and stage most important prognostic factors.
Therapeutic Targets:
HPV-targeted immunotherapy for HPV-positive tumors
Immune checkpoint inhibitors
Bevacizumab for recurrent disease
Targeted therapy based on subtype.
Differential Diagnosis
Similar Entities:
Adenocarcinoma in situ (AIS)
Endometrial adenocarcinoma
Metastatic adenocarcinoma
Benign glandular hyperplasia
Endocervical polyp.
Distinguishing Features:
Invasive adenocarcinoma: Stromal invasion, desmoplasia
AIS: No invasion, intact basement membrane
Endometrial origin: p53+, MLH1 loss possible.
Diagnostic Challenges:
Small biopsy specimens
Distinction from AIS
Assessment of invasion depth
Determining primary site in mixed cases.
Rare Variants:
Gastric-type adenocarcinoma
Clear cell carcinoma
Serous carcinoma
Mesonephric adenocarcinoma
Adenoid basal carcinoma.
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]