Definition/General
Introduction:
Cervical glassy cell carcinoma is a rare, aggressive variant of adenosquamous carcinoma characterized by large cells with abundant ground-glass cytoplasm, prominent nucleoli, and mixed glandular and squamous differentiation
It represents <1% of cervical cancers.
Origin:
Arises from transformation zone with both glandular and squamous differentiation
Develops through HPV-mediated transformation with distinctive cytoplasmic changes
Shows features of both adenocarcinoma and squamous carcinoma.
Classification:
WHO Classification considers this a variant of adenosquamous carcinoma
Characterized by distinctive glassy cytoplasm and mixed differentiation.
Epidemiology:
Peak incidence 30-50 years (younger than typical cervical cancers)
Represents <1% of cervical cancers
Strong HPV association
More aggressive than conventional adenosquamous carcinoma.
Clinical Features
Presentation:
Abnormal vaginal bleeding
Rapidly growing cervical mass
Often advanced stage at presentation
More aggressive than conventional cervical cancers.
Symptoms:
Abnormal vaginal bleeding (heavy, irregular)
Pelvic pain
Vaginal discharge
Constitutional symptoms with advanced disease
Early metastatic symptoms.
Risk Factors:
High-risk HPV infection
Young age
Multiple sexual partners
Early sexual activity
Immunosuppression
DES exposure.
Screening:
Standard cervical screening may detect
Distinctive cytology with glassy cells
Colposcopy with biopsy essential for diagnosis.
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Gross Description
Appearance:
Large, exophytic or ulcerative mass
Firm consistency
Variable hemorrhage and necrosis
May have granular surface texture.
Characteristics:
Size typically >3 cm at presentation
Firm consistency
Irregular borders
Gray-white to tan coloration
Surface ulceration common.
Size Location:
Usually involves transformation zone
Early parametrial extension possible
May extend to vaginal fornices
Lymph node involvement common.
Multifocality:
Usually unifocal but may be extensive
Associated with conventional cervical lesions possible
Field effect with other HPV lesions.
Microscopic Description
Histological Features:
Large cells with abundant ground-glass cytoplasm, prominent nucleoli, and mixed glandular and squamous differentiation
Inflammatory infiltrate with eosinophils characteristic.
Cellular Characteristics:
Large polygonal cells
Abundant ground-glass cytoplasm (glycogen-rich)
Large vesicular nuclei with prominent nucleoli
High nuclear grade.
Architectural Patterns:
Sheets and nests of cells
Mixed glandular and squamous patterns
Prominent inflammatory infiltrate with eosinophils
Stromal desmoplasia.
Grading Criteria:
High-grade by definition
High nuclear grade
Moderate to high mitotic rate
Mixed differentiation patterns
Inflammatory component.
Immunohistochemistry
Positive Markers:
p16 diffuse positive (HPV)
Cytokeratins positive
CEA positive
p63 may be positive in squamous areas
EMA positive.
Negative Markers:
Estrogen receptor usually negative
Progesterone receptor usually negative
TTF-1 negative
CDX2 negative
Neuroendocrine markers negative.
Diagnostic Utility:
p16 confirms HPV association
Mixed epithelial markers support adenosquamous nature
PAS-D may highlight glycogen in cytoplasm.
Molecular Subtypes:
HPV-associated glassy cell carcinoma
Mixed adenosquamous subtype.
Molecular/Genetic
Genetic Mutations:
HPV integration (high-risk types)
TP53 mutations
PIK3CA mutations
KRAS mutations possible
E-cadherin alterations.
Molecular Markers:
High-risk HPV DNA detection
p16 overexpression
High Ki-67 index
Loss of cell adhesion molecules.
Prognostic Significance:
Poor prognosis with aggressive behavior
Higher metastatic potential than conventional cervical cancers
Stage and treatment response important.
Therapeutic Targets:
HPV-targeted therapy
Immune checkpoint inhibitors
Platinum-based chemotherapy
Radiation therapy
Multimodal approach.
Differential Diagnosis
Similar Entities:
Clear cell carcinoma
Adenosquamous carcinoma without glassy features
Poorly differentiated adenocarcinoma
Metastatic clear cell carcinoma.
Distinguishing Features:
Glassy cell: Ground-glass cytoplasm, eosinophils
Clear cell: Hobnail cells, clear cytoplasm
Adenosquamous: No glassy cytoplasm.
Diagnostic Challenges:
Recognition of glassy cytoplasm
Distinction from clear cell carcinoma
Assessment of mixed differentiation
Metastatic disease exclusion.
Rare Variants:
Glassy cell with neuroendocrine features
Pure glassy cell adenocarcinoma
Glassy cell 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]