Definition/General
Introduction:
Fallopian tube glassy cell carcinoma is an extremely rare variant of tubal adenocarcinoma characterized by cells with ground-glass cytoplasm
It represents less than 0.5% of all fallopian tube carcinomas
The tumor is defined by the presence of abundant, glassy, eosinophilic cytoplasm that appears translucent or ground-glass-like
It demonstrates aggressive biological behavior similar to poorly differentiated adenocarcinomas
The cytological appearance is the defining characteristic of this rare entity.
Origin:
Originates from the epithelial cells of the fallopian tube that undergo specific cytoplasmic changes
The glassy cytoplasm results from accumulation of intermediate filaments and altered protein synthesis
Cellular stress responses may contribute to the characteristic morphology
The tumor may arise de novo or from transformation of pre-existing adenocarcinoma
Metabolic alterations in tumor cells lead to the distinctive cytoplasmic appearance.
Classification:
WHO classification recognizes it as a rare morphological variant of tubal adenocarcinoma
Glassy cell features must be present in >50% of tumor cells for diagnosis
High-grade adenocarcinoma with specific cytological features
Not to be confused with clear cell carcinoma (different cytoplasmic quality)
May show mixed patterns with conventional adenocarcinoma
Grading is typically high-grade (Grade 3).
Epidemiology:
Extremely rare with fewer than 20 cases reported in medical literature
Peak incidence in 5th-6th decades (similar to other tubal carcinomas)
No specific racial or ethnic predilection
No established association with BRCA mutations
May be more common in certain geographic regions (insufficient data)
Likely underdiagnosed due to unfamiliarity with morphology
No specific risk factors identified beyond those for tubal carcinomas.
Clinical Features
Presentation:
Pelvic mass with rapid growth pattern
Severe pelvic pain and cramping
Abnormal vaginal bleeding (postmenopausal or irregular)
Watery vaginal discharge (less common than in serous carcinomas)
Abdominal distension and bloating
Constitutional symptoms (weight loss, fatigue)
Advanced stage at presentation in majority of cases.
Symptoms:
Persistent pelvic pain and pressure sensation
Heavy menstrual bleeding or postmenopausal bleeding
Early satiety and abdominal fullness
Urinary frequency due to mass effect
Bowel symptoms (constipation, bloating)
Rapid symptom progression over weeks to months
Back pain from retroperitoneal involvement
Respiratory symptoms if pleural metastases present.
Risk Factors:
Advanced age (>50 years)
Nulliparity and infertility
Family history of gynecological cancers
Personal history of breast cancer
No established association with BRCA mutations for this specific variant
Environmental factors may play a role (insufficient data)
No protective effect of oral contraceptives established.
Screening:
No specific screening protocols due to extreme rarity
Standard gynecological surveillance for high-risk women
Pelvic examination and transvaginal ultrasound
CA-125 monitoring in high-risk patients (non-specific)
High index of suspicion for rapidly growing adnexal masses
Genetic counseling may be considered despite unclear hereditary pattern.
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Gross Description
Appearance:
Solid, firm tumor replacing normal tubal architecture
Tan to gray-white cut surface with smooth, homogeneous appearance
Well-circumscribed to locally infiltrative margins
Minimal necrosis compared to other high-grade carcinomas
Hemorrhage may be present but not prominent
Calcifications uncommon
Smooth, glistening cut surface may suggest the glassy nature.
Characteristics:
Homogeneous, solid appearance with minimal cystic change
Firm consistency with rubbery texture
Tan-pink coloration on cut surface
Smooth surface without prominent papillary projections
Well-demarcated from surrounding normal tissue
Minimal hemorrhage and necrosis
May show areas of conventional adenocarcinoma.
Size Location:
Size ranges from 3-12 cm (variable)
May involve entire fallopian tube or be focal
Ampullary and fimbrial involvement common
Unilateral in majority of reported cases
Extension to ovarian surface may occur
Peritoneal implants present in advanced cases
Retroperitoneal lymph node involvement at diagnosis.
Multifocality:
Usually unifocal within the fallopian tube
May show transition from normal epithelium
Satellite nodules uncommon
Bilateral tubal involvement rare
Ovarian surface involvement may represent metastasis
Peritoneal seeding in advanced cases
Lymphatic spread to regional lymph nodes.
Microscopic Description
Histological Features:
Large epithelial cells with distinctive ground-glass cytoplasm
Abundant, eosinophilic cytoplasm with translucent, glassy appearance
Distinct cell borders with minimal cytoplasmic overlap
Sheet-like growth pattern predominantly
Moderate to high nuclear grade
Prominent nucleoli in enlarged nuclei
Mitotic activity variable (10-25 per 10 HPF).
Cellular Characteristics:
Ground-glass cytoplasm is the defining feature (translucent, eosinophilic)
Large cell size (2-3 times normal epithelial cells)
Well-defined cell boundaries
Central to eccentric nuclei
Nuclear enlargement with irregular contours
Prominent nucleoli (single or multiple)
Moderate nuclear pleomorphism.
Architectural Patterns:
Solid sheet-like pattern is most common
Nesting pattern with peripheral palisading
Minimal glandular formation
Occasional cribriform areas
Infiltrative growth into surrounding stroma
Minimal papillary architecture
Pushing rather than infiltrative borders in some areas.
Grading Criteria:
High-grade adenocarcinoma (Grade 2-3) in most cases
Nuclear grade 2-3 (moderate to marked pleomorphism)
Architectural grade variable (solid pattern suggests higher grade)
Mitotic activity moderate to high (>10 per 10 HPF)
Presence of necrosis influences grading
Overall assessment typically yields high-grade classification.
Immunohistochemistry
Positive Markers:
CK7 (diffusely positive, cytoplasmic staining)
PAX8 (nuclear, positive in 90-95% confirming müllerian origin)
CA125 (positive in cytoplasm and luminal surface)
EMA (epithelial membrane antigen, positive)
WT1 (may be positive, nuclear staining)
p53 (variable pattern depending on mutation status)
Vimentin (may be focally positive).
Negative Markers:
CK20 (negative, excludes gastrointestinal origin)
CDX2 (negative, excludes intestinal differentiation)
TTF-1 (negative, excludes lung origin)
Napsin A (negative, unlike clear cell carcinoma)
HNF-1β (negative, unlike clear cell carcinoma)
p40/p63 (negative, excludes squamous differentiation)
Inhibin (negative, excludes sex cord-stromal tumors).
Diagnostic Utility:
PAX8 positivity confirms müllerian/gynecological origin
CK7+/CK20- pattern supports gynecological primary
Negative clear cell markers (Napsin A, HNF-1β) help exclude clear cell carcinoma
WT1 positivity may support serous-like differentiation
Negative TTF-1 excludes pulmonary metastasis
p53 pattern may provide prognostic information.
Molecular Subtypes:
p53 aberrant subtype (overexpression or null pattern)
ER/PR negative subtype (typically hormone receptor negative)
High proliferation subtype (elevated Ki-67 index)
DNA repair proficient subtype (most cases)
Chromosomally unstable subtype (complex karyotype)
Immune-excluded subtype (low immune infiltrate).
Molecular/Genetic
Genetic Mutations:
TP53 mutations (present in 70-80% of cases)
PIK3CA mutations (less common, 15-25%)
KRAS mutations (uncommon, <10%)
PTEN alterations (may be present)
BRCA1/2 mutations (no established association)
DNA mismatch repair genes (usually intact)
Chromosomal instability genes (various alterations).
Molecular Markers:
p53 protein accumulation (correlates with TP53 mutations)
Ki-67 proliferation index (variable, 20-60%)
Cyclin E overexpression (may be present)
EGFR expression (variable)
HER2 amplification (uncommon)
PD-L1 expression (variable, often low)
Homologous recombination usually proficient.
Prognostic Significance:
Poor prognosis similar to high-grade adenocarcinomas
Advanced stage at diagnosis (majority present as Stage III-IV)
Aggressive clinical behavior with rapid progression
Limited response to standard chemotherapy
High metastatic potential
Short overall survival (median 12-18 months)
p53 mutation status may influence treatment response.
Therapeutic Targets:
Platinum-based chemotherapy (carboplatin plus paclitaxel)
PARP inhibitors (limited efficacy due to HRD-negative status)
PI3K/mTOR inhibitors (for PIK3CA-mutated cases)
Anti-angiogenic agents (bevacizumab)
Immunotherapy (limited efficacy due to low PD-L1 expression)
Targeted therapy based on molecular profiling
Clinical trials for novel agents.
Differential Diagnosis
Similar Entities:
Clear cell carcinoma (clear cytoplasm vs ground-glass)
Poorly differentiated adenocarcinoma (lacks specific glassy features)
Metastatic adenocarcinoma with glassy cell features
Oncocytic variant adenocarcinoma (abundant eosinophilic cytoplasm)
Hepatoid adenocarcinoma (hepatocyte-like morphology)
Secretory carcinoma (specific molecular alterations)
Oxyphilic cell variant of endometrioid carcinoma.
Distinguishing Features:
Glassy vs clear cytoplasm: Ground-glass translucent vs optically clear
Glassy vs oncocytic: Translucent vs granular eosinophilic cytoplasm
Primary vs metastatic: Clinical history, PAX8 positivity, site of origin
Glassy vs hepatoid: Morphology, AFP negativity, site
Nuclear features: Variable pleomorphism vs specific patterns.
Diagnostic Challenges:
Distinguishing from clear cell carcinoma (cytoplasmic quality assessment)
Limited tissue samples may not show characteristic features
Overlap with other eosinophilic cytoplasm variants
Determining primary site when multiple organs involved
Rare entity leading to diagnostic uncertainty
Mixed morphology with conventional adenocarcinoma areas.
Rare Variants:
Mixed glassy cell and conventional adenocarcinoma
Glassy cell with serous features
Glassy cell with endometrioid differentiation
Pleomorphic glassy cell variant
Glassy cell with neuroendocrine features
Microglandular glassy cell pattern
Glassy cell with squamous 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
[Unilateral/Bilateral] salpingo-oophorectomy, fallopian tube measuring [size] cm with solid tumor
Diagnosis
Glassy cell carcinoma of fallopian tube
Classification
High-grade adenocarcinoma with glassy cell features (Grade 2-3)
Histological Features
Shows large cells with distinctive ground-glass, translucent cytoplasm and sheet-like growth pattern
Glassy Cell Features
Ground-glass cytoplasm present in >50% of tumor cells, well-defined cell borders, moderate nuclear pleomorphism
Extent of Disease
Size: [X] cm, Growth pattern: [solid/infiltrative], Necrosis: [minimal/absent]
Special Studies
CK7: positive, PAX8: positive (confirming müllerian origin), CA125: positive
Napsin A: negative, HNF-1β: negative (excluding clear cell carcinoma)
Ki-67 index: [variable, 20-60%]
Molecular Features
p53: [variable pattern], Consider molecular profiling for targeted therapy options
FIGO Staging
FIGO Stage: [IA/IB/IC/II/III/IV] - [staging details]
Prognostic Factors
Glassy cell carcinoma (poor prognosis), High-grade features, Stage: [I/II/III/IV]
Final Diagnosis
Primary fallopian tube glassy cell carcinoma, FIGO Stage [IA/IB/IC/II/III/IV]