Definition/General
Introduction:
Endometrial mucinous carcinoma is a rare variant of endometrial adenocarcinoma characterized by abundant intracytoplasmic mucin
It represents 1-9% of all endometrial carcinomas
It is defined by more than 50% of tumor cells containing intracytoplasmic mucin
It has a generally favorable prognosis when diagnosed at early stage.
Origin:
Arises from endometrial glandular epithelium with mucinous differentiation
May develop from pre-existing endometrial hyperplasia
Endocervical-type and intestinal-type are recognized variants
Molecular pathogenesis involves mucin gene upregulation.
Classification:
WHO classification recognizes mucinous carcinoma as distinct variant
Subtypes include endocervical-type (most common)
Intestinal-type (resembles colorectal adenocarcinoma)
Mixed patterns may occur
Grading follows standard FIGO criteria.
Epidemiology:
Peak incidence in 5th-6th decades
Mean age 55-65 years
Slightly younger than typical endometrioid carcinoma
Risk factors similar to endometrioid type
Better prognosis than high-grade endometrioid carcinoma
Lynch syndrome association reported.
Clinical Features
Presentation:
Abnormal uterine bleeding (most common presentation)
Postmenopausal bleeding (70-80%)
Bulky uterus on examination
Pelvic pressure or pain
Mucoid vaginal discharge (characteristic)
May present with pyometra (mucin obstruction).
Symptoms:
Abnormal uterine bleeding (85-90%)
Mucoid vaginal discharge
Pelvic pain or pressure
Abdominal distension
Secondary amenorrhea (pre-menopausal women)
Constitutional symptoms (advanced cases)
Urinary or bowel symptoms (rare).
Risk Factors:
Similar to endometrioid carcinoma
Obesity
Diabetes mellitus
Nulliparity
Unopposed estrogen therapy
PCOS
Early menarche
Late menopause
Lynch syndrome (rare association)
Tamoxifen therapy.
Screening:
No specific screening for mucinous type
Endometrial sampling for abnormal bleeding
Imaging studies (ultrasound, MRI)
Hysteroscopy may show mucoid secretions
CA-125 may be elevated
CEA elevation possible (intestinal type).
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Gross Description
Appearance:
Soft, mucoid, gelatinous mass with gray-white to tan coloration
Cut surface shows characteristic mucoid consistency
May have cystic areas filled with mucin
Size variable, often bulky lesions.
Characteristics:
Gelatinous, mucoid consistency
Gray-white to yellow coloration
Mucoid secretions on cut surface
May show cystic degeneration
Areas of hemorrhage and necrosis
Well-demarcated from myometrium in early cases.
Size Location:
Usually involves fundus and upper uterine segment
Size ranges from 2-10 cm
May fill entire endometrial cavity
Polyproid growth pattern common
Myometrial invasion variable depending on grade.
Multifocality:
Usually unifocal
May have associated endometrial hyperplasia
Multifocal disease uncommon
Synchronous ovarian tumors possible (exclude metastases)
Cervical involvement in advanced cases.
Microscopic Description
Histological Features:
Glands lined by tall columnar cells with abundant intracytoplasmic mucin
More than 50% of cells contain mucin
Goblet cells may be present (intestinal type)
Nuclear stratification variable
Desmoplastic stroma may be present.
Cellular Characteristics:
Tall columnar epithelial cells
Abundant intracytoplasmic mucin
Nuclei displaced to cell base
Nuclear pleomorphism variable by grade
Mitotic activity variable
Goblet cell differentiation (intestinal type)
Apical mucin secretion.
Architectural Patterns:
Glandular architecture predominates
Simple to complex glandular patterns
Cribriform pattern may be seen
Papillary areas possible
Solid areas in high-grade tumors
Villoglandular pattern (endocervical type)
Mucin lakes may be present.
Grading Criteria:
FIGO grading system applies
Grade 1: <5% solid areas
Grade 2: 6-50% solid areas
Grade 3: >50% solid areas
Nuclear grade also considered
High nuclear grade may upgrade tumor
Most are grade 1-2.
Immunohistochemistry
Positive Markers:
Cytokeratins (CK7, CK19, CK20 variable)
EMA
CEA (especially intestinal type)
MUC2 (intestinal type)
MUC5AC (endocervical type)
PAX8 (supports müllerian origin)
ER/PR (variable, often reduced).
Negative Markers:
Vimentin (usually negative)
p16 (usually negative or patchy)
HPV (negative)
CDX2 (usually negative, may be positive in intestinal type)
CK5/6 (negative)
TTF-1 (negative).
Diagnostic Utility:
Mucin stains (PAS, mucicarmine) highlight intracytoplasmic mucin
PAX8 positivity supports endometrial origin
CK7+/CK20- pattern typical for endocervical type
CK7+/CK20+ pattern suggests intestinal type
CEA helps identify intestinal differentiation.
Molecular Subtypes:
No specific molecular classification
Most are microsatellite stable
p53 wild-type pattern common
PTEN mutations possible
KRAS mutations reported
PIK3CA mutations possible
Generally copy number low subtype.
Molecular/Genetic
Genetic Mutations:
KRAS mutations (20-30%)
PIK3CA mutations (15-25%)
PTEN mutations (10-20%)
ARID1A mutations
p53 mutations (rare in low-grade)
Mucin gene alterations (MUC2, MUC5AC, MUC6).
Molecular Markers:
Microsatellite stability (most cases)
p53 wild-type expression pattern
PTEN loss possible
Low Ki-67 proliferation index (grade-dependent)
Mucin gene overexpression
Chromosomal stability pattern.
Prognostic Significance:
Generally favorable prognosis for low-grade tumors
Stage more important than histological subtype
High-grade tumors have worse prognosis
Intestinal type may have slightly worse prognosis
Early stage disease has excellent outcomes.
Therapeutic Targets:
Hormone therapy (if ER/PR positive)
PI3K/AKT inhibitors (PIK3CA mutations)
PARP inhibitors (DNA repair defects)
Standard chemotherapy for advanced disease
Targeted therapy based on molecular profiling.
Differential Diagnosis
Similar Entities:
Metastatic adenocarcinoma (GI tract, ovary, cervix)
Endocervical adenocarcinoma
Mucinous metaplasia
Atypical hyperplasia with mucinous change
Mucinous carcinoid
Adenomyoma with mucinous metaplasia.
Distinguishing Features:
Primary endometrial: PAX8 positive
Primary endometrial: No cervical primary
Primary endometrial: Associated endometrial changes
Metastatic GI: CDX2 positive
Metastatic GI: CK20 positive
Cervical primary: p16 positive
Cervical primary: HPV positive
Hyperplasia: No stromal invasion.
Diagnostic Challenges:
Distinguishing primary from metastatic mucinous carcinoma
Separating from endocervical adenocarcinoma
Recognizing minimal invasion in well-differentiated tumors
Distinguishing from mucinous metaplasia
Grading predominantly mucinous tumors.
Rare Variants:
Signet ring cell variant
Mucinous carcinoma with neuroendocrine differentiation
Adenosquamous carcinoma with mucinous features
Mixed mucinous and endometrioid
Mucinous carcinoma with clear cell 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
Hysterectomy specimen measuring [X x Y x Z] cm, weighing [X] grams
Diagnosis
Endometrial mucinous carcinoma ([endocervical-type/intestinal-type])
Classification
WHO Classification: Mucinous carcinoma, FIGO Grade: [I/II/III]
Histological Features
Adenocarcinoma with >50% of cells showing mucinous differentiation
Mucinous Features
Mucinous cells: [percentage]%, Type: [endocervical/intestinal], Mucin stains: [positive]
Size and Extent
Tumor size: [X] cm, myometrial invasion: [depth/total thickness], [percent]%
Margins
Margins: [involved/uninvolved], closest margin: [X] mm
Lymphovascular Invasion
Lymphovascular invasion: [present/absent]
Cervical Involvement
Cervical involvement: [present/absent]
Special Studies
Mucin stains: PAS: [positive], Mucicarmine: [positive]
IHC: PAX8: [result], CK7: [result], CK20: [result], CEA: [result]
Molecular studies: [if performed]
FIGO Staging
FIGO Stage: [stage] ([staging criteria])
Prognostic Factors
Grade: [X], Stage: [X], generally favorable prognosis for early stage
Final Diagnosis
Endometrial mucinous carcinoma, FIGO Grade [X], Stage [X]