How is the examination of endometrial cells performed?

Examination of Endometrial Cells: Diagnostic Approach

Endometrial cell examination is performed through tissue sampling using office-based devices (Pipelle or Vabra aspirator) as the first-line diagnostic method, achieving 99.6% and 97.1% sensitivity respectively for detecting endometrial carcinoma, with hysteroscopy-directed biopsy reserved for inadequate initial sampling or focal lesions. 1, 2

Primary Sampling Methods

Office-Based Endometrial Biopsy

• Pipelle endometrial sampling is the gold-standard outpatient technique, requiring no anesthesia or hospital admission, and can be performed in the office setting with minimal patient discomfort 3, 4
• The Pipelle device achieves 99.6% sensitivity for endometrial carcinoma in postmenopausal women and 91% in premenopausal women, making it superior to other sampling devices 4
• Vabra aspiration devices demonstrate 97.1% sensitivity for detecting endometrial carcinoma, providing an alternative to Pipelle when indicated 2
• A minimum endometrial tissue surface of 35 mm² is required for conclusive diagnosis, yielding positive and negative predictive values of 92.6% and 85.7% respectively 5

Limitations and Failure Rates

• Office endometrial biopsy has a 10% false-negative rate, necessitating escalation to fractional D&C under anesthesia or hysteroscopy when initial sampling is negative but symptoms persist 1, 2
• Pipelle sampling has limited capacity to identify focal lesions such as endometrial polyps, which may be missed by blind sampling techniques 3
• Inadequate tissue sampling occurs more frequently in senile and weakly proliferative endometria, requiring repeat sampling or alternative diagnostic approaches 6

Advanced Diagnostic Techniques

Hysteroscopy with Directed Biopsy

• Hysteroscopy provides direct visualization of the endometrial cavity and enables targeted biopsy of suspicious lesions, achieving the highest diagnostic accuracy for endometrial pathology 1, 2
• Hysteroscopy should be performed when initial blind sampling is inadequate, non-diagnostic, or when focal lesions (polyps, submucous fibroids) are suspected on imaging 2, 7
• Hysteroscopy allows simultaneous removal of identified endometrial polyps during the diagnostic procedure 2

Fractional Dilation and Curettage

• Fractional D&C under anesthesia achieves 95% diagnostic accuracy and remains the definitive procedure when office biopsy fails or is contraindicated 1
• D&C has been largely replaced by office-based sampling and hysteroscopy due to the requirement for anesthesia and hospital admission, but remains necessary for inadequate outpatient sampling 7

Specimen Processing and Analysis

Liquid-Based Cytology

• Liquid fixation of endometrial brush cytology yields 4-6 slides per case, with any single slide accurately representing the case diagnosis 6
• Tissue fragments are incidentally collected by brush sampling in 79.9% of cases, and are always obtained from high-grade endometrial hyperplasias and carcinomas 6
• Cytology alone can separate benign endometrium from high-grade atypical hyperplasia and carcinoma, with diagnostic accuracy increasing to 92.5% overall and 100% for high-grade lesions when tissue fragments are included 6

Histological Examination

• Histological examination determines both histological type and tumor grading, which are essential prognostic factors 1
• Immunohistochemistry and hormone receptor evaluation may be performed when diagnostic difficulty arises 1

Molecular and Cellular Analysis Approaches

Compartment-Specific Analysis

• Separate analysis of stromal and epithelial fractions by laser capture microdissection reveals distinct mRNA signatures related to cycle day, providing superior understanding of endometrial physiology compared to whole-tissue analysis 1
• Fluorescence-activated cell sorting (FACS) demonstrates cell-specific gene expression and identifies multiple biological pathways, offering an alternative to laser microdissection 1

Advanced Molecular Techniques

• RNA-seq technology detects more exons and alternative splicing events than microarray analysis, identifying low-abundance transcripts that microarrays routinely miss (25% of genes with low expression) 1
• The endometrial receptivity array (ERA) identifies 238 genes differentially expressed during the transition from pre-receptive to receptive state, proving superior to classical histology methods for defining endometrial cycle phases 1

Clinical Pitfalls to Avoid

• Never accept a negative or inadequate endometrial biopsy as reassuring in symptomatic postmenopausal women, especially those on tamoxifen—persistent bleeding mandates hysteroscopy or D&C 2
• Do not rely on Pap smears for endometrial pathology evaluation, as they are designed for cervical cancer screening and cannot adequately assess endometrial disease 8
• Avoid proceeding with endometrial ablation, uterine artery embolization, or hysterectomy without first obtaining tissue diagnosis, to prevent missing occult malignancy 7
• Recognize that most transcriptome analyses use whole endometrial tissue containing all cell types, which reflects an average mRNA abundance rather than cell-specific expression profiles 1