Cellularity of Routinely Prepared Cell Blocks: Insights From an International Study

OBJECTIVE: Formalin-fixed, paraffin-embedded (FFPE) cell blocks (CBs) are widely used for processing cytology specimens, but preparation methods remain variable and non-standardised. Low cellularity is a common limitation that may compromise diagnostic utility. This study aimed to evaluate the cellularity of routinely prepared CBs across different preparation methods, laboratories and sample types. METHODS: Each laboratory in this multicentre observational study retrospectively assessed 50 consecutive CBs prepared using a single method. Cellularity of Haematoxylin and Eosin (H&E)-stained sections was semi-quantitatively evaluated by two independent reviewers per laboratory in four categories: acellular, low (≤ 100 cells), medium (100-500 cells) and high cellular (> 500 cells). The proportion of poorly cellular CBs (acellular + low cellular) was compared across methods, laboratories and sample types using non-parametric tests. RESULTS: Cellularity was assessed for 1817 CBs prepared using Agar (22%), HistoGel (19%), Plasma-Thrombin (19%), Cellient (17%), In-house (15%) and Shandon/Epredia (8%) methods. The proportion of poorly cellular CBs ranged from 4% to 80% across laboratories (mean 27%, median 25%), with no consistent clustering by method. Median proportions by method ranged from 12% (Cellient) to 35% (Agar), but inter-method differences were not statistically significant (p > 0.05). Substantial variability was observed both across and within sample types and preparation methods. CONCLUSIONS: The study revealed marked variability in the proportion of poorly cellular CBs among preparation methods and laboratories, highlighting the need for improved processing and monitoring of CB adequacy.