Endocervical Cytology: Inter- and Intra-Observer Variability in Conventional Pap Smears.

INTRODUCTION: Although the cytological diagnostic criteria for cervical squamous and glandular lesions are established by the Bethesda System for Reporting Cervical Cytology, the reproducibility of the diagnosis of these lesions has been shown to be variable in previous studies. At best, occasional good kappa (κ) values were reached both inter- and intra-observerly. Generally, consensus on high-grade lesions has been better compared to milder changes. METHODS: Altogether, 167 conventional Pap smears from 50 patients with histologically confirmed endocervical adenocarcinomas (EAC) and adenocarcinomas in situ (AIS) and from 28 patients with histologically proven high-grade intraepithelial lesions were analyzed by four cytopathologists. Twenty of the smears were later re-evaluated by the same cytopathologists. κ-values between cytopathologists in the categories of squamous versus glandular, negative for intraepithelial lesion or malignancy (NILM), atypical, and preneoplastic/neoplastic were calculated. The diagnostic Pap smears of EAC and AIS with best and worst consensus between observers were then morphologically analyzed. RESULTS: The reproducibility ranged from poor to substantial. The overall κ-values between the four cytopathologists were 0.412, 0.314, 0.272, and 0.082, respectively, in the categories of preneoplastic/neoplastic, squamous versus glandular, NILM, and atypical. Overall intra-observer κ-values were correspondingly 0.491, 0.616, 0.345, and 0.241. In the diagnostic smears of AIS and EAC, the nuclear size >2 times the normal and nuclear pleomorphism were the commonest features associated with good diagnostic consensus and the lack of nuclear enlargement and degenerative changes were associated with poor consensus. CONCLUSIONS: The reproducibility of preneoplasia/neoplasia diagnoses was better than that of atypia and NILM both in the inter- and intra-observer part in this study. In the smears from AIS and EAC patients, general neoplasia-associated features were more common in samples with good agreement by the four cytopathologists of the neoplastic nature and the endocervical origin of the lesion.

Hyaluronan expression in differentiated thyroid carcinoma.

The extracellular polysaccharide hyaluronan (HA) controls cell migration, differentiation, and proliferation, and is supposed to contribute to the spreading of several human cancers. Little is known about the role of HA in the development and progression of differentiated thyroid carcinoma (DTC). The expression and prognostic value of HA were therefore evaluated in 204 consecutive patients with DTC. A biotinylated affinity probe specific for HA was applied to paraffin-embedded tumour samples to assay the expression of HA in carcinoma cells and in intra/peritumoural stroma. In a majority of the samples, a high percentage (>or=90%) of normal thyroid follicle epithelial cells were HA-positive. This high percentage was also found in 80 (47%) papillary carcinomas, but only in seven (21%) follicular carcinomas (p=0.004). Age (>60 years) of the patients was significantly associated with a low percentage of HA-positive cancer cells (p=0.013). Cancer cell-associated HA correlated significantly with the percentage of cells expressing total CD44 and its isoforms containing exons v3 and v6 (r=0.223-0.289, p<0.001 for all). The tumour stroma was always positive for HA. Stromal staining intensity did not differ markedly between papillary and follicular carcinomas. A strong stromal HA staining intensity was related to distant metastases (p=0.044), high pTNM stage (p=0.024), old age (>60 years) (p=0.043), and cancer-related mortality (p=0.001). In a log-rank univariate survival analysis, strong stromal HA staining intensity was related to DTC mortality (p=0.0007). Cancer cell-associated HA expression did not significantly correlate with patient survival. In Cox's multivariate survival analysis, age (>60 years, p=0.0164), gender (p=0.0251), and pTNM stage (p=0.0121) were significant independent prognostic factors for DTC-related death. These results suggest that strong stromal HA staining intensity is related to progression and unfavourable outcome in DTC patients, while the clinical factors remain more powerful in predicting DTC-related death.