Simple computational technique to quantify nuclear shape asymmetry.

The nucleus of an eukaryotic cell is a membrane-bound organelle containing a major part of the cellular genome. Nuclear shape is controlled by forces generated in the cytoskeleton, nuclear envelope and matrix of the nucleus and may change when the balance of these forces is disturbed. In certain cases, such changes may be indicative of cell pathology. Nuclear shape feature is being commonly addressed in both experimental research and diagnostics; nevertheless its symmetry-related aspects receive little attention. This article introduces a technique allowing to estimate nuclear shape asymmetry in digital images captured from cyto- or histological preparations. Implemented in a software package, this technique quantifies the asymmetry using two scenarios. The first one presumes the identification of nuclear pixels laying outside the largest inscribed circle. According to the second scenario, the algorithm searches for nuclear pixels lacking pixel-partners symmetric with respect to the nuclear area's centroid. In both cases, the proportion of "asymmetric" pixels is used to estimate the feature of interest. The technique was validated on images of cell nuclei having distinctive shape phenotypes. A conclusion was made that shape asymmetry feature may be useful accessory to the toolbox of nuclear morphometry.

Patterns of papillary thyroid carcinoma cells analyzed in fine-needle aspiration smears may reveal changes in tumor cell behavior.

Fine-needle aspiration (FNA) cytology is widely used to examine thyroid lesions. However, its diagnostic accuracy is limited by the narrow choice of cytopathologic markers indicative of invasive/metastatic powers of a tumor. The aim of this study was to identify features that may serve as such indicators. We have examined FNA smears of 50 histologically proven papillary thyroid carcinoma (PTC) cases applying computer-assisted morphometry to assess patterns formed by PTC cells. Cytokeratine (CK) 8 immunocytochemistry was used to verify the epithelial origin of cells under study. All analyzed smears contained blood, histiocyte-like cells and CK8-positive follicular cells occurring both as single cells and in monolayer cell sheets. In 60% of cases we revealed cell sheets displaying two distinct cell patterns. The first one (pattern R) consisted of moderately pleomorphic, rather regularly arranged cells having an amphophilic cytoplasm. The second one (pattern I) was formed by highly pleomorphic cells with a basophilic cytoplasm. Patterns R and I were clearly different in cell size and shape as well as in nuclear size and shape. These patterns were never observed within the same cell sheet indicating that they may be formed by different subclones of tumor cells. Thus, it can be concluded that PTC frequently displays two definitely different cell patterns. We think that these patterns have a potential to serve as indicators for early events of an invasive/metastatic process. It remains to be seen whether the simultaneous occurrence of these patterns is a PTC-specific feature.

NA cohort study of thyroid cancer and other thyroid diseases after the Chernobyl accident: cytohistopathologic correlation and accuracy of fine-needle aspiration biopsy in nodules detected during the first screening in Ukraine (1998-2000).

BACKGROUND: The Ukrainian American Cohort Study was established to evaluate the risk of thyroid disorders in a group exposed as children and adolescents to 131I by the Chernobyl accident (arithmetic mean thyroid dose, 0.79 grays). Individuals are screened by palpation and ultrasound and are referred to surgery according to fine-needle aspiration biopsy (FNA). However, the accuracy of FNA cytology for detecting histopathologically confirmed malignancy after this level of internal exposure to radioiodines is unknown. METHODS: During the first screening cycle (1998-2000), 13,243 individuals were examined, 356 individuals with thyroid nodules were referred for FNA, 288 individuals completed the procedure, 85 individuals were referred to surgery, 82 individuals underwent surgery, and preoperative cytology was available for review in 78 individuals. Cytologic interpretation for the nodule that resulted in surgical referral was correlated with final pathomorphology; discrepancies were reviewed retrospectively; and the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of FNA cytology were calculated. RESULTS: All 24 cytologic interpretations that were definite for papillary thyroid cancer (PTC) were confirmed histopathologically (PPV, 100%); and, of 11 cytologic interpretations that were suspicious for PTC, 10 were confirmed (PPV, 90.9%). Ten of 41 FNAs that were interpreted as either definite or suspect for follicular neoplasm were confirmed as malignant (PPV, 24.4%), including 2 follicular thyroid cancers and 8 PTCs (all but 1 of the follicular or mixed subtypes). Depending on whether a cytologic interpretation of follicular neoplasm was considered "positive" or "negative," the sensitivity was 100% and 77.3%, respectively; similarly, the respective specificity was 17.6% and 97.1%, the respective PPV was 61.1% and 97.1%, and the respective NPV was 100% and 76.7%. CONCLUSIONS: Among children and adolescents who were exposed to 131I after the Chernobyl accident and were evaluated 12 to 14 years later, thyroid cytology had a sensitivity and a predictive value similar to those reported in unexposed populations.