3-D analysis of the invasion front in squamous cell carcinoma of the uterine cervix: histopathologic evidence for collective invasion per continuitatem.

OBJECTIVE: To investigate spatial tumor invasion using ex vivo specimens and pursue a new morphometric approach for a quantitative assessment of the invasion front. STUDY DESIGN: Based on histologic serial sections with up to 500 slices stained with hematoxylin-eosin, volumes of interest of the tumor invasion front were 3-D reconstructed for 13 specimens from patients with squamous cell carcinoma (SCC) of the uterine cervix. Starting from very sensitive automatic tumor segmentation, 404 presumptive loci of isolated tumor islets were detected within the reconstructed volume data sets. These loci were microscopically inspected on the slides utilizing the volume date set's coordinates. RESULTS: A single detached tumor cell cluster within the stroma could be verified and, additionally, 4 tumor emboli within lymph vessels. The main cause of all other suspect islets (false positive segmentations) was peritumoral inflammatory response. Spatial invasion front quantification was done using discrete compactness (3-D C(D)). A comparison with 2-D C(D) values from single slides yielded strong correlation (correlation coefficient: r = 0.94; p < 0.001). CONCLUSION: Collective migration in SCC of the cervix mainly occurs per continuitatem. 2-D C(D) appears adequate and applicable for the morphometry of tumor invasion front phenotypes.