Frozen section diagnosis of gastrointestinal poorly cohesive and signet-ring cell adenocarcinoma: useful morphologic features to avoid misdiagnosis

Frozen section examination of adenocarcinomas with poorly cohesive growth, including signet-ring cell carcinoma, is challenging. Due to their diffuse morphology, the tumor cells may be indistinct and difficult to distinguish from inflammatory or stromal cells. Misdiagnosis may result in significant adverse clinical outcome. We performed a detailed retrospective analysis of such cases to identify features that are helpful to avoid misdiagnosis at the time of frozen section. We reviewed the original frozen section slides from 50 patients with poorly cohesive carcinoma (PCC) including 32 with positive and 18 with negative frozen section slides. Tumor cells and inflammatory cells were evaluated for 17 distinct cytologic and nine architectural or stromal features. Features with 100% specificity and positive predictive value (PPV) for carcinoma included the presence of cells with a single distinct cytoplasmic mucin vacuole, focal gland formation, and perineural invasion. Features with high specificity, sensitivity, PPV, and negative predictive value (NPV) (all > 75%) included irregular nuclear contours, large nuclear size with many nuclei > 4× the size of a small lymphocyte, and disruption/obliteration of normal structures. Other features with high specificity and PPV (both ≥ 85%) but relatively low sensitivity and NPV-included crescent-shaped/indented nuclei, prominent nucleoli, anisonucleosis (> 4:1 difference in nuclear size), multinucleation, and the presence of mitotic figures. We characterized useful histologic features of poorly cohesive carcinoma that may serve to distinguish carcinoma cells from benign inflammatory or stroma cells. Knowledge of the relatively specific features in particular may help surgical pathologists avoid false-negative interpretation resulting in significant clinical morbidity.