Diagnosing atypia of undetermined significance in thyroid fine needle aspiration samples using nuclear scoring.

BACKGROUND: Atypia of undetermined significance (AUS) is an indeterminate category in the Bethesda system for reporting thyroid cytopathology. Cytological features described as atypia are not always observed in every case, and it is difficult to determine how the small population of cells with enlarged nuclei, a few grooves, and rare elongated nuclei should be classified. Therefore, there is inter-intra observer variability considering these cell types, even though the cytological criteria are well defined. Therefore, this study aimed to establish a nuclear scoring system to help in the differential diagnosis of AUS. METHODS: Fine needle aspiration (FNA) samples that showed AUS and had surgical follow-up were included in this study. The aspirate was scored for the presence of intanuclear cytoplasmic inclusions, nuclear grooves, overlapping, enlargement, and elongation individually. The total nuclear score for each case was calculated. Statistical analysis of the association between each nuclear feature and the presence of papillary thyroid cancer (PTC) in the surgical specimens was performed. Cut-off points from the total score of these nuclear features were also calculated. RESULTS: Nuclear grooves and overlapping were more common in malignant cases (p < 0.001 and p = 0.048, respectively). A cut-off point of ≥5.5 for the total score was sensitive and specific for defining malignancy. CONCLUSION: The risk of PTC was higher in nodules with more prominent nuclear overlapping or nuclear groove in their FNA samples. In order to achieve a more confident AUS diagnosis, our scoring system can be helpful for thyroid FNA samples.

Endometrial cytological findings for a mesonephric-like endometrial adenocarcinoma: A case report.

A mesonephric-like endometrial adenocarcinoma (ML-EAC) is very rare and has a worse prognosis than other endometrial carcinomas. We describe an ML-EAC and report our endometrial cytological findings. A 76-year-old woman presented with irregular genital bleeding and a uterine mass. Endometrial cytology revealed atypical cylindrical or spindle-shaped cells in the form of small aggregates or solitary cells. The cell aggregates exhibited irregularly stacked papillary structures, small glandular structures, and fenestrated structures. The atypical cells had a nucleus with fine-granular chromatin and a granular cytoplasm, and nuclear grooves and intranuclear pseudo-inclusions were present. Hyaline globules were observed in the glandular lumens and in the background. The presumptive histological type was an adenocarcinoma, but the cytological features were different from those of an endometrioid carcinoma. A histological examination of the endometrial biopsy revealed an adenocarcinoma, and a simple hysterectomy was performed. A grayish-white elevated mass measuring 90 mm × 70 mm × 40 mm was observed on the uterine corpus in the hysterectomy specimen. Histologically, the tumor proliferated as complex tubular structures containing eosinophilic colloid-like materials and trabecular structures. The tumor cells were diffuse and positive for GATA-3 and partially positive for thyroid transcription factor-1. Estrogen and progesterone receptors were negative. An ML-EAC was diagnosed. The tumor was invasive and extended beyond one-half of the muscle layer with a high degree of vascular invasion. In conclusion, we need to focus on the various shapes of the cell aggregate, nuclear grooves, and intranuclear pseudo-inclusions of tumor cells to distinguish an ML-EAC from other endometrial carcinomas in endometrial cytology.

An oncogenic isoform of septin 9 promotes the formation of juxtanuclear invadopodia by reducing nuclear deformability.

Invadopodia are extracellular matrix (ECM) degrading structures, which promote cancer cell invasion. The nucleus is increasingly viewed as a mechanosensory organelle that determines migratory strategies. However, how the nucleus crosstalks with invadopodia is little known. Here, we report that the oncogenic septin 9 isoform 1 (SEPT9_i1) is a component of breast cancer invadopodia. SEPT9_i1 depletion diminishes invadopodium formation and the clustering of the invadopodium precursor components TKS5 and cortactin. This phenotype is characterized by deformed nuclei and nuclear envelopes with folds and grooves. We show that SEPT9_i1 localizes to the nuclear envelope and juxtanuclear invadopodia. Moreover, exogenous lamin A rescues nuclear morphology and juxtanuclear TKS5 clusters. Importantly, SEPT9_i1 is required for the amplification of juxtanuclear invadopodia, which is induced by the epidermal growth factor. We posit that nuclei of low deformability favor the formation of juxtanuclear invadopodia in a SEPT9_i1-dependent manner, which functions as a tunable mechanism for overcoming ECM impenetrability.

Cytologic features of ovarian granulosa cell tumors in pleural and ascitic fluids.

Adult granulosa cell tumor (AGCT) is an uncommon neoplasm of the ovary with potential for aggressive behavior and late recurrence. The most important prognostic factor for AGCT is tumor stage. Thus, cytological assessment of pleural or ascitic fluids is crucial for initial staging and subsequent patient management. We report herein two cases of ovarian AGCT presenting with exfoliated tumor cells in pleural and ascitic fluid. The first case involved a 61-year-old woman who presented with stage Ic (a) AGCT. Seven years after initial diagnosis, pleural effusion and pleural dissemination were identified. The second case involved a 50-year-old woman who presented with stage IV AGCT with massive ascites and right pleural effusion. Fluid cytology from both cases showed cohesive or loose clusters of small uniform neoplastic cells with round-to-oval nuclei, coffee-bean-shaped nuclear grooves, small nucleoli, and scant cytoplasm. Call-Exner bodies were also observed in these cytologic specimens. In the differential diagnosis of small monomorphic tumor cells in pleural effusion or ascites, coffee-bean-shaped nuclear grooves and cell clusters forming Call-Exner bodies are diagnostic clues of AGCT.