Gastric glomus tumor on EUS-FNA-based cytology: clinicopathologic and immunohistochemical features of 4 cases, including 1 case with associated MIR143HG-NOTCH2 fusion gene.

INTRODUCTION: Gastric glomus tumor (GT) is a rare submucosal tumor for which the preoperative diagnosis can be challenging. We report the cytomorphologic and immunohistochemical features of 4 gastric GTs diagnosed by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) cytology. MATERIALS AND METHODS: Files were searched to identify gastric GTs diagnosed by EUS-FNA between 2018 and 2021. A total of 4 cases of gastric GTs (3 men and 1 women; mean age, 60 years) were included. RESULTS: Three GTs were located in the gastric antrum and one in the gastric body. Their size ranged from 2 to 2.5 cm. Three patients presented with epigastric discomfort and one with chest wall discomfort. Rapid on-site evaluation was performed for 3 cases; the findings for all 3 were indeterminate. The smears were moderate to highly cellular and showed loose clusters of evenly distributed small- to medium-size bland tumor cells. The tumor cells had centrally located round to oval nuclei with inconspicuous nucleoli and scant to moderate amount of eosinophilic to clear cytoplasm. Examination of the cell blocks revealed branching small vessels surrounded by small- to medium-size cells. The neoplastic cells were positive for smooth muscle actin and synaptophysin and negative for AE1/AE3 and S-100. C-KIT and CD34 were variably positive. Ki-67 was <2% positive. In 1 case, the fusion panel-solid tumor (50 genes) revealed the MIR143HG-NOTCH2 fusion gene. CONCLUSIONS: Smears and cell block preparation revealed angiocentric sheets of uniform, small round to oval tumor cells with pale to eosinophilic cytoplasm, intermingled with endothelial cells. The differential diagnosis of gastric GTs on rapid on-site evaluation includes neuroendocrine tumors and epithelioid or spindled cell neoplasms. Immunohistochemical and molecular studies can be helpful in the preoperative diagnosis of gastric GT.

Cyto-histo correlation and false-negative urine: Before and after the Paris system for reporting urinary cytology.

BACKGROUND: The impact of implementing the Paris system (TPS) on the rate of discrepant cases in the negative for high-grade urothelial carcinoma (NHGUC) category that had a subsequent diagnosis of high-grade urothelial carcinoma (HGUC) on histology is not well studied. METHODS: We adopted TPS in May 2019. We searched discrepant cases with negative urine cytology 2017-2019 in our cyto-histo correlation database. The urine cytology and follow-up biopsy/resection were reviewed by a cytopathologist who also did Genitourinary (GU) Pathology subspecialty sign-out. Voided urine and instrumented urine were included in this study. RESULTS: There were total of 70 discrepant cases with negative cytology interpretation but HGUC on the subsequent biopsy or resected specimen. Following the TPS criteria, the rate of discrepant negative cytology cases increased from 6 cases between January 2017 and May 2019 to 64 cases after May 2019 when we adopted TPS. There were 2 discrepant negative cases in 2017, 3 cases in 2018, and 65 cases in 2019. Out of 65 cases in 2019, 64 cases were identified after May 2019. Additional 55 urine cytology slides were reviewed according to the TPS criteria, of which, the diagnoses remained unchanged in 45 (82%) cases and 10 (19%) cases were reassigned to either atypical or suspicious categories. The discrepancy was noted more on the instrumented urine and the upper tract urine. However, the false-negative rate rose faster in voided urine and lower tract urine. The risk of HGUC with the category of NHGUC was 0.03% in 2017, 0.05% in 2018, and 1.06% in 2019 at our institution. The increase in false-negative rate could not be attributed to a single cytopathologist. CONCLUSION: After adopting TPS for reporting urine cytology, there was an increase in HGUC from negative urine cytology which was subsequently confirmed on histology as cases of HGUC. The quality control of negative urines could be important monitoring the process when implementing TPS.

BRD3-NUTM1-expressing NUT carcinoma of lung on endobronchial ultrasound-guided transbronchial needle aspiration cytology, a diagnostic pitfall.

BACKGROUND: Nuclear protein in testis (NUT) carcinoma (NC) is an aggressive type of poorly differentiated carcinoma with a variable degree of squamous differentiation. NC is defined by the presence of BRD-NUT fusion oncogenes, the most common fusion form being the BRD4-NUTM1 gene. Variant rearrangements involving the BRD3 and NSD3 genes. Variant rearrangements involving the BRD3 and NSD3 genes occur in approximately one-third of the cases. AIMS: This is the first case regarding the study of cytological features of NC of the lung with BRD3-NUTM1 fusion. MATERIALS AND METHODS: A 36-year-old female with chest heaviness and shortness of breath was found to have a right-sided pleural effusion; she was non-smoker and denied any significant past medical illness. CT-chest revealed an 8.5 cm heterogeneous mass in the right and mid-upper lung. She underwent endobronchial ultrasound-guided (EBUS) transbronchial fine-needle aspiration (FNA) of the lung mass. Thoracocentesis was performed, and pleural fluid was sent to the laboratory for cytological evaluation RESULTS: The cytopathological findings showed atypical squamoid cells with variably prominent single or multiple nucleoli. Monotonous-looking cells with high nuclear to cytoplasmic ratio and hyperchromasia were also present. The atypical squamoid cells showed abundant clear to eosinophilic cytoplasm with rare individual cell keratinization and focal keratin pearl formation. The atypical cells were positive for CK7, p40, p63, mCEA and equivocal for NUT-specific antibody. The cytopathological findings were consistent with squamous cell carcinoma with focal keratinization. The Fusion Panel-Solid Tumor (50 genes) revealed BRD3-NUTM1 fusion gene. Diagnosis was amended to pulmonary NC. DISCUSSION: NC is a diagnostic challenge for pathologists as it can morphologically mimic undifferentiated carcinoma, squamous cell carcinoma, or neuroendocrine carcinoma. The challenge is not how to diagnose NC but rather determining when to include it in the differential diagnosis and perform the diagnostic molecular tests (FISH or NGS) or IHC study for NUT-specific antibody. CONCLUSION: When a specimen demonstrates a dual cell population of squamoid cells and primitive-looking tumor cells in the wrong clinical context (i.e., young patient with no smoking history), further molecular profiling is warranted to include the differential of a primary NC of the lung. The cytological features of NC itself have rarely been documented and moreover, that of a primary NC of the lung with BRD3-NUTM1 fusion has never been reported. We herein report cytological findings of a primary NC of the lung with BRD3-NUTM1 fusion gene.