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Introduction: Urine cytology using the Paris system (TPS) classification is useful for the detection and monitoring of bladder urothelial carcinoma (UC). However, the categories "Atypical Urothelial Cells" (AUC) and "Suspicious for High-Grade Urothelial Carcinoma" (SHGUC) do not establish a clear diagnosis. This pilot study aimed to investigate whether the presence of mutations in fibroblast growth factor receptor 3 (FGFR3) and telomerase reverse transcriptase (TERT) genes, in urine processed with liquid-based cytology (LBC) could enhance the diagnostic performance of cytology, particularly in defining the indeterminate categories of AUC and SHGUC., Methods: Urine samples from 82 UC patients with primary tumors or under surveillance and 10 healthy individuals were examined. The THIN PREP method was used for cytology followed by DNA isolation from urine sediments. Targeted molecular analysis was achieved in 70 cases (63 patients and 7 controls) for exons 7 and 10 of the FGFR3 gene and the TERT gene promoter (pTERT), using PCR and Sanger sequencing. Molecular results were correlated with TPS cytology categories and validated by histopathological findings following cystoscopy., Results: In healthy subjects, cytology was negative for high-grade urothelial carcinoma (NHGUC) and no mutations were found. No mutations were found in patients with NHGUC cytology, except for one case with equivocal cystoscopy that carried a pTERT mutation. In high-grade urothelial carcinoma cytology (HGUC) (15/20, 75%) of the cases with histologically confirmed UC, molecular analysis revealed the presence of pTERT without FGFR3 mutations. In SHGUC and AUC cytology, FGFR3 and/or pTERT mutations were detected in (3/4, 75%) and 4/4 (100%) histologically confirmed UC cases, respectively. Cytology sensitivity was 85.7% increasing to 100% with the combined cytology-molecular test, whereas specificity remained unchanged at 86.3%., Conclusions: This pilot study suggests that the incorporation of FGFR3/pTERT molecular testing in urine LBC could enhance the diagnostic value of cytology by diagnosing BUC in indeterminate cytology categories., (S. Karger AG, Basel.)

"Small-cell malignancies of thyroid" is an unsolved dilemma. This term represents an umbrella terminology in thyroid, encompassing for a small group of tumors in which some of them are well-recognized tumors like medullary thyroid carcinoma, poorly differentiated thyroid carcinoma, and primary thyroid lymphomas and teratoma, whereas the remaining are less known as primary neuroendocrine carcinoma of thyroid, primary extraskeletal Ewing family tumors, and adamantinoma-like Ewing sarcoma. When the issue comes to evaluate a cytological sample predominantly composed of small-cell morphology, metastatic small-cell carcinomas to thyroid also should be excluded. In this review, our group focused on the main cytomorphological and clinical clues of each entity that help to set up a correct differential diagnosis. The literature discussions were also included for the entities that are not yet recognized by the mother publication WHO. A key point of the issue's simple algorithm based on FNAC with small-cell morphology of thyroid was suggested by the authors., (© 2022 S. Karger AG, Basel.)