The impact of repeat fine-needle aspiration in thyroid nodules categorized as atypia of undetermined significance or follicular lesion of undetermined significance: A single center experience.

BACKGROUND: Atypia of undetermined significance (AUS) or follicular lesion of undetermined significance (FLUS) is the most controversial category of the Bethesda System. The present study was conducted to compare the histological findings in a series of thyroid nodules diagnosed with AUS/FLUS after single or repeat fine needle aspiration (FNA) cytology. METHODS: Retrospective analysis of our institution's series of 514 patients with an initial diagnosis of AUS/FLUS between 11/2011 and 02/2020. RESULTS: Of 4887 FNA samples, 11.8% were classified as AUS/FLUS. Of patients with an initial AUS/FLUS diagnosis, 11.5% (59/514) underwent surgery after a single FNA, 55.4% (285/514) had a repeat FNA, and 32.7% (168/514) were either observed or lost to follow-up. Surgical pathology was available in 123 cases (23.9%), and malignancy was confirmed in 32.5% (40/123) cases, with similar rates in the single 32.2% (19/59) and repeat FNA 32.8% (21/64) groups. Repeat FNA reclassified 78.9% of the AUS/FLUS cases to a different category: 57.2% were reclassified as benign, 10.5% as follicular neoplasm, and 5.6% as suspicious for malignancy or malignant. The rates of nonneoplastic benign lesions were 52.5% (31/59) and 31.2% (20/64) in the single and repeat FNA groups, respectively (P = .018). The rates of follicular adenomas were higher when repeat FNA was performed (23/64, 35.9%) compared with a single FNA (9/59; 15.2%) (P = .013). CONCLUSION: In this series, a repeat FNA in cases of AUS/FLUS increased detection of follicular adenomas but not the detection of malignancy. Repeat FNA reduced the rate of benign nonneoplastic lesions by 40% in the surgical samples.

Embryonal (botryoides) rhabdomyosarcoma of the uterus harboring a primitive neuroectodermal tumor component.

The association of a uterine sarcoma botryoides of the adolescence with a primitive neuroectodermal tumor is reported in a 12-year-old patient who presented with abnormal vaginal bleeding that occurred after passing per vaginam a polypoid mass. The sarcoma botryoides of the adolescence exhibited foci of cartilage and a central area of primitive neuroectodermal tumor with a trabecular, adamantiform histology and prominent angiogenesis. Primitive neuroectodermal tumor was positive for vimentin, synaptophysin, neuron-specific enolase, CD99, and SOX2 and negative for both the FLI-1 fusion protein and the rearrangement of ESWR1 gene. The neoplasm exhibited a nonaggressive behavior similar to sarcoma botryoides of the adolescence, being alive and well 3 y after its presentation. This is possibly related to its polypoid nature and the absence of invasive features at its uterine insertion level. A conservative approach without further resection and chemotherapy was indicated taking into account the patient's age.

Mutations in FGFR3 and PIK3CA, singly or combined with RAS and AKT1, are associated with AKT but not with MAPK pathway activation in urothelial bladder cancer.

Different members of the phosphoinositide 3 kinase--serine threonine protein kinase (PI3K-AKT) pathway are altered in bladder cancer. Fibroblast growth factor receptor 3 (FGFR3) mutations characterize the low-grade tumors, and RAS genes are mutated in approximately 13% of all bladder tumors. Interestingly, a percentage of bladder tumors have alterations in more than 1 PI3K-AKT or rat sarcoma viral oncogene homolog-RAF mitogen activated protein kinase (RAS-MAPK) pathway gene or their upstream regulators, but some combinations are mutually exclusive. We analyzed mutations in FGFR3, phosphoinositide 3 kinase catalytic alpha polypeptide (PIK3CA), v-akt murine thymoma viral oncogene homolog 1 (AKT1), v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS), v-Ha-ras Harvey rat sarcoma viral oncogene homolog (HRAS), and v-raf murine sarcoma viral oncogene homolog B1 (BRAF) in 88 urothelial cell carcinomas and the immunohistochemical expression of phospho-v-akt murine thymoma viral oncogene homolog (AKT) and mitogen-activated protein kinase 1 and 2 (pERK1/2) in 80 and 77 urothelial cell carcinomas, respectively. Approximately 43% and 20.5% of tumors presented 1 and 2 mutated genes, respectively. FGFR3 mutations were more frequent alone, whereas PIK3CA mutations were associated with another mutated gene (FGFR3 and KRAS). Overall, mutated FGFR3 (FGFR3(mut)) and mutated FGFR3 (FGFR3(mut))-mutated PIK3CA (PIK3CA(mut)) genotypes were associated with low-grade bladder tumors and mutated PIK3CA (PIK3CA(mut))-mutated KRAS (KRAS(mut)) and mutated AKT1 (AKT1(mut)) were only present in high-grade tumors. There are no mutated FGFR3 (FGFR3(mut))-mutated RAS (RAS(mut)) nor mutated PIK3CA (PIK3CA(mut))-mutated AKT1 (AKT1(mut)) combinations. Fifty percent and 56% of tumors showed high levels of pAKT and pERK1/2, respectively. High levels of pAKT were associated with total mutations, FGFR3(mut), and PIK3CA(mut) tumors but not with tumor grade or stage. Wild-type tumors presented significantly higher pERK1/2 expression. Mutations in FGFR3 and FGFR3-PIK3CA but not single PIK3CA mutations characterize low-grade bladder tumors. Single FGFR3 or PIK3CA mutations and the different mutation combinations FGFR3-PIK3CA/AKT1 and PIK3CA-RAS can activate the AKT but not the MAPK pathway. Other genes different from FGFR3 may be related with the pERK activation in bladder tumors.