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Background Many studies have reported several transcriptionally deregulated microRNAs (miRNAs) in papillary thyroid cancer (PTC) tissue in comparison with benign thyroid nodules and normal thyroid tissues. However, the correlation between miRNA expressions and PTC recurrence still remains unclear. Methods The PTC patients who scheduled to undergo total thyroidectomy by the same surgical team in Ningbo NO.2 Hospital from March 1998 to March 2008 were enrolled in this study. The clinical and pathological characteristics of each patient were recorded in detail. The selected miRNA expressions were detected using quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Potential predictive factors for cancer recurrence were evaluated by univariate and multivariate Cox proportional hazard analysis. Results A total of 78 patients were enrolled with 49 females at a mean age of 45.8 years. Enrolled patients were divided into two groups: nonrecurrent group ( n  = 54) and recurrent group ( n  = 24). The results from the univariate Cox proportional hazard analysis revealed that primary tumor size, TNM stage, extrathyroid extension, miR-221, and miR-222 expressions were significantly associated with PTC recurrence ( P  < 0.05). The tissue expression of miR-221 was the only independent risk factor for PTC recurrence (HR 1.41; 95%CI 1.14–1.95, P  = 0.007) by multiple Cox proportional hazard analysis. Conclusions This study identified the potential role of miR-221 as a prognostic biomarker for the recurrence in PTC.

Non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is an indolent thyroid tumor characterized by frequent RAS mutations and an absence of the BRAF V600E mutation commonly seen in classical papillary thyroid carcinoma (cPTC). The ability to differentiate potential NIFTP/follicular variant of papillary thyroid carcinoma (FVPTC) from cPTC at the time of fine-needle aspiration (FNA) can facilitate conservative management of NIFTP. The aim of the current study was to investigate how molecular testing may add to cytologic assessment in the pre-operative differentiation of potential NIFTP/FVPTC and cPTC. We had previously evaluated cytologists’ ability to prospectively distinguish potential NIFTP/FVPTC from cPTC in a cohort of 56 consecutive FNAs diagnosed as malignant or suspicious for malignancy. We utilized this cohort to perform molecular analysis. Detected molecular abnormalities were stratified into two groups: (1) those supporting malignancy and (2) those supporting a diagnosis of potential NIFTP/FVPTC. The cytologists’ characterization of cases and the detected molecular alterations were correlated with the final histologic diagnoses. Molecular testing was performed in 52 (93%) of the 56 cases. For the 37 cases cytologists favored to be cPTC, 31 (84%) had a molecular result that supported malignancy (28 BRAF V600E mutations, 2 NTRK1 fusions, 1 AGK-BRAF fusion). For the 8 cases that were favored to be NIFTP/FVPTC by cytologists, 7 (88%) had a molecular result that supported conservative management (1 NRAS mutation, 6 wild-type result). Seven cases were designated as cytomorphologically indeterminate for NIFTP/FVPTC or cPTC, of which 6 (86%) had a molecular result that would have aided in the pre-operative assessment of potential NIFTP/FVPTC or cPTC/malignancy. These included 3 BRAF V600E mutations in nodules that were cPTC on resection, an HRAS mutation, and a wild-type result in the 2 nodules that were NIFTP, and a TERT promoter mutation along with an NRAS mutation in a poorly differentiated thyroid carcinoma. For nodules with an FNA diagnosis of suspicious for malignancy or malignant, cytologists can differentiate most cases of potential NIFTP/FVPTC from cPTC. However, molecular testing may be valuable for a subset of cases, especially those that are indeterminate for potential NIFTP/FVPTC versus cPTC based on cytologic features alone.

A high prevalence of the BRAF(V600E) somatic mutation was recently reported in several series of papillary thyroid carcinomas (PTC). This mutation appears to be particularly prevalent in PTC with a predominantly papillary architecture. Another BRAF mutation (K601E) was detected in a follicular adenoma and in some cases of the follicular variant of PTC. The few studies on record provided controversial data on the relationship between the occurrence of BRAF mutations and clinicopathologic parameters such as gender, age and tumour staging. In an attempt to clarify such controversies we decided to enlarge our previous series to 315 tumours or tumour-like lesions diagnosed in 280 patients, including a thorough analysis of several clinicopathologic features. The BRAF(V600E) mutation was exclusively detected in PTC with a papillary or mixed follicular/papillary architecture both of the conventional type (46%) and of other histotypes, such as microcarcinoma (43%), Warthin-like PTC (75%) and oncocytic variant of PTC (55%). The BRAF(K601E) mutation was detected in four of the 54 cases of the follicular variant of PTC (7%). The mean age of patients with conventional PTC harbouring BRAF(V600E) (46.7 years) was significantly higher (P<0.0001) than that of patients with conventional PTC without BRAF(V600E) (29.5 years). The BRAF (BRAF(V600E)) mutated PTC did not exhibit signs of higher aggressiveness (size, vascular invasion, extra-thyroid extension and nodal metastasis) and were in fact less often multicentric than PTC without the mutation.

Papillary renal-cell carcinomas account for 15 to 20% of kidney cancers. Type 1, which is often multifocal and more indolent, was associated with mutations in MET . Type 2, which is more heterogeneous and aggressive, was associated with activation of the NRF2-ARE pathway. Kidney cancer, or renal-cell carcinoma, is not a single disease but is made up of various types of cancer that are characterized by different genetic drivers; each type has distinct histologic features and a distinct clinical course and response to therapy. 1 , 2 Papillary renal-cell carcinoma, which accounts for 15 to 20% of kidney cancers, is a heterogeneous disease with histologic subtypes and variations in both disease progression and patient outcomes. Papillary renal-cell carcinoma has two main subtypes: type 1, which is often multifocal, is characterized by papillae and tubular structures covered with small cells containing basophilic cytoplasm and small, uniform, . . .

Thyroid tumors formerly classified as non-invasive encapsulated follicular variant of papillary thyroid carcinoma were recently renamed ‘non-invasive follicular thyroid neoplasm with papillary-like nuclear features’. The current study investigated the frequency of lymph node metastasis and mutational profile of encapsulated follicular variant in the setting of a clinical practice where central neck dissection was the standard of practice. We defined the impact of rigid diagnostic criteria by regrouping such tumors based on the complete absence of papillae or presence of ≤1% papillae. Of a total of 6,269 papillary thyroid carcinomas, 152 tumors fulfilled the criteria for encapsulated follicular variant. The results were stratified according to two different diagnostic cutoff criteria with respect to the extent of papillae. When the cutoff of 1% papillae was used, the rates of lymph node metastasis and BRAFV600E mutation were 3% and 10% in non-invasive tumors and 9% and 4% in invasive tumors, respectively. Despite the lack of invasive growth, one patient with BRAFV600E mutant-tumor displaying predominant follicular growth and subtle papillae developed a bone metastasis. When absence of papillary structure was applied as rigid diagnostic criteria, no BRAFV600E mutation was found in all tumors. However, central lymph node micrometastasis still occurred in 3% of non-invasive tumors. Non-V600E BRAF and RAS mutations were detected in 4% and 47% of non-invasive tumors, respectively. Our findings suggest that non-invasive follicular thyroid neoplasm with papillary-like nuclear features should not be regarded as a benign thyroid neoplasm as it can present with lymph node micrometastasis and should not be diagnosed in the presence of even a single papillary structure. Our findings underscore the original American Thyroid Association recommendation that defined non-invasive encapsulated follicular variants as low risk thyroid cancers. Clinical surveillance similar to low risk differentiated thyroid cancers and capture of this diagnostic category by Cancer Registries should be considered.

Bladder cancer is the sixth most common cancer in humans. This heterogeneous set of lesions including urothelial carcinoma (Uca) and squamous cell carcinoma (SCC) arise from the urothelium, a stratified epithelium composed of K5-expressing basal cells, intermediate cells and umbrella cells. Superficial Uca lesions are morphologically distinct and exhibit different clinical behaviours: carcinoma in situ (CIS) is a flat aggressive lesion, whereas papillary carcinomas are generally low-grade and non-invasive. Whether these distinct characteristics reflect different cell types of origin is unknown. Here we show using lineage tracing in a murine model of carcinogenesis that intermediate cells give rise primarily to papillary lesions, whereas K5-basal cells are likely progenitors of CIS, muscle-invasive lesions and SCC depending on the genetic background. Our results provide a cellular and genetic basis for the diversity in bladder cancer lesions and provide a possible explanation for their clinical and morphological differences. Mendelsohn and colleagues use lineage tracing in a mouse model of bladder cancer to show that different progenitor cell populations give rise to distinct types of urothelial and squamous cell carcinomas.

A novel DEK-AFF2 fusion has been recently identified in four cases of basaloid to nonkeratinizing squamous cell carcinoma (SCC) in the sinonasal tract and middle ear with high-grade morphology. The exceptional response to immune checkpoint inhibitor in the first reported case highlights the potential clinical importance of identifying tumors with DEK-AFF2 fusions. We herein reported the first series of seven cases of DEK-AFF2 fusion-associated sinonasal SCC with deceptively bland morphology, including four cases of low-grade papillary Schneiderian carcinoma, which is a recently described tumor type with unknown molecular underpinnings. The DEK gene rearrangement was confirmed by DEK break-apart fluorescence in situ hybridization and DEK-AFF2 fusion transcripts were detected by reverse transcription polymerase chain reaction. In contrast to the previously reported DEK-AFF2 fusion-positive high-grade carcinomas, these tumors had a monotonous and bland morphology and were all initially diagnosed as sinonasal papilloma (SP) of various types, with or without dysplasia or carcinoma in situ. The tumor was characterized by mixed exophytic and inverted patterns, broad papillary fronds, acantholytic change, cellular monotony, dense neutrophilic infiltrates, and peripheral palisading. All tumors were diffusely positive for p40 or p63 and negative for NUT and p16. Molecular drivers associated with SP, including EGFR and KRAS mutations and both high and low-risk human papillomavirus infection, were negative in all cases. Although there was no overt stromal invasion or desmoplastic reaction in the initial specimens, these tumors tended to progress locoregionally through a prolonged clinical course and occasionally develop lymph node metastases, high-grade transformation, or extensively local destruction eventually leading to death. These justify more aggressive clinical management. Therefore, we propose the new terminology “DEK-AFF2 fusion-associated papillary SCC of the sinonasal tract” to better describe this clinicopathologically and molecularly distinct entity.

Exploring the clinical differences between papillary thyroid micarcinoma (PTMC) and papillary thyroid carcinoma (PTC), optimizing clinical decision-making pathways, and reducing excessive medical behavior while ensuring therapeutic efficacy. Patients diagnosed with PTMC or PTC by pathological histology from May 2023 to May 2024 at Jinan Shizhong District People's Hospital were retrospectively analyzed. PTMC refers to thyroid papillary carcinoma with a maximum diameter of ≤1 cm. There were 186 patients (PTMC group) whose maximum tumor diameter was ≤ 1 cm and 45 patients (PTC group) whose maximum tumor diameter was > 1 cm. The patient's age was (45.97 ± 10.63) years for the PTMC group and (45.31 ± 11.55) years for the PTC group. No statistically significant differences existed between the two groups in sex, age, BRAF V600E gene mutation, tumor multifocality, and capsular invasion (P > 0.05). Between the two groups, there were statistically significant (P < 0.05) differences in TNM staging, the thyroid imaging reporting and data system (TI-RADS) staging, and cervical lymph node metastasis. Thyroid surgery, thermal ablation, and active monitoring are different approaches in the stratified treatment of PTMC and PTC. To avoid overtreatment and improve the quality of life of the patients, personalized treatment plans should be developed according to the test results of TNM stage, TI-RADS classification, and cervical lymph node metastasis.

ObjectiveIntraductal papillary mucinous neoplasms (IPMNs) are precursor lesions that can give rise to invasive pancreatic carcinoma. Although approximately 8% of patients with resected pancreatic ductal adenocarcinoma have a co-occurring IPMN, the precise genetic relationship between these two lesions has not been systematically investigated.DesignWe analysed all available patients with co-occurring IPMN and invasive intrapancreatic carcinoma over a 10-year period at a single institution. For each patient, we separately isolated DNA from the carcinoma, adjacent IPMN and distant IPMN and performed targeted next generation sequencing of a panel of pancreatic cancer driver genes. We then used the identified mutations to infer the relatedness of the IPMN and co-occurring invasive carcinoma in each patient.ResultsWe analysed co-occurring IPMN and invasive carcinoma from 61 patients with IPMN/ductal adenocarcinoma as well as 13 patients with IPMN/colloid carcinoma and 7 patients with IPMN/carcinoma of the ampullary region. Of the patients with co-occurring IPMN and ductal adenocarcinoma, 51% were likely related. Surprisingly, 18% of co-occurring IPMN and ductal adenocarcinomas were likely independent, suggesting that the carcinoma arose from an independent precursor. By contrast, all colloid carcinomas were likely related to their associated IPMNs. In addition, these analyses showed striking genetic heterogeneity in IPMNs, even with respect to well-characterised driver genes.ConclusionThis study demonstrates a higher prevalence of likely independent co-occurring IPMN and ductal adenocarcinoma than previously appreciated. These findings have important implications for molecular risk stratification of patients with IPMN.

Thyroid nodules can be detected by ultrasonography in up to 68% of the general population. They are typically benign and are often discovered incidentally. The primary goal of thyroid nodule evaluation is to determine whether it is malignant. After thyroid ultrasonography has been performed, the next step is measurement of serum thyroid-stimulating hormone. If levels are low, a radionuclide thyroid uptake scan is indicated. Hyperfunctioning nodules are rarely malignant and do not require tissue sampling. Nonfunctioning nodules and nodules in a patient with a normal or high thyroid-stimulating hormone level may require fine-needle aspiration based on ultrasound characteristics and size. Nodules with suspicious features and solid hypoechoic nodules 1 cm or larger require aspiration. The Bethesda System (categories 1 through 6) is used to classify samples. Molecular testing can be used to guide treatment when aspiration yields an indeterminate result. Molecular testing detects mutations associated with thyroid cancer and can help inform decisions about surgical excision vs. continued ultrasound monitoring. Treatment of pregnant women with nonfunctioning thyroid nodules and of children with thyroid nodules is similar to that for nonpregnant adults, with the exception of molecular testing, which has not been validated in these populations.