Search

Background: Papillary thyroid microcarcinoma (PTMC) is characterized by its favorable prognosis and potential for active surveillance (AS) as a management option. However, the presence of cervical lymph node (LN) metastasis, especially lateral LN metastasis, significantly impacts management and prognosis. Previous studies have focused on post-surgery risk factors for cervical LN metastasis. This study aims to identify predictors of lateral LN metastasis by analyzing pre)operative ultrasonographic findings alongside clinicopathological factors. Methods: A retrospective review of medical records was conducted for patients with PTMC who underwent surgery at Chonnam National University Hwasun Hospital between 2004 and 2013. This is a case–control study that compares patients with lateral LN metastasis (N1b) to age- and sex-matched patients without LN metastasis (N0). Subgroup analysis was performed to evaluate risk factors of skip metastasis. Results: The study included 90 patients with PTMC with lateral LN metastasis (N1b) and 268 age- and sex-matched patients without LN metastasis (N0). The mean age was 49.3 years, and female patients were dominant in both groups. Structural recurrences of 4.4% (4/90) were observed only in the N1b group. The N1b group exhibited a higher frequency of upper lobe tumor location compared to the N0 group (38.9% vs. 16.0%, p < 0.001). There was no significant difference in the locations with the presence of invasion to adjacent organs. A higher proportion of non-parallel shape was observed in the N1b group than the N0 group (80.0% vs. 66.0%, p = 0.013). There were no differences in echogenicity, sonographic feature, margin, and AP diameter of the thyroid gland between the two groups. In multivariate analysis, independent risk factors for lateral LN metastasis included extrathyroidal extension, multiplicity, upper lobe tumor location, and non-parallel shape. Skip metastasis in patients with PTMC was associated with upper lobe tumor location. Conclusion: Detailed ultrasound examinations, evaluating tumor location, number, orientation, and the presence of ETE, are crucial in accurately predicting lateral LN metastasis especially when primary tumor was in the upper lobe to avoid missing skip metastasis. These evaluations can help guide the decision between AS and immediate surgery in patients with PTMC. [ABSTRACT FROM AUTHOR]

Aim This study aimed to demonstrate the role of Epstein-Barr Virus (EBV) in papillary thyroid carcinomas (PTC) developing on the background of Hashimotoʼs thyroiditis (HT). Methods The presence of EBV in tumoral tissue, lymphocytes, and peritumoral normal thyroid tissue was investigated using the in situ hybridization method in paraffin blocks. The subtypes of PTC, tumor diameter, TNM stage, multifocality, invasion of thyroid capsule, perineural invasion, and muscular tissue invasion were identified and compared according to EBV involvement. Results Eighty-one patients with HT diagnosis, with 93.8% (n=76) female and 6.2% (n=5) male, were included in the study. Papillary microcarcinoma was the pathological diagnosis in 24.2% (n=15) of the cases. EBV was identified in 58.06% (n=36) of the tumor cells nuclei, 58.06% (n=36) in the tumor cell cytoplasm, 16.12% (n=10) in tumor infiltrative lymphocytes, and 53.2% (n=33) in normal parenchymal follicle epithelial cells (NPFEC). In the T2 stage, the rate of EBV nuclear positivity in patients was significantly higher (p=0.034). The classic variant of papillary carcinoma was accompanied by a significantly higher rate of EBV-negative NPFEC (67.6%, p=0.049). In multifocal tumors, EBV positivity was found to be significantly higher in lymphocytes in the surrounding tissues (58.3%, p=0.034). Conclusion A significant increase in EBV positivity in the surrounding tissue lymphocytes was observed in multifocal PTC developing on a background of HT. This suggests a possible association between HT and EBV. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to evaluate the factors associated with bilateral papillary thyroid carcinoma (PTC) and lateral cervical lymph node metastasis (LLNM) in patients with suspicious unilateral PTC. Methods: This study analyzed patients with suspicious unilateral PTC who were enrolled in a university hospital between 2016 and 2019 in Zhejiang, China. Using logistic regression, the study examined the factors associated with bilateral PTC and LLNM in demographic data, anthropometric measurements, lifestyle factors, medical history, preoperative diagnostic tests, and histopathological factors. Results: A total of 256 patients, with a mean age of 49 years, were enrolled. Bilateral PTC was associated with multifocality (aOR: 5.069, 95% CI: 2.440–10.529, P < 0.001), and contralateral nodule in the upper (aOR: 9.073, 95% CI: 2.111–38.985, P = 0.003) and middle (aOR: 9.926, 95% CI: 2.683–36.717, P < 0.001). LLNM was positively associated with bilateral PTC (aOR, 4.283, 95% CI: 1.378–13.308, p = 0.012), male (aOR, 3.377, 95% CI: 1.205–9.461, P = 0.021), upper location of carcinoma (aOR, 3.311, 95% CI: 1.091–10.053, p = 0.035), and punctate echogenic foci (aOR, 3.309, 95% CI: 1.165–9.394, P = 0.025). Contralateral maximal nodule in the upper (aOR: 0.098, 95% CI: 0.015–0.628, p = 0.014), middle (aOR: 0.114, 95% CI: 0.033–0.522, p < 0.001), and lower (aOR, 0.028, 95% CI: 0.003–0.276, P = 0.002) location were inversely associated with LLNM. Conclusion: Upper and middle location of contralateral nodule and tumor multifocality predicted the risk bilateral PTC. Bilateral PTC, male, upper tumor location, punctate echogenic foci and contralateral nodule location in the entire lobes were independent predictors for LLNM. [ABSTRACT FROM AUTHOR]

Purpose: Multifocal disease in PTC is associated with an increased recurrence rate. Multifocal disease (MD) is underdiagnosed with the current gold standard of pre-operative ultrasound staging. Here, we evaluate the use of EMI-137 targeted molecular fluorescence-guided imaging (MFGI) and spectroscopy as a tool for the intra-operative detection of uni- and multifocal papillary thyroid cancer (PTC) aiming to improve disease staging and treatment selection. Methods: A phase-1 study (NCT03470259) with EMI-137 was conducted to evaluate the possibility of detecting PTC using MFGI and quantitative fiber-optic spectroscopy. Results: Fourteen patients underwent hemi- or total thyroidectomy (TTX) after administration of 0.09 mg/kg (n = 1), 0.13 mg/kg (n = 8), or 0.18 mg/kg (n = 5) EMI-137. Both MFGI and spectroscopy could differentiate PTC from healthy thyroid tissue after administration of EMI-137, which binds selectively to MET in PTC. 0.13 mg/kg was the lowest dosage EMI-137 that allowed for differentiation between PTC and healthy thyroid tissue. The smallest PTC focus detected by MFGI was 1.4 mm. MFGI restaged 80% of patients from unifocal to multifocal PTC compared to ultrasound. Conclusion: EMI-137-guided MFGI and spectroscopy can be used to detect multifocal PTC. This may improve disease staging and treatment selection between hemi- and total thyroidectomy by better differentiation between unifocal and multifocal disease. Trial registration: NCT03470259 [ABSTRACT FROM AUTHOR]

Multifocal practices allow transnational migrant entrepreneurs (TMEs) to access extended opportunity structures in diverse entrepreneurial ecosystems (EEs). National and regional regulations, customer relations, market demands, networks, and country- specific entrepreneurial statuses facilitate the strategic coupling of informal and formal business structures toward hybrid business models. However, "how" TMEs innovate and develop approaches to build from informal, formal business models in parallel across national borders remains largely underexplored. Our multiple case study presents three Polish--German TMEs who operate on a multifocal basis in different ecosystems. The longitude study of these entrepreneurs illustrates how transnational migrant businesses can change the owners' power dynamics, habitus, and feelings of belonging while counteracting social exclusion and self- discrimination. Our study contributes to the theoretical debate by illuminating the pathway between informality and formality facilitated by migrant entrepreneurs' transnational business models and their multifocal practices, possibly turning into transnational embeddedness in two or more ecosystems. [ABSTRACT FROM AUTHOR]

The following study describes the core modeling principles of correspondence of private pertinence to collective relevance, analyzes the mechanisms for creating generalized content, and the formation of common significance areas in the value space of network communication. The methodological principle of the individual and collective transgression is the concept of contextual models with focal detalization. The formation of the pertinence field is described as internal relevance characterizing polylogue delayed interaction within internet communication. The inclusion of consituational formants in the contextual model as a part of prognostication of modificational potencies of pertinences in the pentatomic field “speaker – moderator – text – recipient – moderator” allows for a description of communication process in the “downtime” situation as a substantiation of personal pertinence fields into a single relevance field, but also for the algorithmization of deriving generalized content in any indirect delayed discoursive practices. Based on a number of different property classifications, the authors derive a list of criteria features of pertinence and relevance transgression mechanisms. The authors conclude that the transaction of individual components and their introduction into the general space of significance should be accompanied by compliance with certain criteria: interpretation of the horizontal context in a wide field, transmodality, continuality of communicative action, creation of boundary models within the contextualization framework, referential eventfulness, variability of models and their permanent contextual modification, correspondence of models to the horizontal context, complexity of structure and simplification of formal composition, the presence of intersection areas of cognitive assets, the fundamental possibility of significance awareness, context hierarchy, preliminary conventionalization, forecasting the productivity of the applied model, unity of representation patterns, discursive conditionality of meanings, individual and collective alternations of meanings, variability of situations, coherence of discursive moves, mandatory verbalization of consituative components, role hierarchy of particular meanings functionality.

Abstract Introduction The prognostic value of multifocality in paediatric papillary thyroid carcinoma (PTC) patients remains a subject of debate. This study aimed to explore the clinical significance and prognostic value of multifocality in children and adolescents with PTC. Methods This study retrospectively analysed the clinicopathological characteristics and postoperative follow-up data of 338 PTC patients aged ≤ 20 years from May 2012 to July 2022. The clinical and pathological characteristics of 205 patients with unifocal lesions and 133 patients with multifocal lesions were compared. A logistic regression model evaluated the relationship between multifocal lesions and disease recurrence/persistence in children and adolescents with PTC. Based on the median follow-up time of children with multifocal PTC, 114 patients with multifocal PTC older than 20 years were added, and the clinicopathological characteristics were compared between the 133. paediatric/adolescent patients and 114 adult patients with multifocal PTC. Results Among the paediatric and adolescent patients, over a median follow-up time of 49 months, 133 had multifocal disease and 205 had unifocal disease. Multifocal PTC patients exhibited stronger invasiveness in the form of extrathyroidal extension, tumour diameter, lymph node metastasis, and distant metastasis. Multifocality (OR 2.68; p = 0.017), lateral lymph node metastasis (OR 2.85; p = 0.036), and distant metastasis (OR 4.28; p = 0.010) were identified as independent predictive factors for the recurrence/persistence of disease. Comparing the paediatric/adolescent vs. adult multifocal patients, the former demonstrated greater tumour invasiveness. Lateral lymph node metastasis (OR 6.36; P = 0.012) and distant metastasis (OR 3.70; P = 0.027) were independent predictive factors for recurrence/persistence of disease in multifocal patients, while age was not (OR 0.95; P = 0.455). Conclusion Tumour multifocality independently predicts persistent/recurrent disease in paediatric and adolescent PTC patients.

Abstract Background Pancreatic neuroendocrine tumors (PNETs) represent 1–2% of pancreatic tumors, with recent guidelines recommending active surveillance for non-functioning PNETs (NF-PNETs) smaller than 2 cm. However, the management of multiple NF-PNETs, as well as the influence of tumor number on prognosis, remains under-researched. Methods This retrospective study analyzed NF-PNET patients who underwent pancreatic resection at Severance Hospital between February 1993 and August 2023, comparing the characteristics of patients diagnosed with multifocal tumors and those with unifocal tumors. A subgroup analysis of overall survival (OS) and recurrence-free survival (RFS) was performed based on multifocality employing the Kaplan-Meier method and the log-rank test. Results Of 187 patients, 169 (90.4%) had unifocal and 18 (9.6%) had multifocal tumors. Multifocal tumors were more likely to be diffusely spread, necessitating more total pancreatectomies (diffuse tumor location: 4.7% in unifocal vs. 38.9% in multifocal cases, p

Introduction: The prognostic value of multifocality in paediatric papillary thyroid carcinoma (PTC) patients remains a subject of debate. This study aimed to explore the clinical significance and prognostic value of multifocality in children and adolescents with PTC. Methods: This study retrospectively analysed the clinicopathological characteristics and postoperative follow-up data of 338 PTC patients aged ≤ 20 years from May 2012 to July 2022. The clinical and pathological characteristics of 205 patients with unifocal lesions and 133 patients with multifocal lesions were compared. A logistic regression model evaluated the relationship between multifocal lesions and disease recurrence/persistence in children and adolescents with PTC. Based on the median follow-up time of children with multifocal PTC, 114 patients with multifocal PTC older than 20 years were added, and the clinicopathological characteristics were compared between the 133. paediatric/adolescent patients and 114 adult patients with multifocal PTC. Results: Among the paediatric and adolescent patients, over a median follow-up time of 49 months, 133 had multifocal disease and 205 had unifocal disease. Multifocal PTC patients exhibited stronger invasiveness in the form of extrathyroidal extension, tumour diameter, lymph node metastasis, and distant metastasis. Multifocality (OR 2.68; p = 0.017), lateral lymph node metastasis (OR 2.85; p = 0.036), and distant metastasis (OR 4.28; p = 0.010) were identified as independent predictive factors for the recurrence/persistence of disease. Comparing the paediatric/adolescent vs. adult multifocal patients, the former demonstrated greater tumour invasiveness. Lateral lymph node metastasis (OR 6.36; P = 0.012) and distant metastasis (OR 3.70; P = 0.027) were independent predictive factors for recurrence/persistence of disease in multifocal patients, while age was not (OR 0.95; P = 0.455). Conclusion: Tumour multifocality independently predicts persistent/recurrent disease in paediatric and adolescent PTC patients. [ABSTRACT FROM AUTHOR]

Purpose: To analyze concordance rates between individual foci of bifocal BC for histological grade, type and intrinsic subtype based on immunohistochemical (IHC) and mRNA-testing using MammaTyper. Methods: We evaluated histological grade and type as well as intrinsic subtype based on IHC status for estrogen and progesterone receptors, HER2 and the mitotic activity index in 158 individual foci of 79 bifocal BC. A subgroup of 31 cases additionally underwent mRNA-based subtyping using the MammaTyper (MT) test. We calculated concordance rates between individual foci, as well as Cohen's Kappa (k). Results: For 79 bifocal BC, concordance rates between individual foci for grade, histological type, and IHC-based subtype were 69.6% (k=0.53), 92.4% (k=0.81), and 74.7% (k=0.62), respectively. In the MT subgroup of 31 bifocal BC, concordance rates between individual foci for grade, histological type, IHC-based and mRNA-based intrinsic subtype were 87.1% (k=0.78), 90.3% (k=0.73), 87.1% (k=0.82), and 87.1% (k=0.7), respectively. Overall concordance between IHC- and mRNA-based subtype in the MT subgroup was 79% (k=0.7). In 6/79 cases (7.6%), testing of the smaller focus added clinically relevant information either on IHC- or mRNA-level: four cases showed high hormonal receptor expression while the expression in the larger focus was negative or low, warranting additional endocrine treatment; two cases presented with higher proliferative activity in the smaller focus, warranting additional chemotherapy. Conclusion: In bifocal BC, intertumoral heterogeneity on the morphological, immunohistochemical and molecular level is common, with discordant intrinsic subtype in up to 25% between individual foci, with about 8% clinically relevant discordances. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer is a heterogenous disease from many aspects. The most common special-type, invasive lobular carcinoma, is not homogenous either. It may have several mammographic appearances, some of which make screen detection difficult. Histologically, lobular carcinoma has a peculiar morphology consisting of non-cohesive cells often arranged in single file, but this classical morphology may often be admixed with less easily recognizable histological patterns, such as the solid, the alveolar, the trabecular, or the tubule-forming, some of which are characterized by the regained cohesion of the tumor cells. Whether the dominant histological patterns are associated with specific mammographic presentation is not known, but such associations may be important from diagnostic aspects looking at radio-pathological correlations. It was believed that the classical histologic pattern might be more often occult, whereas more cohesive or dense patterns might be more often mass forming. Our analysis failed to demonstrate obvious associations between radiological and pathological presentations. Invasive lobular carcinoma of the breast has different mammographic appearances, including spiculated or lobulated masses, architectural distortion, increased breast density, and the possibility of also being occult. Histologically, the morphology is also variable, as several patterns have been described beside the classical one, including the solid, the alveolar, the trabecular, the one with tubular elements, and others. Of 146 ILC cases, 141 were reviewed for mammographic appearance and 136 for histological patterns by two radiologist and two pathologists, respectively; 132 common cases were analyzed for possible associations between mammographic presentation and the histological patterns. Interobserver agreement on the presence or absence of a given mammographic morphology ranged from 45% (increased density) to 95% (occult lesion); the most common radiomorphology was that of a spiculated mass. Interobserver agreement on the presence or absence of a given histological pattern ranged between 79% (solid) and 99% (classical) but was worse when semi-quantification was also included. The mammography–pathology correlation was less than optimal. Multifocality was more commonly detected by histology. The identification of a mammographic mass lesion often coincided with a mass-like lesion on the histological slides and vice versa, but nearly half of the mammographically occult lesions were felt to have masses on histological slides assessed grossly. Histological patterns showed no obvious associations with one or the other mammographic appearance. [ABSTRACT FROM AUTHOR]

Whereas multifocality typically concerns papillary thyroid carcinoma (PTC) without specification of intrathyroidal metastatic or independent nature of tumor foci, the designation of the latter as Multi‐UniFocal (MUF) may be relevant for select cases. A case series involving multifocal thyroid lesions with divergent histopathological morphology and/or molecular profile, with molecular evaluation of multiple individual tumor foci per patient based on a next‐generation sequencing approach, was retrospectively reviewed. Twenty‐five patient cases with multifocal thyroid lesions suggestive of MUF, with 2–6 (median 3) tumor foci per patient, were described. Tumor lesions comprised diverse histopathology, including PTC, (E)FVPTC, NIFTP, FA, FTC, and oncocytic. Morphologically similar and/or diverse tumor foci harbored different molecular alterations (suggestive of non‐shared clonality); with(out) coexistent similar foci harboring identical molecular alterations; or (partly) shared molecular alterations. MUF was associated with chronic lymphocytic thyroiditis in almost half of the cases. The recognition of MUF may justify the independent clinical consideration per individual tumor focus; as separate lesions albeit within a multifocal context. The potential clinical relevance and prognostic value of MUF remain to be further established. [ABSTRACT FROM AUTHOR]

Background: Pancreatic neuroendocrine tumors (PNETs) represent 1–2% of pancreatic tumors, with recent guidelines recommending active surveillance for non-functioning PNETs (NF-PNETs) smaller than 2 cm. However, the management of multiple NF-PNETs, as well as the influence of tumor number on prognosis, remains under-researched. Methods: This retrospective study analyzed NF-PNET patients who underwent pancreatic resection at Severance Hospital between February 1993 and August 2023, comparing the characteristics of patients diagnosed with multifocal tumors and those with unifocal tumors. A subgroup analysis of overall survival (OS) and recurrence-free survival (RFS) was performed based on multifocality employing the Kaplan-Meier method and the log-rank test. Results: Of 187 patients, 169 (90.4%) had unifocal and 18 (9.6%) had multifocal tumors. Multifocal tumors were more likely to be diffusely spread, necessitating more total pancreatectomies (diffuse tumor location: 4.7% in unifocal vs. 38.9% in multifocal cases, p < 0.001; total pancreatectomy: 4.1% in unifocal vs. 33.3% in multifocal cases, p < 0.001). In patients with NF-PNET who underwent the same extent of pancreatic resection, no significant difference in the incidence of complication was observed regardless of multifocality. Moreover, no significant difference in OS was seen between the unifocal and multifocal groups (log-rank test: p = 0.93). However, the multifocal group exhibited a poorer prognosis in terms of RFS compared to the unifocal group (log-rank test: p = 0.004) Hereditary syndrome, tumor grade, size, lymphovascular invasion, and lymph node metastasis were key factors in the recurrence. Conclusion: This study's findings suggest that the presence of multiple tumors was associated with poorer recurrence-free survival but did not affect long-term survival following surgery. Given the long-term oncologic outcome and quality of life following surgery, resection of tumors over 2 cm is advisable in patients with multifocal PNETs, while a cautious "wait-and-see" approach for smaller tumors (under 2 cm) can minimize the extent of resection and improve the quality of life. In cases with only small multifocal NF-PNETs (< 2 cm), immediate resection may not be crucial, but the higher recurrence rate than that in solitary NF-PNET necessitates intensified surveillance. [ABSTRACT FROM AUTHOR]

Background: Active surveillance has been an option for patients with low-risk papillary thyroid carcinoma (PTC). However, whether delayed surgery leads to an increased risk of local tumor metastasis remain unclear. We sought to investigate the impact of observation time on central lymph node metastasis (CLNM) and multifocal disease in patients with low-risk PTC. Methods: Patients who were diagnosed with asymptomatic low-risk PTC, and with a pathological maximum tumor size =1.5 cm by were included. The patients were classified into observation group and immediate surgery group, and subgroup analyses were conducted by observation time period. The prevalence of CLNM, lymph node (LN) involved >5, multifocal PTC and bilateral multifocal PTC were considered as outcome variables. The changing trend and risk ratio of prevalence over observation time were evaluated by Mann-Kendall trend test and Logistics regression. Results: Overall, 3,427 and 1,860 patients were classified to the observation group and immediate surgery group, respectively. Trend tests showed that decreasing trends both on the prevalence of CLNM and LN involved >5 over the observation time, but the difference was not statistically significant, and the prevalence of multifocal PTC and bilateral multifocal PTC showed the significant decreasing trends. After adjustment, multivariate analysis showed no statistically significant difference between observed and immediate surgery groups in the four outcome variables. Conclusion: In patients with subclinical asymptomatic low-risk PTC, observation did not result in an increased incidence of local metastatic disease, nor did the increased surgery extent in patients with delayed surgery compared to immediate surgery. These findings can strengthen the confidence in the active surveillance management for both doctors and patients. [ABSTRACT FROM AUTHOR]

Background and Aim: Patients with hepatocellular carcinoma (HCC) are managed in various hospital departments, which complicates the assessment of the overall picture. In our large liver transplant institute, we evaluate all HCC patients in a weekly multi-disciplinary liver tumor board, and their data are prospectively collected in an institutional HCC database to evaluate HCC causes, tumor features, treatments, and survival. Materials and Methods: Baseline data for patients (n=1322) were prospectively recorded, including hepatitis status, routine clinical serum parameters, radiological assessment of maximum tumor diameter (MTD), tumor number, presence of macroscopic portal vein thrombosis (PVT), and serum alpha-fetoprotein (AFP) levels. Results: Cirrhosis was found in 81.1% of patients; 58.5% had hepatitis B virus (HBV), 14.9% hepatitis C virus (HCV), 8.9% cryptogenic cirrhosis, and less than 2% had alcoholism. MTD was <5 cm in 61.95% of patients, and 31.9% had PVT. The median overall survival was more than six-fold greater for the 444 liver transplant patients than for those without surgery. Transplanted patients had smaller tumors, whereas larger tumors (MTD >10 cm) were primarily in the no-surgery group. Parallel differences were found for AFP levels (highest in the no-surgery group). PVT was present in similar proportions (25.0% for transplant, 28.0% for no-surgery). The presence of cirrhosis was higher in the transplant group. MTD and levels of serum AFP, gamma-glutamyl transferase (GGT), and blood platelets were prognostic parameters for transplant. Furthermore, AFP and GGT levels were prognostic for transplanted PVT patients. Only albumin was prognostic in the no-surgery patients. Conclusion: Transplanted HCC patients have longer survival, smaller tumors, and more severe liver damage than no-surgery patients. Prognostic subsets were identified within the surgery and the PVT groups. [ABSTRACT FROM AUTHOR]

BackgroundSmall intestinal neuroendocrine tumors (SI-NETs) are the most common neoplasms of the small bowel. The majority of tumors are located in the distal ileum with a high incidence of multiple synchronous primary tumors. Even though up to 50% of SI-NET patients are diagnosed with multifocal disease, the mechanisms underlying multiple synchronous lesions remain elusive.MethodsWe performed whole genome sequencing of 75 de-identified synchronous primary tumors, 15 metastases, and corresponding normal samples from 13 patients with multifocal ileal NETs to identify recurrent somatic genomic alterations, frequently affected signaling pathways, and shared mutation signatures among multifocal SI-NETs. Additionally, we carried out chromosome mapping of the most recurrent copy-number alterations identified to determine which parental allele had been affected in each tumor and assessed the clonal relationships of the tumors within each patient.ResultsAbsence of shared somatic variation between the synchronous primary tumors within each patient was observed, indicating that these tumors develop independently. Although recurrent copy-number alterations were identified, additional chromosome mapping revealed that tumors from the same patient can gain or lose different parental alleles. In addition to the previously reported CDKN1B loss-of-function mutations, we observed potential loss-of-function gene alterations in TNRC6B, a candidate tumor suppressor gene in a small subset of ileal NETs. Furthermore, we show that multiple metastases in the same patient can originate from either one or several primary tumors.ConclusionsOur study demonstrates major genomic diversity among multifocal ileal NETs, highlighting the need to identify and remove all primary tumors, which have the potential to metastasize, and the need for optimized targeted treatments.

Multifocal (MF) and multicentric (MC) breast cancers are seen with increasing frequency with advances in imaging methods. However, there is no consensus on the behavior and management of these tumors. In this study, we aimed to investigate the characteristics of MF/MC breast cancers and their relationship with axillary lymph node metastasis (ALNM). Patients who underwent surgery for breast cancer between January 2015 and January 2023 were retrospectively scanned. Exclusion criteria were as follows; male breast cancer, second primary cancer diagnosis, previous breast cancer history, previous excisional/incisional breast biopsy, neoadjuvant chemotherapy, and occult breast cancer. Multiple tumors that were closer than 5 cm to each other were defined as MF, and the others were defined as MC. T stage was determined in two different ways, using the largest tumor diameter (Tmax) and the aggregate tumor diameter (Tsum), and two different multivariate analysis models were applied. A total of 156 patients were enrolled in the study, including 130 unifocal (UF), 17 MF and 9 MC. Lymphovascular invasion (LVI) (p=0.43), ALNM (p=0.23), younger age (<50) (p=0.41) and invasive lobular carcinoma (ILC) (p<0.001) were higher in MF/MC tumors than in UFs. When comparing MF and MC, no difference was seen except progesterone receptor positivity (p=0.017). In both multivariate analyses, LVI and ILC had an effect on ALNM, while no effect of MF/MC was seen. In addition, while T stage had a significant effect on ALNM in the model using Tsum, it did not have a significant effect in the Tmax model. Our retrospective data supports that MF/MC is not a direct risk factor for ALNM and that the main factor affecting ALNM is the total tumor burden. [ABSTRACT FROM AUTHOR]

There are limited data regarding the significance of multifocality in testicular cancer patients. This study evaluated the relationship between multifocality and clinicopathological features determined at the time of radical orchiectomy. The study involved 280 consecutive patients who underwent radical orchiectomy between 2018 and 2023. Multifocality was defined as a distinct tumor focus characterized by a group of malignant cells > 1 mm, clearly differentiated from the primary tumor mass. Uni- and multivariate logistic regression analyses were employed to investigate the association between multifocality and histopathological parameters along with potential risk factors for clinical stages II + III. Multifocality was identified in 44 (15.7%) patients. Significantly smaller primary tumors were observed in subjects with multifocality (20.0 mm vs. 30.0 mm, p = 0.0001), while those exhibiting monofocality presented a markedly elevated rate of tumors exceeding 4 cm (40.3% vs. 18.2%, p = 0.005). Furthermore, multifocality was associated with a significantly higher rate of primary tumors < 2 cm (52.3% vs. 29.2%, p = 0.003). Univariate logistic regression analysis revealed a substantial decrease in the likelihood of multifocality occurrence in seminoma patients with tumors > 4 cm (OR = 0.38, p = 0.017). Meanwhile, in multivariate logistic regression, multifocality did not emerge as a significant risk factor for clinical stages II + III in either seminoma (p = 0.381) or non-seminoma (p = 0.672) cases. Our study suggests that multifocality holds no substantial prognostic relevance for clinically advanced disease in testicular cancer patients. The findings indicate that multifocality is associated with smaller primary tumors, particularly those measuring less than 2 cm. [ABSTRACT FROM AUTHOR]

Papillary thyroid microcarcinoma (PTMC) represents 35–40% of all papillary cancers; it is defined as a nodule ≤ 10 mm at the time of histological diagnosis. The clinical significance of PTMC is still controversial, and it may be discovered in two settings: incidental PTMC (iPTMC), in which it is identified postoperatively upon histological examination of thyroid specimens following thyroid surgery for benign disease, and nonincidental PTMC (niPTMC), in which it is diagnosed before surgery. While iPTMC appears to be related to mild behavior and favorable clinical outcomes, niPTMC may exhibit markers of aggressiveness. We retrospectively review our experience, selecting 54 PTMCs: 28 classified as niPTMC (52%) and 26 classified as iPTMC (48%). Patients with niPTMC showed significant differences, such as younger age at diagnosis (p < 0.001); a lower male/female ratio (p < 0.01); a larger mean nodule diameter (p < 0.001); and a higher rate of aggressive pathological findings, such as multifocality, capsular invasion and/or lymphovascular invasion (p = 0.035). Other differences found in the niPTMC subgroup included a higher preoperative serum TSH level, higher hospital morbidity and a greater need for postoperative iodine ablation therapy (p < 0.05), while disease-free long-term survival did not differ between subgroups (p = 0.331) after a mean follow-up (FU) of 87 months, with one nodal recurrence among niPTMCs. The differences between iPTMC and niPTMC were consistent: patients operated on for total thyroidectomy and showing iPTMC can be considered healed after surgery, and follow-up should be designed to properly calibrate hormonal supplementation; conversely, niPTMC may sometimes exhibit aggressive behavior, and so the FU regimen should be closer and aimed at early detection of cancer recurrence. [ABSTRACT FROM AUTHOR]

(1) Introduction: The impact of multifocality/bilaterality on the prognosis of papillary thyroid carcinoma (PTC) is a matter of debate. In order to clarify this debate, several studies have attempted to identify additional parameters associated with poor prognosis, including total tumor diameter (TTD), in the context of multifocal PTCs. In this context, this study was carried out to investigate the impact of TTD on tumor recurrence and lymph node metastasis (LNM) in PTCs. (2) Materials and Methods: The sample of this single-center retrospective study consisted of 706 patients diagnosed with PTC. TTD was calculated as the sum of the largest diameters of tumor foci in multifocal tumors. The resulting TTDs were grouped into TTDs ≤ 10 mm, TTDs > 10 mm, TTDs ≤ 20 mm, and TTDs > 20 mm, using 10 mm and 20 mm as cutoff values. (3) Results: There was no significant difference between multifocal papillary microcarcinomas (PTMCs) with a TTD of >10 mm and unifocal PTCs with a primary tumor diameter (PTD) of >10 mm except for advanced age and lymphovascular invasion (LVI). In addition, perineural invasion (PNI) and TTD > 10 mm were found to be significant risk factors for LNM, and PNI, TTD > 10 mm, TTD > 20 mm, and bilaterality were found to be significant risk factors for recurrence. LVI, and TTD > 10 mm were found to be independent significant predictors for recurrence, and LVI and extrathyroidal extension (ETE) were found to be independent significant predictors for LNM. (4) Conclusions: Considering TTD > 10 mm in recurrence risk categorization models and adopting a clinical approach that takes into account multifocal PTMCs with TTD > 10 mm along with unifocal PTCs with PTD > 10 mm may be more useful in terms of clinical management of the disease. [ABSTRACT FROM AUTHOR]

Background It has been identified that ionising radiation is the definitive cause of human cancer. One-third of the tumours that develop after radiation exposure are malignant, with papillary thyroid cancer (PTC) being the most common cancer type. This study investigated the relationship between total radiation dose (TRD) received during imaging tests and thyroid cancer occurrence in patients diagnosed with PTC. Methods The study was designed to retrospectively review the data of adult patients aged =18 years diagnosed with PTC between 2005 and 2022. Patients diagnosed with a condition other than PTC were excluded from the study. Results Three hundred seven patients with papillary thyroid cancer were 256 (83.4%) women, with a mean age of 44.7±13.5 years. A statistically significant relationship was observed between TRD and multifocality (p=0.02). Tumour size (r=0.200, p=0.07) weakly correlated with TRD, and TRD (OR: 0.9, 95% CI: 1.0-1.1, p=0.006) was found to be significant according to multifocality. Conclusion This study found an association between TRD taken during imaging tests and multifocality. As a result, the authors aimed to remind clinicians that the disease may progress more aggressively and that thyroid cancer may develop in patients exposed to radiation due to excessive imaging tests. [ABSTRACT FROM AUTHOR]

Objective: Serum 25-hydroxyvitamin D (25(OH)D) deficiency has been known to be associated with the risk and mortality of several cancers. However, the role of 25(OH)D in papillary thyroid cancer (PTC) remains controversial. This study aimed to investigate the association between 25(OH)D and clinicopathologic features of PTC. Methods: Patients who underwent thyroidectomy were retrospectively reviewed. Serum 25(OH)D levels were measured within a week prior to surgery. The patients were categorized into four quartiles according to season-specific 25(OH)D levels. The association between 25(OH)D levels and clinicopathologic features of PTC was analyzed. Results: A total of 2932 patients were enrolled in the study. The 25(OH)D levels were significantly higher in patients with lymph node metastasis (LNM; P < 0.001), lateral LNM (P < 0.001), and multifocal tumors (P < 0.001). Compared to the first quartile (Q1) of 25(OH)D level, the third quartile (Q3) and the fourth quartile (Q4) showed an unadjusted OR of 1.36 (95% CI: 1.09–1.69; P = 0.006) and 1.76 (95% CI: 1.42–2.19; P < 0.001) for LNM (P for trend < 0.001), respectively. An increased risk of multifocal tumors was strongly associated with high 25(OH)D concentration (P for trend

Background: Evidence suggests that patients with Hashimoto thyroiditis (HT) are at significantly higher risk of developing papillary thyroid cancer (PTC). However, the course of PTC in patients with both diseases concomitantly has been found to be more indolent than conventional PTC. Additionally, it has been well proven that BRAF mutation results in an aggressive course of PTC. The aims of this metaanalysis were to identify prevalence of BRAF mutation and its impact on clinicopathological features in patients with concomitant PTC-HT. Methods: Medline, Cochrane Library, Scopus, and Web of Science were searched until 16.09.2022, resulting in 227 articles, of which nine studies were included. Summary estimates, comparing patients with (A) BRAF (+) PTC-HT versus BRAF (+) PTC, and (B) BRAF (+) PTC-HT versus BRAF (-) PTC-HT, were generated with Review Manager 5.0. Results: In total, 6395 patients were included in this review. PTC-HT patients had significantly less BRAF mutation than PTC patients (Odds Ratio (OR) (95% Confidence Interval (CI))=0.45 (0.35-0.58), P<0.001). BRAF (+) PTC-HT patients were significantly more likely to have multifocal lesions (OR (95% CI)=1.22 (1.04-1.44), P=0.01) but less likely to have lymph node metastasis (OR (95% CI)=0.65 (0.46-0.91), P=0.01) and extrathyroidal extension (OR (95% CI)=0.55 (0.32-0.96), P=0.03) compared to BRAF (+) PTC patients. BRAF (+) PTC-HT patients were more likely to have multifocal lesions (OR (95% CI)=0.71 (0.53-0.95), P=0.02), lymph node metastasis (OR (95% CI)=0.59 (0.44-0.78), P<0.001) and extrathyroidal extension (OR (95% CI)=0.72 (0.56-0.92), P=0.01) compared to BRAF (-) PTC-HT patients. Conclusion: This meta-analysis highlights that the lower prevalence of BRAF mutation in patients with PTC-HT than conventional PTC may explain the indolent clinicopathological course in this cohort. [ABSTRACT FROM AUTHOR]

Context: Total thyroidectomy in pediatric papillary thyroid carcinoma (PTC) is recommended in national guidelines because of the high incidence of multifocal disease (MFD). Objective: To determine the incidence of MFD in childhood and adolescent vs adult PTC and whether MFD is a predictor for poorer outcomes in childhood and adolescent PTC. Methods: We conducted an institutional review board-approved review of patients with PTC undergoing surgery (1986-2021) at Memorial Sloan Kettering Cancer Center. Clinical and pathological characteristics in patients with unifocal disease (UFD) and MFD were compared using Pearson's χ² test. Survival outcomes were analyzed using the Kaplan-Meier method and log-rank test. Multivariate analysis assessed the impact of MFD on outcome. Results: MFD was less common in childhood and adolescent patients with PTC (45%; 127/283) than in adults (54%; 3023/5564; P = .002). Childhood and adolescent patients with UFD and MFD had similar tumor stage and PTC subtype at presentation, with no significant difference in histopathologic features. Median follow-up was 68 months. There was no significant difference in 5-year recurrence-free probability and overall survival was 100% in both groups. There was no significant difference in 5-year contralateral lobe PTC-free probability between patients with UFD and MFD treated with lobectomy. Multivariate analysis showed MFD was not a predictor for recurrence. Conclusion: MFD was less common in childhood and adolescent patients with PTC than adults and was not a predictor of poor outcome on multivariate analysis, with excellent long-term outcomes in all patients with PTC. MFD does not appear to warrant completion thyroidectomy in childhood and adolescent patients selected for lobectomy. [ABSTRACT FROM AUTHOR]

Simple Summary: About 30% of thyroid cancer is found on both thyroid lobes simultaneously. However, the prognostic effect of bilaterality remains unestablished and controversial. This study of 1258 patients demonstrated that patients with bilaterality were associated with a more aggressive disease. We also found that patients with bilateral thyroid cancer showed higher recurrence rates than those with unilateral tumors. Therefore, patients with bilateral thyroid cancer might require careful treatment and follow-up approaches. Previous studies suggested that the multifocality of papillary thyroid carcinoma (PTC) would increase the risk of recurrence; however, the impact of its bilaterality remains unclear. Between 2011 and 2018, 1258 patients with PTC underwent total thyroidectomy at Ewha University Medical Center. The 5-year recurrence-free survival rate was 95.7% in patients with bilateral PTC, while those with unilateral multifocal PTC and a unifocal tumor showed a 5-year event-free survival rate of 97.0% and 97.8%, respectively (p = 0.004). A multivariable Cox proportional hazards model indicated that bilaterality (HR 2.550, 95% CI 1.354–4.800), male sex (HR 2.010, 95% CI 1.007–4.013), and tumor size (HR 1.748, 95% CI 1.316–2.323) were associated with recurrence, although unilateral multifocality did not increase the risk of recurrence (HR 1.211, 95% CI 0.348–4.213). In conclusion, bilaterality was associated with aggressive features, including tumor size and microscopic ETE. Moreover, bilaterality was an independent predictor of recurrence in patients with PTC. Patients with bilateral PTC might require careful treatment and follow-up approaches. [ABSTRACT FROM AUTHOR]

Purpose: To extend the indications of kidney-sparing surgery (KSS) for ureter cancer by comparing the oncological outcomes between patients with upper tract urothelial carcinoma (UTUC) who underwent radical nephroureterectomy (RNU) or KSS. Methods: We retrospectively reviewed 708 patients with UTUC who underwent RNU (N = 646) or KSS (N = 62) between 2011 and 2019 to analyze the oncologic outcomes and prognostic factors. Subgroup analyses were performed for patients with unifocal ureteral urothelial carcinoma (UC). Results: No significant difference was observed in the overall survival (OS) or cancer-specific survival (CSS) between RNU and KSS (distal ureterectomy with reimplantation (N = 33), ureterectomy with ileal ureter (N = 14), ureteroscopic tumor resection (N = 10), and ureterectomy with ureteroureterostomy (N = 5)). Among 269 (38.0%) patients with unifocal ureteral UC, 219 and 50 patients underwent RNU and KSS, respectively. OS and CSS were not significantly different between these two groups. Pathologic stage was a significant risk factor in multivariate analysis (hazard ratio = 2.621; p = 0.000). Among 646 RNU patients, 219 (33.9%) had unifocal ureteral UC, 40 (18.3%) with low-grade tumors. Among these, 13 (5.9%) patients with unifocal, low-grade and small (< 2 cm) tumors received nephroureterectomy. Conclusion: Kidney-sparing surgery should be regarded as an important alternative to RNU for patients with unifocal ureteral UC thought to have noninvasive disease to preserve renal function and reduce overtreatment. [ABSTRACT FROM AUTHOR]

Aim: The incidence of thyroid cancer has increased dramatically in recent decades. Multifocality is considered a poor prognostic factor for papillary thyroid carcinoma (PTC). Patients with multifocal PTC (MPTC) are at high risk for local recurrence, as well as lymphatic and distal metastases. This study examined the features and outcomes of MPTC. Material and Methods: This retrospective study was conducted on 300 patients with PTC. Patients were classified into a multifocal group and a unifocal group. The pathological features of the PTC and the patients’ outcomes were analyzed and compared. Results: The multifocal group included 146 patients (48.7%), while the unifocal group included 154 patients (51.3%). The occurrence of multifocality was higher in females than in males (Odds ratio, OR: 2.37, 95% confidence interval, CI: 1.20-4.67, p=0.015). Tumor size of >1 cm in the multifocal group was larger than in the unifocal group (2.5 and 2.2 cm, respectively, p=0.021). Moreover, in multifocal group higher moderate risk of recurrence was detected than in the unifocal group (OR: 1.63, 95% CI: 1.01-2.60, p=0.044). At follow-up after treatment, MPTC patients had higher lymph node metastasis (OR: 2.89, 95% CI: 1.23-6.80, p=0.014). In addition, significantly higher thyroglobulin plasma levels (p=0.026) and disease recurrence (OR: 2.41, 95% CI: 1.05-5.52, p=0.037) were found in the multifocal group compared to the unifocal group. Conclusion: Patients with MPTC had a higher risk of disease recurrence, and multifocality was concluded to be an independent prognostic factor for overall disease recurrence.

BackgroundEvidence suggests that patients with Hashimoto thyroiditis (HT) are at significantly higher risk of developing papillary thyroid cancer (PTC). However, the course of PTC in patients with both diseases concomitantly has been found to be more indolent than conventional PTC. Additionally, it has been well proven that BRAF mutation results in an aggressive course of PTC. The aims of this meta-analysis were to identify prevalence of BRAF mutation and its impact on clinicopathological features in patients with concomitant PTC-HT. MethodsMedline, Cochrane Library, Scopus, and Web of Science were searched until 16.09.2022, resulting in 227 articles, of which nine studies were included. Summary estimates, comparing patients with (A) BRAF (+) PTC-HT versus BRAF (+) PTC, and (B) BRAF (+) PTC-HT versus BRAF (-) PTC-HT, were generated with Review Manager 5.0. ResultsIn total, 6395 patients were included in this review. PTC-HT patients had significantly less BRAF mutation than PTC patients (Odds Ratio (OR) (95% Confidence Interval (CI))=0.45 (0.35-0.58), P

Objective: To determine the predictive ability of multifocality for central lymph node metastasis in initially treated 18-55 years old female patients with unilateral papillary thyroid microcarcinoma. Study design: Retrospective review. Setting: Tertiary medical center. Methods: We retrospectively collected clinical data from initially treated papillary thyroid microcarcinoma (PTMC) patients at Cancer Hospital Chinese Academy of Medical and sciences between January 1st, 2018, and December 31st, 2018. Data from 975 initially treated 18-55 years old female patients with unilateral PTMC was collected. We also collected data from 340 initially treated 18-55 years old male patients with unilateral PTMC patients to compare the results between genders. Clinicopathological factors associated with central lymph node metastasis (CLNM) were investigated by univariate and multivariate analysis. Results: (1) In the female group, there were 196 (20.1%) cases that had tumor multifocality, including 126 (12.9%) with 2 foci and 70 (7.2%) with >2 foci. The risk of CLNM in patients with 2 foci was not significantly higher than patients with 1 focus (37.3% vs 38.6%, P=0.775). However, diagnosed with >2 foci were independently and positively correlated with CLNM (OR=2.708, 95%CI=1.592-4.607, P<0.001), as was tumor diameter >0.55cm (OR=2.047, 95%CI=1.535-2.730, P<0.001). (2) In the male group, the risk of CLNM with 2 foci was significantly higher than 1 focus (P=0.008). Compared to female patients, the risk of CLNM was significantly higher in patients with 1 focus (P<0.001) or 2 foci (P<0.001). Conclusion: In summary, the risk of CLNM in patients with 2 foci was not significantly higher than patients with 1 focus, while multifocality with over 2 foci was an independent risk factor of CLNM. Therefore, multifocality in this subgroup should not be simply defined as "more than 1 focus". Future models that include multifocality as a predictive factor for cervical lymph node metastasis could consider stratifying the cohort into smaller subgroups for more accurate conclusions. [ABSTRACT FROM AUTHOR]

Calcifying pseudoneoplasm of the neuraxis (CAPNON) is thought to be a rare tumefactive lesion with unknown pathogenesis. Its prevalence is questionable with few previously reported cases of incidental CAPNON, and likely underdiagnosis. We report a unique case of incidental multifocal CAPNON. A 64-year-old female was admitted with loss of consciousness due to a ruptured right middle cerebral artery aneurysm with subarachnoid and intraventricular hemorrhage. She has a craniotomy and clipping. At time of operation, numerous small dural-based nodules were found, and one was excised for biopsy and was diagnosed as CAPNON. Retrospective review of her CT images identified nodules that were all ipsilateral to the ruptured aneurysm. A literature review revealed that incidental and/or multifocal CAPNONs are rare but likely underreported. Our case suggests a reactive process in the pathogenesis of CAPNON. [ABSTRACT FROM AUTHOR]

Multifocality is a frequent feature of papillary thyroid carcinoma (PTC). Its prognostic value is controversial although national guidelines recommend treatment intensification if present. However, multifocality is not a binary but discrete variable. This study aimed to examine the association between increasing number of foci and risk of recurrence following treatment. 577 patients with PTC were identified with median follow-up of 61 months. Number of foci were taken from pathology reports. Log-rank test was used to assess significance. Multivariate analysis was performed and Hazard Ratios were calculated. Of 577 patients, 206(35%) had multifocal disease and 36(6%) recurred. 133(23%), 89(15%) and 61(11%) had 3+, 4+ or 5+ foci respectively. The 5-year RFS stratified by number of foci was 95%v93% for 2+foci (p = 0.616), 95%v96% for 3+foci (p = 0.198) and 89%v96% for 4+foci (p = 0.022). The presence of 4 foci was associated with an over 2-fold risk of recurrence (HR 2.296, 95% CI 1.106–4.765, p = 0.026) although this was not independent of TNM staging. Of the 206 multifocal patients, 31(5%) had 4+foci as their sole risk factor for treatment intensification. Although multifocality per se does not confer worse outcome in PTC, finding 4+foci is associated with worse outcome and could therefore be appropriate as a cut-off for treatment intensification. In our cohort, 5% of patients had 4+foci as a sole indication for treatment intensification, suggesting that such a cut off could impact clinical management. [ABSTRACT FROM AUTHOR]

Background/Aim: Many studies indicate that multifocality is associated with high-risk features of differentiated thyroid cancer (DTC). Herein, we evaluated the impact of the unilateral multifocality on post-lobectomy recurrence in patients with DTC. Patients and Methods: We retrospectively analyzed 1,684 patients with DTC who underwent thyroid lobectomy from 2008 to 2015 using logistic regression models to calculate the relative risk on postlobectomy recurrence. Results: Tumor diameter increased from 4.9 mm to 8.1 mm and the proportion of extrathyroidal extension (ETE) and unilateral multifocality progressively increased from 2008 to 2015 (2.1% to 24.3% and 4.2% to 22.8%, respectively). During the 88.6-month follow-up period, 67 (3.98%) recurrences and 2 (0.12%) deaths were observed. There were 269 (16.0%) multifocal DTC cases. There was no significant difference between the multifocal and unifocal groups in terms of the proportion of recurrences (5.2% vs. 3.7%) and distant metastasis (0.4% vs. 0.1%). Logistic regression analysis revealed age <42.5 years (OR=1.83), tumor diameter greater than 7.5 mm (OR=1.89), and N1a (OR=2.04) were potent risk factors for post-lobectomy recurrence. Conversely, male sex (OR=0.77; p=0.407), ETE (OR=1.16; p=0.698) and multifocality (OR=1.23; p=0.526) were not risk factors for recurrence after thyroid lobectomy. A positive node ratio (PNR) =42.0%, N1a stage, a tumor diameter =7.5mm and age <42.5 years were significant risk factors for recurrence (Log-rank p=0.001, p=0.001, p=0.004 and p=0.009, respectively). Contrariwise, multifocality and ETE were proven to not be risk factors for DTC recurrence after thyroid lobectomy (Log-rank p=0.099 and p=0.126, respectively). Conclusion: Unilateral multifocality was not a risk factor for DTC recurrence after thyroid lobectomy and could not be considered an indication for immediate completion or total thyroidectomy. [ABSTRACT FROM AUTHOR]

Background: Much is still unknown regarding the clinicopathology and prognosis of patients with multifocal/multicentric breast cancer (MMBC). We herein compared the clinicopathology and prognosis of patients with unifocal and MMBCs.Method: This cross-sectional research is a part of Shiraz Breast Cancer Registry (SBCR). We studied all the patients in the SBCR (n=6145). Ultrasound reports were used to differentiate between MMBCs and unifocal breast cancers (BCs). All the patients were examined with mammography and the diagnosis was confirmed postoperatively via pathology reports.Results: After exclusion, 4045 patients entered the study (n=1072 and n=2973 for multifocal/multicentric and unifocal BCs, respectively). The mean follow-up period was 57.9 (0.27-275) months. Patients with MMBCs had higher rates of mastectomy (48% vs. 40.1%; P < 0.001) and higher rates of HER-2 overexpression (32.1% vs. 26%; P = 0.001) compared with those with unifocal BCs. Tumor size, lymph node involvement, type of axillary management, chemotherapy, radiotherapy, hormonal therapy, recurrence rates, histological grade, lymphovascular invasion, axillary node involvement, estrogen and progesterone receptor expression status, tumor, node, and metastasis staging were not significantly different between the groups. Five-year overall survival was 88.3% and 89% (P = 0.8) for unifocal and MMBCs, respectively; moreover, five-year disease-free survival was 80.2% and 81.2% (P = 0.41), respectively.Conclusion: Despite the controversy regarding prognosis and surgical management in MMBCs, we found that MMBCs had similar clinicopathological features and prognosis compared to unifocal BCs. Survival, recurrence, and metastasis were similar among the two groups.

The aim of this study is to analyze and identify the main predictors that may indicate multifocal growth of PTC. Materials and methods. The main and control groups included patients with the category of malignant multifocal process T1-3mN0Mx (n=109) and unifocal T1- T3N0Mx (n=50) respectively, who underwent thyroidectomy with lymphadenectomy. Ultrasound characteristics of the nodes, tissue changes of the thyroid gland were taken into account. Results. Fibrous changes can be considered as one of the risk factors of the presence of additional PTC lesion. Discussion. There is no unambiguity in the definition of predictors of multifocal PTC growth. Conclusions. No clear predictors of multifocal PTC have been identified. It is advisable to improve the quality of ultrasound, to focus on single-focus PTC in patients with fibrinous changes in the thyroid gland at normal levels of TSH. [ABSTRACT FROM AUTHOR]

Papillary thyroid cancer (PTC) is the most common type of thyroid cancer, and its incidence continues to increase. Multifocality is common in PTC, and it has been suggested in many studies that multifocality may be associated with poor prognosis. In this study, data of patients followed with multifocal PTC were evaluated. Following the approval of the local ethics committee, the data of patients who received total thyroidectomy and subsequent radioactive iodine (RAI) treatment for thyroid cancer between 2012 and 2020 were evaluated. Multifocality was detected in 142 (19.88%) of the 714 PTC patients studied. The rate of multifocality among PTC patients was 3.29% in 2012, 7.2% in 2013, 10.1% in 2014, 10.5% in 2015, 38.15% in 2016, 31.6% in 2017, 33.33% in 2018, 32.58% in 2019 and 22.22% in 2020. Of these patients, 52.1% had 2 foci, 20.4% had 3 foc i, 15.5% had 4 foci, and 12% had 5 or more foci. Multifocality was observed in the right and left lobe in 54.2% of the patients, the right lobe in 21.1% of the patients and the left lobe in 12.7% of the patients. Multifocality was not detected in the isthmus only. It was found that as the number of tumor foci increased, differentiation decreased. It was observed that multifocality was more common in microcarcinomas. In our clinic, it has been observed that the rate of multifocal PTC has increased in recent years. This significant increase may be the result of morphological changes as well as improvements in diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Although multifocality is common in patients with papillary thyroid cancer, its effects on lymphatic metastasis and the necessity of central dissection in the presence of multifocality are still controversial. In our clinic, 258 patients who underwent thyroidectomy between 2015 and 2020 and were found to have papillary thyroid cancer in postoperative pathology reports were analyzed. The tumor characteristics contributing to central lymph node metastasis positivity were evaluated. Lymph node metastases were not significantly increased in the presence of multifocality. In cases with bilateral multifocal tumors, compared to cases with unilateral multifocal tumors, capsular invasion (p = 0.02), vascular invasion (p = 0.01) and cervical lymphatic metastasis (p = 0.004) were observed to increase. Bilateral multifocal tumors have more aggressive clinicopathological features than unilateral tumors. We found that the risk of central lymph node metastasis increased significantly in bilateral multifocal tumors in our study. Prophylactic central lymph node dissection may be considered in patients with no preoperative or intraoperative lymph node metastasis but thought to have a multifocal tumor. [ABSTRACT FROM AUTHOR]

There are limited data regarding the significance of multifocality in testicular cancer patients. This study evaluated the relationship between multifocality and clinicopathological features determined at the time of radical orchiectomy. The study involved 280 consecutive patients who underwent radical orchiectomy between 2018 and 2023. Multifocality was defined as a distinct tumor focus characterized by a group of malignant cells > 1 mm, clearly differentiated from the primary tumor mass. Uni- and multivariate logistic regression analyses were employed to investigate the association between multifocality and histopathological parameters along with potential risk factors for clinical stages II + III. Multifocality was identified in 44 (15.7%) patients. Significantly smaller primary tumors were observed in subjects with multifocality (20.0 mm vs. 30.0 mm, p = 0.0001), while those exhibiting monofocality presented a markedly elevated rate of tumors exceeding 4 cm (40.3% vs. 18.2%, p = 0.005). Furthermore, multifocality was associated with a significantly higher rate of primary tumors < 2 cm (52.3% vs. 29.2%, p = 0.003). Univariate logistic regression analysis revealed a substantial decrease in the likelihood of multifocality occurrence in seminoma patients with tumors > 4 cm (OR = 0.38, p = 0.017). Meanwhile, in multivariate logistic regression, multifocality did not emerge as a significant risk factor for clinical stages II + III in either seminoma (p = 0.381) or non-seminoma (p = 0.672) cases. Our study suggests that multifocality holds no substantial prognostic relevance for clinically advanced disease in testicular cancer patients. The findings indicate that multifocality is associated with smaller primary tumors, particularly those measuring less than 2 cm.

(1) Introduction: The impact of multifocality/bilaterality on the prognosis of papillary thyroid carcinoma (PTC) is a matter of debate. In order to clarify this debate, several studies have attempted to identify additional parameters associated with poor prognosis, including total tumor diameter (TTD), in the context of multifocal PTCs. In this context, this study was carried out to investigate the impact of TTD on tumor recurrence and lymph node metastasis (LNM) in PTCs. (2) Materials and Methods: The sample of this single-center retrospective study consisted of 706 patients diagnosed with PTC. TTD was calculated as the sum of the largest diameters of tumor foci in multifocal tumors. The resulting TTDs were grouped into TTDs ≤ 10 mm, TTDs > 10 mm, TTDs ≤ 20 mm, and TTDs > 20 mm, using 10 mm and 20 mm as cutoff values. (3) Results: There was no significant difference between multifocal papillary microcarcinomas (PTMCs) with a TTD of >10 mm and unifocal PTCs with a primary tumor diameter (PTD) of >10 mm except for advanced age and lymphovascular invasion (LVI). In addition, perineural invasion (PNI) and TTD > 10 mm were found to be significant risk factors for LNM, and PNI, TTD > 10 mm, TTD > 20 mm, and bilaterality were found to be significant risk factors for recurrence. LVI, and TTD > 10 mm were found to be independent significant predictors for recurrence, and LVI and extrathyroidal extension (ETE) were found to be independent significant predictors for LNM. (4) Conclusions: Considering TTD > 10 mm in recurrence risk categorization models and adopting a clinical approach that takes into account multifocal PTMCs with TTD > 10 mm along with unifocal PTCs with PTD > 10 mm may be more useful in terms of clinical management of the disease.

Abstract Background Small intestinal neuroendocrine tumors (SI-NETs) are the most common neoplasms of the small bowel. The majority of tumors are located in the distal ileum with a high incidence of multiple synchronous primary tumors. Even though up to 50% of SI-NET patients are diagnosed with multifocal disease, the mechanisms underlying multiple synchronous lesions remain elusive. Methods We performed whole genome sequencing of 75 de-identified synchronous primary tumors, 15 metastases, and corresponding normal samples from 13 patients with multifocal ileal NETs to identify recurrent somatic genomic alterations, frequently affected signaling pathways, and shared mutation signatures among multifocal SI-NETs. Additionally, we carried out chromosome mapping of the most recurrent copy-number alterations identified to determine which parental allele had been affected in each tumor and assessed the clonal relationships of the tumors within each patient. Results Absence of shared somatic variation between the synchronous primary tumors within each patient was observed, indicating that these tumors develop independently. Although recurrent copy-number alterations were identified, additional chromosome mapping revealed that tumors from the same patient can gain or lose different parental alleles. In addition to the previously reported CDKN1B loss-of-function mutations, we observed potential loss-of-function gene alterations in TNRC6B, a candidate tumor suppressor gene in a small subset of ileal NETs. Furthermore, we show that multiple metastases in the same patient can originate from either one or several primary tumors. Conclusions Our study demonstrates major genomic diversity among multifocal ileal NETs, highlighting the need to identify and remove all primary tumors, which have the potential to metastasize, and the need for optimized targeted treatments.

Abstract Objective Papillary thyroid cancer (PTC) is the most common endocrine malignancy with a steadily increasing incidence. Researches have reported that tumor multifocality occurs in an extensive number of cases. Nevertheless, the clinical characteristics and prognostic value remained controversial. This study was performed to investigate the relationship between multifocal PTC and adverse clinicopathologic features and the prognosis. Methods A systematic review and meta‐analysis were conducted based on three electronic databases up to December 31, 2021. Parameters of interest included five clinical features (extrathyroidal extension, lymphovascular invasion, central lymph node metastasis, lateral lymph node metastasis, distant metastasis) and were pooled into risk ratios (RRs). Time‐to‐event data (recurrence‐free survival and all‐cause mortality) were evaluated using hazard ratios (HRs). Publication bias was examined using funnel plots and Egger's test. Results A total of 23 articles were included according to the inclusion criteria; all of the studies were retrospective cohorts. In comparison with unifocality, multifocality showed an increased risk of extrathyroidal extension (RR 1.38, 95% CI 1.25–1.53), lymphovascular invasion (RR 1.27, 95% CI 1.04–1.55), central lymph node metastasis (RR 1.21, 95% CI 1.12–1.30), lateral lymph node metastasis (RR 1.86, 95% CI 1.62–2.14), and distant metastasis (RR 1.35, 95% CI 1.03–1.76). Multifocal patients were predisposed to postoperative recurrence (HR 1.76, 95% CI 1.50–2.07). The rate of all‐cause mortality did not reach a statistical difference. Level of Evidence 2. Conclusion Multifocal PTC is more aggressive in contrast to unifocal PTC and is accompanied by an increased risk of recurrence. They were usually diagnosed in higher grades and stages. To achieve the maximal benefit, we recommend personalized therapy and close follow‐up for multifocal PTC patients. Further prospective studies will clarify the best‐fitted treatment plans.

Background: Based on risk stratification, the therapeutic options in papillary microcarcinoma (PTMC) can be active surveillance or surgery. Multifocal tumor occurrence can be decisive in determining the treatment strategy. The objective of this study was to identify risk factors for bilateral tumor occurrence in PTMC to enable individual therapy planning. Methods: A total of 545 PTMC patients who underwent thyroidectomy from 2008 to 2020 were retrieved. Univariate and multivariate analyses were performed to evaluate risk factors for bilateral PTMC. Results: 25.1% (n = 137) of all patients had multifocal PTMC, and 13.2% (n = 72) bilateral PTMC, respectively. In contrast to the maximum tumor size, the total tumor size significantly influenced a bilateral tumor manifestation (median total tumor size 5 mm versus 8.5 mm for bilateral PTMC, p < 0.001). A cut-off level for the total tumor size of >10 mm resulted in a sensitivity and specificity of 29.2% and 94.7%, respectively, in predicting a bilateral tumor manifestation, AUC 0.680 (95% CI, 0.611–0.748, p < 0.001). A cut-off of >4 tumors showed a sensitivity of 99.4% and a specificity of 97.5%, AUC 0.897 (95% CI, 0.870–0.924, p < 0.001) in predicting bilaterality. Conclusion: We could demonstrate for the first time that a total tumor size of >10 mm and more than four tumors significantly increased the risk of bilateral PTMC tumor involvement. These findings enable a risk-adjusted patient treatment.

Primary prostate cancer shows a striking intraorgan molecular heterogeneity, with multiple spatially separated malignant foci in the majority of patients. Metastatic prostate cancer, however, typically reveals more homogenous molecular profiles, suggesting a monoclonal origin of the metastatic lesions. Longitudinal mutational spectra, comparing multiple primary lesions with metastases from the same patients remain poorly defined. We have here analyzed somatic mutations in multisampled, spatio‐temporal biobanked lesions (38 samples from primary foci and 1 sample from each of 8 metastases from seven prostate cancer patients) applying a custom‐designed panel targeting 68 prostate cancer relevant genes. The metastatic samples were taken at time of primary surgery and up to 7 years later, and sampling included circulating tumor DNA in plasma or solid metastatic tissue samples. A total of 282 somatic mutations were detected, with a range of 0 to 25 mutations per sample. Although seven samples had solely private mutations, the remaining 39 samples had both private and shared mutations. Seventy‐four percent of mutations in metastases were not found in any primary samples, and vice versa, 96% of mutations in primary cancers were not found in any metastatic samples. However, for three patients, shared mutations were found suggesting the focus of origin, including mutations in AKT1, FOXA1, HOXB13, RB1 and TP53. In conclusion, the spatio‐temporal heterogeneous nature of multifocal disease is emphasized in our study, and underlines the importance of testing a recent sample in genomics‐based precision medicine for metastatic prostate cancer. [ABSTRACT FROM AUTHOR]

Background: Tumor multifocality is frequently seen in Papillary thyroid carcinoma (PTC). However, few studies have analysed the impact of bilateral multifocality in PTC. The incidence of bilateral multifocality, its clinicopathological associations and prognostic impact in PTC from Middle Eastern ethnicity remains unestablished. Methods: We retrospectively evaluated 1283 patients who underwent total thyroidectomy for PTC. Bilateral and unilateral multifocality were decided based on the final pathology result. Primary outcome was recurrence free survival (RFS). Risk factors for bilateral multifocality were analyzed by multivariate logistic regression analysis. Results: Multifocal PTC was found in 54.3% (697/1283) of patients. Among the 697 multifocal PTCs, 210 patients (30.1%) had unilateral multifocal PTC and 487 patients (69.9%) had bilateral multifocality. Bilateral multifocality was significantly associated with older age at diagnosis (p = 0.0263), male gender (p = 0.0201), gross extrathyroidal extension (p = 0.0332), larger primary tumor size (>4cm; p = 0.0002), lateral lymph node metastasis (p = 0.0008), distant metastasis at diagnosis (p = 0.0195) and recurrence (p = 0.0001). Bilateral multifocality was also found to be an independent predictor of RFS (Hazard ratio = 1.60; 95% Confidence Interval = 1.05 - 2.55; p = 0.0300). Multivariate logistic regression analysis demonstrated tumor diameter >4cm to be the only independent risk factors for bilaterality in multifocal PTC (Odds ratio = 1.86; 95% Confidence Interval = 1.13 - 3.07; p = 0.0155). Conclusions: Incidence of bilateral multifocality is high in Middle Eastern PTC. Tumor diameter >4cm can be considered as a predictive factor for bilateral multifocal PTC. Bilateral multifocality appears to be an important prognostic factor for PTC and an independent predictor of RFS. Therefore, patients with bilateral multifocal PTC may benefit from more frequent follow-up to identify recurrences earlier. [ABSTRACT FROM AUTHOR]

Background: Much is still unknown regarding the clinicopathology and prognosis of patients with multifocal/multicentric breast cancer (MMBC). We herein compared the clinicopathology and prognosis of patients with unifocal and MMBCs. Method: This cross-sectional research is a part of Shiraz Breast Cancer Registry (SBCR). We studied all the patients in the SBCR (n=6145). Ultrasound reports were used to differentiate between MMBCs and unifocal breast cancers (BCs). All the patients were examined with mammography and the diagnosis was confirmed postoperatively via pathology reports. Results: After exclusion, 4045 patients entered the study (n=1072 and n=2973 for multifocal/multicentric and unifocal BCs, respectively). The mean follow-up period was 57.9 (0.27-275) months. Patients with MMBCs had higher rates of mastectomy (48% vs. 40.1%; P < 0.001) and higher rates of HER-2 overexpression (32.1% vs. 26%; P = 0.001) compared with those with unifocal BCs. Tumor size, lymph node involvement, type of axillary management, chemotherapy, radiotherapy, hormonal therapy, recurrence rates, histological grade, lymphovascular invasion, axillary node involvement, estrogen and progesterone receptor expression status, tumor, node, and metastasis staging were not significantly different between the groups. Five-year overall survival was 88.3% and 89% (P = 0.8) for unifocal and MMBCs, respectively; moreover, five-year disease-free survival was 80.2% and 81.2% (P = 0.41), respectively. Conclusion: Despite the controversy regarding prognosis and surgical management in MMBCs, we found that MMBCs had similar clinicopathological features and prognosis compared to unifocal BCs. Survival, recurrence, and metastasis were similar among the two groups. [ABSTRACT FROM AUTHOR]

Aim: The incidence of thyroid cancer has increased dramatically in recent decades. Multifocality is considered a poor prognostic factor for papillary thyroid carcinoma (PTC). Patients with multifocal PTC (MPTC) are at high risk for local recurrence, as well as lymphatic and distal metastases. This study examined the features and outcomes of MPTC. Material and Methods: This retrospective study was conducted on 300 patients with PTC. Patients were classified into a multifocal group and a unifocal group. The pathological features of the PTC and the patients' outcomes were analyzed and compared. Results: The multifocal group included 146 patients (48.7%), while the unifocal group included 154 patients (51.3%). The occurrence of multifocality was higher in females than in males (Odds ratio, OR: 2.37, 95% confidence interval, CI: 1.20-4.67, p=0.015). Tumor size of >1 cm in the multifocal group was larger than in the unifocal group (2.5 and 2.2 cm, respectively, p=0.021). Moreover, in multifocal group higher moderate risk of recurrence was detected than in the unifocal group (OR: 1.63, 95% CI: 1.01-2.60, p=0.044). At follow-up after treatment, MPTC patients had higher lymph node metastasis (OR: 2.89, 95% CI: 1.23-6.80, p=0.014). In addition, significantly higher thyroglobulin plasma levels (p=0.026) and disease recurrence (OR: 2.41, 95% CI: 1.05-5.52, p=0.037) were found in the multifocal group compared to the unifocal group. Conclusion: Patients with MPTC had a higher risk of disease recurrence, and multifocality was concluded to be an independent prognostic factor for overall disease recurrence. [ABSTRACT FROM AUTHOR]

Abstract Background Papillary thyroid carcinoma (PTC), the most common endocrine cancer, accounts for 80–85% of all malignant thyroid tumors. This study focused on identifying targets that affect the multifocality of PTC. In a previous study, we determined 158 mRNAs related to multifocality in BRAF-mutated PTC using The Cancer Genome Atlas. Methods We used multi-omics data (miRNAs and mRNAs) to identify the regulatory mechanisms of the investigated mRNAs. miRNA inhibitors were used to determine the relationship between mRNAs and miRNAs. We analyzed the target protein levels in patient sera using ELISA and immunohistochemical staining of patients’ tissues. Results We identified 44 miRNAs that showed a negative correlation with mRNA expression. Using in vitro experiments, we identified four miRNAs that inhibit TEK and/or AXIN2 among the target mRNAs. We also showed that the downregulation of TEK and AXIN2 decreased the proliferation and migration of BRAF ( +) PTC cells. To evaluate the diagnostic ability of multifocal PTC, we examined serum TEK or AXIN2 in unifocal and multifocal PTC patients using ELISA, and showed that the serum TEK in multifocal PTC patients was higher than that in the unifocal PTC patients. The immunohistochemical study showed higher TEK and AXIN2 expression in multifocal PTC than unifocal PTC. Conclusions Both TEK and AXIN2 play a potential role in the multifocality of PTC, and serum TEK may be a diagnostic marker for multifocal PTC.

Available studies report conflicting results on the association of body mass index (BMI) and pathohistological features of thyroid cancer. This study aimed to investigate the relationship between BMI and the pathohistological features of different thyroid cancer types. We analyzed the following data from 95 patients with thyroid cancer: age, gender, BMI, pathohistological characteristics of cancer (tumor size, multifocality, lymphovascular invasion, extrathyroidal invasion) and the presence of regional metastases. The BMI of all patients with thyroid cancer was 27.1 ± 4.2. Significantly more patients with obesity class I had cancer size less than 2 cm (p = 0.02). There is a significant association between BMI and extrathyroid invasion (p = 0.03; OR, 1.18), but not with lymphovascular invasion, tumor size, and multifocality. We can conclude that although obesity is a risk factor for the development of thyroid cancer, higher BMI is only partially associated with more aggressive pathohistological features of thyroid cancer.

Hepatic epithelioid hemangioendothelioma (EHE) is a rare malignant vascular neoplasm with unpredictable clinical behavior. These lesions are frequently misdiagnosed owing to its non-specific symptomatology, ambiguous radiological features, and overlapping histomorphology. We report three cases of hepatic EHE, of which one was male and two were female patients. While all three patients presented with abdominal pain, the male patient gave an additional history of weight loss and was jaundiced. The radioimaging showed multiple nodules in the liver and two of the patients also had pulmonary metastasis. The biopsies of the liver nodules revealed a tumor composed of spindle, epithelioid, and stellate tumor cells, some with characteristic intracytoplasmic vacuolations/lumina surrounded by myxohyaline stroma. Some of these intracytoplasmic vacuoles/lumina showed erythrocytes, suggesting its vascular origin which was confirmed by CD31 and CD34 positivity. The article highlights the importance of histopathology and IHC in the precise diagnosis of EHE.