Intertumoral heterogeneity of bifocal breast cancer: a morphological and molecular study.

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.

The significance and prognostic value of multifocal papillary thyroid carcinoma in children and adolescents.

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.

Multi-UniFocality (MUF), in contrast to multifocality, in thyroid lesions: Relation to lymphocytic thyroiditis.

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.

Associations Between Metabolic Obesity Phenotypes and Pathological Characteristics of Papillary Thyroid Carcinoma.

OBJECTIVE: The association between obesity, metabolic dysregulation, and the aggressive pathological traits of papillary thyroid carcinoma (PTC) continues to be a contentious issue. To date, no investigations have examined the impact of metabolic status on the malignant pathological features of PTC in relation to obesity. METHODS: This research involved 855 adult patients with PTC from Shandong Provincial Hospital, classified into 4 groups based on metabolic and obesity status: metabolically healthy nonobese, metabolically unhealthy nonobese (MUNO), metabolically healthy obese, and metabolically unhealthy obese. We employed logistic regression to investigate the relationship between these metabolic obesity phenotypes and PTC's pathological characteristics. Mediation analysis was also performed to determine metabolic abnormalities' mediating role in the nexus between obesity and these characteristics. RESULTS: Relative to metabolically healthy nonobese individuals, the metabolically unhealthy obese group was significantly associated with an elevated risk of larger tumor sizes and a greater number of tumor foci in PTC. Mediation analysis indicated that obesity directly influences tumor size, whereas its effect on tumor multifocality is mediated through metabolic dysfunctions. Specifically, high-density lipoprotein cholesterol levels were notably associated with tumor multifocality within obese subjects, serving as a mediator in obesity's impact on this trait. CONCLUSION: The concurrent presence of obesity and metabolic dysregulation is often connected to more aggressive pathological features in PTC. The mediation analysis suggests obesity directly affects tumor size and indirectly influences tumor multifocality via low high-density lipoprotein cholesterol levels.

Optimal surgical management of unifocal vs. multifocal NF-PNETs: a respective cohort study.

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.

Somatic mutations reveal complex metastatic seeding from multifocal primary prostate cancer.

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.

MET-receptor targeted fluorescent imaging and spectroscopy to detect multifocal papillary thyroid cancer.

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.

Contrast-enhanced mammography versus breast MRI in the assessment of multifocal and multicentric breast cancer: a retrospective study.

BACKGROUND: Breast cancer multifocality and multicentricity diagnosis influences the surgeon's choice between applying breast conservative therapy or performing mastectomy. PURPOSE: To assess the role of contrast enhanced mammography (CEM) and breast magnetic resonance imaging (MRI) in the assessment of preoperative breast cancer multifocality and multicentricity and to assess their accuracy, agreement and impact on the surgical management. MATERIAL AND METHODS: The study retrospectively included cases over a 5-year period. After analysis and interpretation of suspicious breast lesions, a comparative evaluation of CEM and MRI was conducted with the assessment of diagnostic indices, including sensitivity, specificity and diagnostic accuracy. The kappa (κ) measure of agreement between both modalities was measured. The postoperative specimen pathology was the reference standard. RESULTS: One hundred and twenty-two female cases with 126 breast lesions were evaluated. Specimen pathology, MRI and CEM showed a single neoplastic lesion in 67.5%, 35% and 48.5% of cases, respectively, and multiple neoplastic lesions in 32.5%, 65% and 51.6% of cases, respectively. The sensitivity, specificity and accuracy of MRI were 95.12%, 49.41%,and 64.29%, and the CEM values were 85.37%, 64.71% and 71.43%, respectively. The κ value was 0.592 with an intermediate agreement between both modalities. When comparing between both modalities, enhancing foci showed a statistically significant difference, although there were no statistically significant difference in terms of high breast density or molecular subtype. CONCLUSION: In terms of breast cancer multifocality and multicentricity evaluation, MRI showed a higher sensitivity, while CEM showed a higher specificity, and there was moderate agreement between the two modalities.

Incidental multifocal calcifying pseudoneoplasm of the neuraxis: case report and literature review.

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.

Multi-omics analysis revealed TEK and AXIN2 are potential biomarkers in multifocal papillary thyroid cancer.

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.

[Bilateral giant cell central granuloma of the jaws in a Noonan syndrome: About one case with emphasizing on bone giant cell lesions of the jaws]. / Granulome central à cellules géantes des maxillaires bilatéral dans le cadre d'un syndrome de Noonan : à propos d'un cas avec mise au point sur les lésions osseuses riches en cellules géantes des maxillaires.

We report the case of a 10-year-old child with bilateral mandibular localization of a central giant cell granuloma occurring in the setting of Noonan syndrome. The histological appearance was classic with two intermigled components, one fibrous with non-atypical mononuclear cells, the other consisting of numerous osteoclast-like giant cells. This aspect is similar to that observed in the brown tumor as well as that of cherubism, which can also give multiple bone lesions. We will discuss the other lesions to consider in case of benign giant cell bone lesions affecting the jawbones, sometimes multiple and part of which falls within the scope of RASopathies.

RELATIONSHIP BETWEEN BODY MASS INDEX AND PATOHISTOLOGICAL FEATURES OF THYROID CANCER.

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.

PREDICTORS OF MULTIFOCAL PAPILLARY THYROID CANCER. DO THEY EXIST?

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.

Bilateral multifocality, a marker for aggressive disease, is not an independent prognostic factor for papillary thyroid microcarcinoma: A propensity score matching analysis.

CONTEXT: Multifocality and bilaterality are common in patients with papillary thyroid microcarcinoma (PTMC). However, their clinical behaviours and prognostic implications remain controversial. OBJECTIVE: To investigate the relationship between multifocality and classically aggressive characteristics and outcomes in patients with PTMC. METHODS: Clinical data of 3005 patients with PTMC were retrospectively reviewed at a tertiary medical centre. The role of unilateral and bilateral multifocality in aggressive characteristics and clinical outcomes of PTMC was evaluated using propensity score matching (PSM). RESULTS: A total of 573 patients had bilateral multifocal disease (B-MFD), 272 had unilateral multifocal disease (U-MFD), and 2160 had unifocal disease (UFD). Univariate analysis showed that patients in the multifocal disease (MFD) groups showed significantly different characteristics compared to patients in the UFD group in terms of age, chronic lymphocytic thyroiditis (CLT), follicular variant PTMC, tumour diameter, aggressive growth, including extrathyroidal extension (ETE), central lymph node metastasis (CLNM) and lateral lymph node metastasis (LLNM), and TNM stage, and underwent radioactive iodine (RAI) therapy. Further stratified analysis revealed that patients in the B-MFD group reflected the differences between the MFD and UFD groups. However, those in the U-MFD group showed slight differences only in sex, CLT and cell subtypes, compared to the UFD group. In addition, PSM indicated differences in ETE, CLNM and LLNM between the B-MFD and UFD groups (p < .001), while only ETE differed between the U-MFD and UFD groups (p < .001). After a median follow-up period of 60 months, no difference was observed in recurrence-free survival between the UFD and B-MFD (p = .294) or U-MFD (p = .603) groups using PSM. CONCLUSION: This propensity score matching analysis provides strong evidence that bilateral multifocality, rather than unilateral multifocality, should be considered as an aggressive marker at presentation, and neither is an independent prognostic factor for clinical outcome in PTMC.

Enemy Beyond the Wall: Clinicopathological Features of Intrathyroidal Papillary Thyroid Carcinoma (T1-T3a) That Metastasize to Lymph Nodes Without Extrathyroidal Extension.

The aim of this study was to determine the clinicopathological features of papillary thyroid carcinomas (PTC) without extrathyroidal extension (ETE) and with lymph node metastasis (LNM). PTC > 1 cm increased the risk of LNM by 2.161 times compared to papillary thyroid microcarcinoma. The risk increased by 3.774 times in males and 1.553 times in the presence of multifocality. Presence of vascular invasion (VI) increased the risk of LNM by 3.093 times in patients without capsular invasion (CI). Clinicians should be careful about possible LNM in patients with large primary tumor diameter, multifocal tumors, CI and VI.

Uncovering the invisible-prevalence, characteristics, and radiomics feature-based detection of visually undetectable intraprostatic tumor lesions in 68GaPSMA-11 PET images of patients with primary prostate cancer.

INTRODUCTION: Primary prostate cancer (PCa) can be visualized on prostate-specific membrane antigen positron emission tomography (PSMA-PET) with high accuracy. However, intraprostatic lesions may be missed by visual PSMA-PET interpretation. In this work, we quantified and characterized the intraprostatic lesions which have been missed by visual PSMA-PET image interpretation. In addition, we investigated whether PSMA-PET-derived radiomics features (RFs) could detect these lesions. METHODOLOGY: This study consists of two cohorts of primary PCa patients: a prospective training cohort (n = 20) and an external validation cohort (n = 52). All patients underwent 68Ga-PSMA-11 PET/CT and histology sections were obtained after surgery. PCa lesions missed by visual PET image interpretation were counted and their International Society of Urological Pathology score (ISUP) was obtained. Finally, 154 RFs were derived from the PET images and the discriminative power to differentiate between prostates with or without visually undetectable lesions was assessed and areas under the receiver-operating curve (ROC-AUC) as well as sensitivities/specificities were calculated. RESULTS: In the training cohort, visual PET image interpretation missed 134 tumor lesions in 60% (12/20) of the patients, and of these patients, 75% had clinically significant (ISUP > 1) PCa. The median diameter of the missed lesions was 2.2 mm (range: 1-6). Standard clinical parameters like the NCCN risk group were equally distributed between patients with and without visually missed lesions (p < 0.05). Two RFs (local binary pattern (LBP) size-zone non-uniformality normalized and LBP small-area emphasis) were found to perform excellently in visually unknown PCa detection (Mann-Whitney U: p < 0.01, ROC-AUC: ≥ 0.93). In the validation cohort, PCa was missed in 50% (26/52) of the patients and 77% of these patients possessed clinically significant PCa. The sensitivities of both RFs in the validation cohort were ≥ 0.8. CONCLUSION: Visual PSMA-PET image interpretation may miss small but clinically significant PCa in a relevant number of patients and RFs can be implemented to uncover them. This could be used for guiding personalized treatments.

The Effects of Chronic Lymphocytic Thyroiditis on Clinicopathologic Factors in Papillary Thyroid Cancer.

OBJECTIVE: This study evaluated the impact of chronic lymphocytic thyroiditis (CLT) on clinicopathologic parameters, prognostic outcome, and initial treatment responses in patients with papillary thyroid cancer (PTC). METHODS: A retrospective review was conducted of 1409 patients with PTC, comprising 443 patients with pathology-proven PTC with CLT and 447 patients with PTC without CLT. RESULTS: The median follow-up time was 58 months (range, 8-380 months), and the median age at the time of diagnosis was 43 years. The age at diagnosis was significantly lower in patients with CLT than in those without CLT (42 years vs 45 years, respectively; P = .001). The preoperative thyroid-stimulating hormone level was found to be significantly higher in patients with CLT than in those without CLT (1.71 mIU/L vs 1.28 mIU/L, respectively; P < .001). Multifocality and capsular, lymphovascular, and perineural invasion were detected at a higher rate in the group with CLT than in the group without CLT (P = .015, P = .024, P = .004, and P = .039, respectively). No difference was found between the 2 groups in terms of tumor size, bilaterality, extrathyroidal invasion, lymph node metastasis, disease stage, or response to treatment (P > .05). CONCLUSION: The results of the present study demonstrated that the coexistence of PTC and CLT is very frequent. Patients with the coexistence of PTC and CLT were diagnosed at a younger age, and the thyroid-stimulating hormone level was higher in these patients. Contrary to previous studies, no positive effect of the CLT and PTC combination was detected on any clinicopathologic factor. In addition, lymphovascular and perineural invasions, which had negative effects on prognosis, were more common in the group with CLT.

Papillary thyroid microcarcinomas that metastasize to lymph nodes.

PURPOSE: We aimed to determine clinicopathological features that can predict lymph node metastasis (LNM) in papillary thyroid microcarcinomas (PTMC). METHODS: Medical records of 872 patients with papillary thyroid cancer >1 cm (PTC > 1 cm) and 1184 patients with papillary thyroid microcancer (PTMC) (≤1 cm) were reviewed retrospectively. Demographical, clinical and histopathological features of (PTC > 1 cm) and PTMC were compared. Association between clinicopathological features and LNM in PTMC was investigated. RESULTS: The median age of patients with PTMC was significantly higher than patients with PTC > 1 cm (49 vs 46 years old, p < 0.001). Multifocality, capsular invasion, vascular invasion, extrathyroidal extension (ETE) and LNM were more frequent in patients with PTC > 1 cm compared to patients with PMTC (p < 0.001 for each). In PTMC group, those with LNM had significantly higher proportion of multifocality, capsular invasion, vascular invasion and ETE compared to those without LNM (p = 0.007, <0.001, p = 0.011 and p < 0.001, respectively). Multifocality and ETE were significant factors for LNM with logistic regression analysis. Multifocality increased the risk of LNM by 1.737 times (95% CI: 1.079-2.979) and ETE increased the risk by 3.528 times (95%: 1.914-6.503). Primary tumor diameter ≥ 5.75 mm was predictive for LNM with a sensitivity of 0.782 and a specificity of 0.517 in PTMC. CONCLUSIONS: LNM should be investigated more carefully in patients with PTMC in the presence of tumor diameter ≥ 5.75 mm, multifocality or ETE.

Factors associated with MRI detection of occult lesions in newly diagnosed breast cancers.

BACKGROUND: The use of preoperative magnetic resonance imaging (MRI) for newly diagnosed breast cancer remains controversial. We examined factors associated with detection of occult multicentric, multifocal, and contralateral malignant lesions only seen by MRI. METHODS: We performed a retrospective analysis of consecutive patients undergoing preoperative MRI for breast cancer. Clinicopathologic data were assessed regarding the findings of multifocality, multicentricity, and the presence of contralateral lesions. We analyzed the association of factors with these findings on MRI. RESULTS: Of 857 patients undergoing MRI, 770 patients met inclusion criteria. Mean age was 54.7 years. Biopsy-proven detection rates by MRI for multifocal, multicentric, and contralateral cancers were 6.2% (48 of 770), 1.9% (15 of 770) and 3.1% (24 of 770), respectively. African American race and heterogeneously or extremely dense mammographic density were associated with multifocal cancers on MRI. Larger lesion size and mammographic density were associated with multicentric cancers. Invasive lobular carcinoma (ILC) and progesterone receptor (PR)-positivity were associated with contralateral cancers. CONCLUSIONS: African American race, heterogeneously or extremely dense mammographic density, ILC, and PR-positivity were associated with additional biopsy-proven cancers based on MRI. These factors should be considered when assessing the clinical utility of preoperative breast MRI.

Total tumor diameter: the neglected value in papillary thyroid microcarcinoma.

BACKGROUND: Tumor multifocality is not uncommon in papillary thyroid carcinoma (PTC), especially in micro-PTC. However, assessing the size of the largest tumor may underestimate effect of additional foci. We aimed to investigate the effect of total tumor diameter (TTD) on clinicopathological features of micro-PTC. METHODS: Data from 442 patients who underwent thyroidectomy with cervical lymph node dissection for PTC were retrospectively analyzed. Patients were classified into subgroups according to multifocality and TTD. The relationships of clinicopathological features among these groups were analyzed. RESULTS: Multifocality was observed in 119 patients (26.9%). TTD > 1 cm and presence of extrathyroidal extension (ETE) were significantly higher in multifocal tumors compared to unifocal tumor (P < 0.001, P = 0.016, respectively). When comparing multifocal micro-PTC with TTD > 1 cm to those with unifocal micro-PTC or multifocal micro-PTC with TTD ≤ 1 cm, the proportions of cases with ETE, central lymph node metastasis (CLNM), and lateral lymph node metastasis (LLNM) were significantly higher (all P < 0.05). There was no significant difference in terms of these parameters between multifocal micro-PTC with TTD > 1 cm and macro-PTC or multifocal macro-PTC. The risk of CLNM was 2.056 (P = 0.044) times higher in multifocal micro-PTC with TTD > 1 cm than in unifocal micro-PTC. CONCLUSION: For multifocal micro-PTC, TTD can better assess the aggressiveness of the tumor. Multifocal micro-PTC with TTD > 1 cm was more aggressive than unifocal micro-PTC or multifocal micro-PTC with TTD ≤ 1 cm.