Aggressive Histopathological Features Research Articles

Risk factors, histopathological landscape, biomarkers, treatment patterns and survival of early-onset colorectal cancer: A narrative review.

Early-onset colorectal cancer (EOCRC) incidence has increased in most Western countries over the last decade, with Australia at the forefront. Recent literature has thus focused on characterizing EOCRC from later-onset colorectal cancer (LOCRC). Earlier exposure to modifiable risk factors resulting in gut dysbiosis has been linked with EOCRC development. EOCRCs have more aggressive histopathological features with somatic mutations resulting in pro-inflammatory tumor microenvironments. There is a tendency to treat EOCRCs with multimodal chemotherapeutic regimens and more extensive surgery than LOCRCs with conflicting postoperative outcomes and survival data. Current research is limited by a lack of Australasian studies, retrospective study designs, and heterogeneous definitions of EOCRC. Future research should address these and focus on investigating the role of immunotherapies, establishing minimally invasive diagnostic biomarkers and nomograms, and evaluating the survival and functional outcomes of EOCRC.

Facilitation of Definitive Cancer Diagnosis With Quantitative Molecular Assays of BRAF V600E and TERT Promoter Variants in Patients With Thyroid Nodules

Molecular testing of the presence of pathogenic genomic variants in a tumor without quantifying the variant allele fraction (VAF) does not differentiate the variation extent among tumors, often resulting in an inconclusive diagnosis because of interpatient variability. To examine the association between the quantification of VAFs of BRAF V600E and TERT promoter variants and a definitive cancer diagnosis of thyroid tumors. This diagnostic study analyzed a cohort of 378 surgically resected thyroid tumors with a maximum dimension of 1 cm or larger between March 15, 2016, and March 16, 2020, and a separate cohort of 217 residual thyroid fine-needle aspiration (FNA) biopsy specimens obtained from January 22, 2020, to March 2, 2021, at Mount Sinai Hospital, Toronto, Ontario, Canada. Data analysis was conducted between February 1, 2021, and February 1, 2023. Quantitative VAF assays of BRAF V600E and TERT promoter variants (C228T and C250T) were performed by digital polymerase chain reaction molecular assays. The VAFs of BRAF V600E and TERT promoter variants were correlated with tumor histologic diagnoses and histopathologic features to delineate the association of VAF assays with tumor malignancy. The receiver operating characteristic curve analysis, sensitivity, specificity, positive predictive value, negative predictive value, and logistic regression analysis based on follow-up histopathologic types were used to determine the diagnostic utility of the quantitative molecular assays. A total of 595 specimens, including 378 surgically resected thyroid tumors and 217 thyroid nodule FNA biopsy specimens, were collected from 580 patients (436 [75.2%] female with a mean [SD] age of 50 [16] years and 144 [24.8%] male with a mean [SD] age of 55 [14] years). Sensitive VAF assays of 378 thyroid tumors revealed the presence of the BRAF V600E variant in 162 tumors (42.9%), with 26 (16.0%) at a low VAF of 1% or less and 136 (84.0%) at a high VAF of greater than 1%, and the presence of TERT promoter variants in 49 tumors (13.0%), including 45 C228T variants (91.8%), 15 (33.3%) of which were quantified as having a low VAF (≤1%) and 30 (66.7%) as having a high VAF (>1%), and 4 C250T variants (8.2%) with VAFs between 40.0% and 47.0%. All tumors detected with BRAF V600E and/or TERT promoter variants, whether at low or high VAFs, received a definitive cancer diagnosis. Further analysis delineated a significant association between high VAFs of either variant individually or different VAF levels for both variants in coexistence and aggressive histopathologic features of tumors. Excluding low VAFs assisted in identifying patients at an intermediate-to-high risk of recurrence (odds ratio, 5.3; 95% CI, 1.9-14.6; P = .001). The VAF assays on the residual FNA biopsy specimens showed a high agreement to those on surgical tissues (κ = 0.793, P < .001) and stratified malignancy in 40 of 183 indeterminate FNA cases (21.9%), with a sensitivity of 93.8% (95% CI, 67.7%-99.7%), specificity of 90.0% (95% CI, 75.4%-96.7%), positive predictive value of 78.9% (95% CI, 53.9%-93.0%), and negative predictive value of 97.3% (95% CI, 84.2%-99.9%). This diagnostic study suggests that sensitive quantitative VAF assays of BRAF V600E and TERT promoter variants can elucidate the interpatient variability in tumors and facilitate a definitive cancer diagnosis of thyroid nodules by differentiating the variation extent of genomic variants, even at low VAFs.

Correlation of shear-wave elastography parameters with the molecular subtype and axillary lymph node status in breast cancer

PurposeTo examine correlations between shear-wave elastography (SWE) parameters with molecular subtype and axillary lymph node (LN) status of breast cancer. MethodsWe retrospectively analyzed 545 consecutive women (mean age, 52.7 ± 10.7 years; range, 26–83) with breast cancer who underwent preoperative breast ultrasound with SWE between December 2019 and January 2021. SWE parameters (Emax, Emean, and Eratio) and the histopathologic information from surgical specimens including histologic type, histologic grade, size of invasive cancer, hormone receptor and HER2 status, Ki-67 proliferation index, and axillary LN status were analyzed. The relationships between SWE parameters and histopathologic findings were analyzed using an independent sample t-test, one-way ANOVA test with Tukey's post hoc test, and logistic regression analyses. ResultsHigher stiffness values of SWE were associated with larger lesion size (>20 mm) on ultrasound, high histologic grade, larger invasive cancer size (>20 mm), high Ki-67, and axillary LN metastasis. Emax and Emean were the lowest in the luminal A-like subtype, and all three parameters were the highest in the triple-negative subtype. Lower value of Emax was independently associated with the luminal A-like subtype (P = 0.04). Higher value of Emean was independently associated with axillary LN metastasis for tumors ≤ 20 mm (P = 0.03). ConclusionIncreases in the tumor stiffness values on SWE were significantly associated with aggressive histopathologic features of breast cancer. Lower stiffness values were associated with the luminal A-like subtype, and tumors with higher stiffness values were associated with axillary LN metastasis in small breast cancers.

Diffuse Sclerosing Papillary Thyroid Carcinoma: Clinicopathological Characteristics and Prognostic Implications Compared with Classic and Tall Cell Papillary Thyroid Cancer.

The clinical behaviour and oncologic outcome of diffuse sclerosing papillary thyroid carcinoma (DS-PTC) is poorly understood. The objectives of this study were to compare the clinicopathological characteristics and oncological outcomes of DS-PTC to classic PTC (cPTC) and tall cell PTC (TC-PTC). After institutional review board approval, 86 DS-PTC, 2,080 cPTC, and 701 TC-PTC patients treated at MSKCC between 1986 and 2021 were identified. Clinicopathological characteristics were compared by using chi-squaretest. Kaplan-Meier and log rank were used to compare recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS). DS-PTC patients were propensity matched to cPTC and TC-PTC patients for further comparison. DS-PTC patients were younger with more advanced disease than cPTC and TC-PTC (p < 0.05). Lymphovascular invasion (LVI), extranodal extension, and positive margins were more common in DS-PTC (p < 0.02). Propensity matching confirmed more aggressive histopathological features in DS-PTC. The median number of metastatic lymph nodes was significantly greater and DS-PTC metastases were RAI avid. DS-PTC 5-year RFS was 50.4% compared with 92.4% in cPTC and 88.4% in TC-PTC (p < 0.001). Multivariate analysis confirmed DS-PTC as an independent prognostic factor of recurrence. Ten-year DSS for DS-PTC was 100% compared with 97.1% in cPTC and 91.1% in TC-PTC. Differentiated high-grade, thyroid carcinoma DS had more advanced T-stage and worse 5-year RFS than DS-PTC. DS-PTC presents with more advanced clinicopathological features than cPTC and TC-PTC. Large-volume nodal metastases and LVI are characteristic features. Almost half of patients develop recurrence despite aggressive initial management. Despite this, with successful salvage surgery DSS is excellent.

Molecular Correlates of Aggressive Behavior and Biological Progression in Testicular Sertoli Cell Tumors

Sertoli cell tumor (SCT) is the second most common type of sex cord-stromal tumor in men, and ∼10% exhibit malignant behavior. Although CTNNB1 variants have been described in SCTs, only a limited number of metastatic cases have been analyzed, and the molecular alterations associated with aggressive behavior remain largely unexplored. This study evaluated a series of nonmetastasizing and metastasizing SCTs using next-generation DNA sequencing to further characterize their genomic landscape. Twenty-two tumors from 21 patients were analyzed. Cases were divided into metastasizing SCTs and nonmetastasizing SCTs. Nonmetastasizing tumors were considered to have aggressive histopathologic features if they exhibited ≥1 of the following: size >2.4 cm, necrosis, lymphovascular invasion, ≥3 mitoses per 10 high-power fields, severe nuclear atypia, or invasive growth. Six patients had metastasizing SCTs, and the remaining 15 patients had nonmetastasizing SCTs; 5 nonmetastasizing tumors had ≥1 aggressive histopathologic feature(s). Gain-of-function CTNNB1 or inactivating APC variants were highly recurrent in nonmetastasizing SCTs (combined frequency >90%), with arm-level/chromosome-level copy number variants, loss of 1p, and CTNNB1 loss of heterozygosity occurring exclusively in CTNNB1-mutant tumors with aggressive histopathologic features or size >1.5 cm. Nonmetastasizing SCTs were almost invariably driven by WNT pathway activation. In contrast, only 50% of metastasizing SCTs harbored gain-of-function CTNNB1 variants. The remaining 50% of metastasizing SCTs were CTNNB1-wild-type and harbored alterations in the TP53, MDM2, CDKN2A/CDKN2B, and TERT pathways. These findings suggest that ∼50% of aggressive SCTs represent progression of CTNNB1-mutant benign SCTs, whereas the remaining ones are CTNNB1-wild-type neoplasms that exhibit alterations in genes of the TP53, cell cycle regulation, and telomere maintenance pathways.

Ovarian cancer in the older patient: where are we now? What to do next?

In recent years, major advances have been made toward the individualization of epithelial ovarian cancer care, leading to an overall improvement of patient outcomes. However, real-life data indicate that the oldest populations do not benefit from this, due to aspects related to cancer (more aggressive histopathological features), treatment (i.e. frequently suboptimal), and the host (increased toxicities in patients with lower physiological reserve). A specific risk-benefit perspective should therefore be taken when considering surgery, chemotherapy, and maintenance treatments: the decision for cytoreductive surgery should include geriatric vulnerability and surgical complexity, neo-adjuvant chemotherapy being an option when primary surgery appears at high risk; carboplatin paclitaxel association remains the standard even in vulnerable older patients; and bevacizumab and poly(ADP-ribose) polymerase inhibitors maintenance are interesting options provided they are prescribed according to their indications with a close monitoring of their toxicities. Future studies should aim to individualize care without limiting access of older patients to innovation. A specific focus is needed on age-specific translational analyses (focusing on tumor mutational burden and impaired biological pathways), a better patient stratification according to geriatric parameters, an adaptation of both oncological treatment and geriatric interventions, and treatment adaptations not a priori but according to formal pharmacokinetic data.

Evaluation of Lymphovascular Invasion by CD31 Expression in Gastric Adenocarcinoma.

Lymphovascular tumoral invasion is a typical histopathological feature of gastric carcinomas and supports the recognition of high-risk patients for the recurrence. We aimed to study CD31 expression in diverse subtypes of gastric carcinomas and to show its association with the histopathologic findings of the carcinoma to assess the prognosis. This cross-sectional study was conducted on 40 established patients with gastric adenocarcinoma from radical gastrectomy. The patients were classified according to the pathology assessments. Tumoral tissues were assessed by immunohistochemical staining for CD31 expression. Malignant behavior was estimated by histopathological evaluations. CD31 positivity was described in 23 (57.5%) of all evaluated patients. In assessment of CD31 expression and tumor features presented, no significant association between the CD31 expression and patients' age, sex, tumor site, size, grade and stage, subtypes of carcinoma, perineural invasion, and also lymphovascular invasion was found. (P>0.05). Lymphovascular invasion may make valuable additional evidence and may be useful to detect gastric carcinoma patients at high risk for recurrence, who could be candidates for more supplementary therapies. However, in our study, CD31 expression did not show any association with the aggressive histopathologic features of this tumor.

Clinicopathologic and molecular spectrum of testicular sex cord-stromal tumors not amenable to specific histopathologic subclassification

A subset of testicular sex cord-stromal tumors (SCST), which includes neoplasms with mixed histology, cannot be classified into a specific histologic subtype. This study evaluated the clinicopathologic, immunophenotypic and molecular features of 26 SCST not amenable to specific classification by expert uropathologists. Median age at diagnosis was 43 years and median tumor size was 2.4 cm. Follow-up information was available for 18 (69%) patients, with evidence of an aggressive clinical course in 6 patients (4 alive with disease, 2 dead of disease 3 months and 6 months after orchiectomy). Microscopically, SCST not amenable to specific classification demonstrated monophasic epithelioid (9/26, 35%), monophasic spindle cell (5/26, 19%), and biphasic or mixed histology (12/26, 46%). One or more aggressive histopathologic features were seen in 11 cases. DNA sequencing was successful in 22 tumors. Pathogenic CTNNB1 and APC alterations were seen in 7 (33%) and 2 (10%) cases, respectively, with additional variants (e.g., CDKN2A, RB1, TP53, BRCA2) being identified in individual cases. Combined evaluation of morphology, sequencing data and beta-catenin immunohistochemistry resulted in reclassification of 6 (23%) tumors as Sertoli cell tumor, not otherwise specified. This was supported by comparing the methylation profiles of a subset of these tumors and those of typical Sertoli cell tumors. Additionally, a subset of 5 neoplasms (19%) with spindle cell or biphasic histology and SMA expression was characterized by hyperdiploid genomes with recurrent chromosomal gains and absence of driver mutations, possibly representing a distinct tumor type. The SCST that remained not amenable to specific histologic classification (15/26, 58%) were enriched for aggressive histologic features and malignant clinical behavior. In conclusion, this study demonstrated that a subset of testicular SCST that were originally not amenable to specific classification could be reclassified by combined evaluation of morphology, immunohistochemistry and molecular data.

Tissue Characteristics of Endometrial Carcinoma Analyzed by Quantitative Synthetic MRI and Diffusion-Weighted Imaging.

This study investigates the association of T1, T2, proton density (PD) and the apparent diffusion coefficient (ADC) with histopathologic features of endometrial carcinoma (EC). One hundred and nine EC patients were prospectively enrolled from August 2019 to December 2020. Synthetic magnetic resonance imaging (MRI) was acquired through one acquisition, in addition to diffusion-weighted imaging (DWI) and other conventional sequences using 1.5T MRI. T1, T2, PD derived from synthetic MRI and ADC derived from DWI were compared among different histopathologic features, namely the depth of myometrial invasion (MI), tumor grade, cervical stromal invasion (CSI) and lymphovascular invasion (LVSI) of EC by the Mann-Whitney U test. Classification models based on the significant MRI metrics were constructed with their respective receiver operating characteristic (ROC) curves, and their micro-averaged ROC was used to evaluate the overall performance of these significant MRI metrics in determining aggressive histopathologic features of EC. EC with MI had significantly lower T2, PD and ADC than those without MI (p = 0.007, 0.006 and 0.043, respectively). Grade 2-3 EC and EC with LVSI had significantly lower ADC than grade 1 EC and EC without LVSI, respectively (p = 0.005, p = 0.020). There were no differences in the MRI metrics in EC with or without CSI. Micro-averaged ROC of the three models had an area under the curve of 0.83. Synthetic MRI provided quantitative metrics to characterize EC with one single acquisition. Low T2, PD and ADC were associated with aggressive histopathologic features of EC, offering excellent performance in determining aggressive histopathologic features of EC.

TSPO PET signal using [18F]GE180 is associated with survival in recurrent gliomas

PurposeGlioma patients, especially recurrent glioma, suffer from a poor prognosis. While advances to classify glioma on a molecular level improved prognostication at initial diagnosis, markers to prognosticate survival in the recurrent situation are still needed. As 18 kDa translocator protein (TSPO) was previously reported to be associated with aggressive histopathological glioma features, we correlated the TSPO positron emission tomography (PET) signal using [18F]GE180 in a large cohort of recurrent glioma patients with their clinical outcome.MethodsIn patients with [18F]GE180 PET at glioma recurrence, [18F]GE180 PET parameters (e.g., SUVmax) as well as other imaging features (e.g., MRI volume, [18F]FET PET parameters when available) were evaluated together with patient characteristics (age, sex, Karnofsky-Performance score) and neuropathological features (e.g. WHO 2021 grade, IDH-mutation status). Uni- and multivariate Cox regression and Kaplan–Meier survival analyses were performed to identify prognostic factors for post-recurrence survival (PRS) and time to treatment failure (TTF).ResultsEighty-eight consecutive patients were evaluated. TSPO tracer uptake correlated with tumor grade at recurrence (p < 0.05), with no significant differences in IDH-wild-type versus IDH-mutant tumors. Within the subgroup of IDH-mutant glioma (n = 46), patients with low SUVmax (median split, ≤ 1.60) had a significantly longer PRS (median 41.6 vs. 25.3 months, p = 0.031) and TTF (32.2 vs 8.7 months, p = 0.001). Also among IDH-wild-type glioblastoma (n = 42), patients with low SUVmax (≤ 1.89) had a significantly longer PRS (median not reached vs 8.2 months, p = 0.002). SUVmax remained an independent prognostic factor for PRS in the multivariate analysis including CNS WHO 2021 grade, IDH status, and age. Tumor volume defined by [18F]FET PET or contrast-enhanced MRI correlated weakly with TSPO tracer uptake. Treatment regimen did not differ among the median split subgroups.ConclusionOur data suggest that TSPO PET using [18F]GE180 can help to prognosticate recurrent glioma patients even among homogeneous molecular subgroups and may therefore serve as valuable non-invasive biomarker for individualized patient management.Graphical abstract

INVASIVE BREAST CARCINOMA WITH MEDULLARY FEATURES AND HER2/NEU POSITIVITY: A RARE CASE STUDY.

Invasive breast carcinoma with medullary features is a rare variant of invasive ductal carcinoma. It accounts for &lt;5% of invasive breast carcinomas. Despite its aggressive histopathological features, the prognosis is favourable. We are reporting a case in a 60 years female having a mass in the right breast for 8 months. Detailed history, routine investigations, radiological investigation, ne needle aspiration, histopathological examination and immunohistochemistry were performed. The nal diagnosis of the case was given as Invasive Breast Carcinoma with medullary features and Her2/neu positive. TNM staging is T2N0M0. No lymphovascular invasion noted. We are reporting this case for being an uncommon nding.

Qualitative imaging features of pancreatic neuroendocrine neoplasms predict histopathologic characteristics including tumor grade and patient outcome.

To identify PanNEN imaging features associated with tumor grade and aggressive histopathological features. Associations between histopathological and imaging features of resected PanNEN were retrospectively tested. Histopathologic features included WHO grade, lymphovascular invasion (LVI), growth pattern (infiltrative, circumscribed), and intratumoral fibrosis (mature, immature). Imaging features included size, degree/uniformity of enhancement, progressive enhancement, contour, infiltrative appearance (infiltrativeim), calcifications, cystic components, tumor thrombus, vascular occlusion (VO), duct dilatation, and atrophy. Multinomial logistic regression analyses evaluated the magnitude of associations. Association of variables with outcome was assessed using Cox-proportional hazards regression. 133 patients were included. 3 imaging features (infiltrativeim, ill-defined contour [contourill], and VO) were associated with all histopathologic parameters and poor outcome. Increase in grade increased odds of contourill by 15.6 times (p = 0.0001, 95% CI 3.8-64.4). PanNEN with VO were 51.1 times (p = 0.0002, 6.5-398.6) more likely to demonstrate LVI. For PanNEN with contourill, infiltrative growth pattern was 51.3 times (p < 0.0001, 9.1-288.4), and fibrosis was 14 times (p = 0.0065, 2.1-93.7) more likely. Contourill was associated with decreased recurrence-free survival (p = 0.0003, HR 18.29, 3.83-87.3) and VO (p = 0.0004, HR6.08, 2.22-16.68) with decreased overall survival. Infiltrativeim, contourill, and VO on imaging are associated with higher grade/histopathological parameters linked to tumor aggression, and poor outcome.

Evaluation of the Histopathological Features of Early-stage Invasive Ductal Breast Carcinoma by 18Fluoride-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography

Objectives:This study investigates the relationship between 18fluoride-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) parameters and histopathological features in patients with early-stage invasive ductal breast carcinoma (IDBC).Methods:Patients with early-stage IDBC who underwent 18F-FDG PET/CT scan for staging were included in this retrospective study. The status of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2, Ki-67 proliferative index, and grades of tumors were recorded. The conventional metabolic parameters [maximum standard uptake value (SUVmax) and average standard uptake value] and volume-based parameters [metabolic tumor volume (MTV) and total lesion glycolysis] of the primary tumor were obtained from the 18F-FDG PET/CT images. The associations and correlations between the 18F-FDG PET/CT parameters and histopathological features were assessed.Results:One hundred forty-three patients were included. 18F-FDG PET/CT parameters, other than MTV, were significantly associated with the ER and PR status and Ki-67 index, while T-staging was significantly associated with all 18F-FDG PET/CT parameters. In the axillary lymph node (ALN) involvement, no significant difference was found in the 18F-FDG PET/CT parameters. In terms of the pathological stage, a significant difference was found in all 18F-FDG PET/CT parameters. 18F-FDG PET/CT parameters, other than MTV, were significantly higher in non-luminal breast tumors than luminal tumors and in high-grade tumors than low-grade ones. Triple-negative tumors had the highest 18F-FDG PET/CT parameter, but the difference was insignificant for MTV. The SUVmax had the strongest correlation with Ki-67 proliferative index.Conclusion:Tumors with aggressive histopathological features had higher 18F-FDG PET/CT parameter values. This study suggests that 18F-FDG PET/CT may provide prognostic information in patients with early-stage IDBC.

Pre-existing Thyroiditis Ameliorates Papillary Thyroid Cancer: Insights From a New Mouse Model.

Papillary thyroid cancer (PTC) often co-occurs with Hashimoto's thyroiditis, an association that has long been reported in clinical studies yet remains controversial. Some studies, in fact, have suggested a protective effect of thyroiditis while others have not. We generated a mouse model where PTC and thyroiditis develop in a predictable manner, combining the oncogenic drive of the BRAFv600E mutation (inducible by tamoxifen) to the thyroiditis susceptibility of the NOD.H2h4 strain (inducible by iodine). A total of 113 NOD.H2h4_TPO-CRE-ER_BRAFV600E mice (50 followed throughout lifetime and 63 sacrificed at 16 weeks post tamoxifen) were used to determine whether the PTC phenotype differs when thyroiditis precedes or coincides with the onset of PTC. Mice with pre-existing thyroiditis lived longer (median survival of 28.2 weeks post tamoxifen) than those with concomitant (25.6 weeks) or no (24.5 weeks) thyroiditis (P < 0.01 by Laplace regression). PTC developed less frequently (33%) in the pre-existing thyroiditis group than the concomitant (100%) or no (100%) thyroiditis groups (P < 0.001 by chi-squared) and showed less aggressive histopathological features. The intratumoral mononuclear cell infiltration was more prominent in mice with pre-existing thyroiditis (P = 0.002 vs the other groups) and sustained by a significant expansion of effector memory CD8 + T cells and CD19 + B cells. These findings shed light on the controversial PTC-thyroiditis association and emphasize the contribution of intratumoral T and B lymphocytes to the evolution of PTC.

Investigation and management of papillary thyroid microcarcinoma - a Scottish regional case series and literature review.

Papillary thyroid microcarcinoma is defined as papillary thyroid cancer with a diameter of ≤1 cm. Despite its prevalence, there is wide variation in practice in the investigation and management of patients with papillary thyroid microcarcinoma throughout the UK and internationally. The primary aim of this paper is to describe the experience of investigation and management in a Scottish health board over the past 10 years. Retrospective analysis of thyroidectomy and hemithyroidectomy resection samples from March 2009 to March 2020. 532 specimens were reviewed and 20 patients with PTMC were identified. 12 patients had an incidental finding of PTMC. Median U score- 3, Median Thy score- 2.5 for dominant or radiologically suspicious nodules. 8 specimens demonstrated aggressive histopathological features. 1 patient with positive nodal disease in the neck and 0 patients with positive nodal disease in the thorax on CT Neck and Chest. Here we report the first UK Cohort describing the radiological investigation and management of papillary thyroid microcarcinoma. The results of our study are in accordance with a recent meta-analysis which found 4% nodal disease and 0.025% distant metastasis at time of presentation in patients with PTMC.

Race-Related Differences in the Clinical Presentation and Histopathologic Features of Phyllodes Tumor.

Phyllodes tumor (PT) is a rare fibroepithelial lesion of the breast with variable malignant potential. Black women have a higher incidence of a related benign tumor, fibroadenoma, but there are limited epidemiological data on PT. The aim of our study was to evaluate race-related differences in the clinicopathologic features and outcomes of PT. Our institutional pathology database was queried for breast specimen reports from 01/2009 to 10/2019 to identify patients with a pathologic diagnosis of PT. Chart review and detailed slide review were performed to obtain clinical and histopathologic variables, respectively. Among twelve patients, two had malignant PT, three had borderline PT, and seven had benign PT. All patients with malignant and borderline PT were black, compared with 29% of those with benign PT. There were no apparent race-related differences in specific histopathologic features among black vs. non-black women with benign PT. Malignant and borderline PT were relatively larger than benign PT, with mean tumor sizes of 9.0cm (standard deviation [SD] 4.7cm), 12.2cm (SD 9.4cm), and 5.4cm (SD 5.8cm), respectively. Two women had a local recurrence, both of whom were black. In this single-institution retrospective study, we observed disproportionate rates of aggressive histopathologic features and disparate outcomes among black women with PT. A multi-institutional PT registry would facilitate improved knowledge about race-related differences in the presentation and outcomes of this rare tumor.

Clinicopathological characteristics of young versus older patients with breast cancer: A retrospective comparative study from the Madinah region of Saudi Arabia.

Objectives:To compare the clinicopathological, histological and immunohistochemical features of breast cancer (BC) in between young (≤40 years) and older (>40 years) patients.Methods:This retrospective study included histopathological reports of all patients with primary BC diagnose at the King Fahad Hospital, Madinah, Saudi Arabia between January 2006 and November 2020.Results:During the study period, a total of 708 patients with BC were identified; 173 cases (24.4%) were ≤40 years old and 535 (75.6%) were above 40 years. There were significant differences in tumor size (p=0.046), tumor grade (p<0.0001), tumor stage (p=0.047), lymphovascular invasion (p<0.0001), and distant metastasis (p<0.0001) between the 2 groups. Comparing the status of the hormone receptors and molecular subtypes between the 2 age groups, BCs in the younger patients were triple–negative (p=0.008) in majority of the cases and less likely to be estrogen receptor (ER) and progesterone receptor (PR) hormone receptors–positive (p=0.0001, p<0.0001). Young patients exhibited the HER2/neu type with more frequent statistical significance (p=0.016) and the tumor type luminal A (p=0.002) with less frequent statistical significance compared to old patients.Conclusion:Although BC in young women is uncommon, it may be different with regards to poor prognostic outcomes, which are attributed to more aggressive histopathological features and less favorable receptor status when compared to the cases diagnosed in older women.

Comparative molecular analysis of testicular Leydig cell tumors demonstrates distinct subsets of neoplasms with aggressive histopathologic features.

Testicular Leydig cell tumor (LCT), the most common sex-cord stromal tumor in men, represents a small fraction of all testicular tumors (~1 to 3%). Although most testicular LCTs are indolent and cured by radical orchiectomy, 5-10% have aggressive biology and metastatic potential. In primary LCTs, large size, cytologic atypia, necrosis, increased mitotic activity, and vascular invasion have been associated with clinically aggressive tumors. From a molecular perspective, the characteristics of aggressive LCTs and the differences between aggressive and nonaggressive LCTs remain largely unexplored. This study compares the genomic landscape of aggressive and nonaggressive testicular LCTs. Twenty-six cases were analyzed using next-generation DNA sequencing (NGS) and immunohistochemistry. Cases were classified as aggressive LCT if they met published criteria for malignancy in primary (i.e., testicular) tumors or if they had pathology-proven metastatic disease; otherwise, cases were considered nonaggressive. This multi-institutional series included 18 aggressive LCTs (14 primary/testicular, 4 metastatic) and 8 nonaggressive LCTs. Two cases (2/26, 8%; both aggressive LCTs) failed sequencing and had negative (i.e., uninformative) FH immunohistochemistry results. One additional primary aggressive LCT failed sequencing but had informative FH immunohistochemistry results. Combined NGS and immunohistochemical analysis demonstrated FH inactivation in 5/26 cases (19%). In addition, NGS demonstrated CTNNB1 mutations or biallelic APC inactivation in 9/23 cases (39%), copy number changes without recurrent mutations in 6/23 (26%) cases, and no alterations in 4/23 cases (17%). CTNNB1 mutations were present in both aggressive and nonaggressive LCTs. In contrast, FH inactivation and multiple copy number changes were only identified in aggressive LCTs. In conclusion, three distinct subgroups of aggressive LCTs were characterized by FH inactivation, Wnt pathway activation, and copy number changes without recurrent mutations, respectively. Nuclear translocation of β-catenin and Wnt pathway activation appear to be early driver events that provide an environment conducive for progression to aggressive biology in a subset of LCTs.

Relationship between clinicopathologic factors and FDG avidity in radioiodine-negative recurrent or metastatic differentiated thyroid carcinoma

BackgroundIn this study, we investigated the relationship between clinicopathologic factors, BRAFV600E mutation status and [18F] F-fluoro-2-deoxyglucose (FDG) avidity in patients with radioiodine (RAI)-negative recurrent or metastatic differentiated thyroid cancer (DTC).MethodsFrom 2015 to 2018 all patients with suspected recurrent or metastatic radioiodine-negative DTC patients who underwent FDG positron emission tomography/computed tomography (PET/CT) were retrospectively reviewed. Suspected lesions on FDG PET/CT were biopsied and underwent BRAFV600E mutation testing by immunohistochemistry and real-time PCR. Tumor size, recurrent versus metastatic disease, histopathologic features including classical type versus aggressive subtypes (poorly differentiated, tall cell, columnar cell, hobnail variants) and BRAFV600E mutation status were correlated with the SUVmax of highest hypermetabolic lesions on FDG PET/CT by the univariate analysis using logistic regression.ResultsSixty-three consecutive patients, 55 (87.3%) female, with median age of 48 (range 17–81) were included. The majority of patients had BRAFV600E mutation and classical subtype, 55/63 (87.3%) and 45/63(71.4%), respectively. Thyroglobulin at the time of suspected recurrence was 262.7 ng/ml (range 16.3–1000) and patients received a median 3 prior RAI treatments. Fifty-four patients (85.7%) had local recurrence. The majority of patients 58/63 (92.1%) had FDG-avid disease on PET/CT. On univariate analysis, tumor size aggressive histopathologic types and distant metastasis are the significant factors for predicting FDG uptake, p = 0.04, p = 0.001 and p = 0.004 respectively. Although FDG uptake of BRAFV600E bearing recurrent/metastatic RAIR DTC lesions was higher than those without the mutation, the difference did not reach statistical significance, SUVmax of 7.11 versus 4.91, respectively, p = 0.2.ConclusionThe majority of recurrent or metastatic RAI-negative DTC have BRAFV600E mutation and detectable disease on FDG PET/CT. FDG avidity of the recurrent or metastatic RAI-negative DTC is independently associated with the aggressive histopathologic features.

PRIMARY HYPERPARATHYROIDISM AND SERUM CALCIUM IN BREAST CANCER PATIENTS EVALUATED FOR LOW BONE MASS - A SINGLE CENTER EXPERIENCE.

SUMMARYThe bone health guidelines for breast cancer (BC) patients recommend bone mineral density (BMD) testing. Patients with low BMD and elevated serum calcium levels (SCLs) are further evaluated for primary hyperparathyroidism (PHPT). We aimed to determine the prevalence of PHPT in treated BC patients with low BMD and analyze the association of SCLs with histopathologic tumor features and cancer treatment. This retrospective study included postmenopausal BC patients examined at Osteoporosis Clinic between 2013 and 2020. Clinical and BMD data were collected from patient medical records. Patients with biochemical suspicion of PHPT underwent standard parathyroid imaging procedures. Nine out of 137 (6.6%) patients were diagnosed with PHPT; 8/9 patients underwent parathyroidectomy and one patient was advised to follow-up. Among the rest of 128 non-PHPT patients, higher SCLs showed a trend of positive association with higher tumor grade and axillary lymph node involvement, and received immunotherapy, although without statistical significance. We found a higher prevalence of PHPT in treated BC patients compared to the general population. Higher SCLs show a trend of positive correlation with some more aggressive histopathologic tumor features and with immunotherapy. The results of this study suggest that assessment of SCLs should be routinely performed to rule out PHPT in treated BC patients with low BMD.