Search

Inflammatory sarcomatoid carcinoma is an aggressive tumor with an unusually benign appearance. We report the case of a 65-year-old man with a history of inoperable poorly differentiated carcinoma of the right lung, for which he had received chemoradiotherapy. A new solitary mass was discovered 4 years later in the left lung on surveillance computed tomography. The patient underwent thoracotomy with a wedge biopsy on which frozen section was performed. The nodule was vaguely granulomatous and associated with a mixed inflammatory infiltrate and a deceptively bland spindle cell proliferation. Results of immuno-peroxidase studies, however, showed that the nodule contained neoplastic cells with an epithelial phenotype that were invading the pulmonary vessels. These are features of the rare inflammatory sarcomatoid carcinoma. In contrast to sarcomatoid carcinomas, this case highlights the deceptively benign appearance of inflammatory sarcomatoid carcinoma. This leads us to concur with the recommendation to exercise caution when attempting the diagnosis of apparently benign lesions on intraoperative frozen section in patients with high clinical suspicion of malignancy. [ABSTRACT FROM AUTHOR]

The main purpose of this study was to determine the relation between the degree of acquaintance and assessment of other persons’ personality traits and attribution of their behaviour. The second aim was to examine relation between personality traits of observers and their perception of actor’s personality traits and attribution of actor’s behaviour. The study was conducted on a sample of 76 subjects divided into two groups, on the basis of degree of acquaintance with actors. First group estimated a close person, a best friend. Second group estimated a person they are not acquainted with. This person was described in an invented interview. In the first part of the research, all subjects completed The Big Five Inventory (John, 1991). In the second part of the research, subjects estimated personality traits of actors (using BFI) and attributed actor’s behaviour using The Attributional Style Questionnaire (Peterson et al., 1982). The results suggest that there are at least two types of bias in estimation of other people. One type is in relation with acquaintance. Observers estimate close persons more positively than persons they don’t know. Second type of bias is in relation to personality traits of observers. These personality traits are Consciousness, Extraversion and Openness.

Abstract Background Little is known about the association between cigarette smoking and asthma severity. We assessed smoking as a determinant of disease severity and control in a cohort of clinic-referred allergic subjects who developed new onset asthma. Methods Allergic rhinitis subjects with no asthma (n = 371) were followed-up for 10 years and routinely examined for asthma diagnosis. In those who developed asthma (n = 152), clinical severity and levels of asthma control were determined. Among these subjects, 74 (48.7%) were current smokers, 17 (11.2%) former smokers, and 61 (40.1%) never smokers. Results When comparing current or past smokers to never smokers they had a higher risk of severe asthma in the univariate analysis, which became non-significant in the multivariate analysis. On the other hand, the categories of pack-years were significantly related to severe asthma in a dose response relationship in both the univariate and multivariate analysis: compared to 0 pack years, those who smoked 1-10 pack-years had an OR(95% CI) of 1.47(0.46-4.68), those who smoked 11-20 pack-years had an OR of 2.85(1.09-7.46) and those who smoked more than 20 pack-years had an OR of 5.59(1.44-21.67) to develop more severe asthma. Smokers with asthma were also more likely to have uncontrolled disease. A significant dose-response relationship was observed for pack-years and uncontrolled asthma. Compared to 0 pack years, those who smoked 1-10 pack-years had an OR of 5.51(1.73-17.54) and those who smoked more than 10 pack-years had an OR of 13.38(4.57-39.19) to have uncontrolled asthma. Conclusions The current findings support the hypothesis that cigarette smoking is an important predictor of asthma severity and poor asthma control.

Purpose: This study investigates whether quantitative MRI and histology of the prostate reveal differences between races, specifically African Americans (AAs) and Caucasian Americans (CAs), that can affect diagnosis. Materials and Methods: Patients (98 CAs, 47 AAs) with known or suspected prostate cancer (PCa) underwent 3T MRI (T2W, DWI, and DCE-MRI) prior to biopsy or prostatectomy. Quantitative mpMRI metrics: ADC, T2, and DCE empirical mathematical model parameters were calculated. Results: AAs had a greater percentage of higher Gleason-grade lesions compared to CAs. There were no significant differences in the quantitative ADC and T2 values between AAs and CAs. The cancer signal enhancement rate (α) on DCE-MRI was significantly higher for AAs compared to CAs (AAs: 13.3 ± 9.3 vs. CAs: 6.1 ± 4.7 s -1 , p < 0.001). The DCE signal washout rate (β) was significantly lower in benign tissue of AAs (AAs: 0.01 ± 0.09 s -1 vs. CAs: 0.07 ± 0.07 s -1 , p < 0.001) and significantly elevated in cancer tissue in AAs (AAs: 0.12 ± 0.07 s -1 vs. CAs: 0.07 ± 0.08 s -1 , p = 0.02). DCE significantly improves the differentiation of PCa from benign in AAs (α: 52%, β: 62% more effective in AAs compared to CAs). Histologic analysis showed cancers have a greater proportion ( p = 0.04) of epithelium (50.9 ± 12.3 vs. 44.7 ± 12.8%) and lower lumen (10.5 ± 6.9 vs. 16.2 ± 6.8%) in CAs compared to AAs. Conclusions: This study shows that AAs have different quantitative DCE-MRI values for benign prostate and prostate cancer and different histologic makeup in PCa compared to CAs. Quantitative DCE-MRI can significantly improve the performance of MRI for PCa diagnosis in African Americans but is much less effective for Caucasian Americans.

Background: Spindle cell carcinoid tumor (SCCT) is a rare variant of lung carcinoid tumor consisting predominantly or exclusively of spindle cells. To the authors' knowledge, this is the first study to date investigating the molecular characteristics of SCCTs., Methods: Eighty-five carcinoid tumors initially diagnosed by fine-needle aspiration over a period of 10 years were reviewed. The final diagnostic classification was based on resection specimens. Six SCCTs were identified and characterized based on cytomorphology, and immunohistochemical and molecular features., Results: Most patients with SCCT were Caucasian (100.0%), women (83.3%), asymptomatic (66.7%), and nonsmokers (83.3%). The median age at diagnosis was 78.0 years (range, 58.2-80.3 years). A higher proportion of patients who had SCCT were diagnosed with distant metastasis. The smears were cellular and demonstrated clean backgrounds without necrosis or mitotic activity. SCCTs comprised of bipolar-to-elongated cells with finely granular chromatin, inconspicuous nucleoli, scant cytoplasm, and minimal atypia or pleomorphism. The tumor cells sometimes appeared boomerang-shaped and might mimic granulomas or blood vessels. SCCTs showed strong expression for pan-cytokeratin, synaptophysin, chromogranin, and CD56, with weak TTF-1 and a very low Ki-67 proliferation index. All SCCTs had low tumor mutational burden and were microsatellite-stable. One case showed multiple whole-gene losses in chromosome 11, whereas another harbored duplication in ARID1A. Two cases demonstrated gains in chromosomes 17, one of which also showed gains in chromosome 18. None had a single nucleotide mutation., Conclusions: SCCT is a rare subset of lung carcinoid tumors. These tumors harbor unique cytologic, prognostic, and molecular features that may have significant diagnostic and clinical implications., (© 2024 The Author(s). Cancer Cytopathology published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Background: Thyroid nodules may be detected during the workup of thyroid hormone abnormalities and as incidental findings during unrelated imaging studies. The diagnosis of a thyroid nodule is mainly established by performing fine needle aspiration (FNA) under ultrasound guidance. Thyroid nodules are classified as nondiagnostic, defined in the Bethesda System for Reporting Thyroid Cytopathology as samples with excess blood, cyst fluid only, and lack of thyroid follicular cells. The current study evaluates a series of nondiagnostic FNAs to assess whether repeat sampling improves yield and what patient management, and outcomes are after a nondiagnostic FNA., Methods: Thyroid FNAs from 2016 to 2023 were retrieved from our institution archives. All cases were performed under ultrasound guidance and with rapid on-site evaluation. Cases were assigned the Bethesda System Category. Nondiagnostic FNAs were further reviewed for repeat FNA procedures, potential molecular testing, or diagnostic resections., Results: In total 3104 thyroid FNAs were reviewed, with 153 (4.9%) being nondiagnostic. Of the 154 FNAs, there were 129 patients with an average age of 60 and a male-to-female ratio of 1:3.2. Of the 130 patients, there were 50 patients who underwent 55 repeat FNAs. Thirty-seven (67%) of the repeats were benign, 13 (24%) were nondiagnostic again, and 5 (9%) were atypia of undetermined significance (AUS). Molecular testing was performed on repeat FNAs diagnosed AUS. Four cases showed no mutations and had a high likelihood of being benign. One case did have an NRAS Q61R mutation, and resection revealed a noninvasive follicular thyroid neoplasm with papillary-like nuclear features. Seventeen (13% of all cases) with nondiagnostic FNA were resected. Twelve (71%) thyroidectomies showed benign adenomatous nodules. The remainder showed incidental papillary thyroid microcarcinoma (0.1 cm), an infarcted follicular adenoma, a noninvasive follicular thyroid neoplasm with papillary-like nuclear features, and metastatic renal cell carcinoma (2×)., Conclusion: Thyroid nodules with nondiagnostic cytology are reassuring of being highly likely a benign nodule. Only 5 of the 55 (9%) repeat FNAs yielded abnormalities, with only one of those being truly a follicular neoplasm (confirmed by molecular testing and resection). No primary thyroid malignancies have been identified in follow-up (repeat FNA or surgery). Clinical and ultrasound follow-up may be more appropriate management for nondiagnostic thyroid FNAs., (© 2024 The Author(s). Diagnostic Cytopathology published by Wiley Periodicals LLC.)

Introduction: There is a lack of documentation regarding cytopathology of renal neuroendocrine neoplasms (NENs) due to their rarity., Materials and Methods: Five cytology cases were gathered from 3 institutes., Results: Cohort consisted of 4 females and 1 male. Fine needle aspiration biopsy and touch preparation slides of core needle biopsy revealed cellular samples, composed of round, plasmacytoid, or columnar cells. Tumor cells were present in nested, acinar, 3D cluster, and individual cell patterns. Tumor cells in 3 cases exhibited uniformly round to oval small nuclei with inconspicuous nucleoli, finely granular chromatin, and smooth nuclear membranes, whereas 2 other cases showed pleomorphic nuclei with conspicuous nucleoli, nuclear molding, and irregular nuclear membranes. Tumor cells displayed pale or granular cytoplasm, with 1 case showing small vacuoles. Examination of cores and cell blocks demonstrated tumor cells in sheets, nests, or acini. All tumor cells were positive for neuroendocrine immunomarkers. Based on mitotic count, Ki-67 index and morphology, 3 tumors were graded as well-differentiated neuroendocrine tumor (WDNET) (1 grade [G] 3, 1 G2, 1 G1) and 2 as large cell neuroendocrine carcinoma. Deletion of 7q, 10q, and 19q was detected in WDNETs. Two patients with large cell neuroendocrine carcinoma and 1 with WDNET G3 underwent chemotherapy due to aggressiveness, whereas nephrectomy was performed for patients with WDNET G1 and 2 without metastasis., Conclusions: Cytopathological characteristics of renal NENs closely resemble those affecting other organs. Despite its rarity, renal NENs should be kept in mind when confronted with morphological resemblances to NENs, to prevent misdiagnosis and inappropriate therapeutic interventions., (Copyright © 2024 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

Introduction. Angiomyolipoma (AML) is a mesenchymal neoplasm that belongs to the perivascular epithelioid cell tumor family (PEComa). AMLs can be subtyped into several patterns dependent on cell type, morphology, and tissue composition. One of the patterns, oncocytoma-like AML is a rare entity with only three cases published in the literature. Case presentation. We present a case of a previously healthy 29-year-old woman who underwent a left partial nephrectomy secondary to a 4.6 cm heterogeneous renal neoplasm. Gross examination demonstrated a well-circumscribed renal mass. Modified Giemsa stain preparation showed oncocytic cells in syncytial pattern with ample granular cytoplasm and round nuclei with prominent nucleoli. Histology assessment showed an oncocytic neoplasm with interspersed adipose tissue. The tumor exhibited tubular architecture with the tubules lined by eosinophilic epithelioid cells with nuclear atypia and prominent nucleoli. Thick blood vessels with emanating epithelioid cells were present. High-grade histology features were not identified. The tumor cells were positive for HMB-45 and SMA and negative for PAX8, keratins, KIT, and vimentin. A diagnosis of oncocytoma-like AML was rendered. Next-generation sequencing (NGS) and RNA fusion were performed. NGS revealed no pathogenic variants and RNA fusion identified no rearrangements. Chromosomal copy number alterations were present in the long arm of chromosome 1 (1p) and chromosome 22. Conclusions. We describe and discuss the clinical, cytomorphologic, histologic, and molecular findings of oncocytoma-like AML, a rare renal neoplasm, and provide a review of the literature., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Multiple tumors of different lineages merging into a single mass, termed collision tumors, are considered a rare phenomenon in the kidney. Tumor components, or partners, may be malignant (including metastatic disease), borderline, or benign. We report the largest cohort to date of 48 cases. The cases were identified from the archives of three institutions in the last 16 years, including 43 (90%) with 2 tumor partners (dyad) and 5 (10%) with 3 partners (triad), totaling 101 individual neoplasms. The majority of cases involved immunohistochemical workup, and 5 underwent FISH or molecular studies. Forty (83%) cases featured a malignant entity, including all triads. Twenty dyads and two triads were composed entirely of malignant tumors. The most common malignant partner was clear cell renal cell carcinoma (RCC) (N = 19) followed by papillary RCC (N = 17). Nine (19%) cases featured borderline entities, including 5 multilocular cystic neoplasms of low malignant potential and 6 clear cell papillary renal cell tumors. Twenty one (44%) cases contained a benign partner, including 6 benign dyads. Papillary adenoma (N = 13) and oncocytoma (N = 8) were most common. Epithelial tumors were present in all 48 cases, and non-epithelial neoplasms in 9 cases (19%). Our cohort includes many novel combinations and collision partners with rare entities such as SDH-deficient RCC, TFE3-rearranged RCC, eosinophilic solid and cystic RCC, and acquired cystic disease associated RCC. A comprehensive literature review and analysis of collision tumor phenomenon in kidney placed these cases in context suggesting that collision tumors of the kidney are more common than previously recognized., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: TP53 mutation is present in about 50.8% of lung adenocarcinomas, frequently in combination with other genetic alterations. However, a rare subset harbors the TP53 mutation alone., Methods: Next-generation sequencing was performed in 844 lung adenocarcinomas diagnosed by fine needle aspiration. Fourteen cases (1.7%) showed isolated TP53 alteration and were subjected to a comprehensive analysis., Results: The average age at diagnosis was 65.7 years (range 48-79); 9 males and 5 females. All were smokers with an average pack-year of 40.7 (range 10-70). Ten had metastases, mostly in the brain (n = 4) and pleura (n = 4). After a follow-up period of up to 102 months, 9 died, 3 were alive free of disease, 1 was alive with disease, and 1 was lost to follow-up. The median survival was 12.2 months. Most tumors exhibited poor differentiation, composed of solid sheets with moderate to severe atypia, increased mitotic activity, and necrotic background. Half were positive for TTF-1 and showed p53 overexpression. PD-L1 was positive in 5 cases. Most alterations were missense mutations in exons 5-8, and this mutation type was associated with p53 overexpression. Tumors with combined missense mutation and truncated protein had higher PD-L1 expression along with a trend towards an increase in tumor mutational burden (TMB). CEBPA deletion of undetermined significance was the most common copy number alteration., Conclusion: Isolated TP53 mutation was seen in association with smoking, high-grade cytomorphologic features, adverse prognosis, and recurrent CEBPA deletions. These tumors tend to have strong PD-L1 expression and high TMB, suggesting potential benefit from immune checkpoint inhibitors. Hence, the recognition of this molecular group has prognostic and therapeutic implications., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objective This study aims to analyze the diagnostic utility of multiple repeat FNA on thyroid nodules with initially benign diagnosis. Methods In a 5-year period, 1658 thyroid nodules with initially benign FNAs were retrospectively reviewed and followed for subsequent resection and repeat biopsy. Results Out of 2150 thyroid nodules, 1658 (77.1%) were diagnosed as benign on FNAs. The average age was 57.4 years (range 11-93 years), and most were females (83.8%). Repeat FNA was performed on 183 benign nodules, of which 141 (8.5%) were sampled a second time and 42 (2.5%) had 2 or more repeat samplings. For the benign nodules without repeat FNAs, 124 had benign resection. Of cases with one-time repeat FNA, most (n=101) remained benign on repeat FNAs, 13 of which were benign on resection. Eleven had atypical repeat FNAs, 5 were resected, 4 of which were benign and one was atypical follicular neoplasm with HRAS and TERT promoter mutations. Of cases with multiple repeat FNA, most (n=35) were still benign on repeat FNAs, one had benign resection. Two had atypical repeat biopsies, one was PTC on resection with CCD6::RET fusion. The positive predictive value significantly decreased from 41.1% on single FNA to 8.3% on one-time repeat (p<0.001) and 16.7% on multiple repeat (p=0.002). The total cost for workup of previously benign nodules was $285,454. Conclusions Repeat FNA biopsies did not provide an additional diagnostic value in the evaluation of benign thyroid nodules, and often led to unwarranted follow-up procedures and significantly increased health care cost.

We investigated why some prostate cancers (PCas) are not identified on multiparametric MRI (mpMRI) by using ground truth reference from whole-mount prostatectomy specimens. A total of 61 patients with biopsy-confirmed PCa underwent 3T mpMRI followed by prostatectomy. Lesions visible on MRI prospectively or retrospectively identified after correlating with histology were considered "identified cancers" (ICs). Lesions that could not be identified on mpMRI were considered "unidentified cancers" (UCs). Pathologists marked the Gleason score, stage, size, and density of the cancer glands and performed quantitative histology to calculate the tissue composition. Out of 115 cancers, 19 were unidentified on MRI. The UCs were significantly smaller and had lower Gleason scores and clinical stage lesions compared with the ICs. The UCs had significantly ( p < 0.05) higher ADC (1.34 ± 0.38 vs. 1.02 ± 0.30 μm 2 /ms) and T2 (117.0 ± 31.1 vs. 97.1 ± 25.1 ms) compared with the ICs. The density of the cancer glands was significantly ( p = 0.04) lower in the UCs. The percentage of the Gleason 4 component in Gleason 3 + 4 lesions was nominally ( p = 0.15) higher in the ICs (20 ± 12%) compared with the UCs (15 ± 8%). The UCs had a significantly lower epithelium (32.9 ± 21.5 vs. 47.6 ± 13.1%, p = 0.034) and higher lumen volume (20.4 ± 10.0 vs. 13.3 ± 4.1%, p = 0.021) compared with the ICs. Independent from size and Gleason score, the tissue composition differences, specifically, the higher lumen and lower epithelium in UCs, can explain why some of the prostate cancers cannot be identified on mpMRI.

We propose a general method for combining multiple models to predict tissue microstructure, with an exemplar using in vivo diffusion-relaxation MRI data. The proposed method obviates the need to select a single 'optimum' structure model for data analysis in heterogeneous tissues where the best model varies according to local environment. We break signal interpretation into a three-stage sequence: (1) application of multiple semi-phenomenological models to predict the physical properties of tissue water pools contributing to the observed signal; (2) from each Stage-1 semi-phenomenological model, application of a tissue microstructure model to predict the relative volumes of tissue structure components that make up each water pool; and (3) aggregation of the predictions of tissue structure, with weightings based on model likelihood and fractional volumes of the water pools from Stage-1. The multiple model approach is expected to reduce prediction variance in tissue regions where a complex model is overparameterised, and bias where a model is underparameterised. The separation of signal characterisation (Stage-1) from biological assignment (Stage-2) enables alternative biological interpretations of the observed physical properties of the system, by application of different tissue structure models. The proposed method is exemplified with human prostate diffusion-relaxation MRI data, but has potential application to a wide range of analyses where a single model may not be optimal throughout the sampled domain., (© 2023. Springer Nature Limited.)

Purpose: Compare reader performance when adding the Hybrid Multidimensional-MRI (HM-MRI) map to multiparametric MRI (mpMRI+HM-MRI) versus mpMRI alone and inter-reader agreement in diagnosing clinically significant prostate cancers (CSPCa)., Methods: All 61 patients who underwent mpMRI (T2-, diffusion-weighted (DWI), and contrast-enhanced scans) and HM-MRI (with multiple TE/b-value combinations) before prostatectomy or MRI-fused-transrectal ultrasound-guided biopsy between August, 2012 and February, 2020, were retrospectively analyzed. Two experienced readers (R1, R2) and two less-experienced readers (less than 6-year MRI prostate experience) (R3, R4) interpreted mpMRI without/with HM-MRI in the same sitting. Readers recorded the PI-RADS 3-5 score, lesion location, and change in score after adding HM-MRI. Each radiologist's mpMRI+HM-MRI and mpMRI performance measures (AUC, sensitivity, specificity, PPV, NPV, and accuracy) based on pathology, and Fleiss' kappa inter-reader agreement was calculated and compared., Results: Per-sextant R3 and R4 mpMRI+HM-MRI accuracy (82% 81% vs. 77%, 71%; p=.006, <.001) and specificity (89%, 88% vs. 84%, 75%; p=.009, <.001) were higher than with mpMRI. Per-patient R4 mpMRI+HM-MRI specificity improved (48% from 7%; p<.001). R1 and R2 mpMRI+HM-MRI specificity per-sextant (80%, 93% vs. 81%, 93%; p=.51,>.99) and per-patient (37%, 41% vs. 48%, 37%; p=.16, .57) remained similar to mpMRI. R1 and R2 per-patient AUC with mpMRI+HM-MRI (0.63, 0.64 vs. 0.67, 0.61; p=.33, .36) remained similar to mpMRI, but R3 and R4 mpMRI+HM-MRI AUC (0.73, 0.62) approached R1 and R2 AUC. Per-patient inter-reader agreement, mpMRI+HM-MRI Fleiss Kappa, was higher than mpMRI (0.36 [95% CI 0.26, 0.46] vs. 0.17 [95% CI 0.07, 0.27]); p=.009)., Conclusion: Adding HM-MRI to mpMRI (mpMRI+HM-MRI) improved specificity and accuracy for less-experienced readers, improving overall inter-reader agreement., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The spatial two-tissue compartment model (2TCM) was used to analyze prostate dynamic contrast enhanced (DCE) MRI data and compared with the standard Tofts model. A total of 29 patients with biopsy-confirmed prostate cancer were included in this IRB-approved study. MRI data were acquired on a Philips Achieva 3T-TX scanner. After T2-weighted and diffusion-weighted imaging, DCE data using 3D T1-FFE mDIXON sequence were acquired pre- and post-contrast media injection (0.1 mmol/kg Multihance) for 60 dynamic scans with temporal resolution of 8.3 s/image. The 2TCM has one fast ([Formula: see text] and [Formula: see text]) and one slow ([Formula: see text] and [Formula: see text]) exchanging compartment, compared with the standard Tofts model parameters (K trans and k ep ). On average, prostate cancer had significantly higher values (p < 0.01) than normal prostate tissue for all calculated parameters. There was a strong correlation (r = 0.94, p < 0.001) between K trans and [Formula: see text] for cancer, but weak correlation (r = 0.28, p < 0.05) between k ep and [Formula: see text]. Average root-mean-square error (RMSE) in fits from the 2TCM was significantly smaller (p < 0.001) than the RMSE in fits from the Tofts model. Receiver operating characteristic (ROC) analysis showed that fast [Formula: see text] had the highest area under the curve (AUC) than any other individual parameter. The combined four parameters from the 2TCM had a considerably higher AUC value than the combined two parameters from the Tofts model. The 2TCM is useful for quantitative analysis of prostate DCE-MRI data and provides new information in the diagnosis of prostate cancer., (© 2023. Australasian College of Physical Scientists and Engineers in Medicine.)

Rationale and Objectives: To validate the educational value of a newly created learning application in enhancing prostate MRI training of radiologists for detecting prostate cancer using an observer study., Materials and Methods: An interactive learning app, LearnRadiology, was developed using a web-based framework to display multi-parametric prostate MRI images with whole-mount histology for 20 cases curated for unique pathology and teaching points. Twenty new prostate MRI cases, different from the ones used in the web app, were uploaded on 3D Slicer. Three radiologists (R1: radiologist; R2, R3: residents) blinded to pathology results were asked to mark areas suspected of cancer and provide a confidence score (1-5, with 5 being high confidence level). Then after a minimum memory washout period of 1 month, the same radiologists used the learning app and then repeated the same observer study. The diagnostic performance for detecting cancers before and after accessing the learning app was measured by correlating MRI with whole-mount pathology by an independent reviewer., Results: The 20 subjects included in the observer study had 39 cancer lesions (13 Gleason 3 + 3, 17 Gleason 3 + 4, 7 Gleason 4 + 3, and 2 Gleason 4 + 5 lesions). The sensitivity (R1: 54% → 64%, P = 0.08; R2: 44% → 59%, P = 0.03; R3: 62% → 72%, P = 0.04) and positive predictive value (R1: 68% → 76%, P = 0.23; R2: 52% → 79%, P = 0.01; R3: 48% → 65%, P = 0.04) for all 3 radiologists improved after using the teaching app. The confidence score for true positive cancer lesion also improved significantly (R1: 4.0 ± 1.0 → 4.3 ± 0.8; R2: 3.1 ± 0.8 → 4.0 ± 1.1; R3: 2.8 ± 1.2 → 4.1 ± 1.1; P < 0.05)., Conclusion: The web-based and interactive LearnRadiology app learning resource can support medical student and postgraduate education by improving diagnostic performance of trainees for detecting prostate cancer., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Aritrick Chatterjee reports financial support was provided by Radiological Society of North America. Aritrick Chatterjee reports a relationship with QMIS LLC that includes: equity or stocks. Aytekin Oto reports a relationship with QMIS LLC that includes: equity or stocks. Gregory Karczmar reports a relationship with QMIS LLC that includes: equity or stocks., (Copyright © 2023 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Presented are four cystic renal masses which harbored a MED15::TFE3 gene fusion detected by RNAseq, mimicking multilocular cystic neoplasm of low malignant potential. Clinicopathologic and outcomes data were collected for all cases. Radiologically, three cases were diagnosed as complex cystic masses and one case as a renal cyst, three years prior to surgery. The tumors ranged in size from 1.8 to 14.5 cm. Grossly, all masses were extensively cystic. Microscopically, cells with a clear or minimally granular cytoplasm and nuclei with inconspicuous nucleoli lined the cysts' septa. Focally, small mass-forming aggregates of malignant cells were present between septae and were associated with psammomatous calcifications. In case one, apparent prior cyst wall rupture was associated with reactive changes and cystic spaces filled with fibrin clots. Two of the tumors were staged as T1a, one as T1b, and the other as T2b. By immunohistochemistry, the tumors were positive for TFE3, MelanA, and P504S, with apical CD10 while CAIX and CK7 were negative. RNA sequencing was performed on all cases revealing a MED15::TFE3 gene fusion. The patients were alive and without evidence of disease 11-49 months (mean 29.5) after partial nephrectomy. To date, 12 of the 15 MED15::TFE3 fusion renal cell carcinomas published in the literature are cystic, with three being extensively cystic. Thus, if a multilocular cystic renal neoplasm is encountered in a kidney specimen, translocation renal cell carcinoma should be included in the differential diagnosis as cystic MED15::TFE3 tRCCs carry an uncertain prognosis making recognition for future characterization necessary., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The 2016 World Health Organization (WHO) Classification of Tumors of the Urinary System includes renal cell carcinoma (RCC) with leiomyomatous stroma (RCC-LS) as a provisional category. Recent studies have shown that this category includes at least 4 subtypes: clear cell (CCRCC), clear cell papillary renal cell tumor (CCPRCT), ELOC (TCEB1) mutated, and a subtype of RCC with TSC/MTOR mutations. The most recent 2022 World Health Organization (WHO) Classification of Tumors of the Urinary System includes ELOC mutated RCC-LS as a distinct entity but does not address any other renal tumors with smooth muscle stroma. We reviewed >500 cases of RCC with clear cell phenotype and identified 12 cases that exhibited prominent smooth muscle stroma, of which 4 of the cases had been previously reported. Review of the H&E revealed that all of the tumors were circumscribed with nested, solid, tubular, and tubulopapillary architecture. The epithelium was intimately embedded in the rich smooth muscle stroma. WHO/ISUP grade corresponded to grade 3 and 4. Nuclei were randomly distributed and the cytoplasm had predominantly clear and occasionally flocculent appearance. Immunohistochemically, all the cases showed membranous CAIX staining, although the pattern was combined cup and box-shaped. CK7 was positive in all cases ranging from 25% to 100% of cells. Membranous and apical staining of CD10 was present in all cases. Next generation sequencing (NGS) of these cases identified mutations in TSC1 (n = 4), TSC2 (n = 3), and MTOR (n = 4) with one case exhibiting loss of TSC1. This descriptive study, although small, demonstrates the difficulty in applying the current WHO provisional criteria at a single institution. Given the heterogeneity seen with these cases, we suggest following up an immunohistochemical panel of CAIX, CK7, and CD10 with molecular diagnostic studies to assist in the diagnosis of TSC/MTOR associated RCC-LS, which we believe is a distinct entity., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Genomic alterations are increasingly important in the current paradigms for the classification, diagnosis, and treatment of renal cell carcinoma. Biallelic alterations involving NF2 have been identified across several currently recognized subtypes of renal cell carcinoma including clear cell renal cell carcinoma and papillary renal cell carcinoma among others and may be associated with a more aggressive disease course as well as advanced stage at presentation. In addition, emerging evidence suggests the existence of a clinicopathologically distinct subset of renal cell carcinoma cases driven by biallelic loss of NF2 expression. This subset of tumors is morphologically characterized by a constellation of morphologic features including hyalinizing fibrosis, eosinophilic cytology, psammomatous calcifications, and a nested growth pattern. These tumors include the recently described entities of biphasic hyalinizing psammomatous renal cell carcinoma as well as renal cell tumor with sex cord/gonadoblastoma-like features. Despite their oftentimes aggressive behavior, there is some evidence that these tumors may respond favorably to treatment regimens incorporating immune checkpoint inhibitors., (Copyright © 2023 Elsevier Inc. All rights reserved.)

In cytologically indeterminate thyroid nodules undergoing molecular testing, estimated risk of malignancy is variable. Identification of a non-cancer-specific mutation (RAS-like) confirms a neoplastic process but does not differentiate between benign, malignant, and low-risk neoplasms. This study aims to retrospectively evaluate institutional experience of Interpace (ThyGeNEXT ® and ThyraMIR ® ; Pittsburgh, PA) testing and to determine the rate of malignancy in resected nodules, stratified by mutational analysis and microRNA profile. Of 1917 fine need aspirations, 140 (7.3%) underwent Interpace testing: 47 (33.6%) were molecular-not-benign (harbored mutation, fusion, and/or positive miRNA) and 93 (66.4%) were molecular-benign (no mutations or fusions and negative microRNA). Surgery was spared in 79.6% of molecular-benign and 61.4% of all tested patients. Fifty-four (38.6%) underwent resection. Seventeen (89.5%) of the resected molecular-benign were benign and 2 were malignant. Thirteen (37.1%) of the resected molecular-not-benign were benign, 7 (20%) were noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), and 15 (42.9%) were malignant (p < 0.05, negative predictive value (NPV) 89.4-95.6%, positive predictive value (PPV) 22.3-42.8%). Most molecular-not-benign (72.3%) had RAS-like mutation. Twenty-three were resected: 3 were malignant and 7 were NIFTP. Nodules with non-RAS-like mutations (BRAF V600E-like, others) were more likely to be malignant than RAS-like (H/N/KRAS, BRAF K601E) (p < 0.05, NPV 86.9-96.5%, PPV 100%). Most nodules had RAS-like mutations and most were benign or low-risk neoplasms (NIFTP). This study supports the role of histologic examination in the distinction of malignancy in RAS-like thyroid neoplasms and underscores the role of molecular testing in risk stratification, patient counseling, and operative management., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: To evaluate and quantify inter-directional and inter-acquisition variation in diffusion-weighted imaging (DWI) and emphasize signals that report restricted diffusion to enhance cancer conspicuity, while reducing the effects of local microscopic motion and magnetic field fluctuations., Methods: Ten patients with biopsy-proven prostate cancer were studied under an Institutional Review Board-approved protocol. Individual acquisitions of DWI signal intensities were reconstructed to calculate inter-acquisition distributions and their statistics, which were compared for healthy versus cancer tissue. A method was proposed to detect and filter the acquisitions affected by motion-induced signal loss. First, signals that reflect restricted diffusion were separated from the acquisitions that suffer from signal loss, likely due to microscopic motion, by imposing a cutoff value. Furthermore, corrected apparent diffusion coefficient maps were calculated by employing a weighted sum of the multiple acquisitions, instead of conventional averaging. These weights were calculated by applying a soft-max function to the set of acquisitions per-voxel, making the analysis immune to acquisitions with significant signal loss, even if the number of such acquisitions is high., Results: Inter-acquisition variation is much larger than the Rician noise variance, local spatial variations, and the estimates of diffusion anisotropy based on the current data, as well as the published values of anisotropy. The proposed method increases the contrast for cancers and yields a sensitivity of 98 . 8 % $$ 98.8\% $$ with a false positive rate of 3 . 9 % $$ 3.9\% $$ ., Conclusion: Motion-induced signal loss makes conventional signal-averaging suboptimal and can obscure signals from areas with restricted diffusion. Filtering or weighting individual acquisitions prior to image analysis can overcome this problem., (© 2022 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Aims: Biphasic hyalinizing psammomatous (BHP) renal cell carcinoma (RCC) is a newly described emerging entity within the spectrum of papillary RCC in the WHO 2022 classification. Molecular analyses have discovered that BHP RCC consistently harbour somatic mutations in the neurofibromin 2 (NF2) gene. The NF2 gene product, merlin, is known to primarily function as a tumour suppressor. Merlin protein loss correlates closely with the presence of NF2 mutations in benign and malignant tumours arising in different sites. In the present study we explored the role of merlin immunohistochemistry (IHC) in tumours within the spectrum of BHP RCC to determine the diagnostic utility of this marker., Materials and Methods: We performed merlin IHC in 13 BHP RCC, 18 papillary RCC, 10 TFE3-translocation RCC, 15 TFEB-altered RCC (including 13 TFEB-rearranged and 2 TFEB-amplified), and 10 mucinous tubular and spindle cell carcinomas of unknown mutational status., Results: Unequivocal loss of merlin expression in >90% of the tumour cells was observed in 12/13 BHP-RCC (92%), with the remaining tumour demonstrating weak focal cytoplasmic expression in ~10% of the tumour. In contrast, merlin was diffusely or multifocally expressed in all papillary RCC, TFE3-translocation RCC, and TFEB-altered RCC, as well as in 70% of mucinous tubular and spindle carcinomas., Conclusions: In this study, merlin IHC was ~92% sensitive and ~94% specific for BHP RCC. These data suggest that merlin IHC is a reliable surrogate marker for the presence of underlying NF2 gene inactivation, being diagnostically useful to identify BHP RCC., Conclusions: In this study, merlin IHC was ~92% sensitive and ~94% specific for BHP RCC. These data suggest that merlin IHC is a reliable surrogate marker for the presence of underlying NF2 gene inactivation, being diagnostically useful to identify BHP RCC., (© 2022 John Wiley & Sons Ltd.)

Although rare, a metastatic renal cell carcinoma could present with 68 Ga-DOTATATE avidity. A 66-year-old man with von Hippel-Lindau syndrome (VHL) presented with 68 Ga-DOTATATE uptake in the pancreatic head, splenic hilar region, and multiple osseous sites, including the right lateral portion of the T9 vertebrae. Biopsy of the T9 lesion confirmed metastatic renal cell carcinoma. Various VHL-associated cancers may display 68 Ga-DOTATATE avidity, which can change and guide clinical decisions for the patient., Competing Interests: Conflict of InterestMayank Patel, Abhishek Jha, Tatjana Antic, Sarah M. Nielsen, Jane E. Churpek, Alexander Ling, and Karel Pacak declare no conflict of interest., (© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2022.)

Objectives: Tissue carryovers are contaminants of surgical pathology cases in which extraneous tissue is incorporated into tissue blocks. Carryovers occur most frequently at the grossing or embedding stations, but little is published about them. We sought to analyze their transmission during transit to the histology lab., Methods: Cassettes of friable donor tissue were mixed with cassettes of spongy recipient tissue in formalin-filled containers and agitated by shipment via pneumatic tube. The tissue cassettes were processed, embedded as blocks, and cut as usual. Liquid samples were prepared from the submission containers as well as from workstation submission containers and histology tissue processor waste., Results: A high rate of contamination (14.9%) was observed under these artificial conditions. Friable donor tissue, including urothelium and colorectal adenocarcinoma, were promiscuous contaminants, as were placental villi. Fluid from submission containers showed viable tumor cells and fragments, which were also present in workstation submission containers and in tissue processor waste fluid., Conclusions: This study implicates liquid transport media as a possible avenue of contamination during submission and transportation of tissue cassettes for histologic processing. Attention should be given to the friability of submitted tissue and physical agitation of the cassettes in transit. Such contaminants may be present in the fluid in tissue submission bins and in tissue processor fluid., (© The Author(s) 2022. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Rationale and Objectives: To evaluate whether dynamic contrast enhanced (DCE) MRI with a split injection of 30% followed by 70% of a standard dose (30PSD and 70PSD) of gadoterate meglumine (DOTAREM) can improve diagnosis of prostate cancer (PCa)., Materials and Methods: MRI for twenty patients was performed on a Philips Ingenia 3T scanner without an endorectal coil followed by subsequent radical prostatectomy. DCE 3D T1-FFE data were acquired with injection of 0.03 mmol/kg followed after 2 minutes by 0.07 mmol/kg of DOTAREM. Regions-of-interest on histologically verified PCa and normal tissue in different prostate zones and the iliac artery were drawn. Average signal intensity as function of time was calculated for each ROI and fitted by using the signal intensity form of the Tofts (SI-Tofts) model to extract physiological parameters (K trans and v e ). In addition, the scaled arterial input function (AIF) obtained from 30PSD data was used to analyze 70PSD data., Results: The AIF obtained from 30PSD data showed both first and second passes clearly and had much higher peak magnitude than AIFs from 70PSD data. K trans was significantly (p < 0.05) larger in PCa than in normal tissue in peripheral zone (PZ) and central zone (CZ) for both 70PSD and 70PSD data analyzed with a scaled AIF. K trans in cancer overlapped with that of normal tissue in the transition zone (TZ). There was no statistical difference in v e between cancer and normal tissue. Receiver operating characteristic analysis showed that use of the AIF from 30PSD data to analyze 70PSD data increased the diagnostic efficacy of K trans in the PZ and CZ., Conclusion: The split dose protocol for injection of Dotarem increased diagnostic accuracy of quantitative analysis with the SI-Tofts model., (Copyright © 2021 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Background: Diffusion-weighted imaging (DWI) is commonly used to detect prostate cancer, and a major clinical challenge is differentiating aggressive from indolent disease., Purpose: To compare 14 site-specific parametric fitting implementations applied to the same dataset of whole-mount pathologically validated DWI to test the hypothesis that cancer differentiation varies with different fitting algorithms., Study Type: Prospective., Population: Thirty-three patients prospectively imaged prior to prostatectomy., Field Strength/sequence: 3 T, field-of-view optimized and constrained undistorted single-shot DWI sequence., Assessment: Datasets, including a noise-free digital reference object (DRO), were distributed to the 14 teams, where locally implemented DWI parameter maps were calculated, including mono-exponential apparent diffusion coefficient (MEADC), kurtosis (K), diffusion kurtosis (DK), bi-exponential diffusion (BID), pseudo-diffusion (BID*), and perfusion fraction (F). The resulting parametric maps were centrally analyzed, where differentiation of benign from cancerous tissue was compared between DWI parameters and the fitting algorithms with a receiver operating characteristic area under the curve (ROC AUC)., Statistical Test: Levene's test, P < 0.05 corrected for multiple comparisons was considered statistically significant., Results: The DRO results indicated minimal discordance between sites. Comparison across sites indicated that K, DK, and MEADC had significantly higher prostate cancer detection capability (AUC range = 0.72-0.76, 0.76-0.81, and 0.76-0.80 respectively) as compared to bi-exponential parameters (BID, BID*, F) which had lower AUC and greater between site variation (AUC range = 0.53-0.80, 0.51-0.81, and 0.52-0.80 respectively). Post-processing parameters also affected the resulting AUC, moving from, for example, 0.75 to 0.87 for MEADC varying cluster size., Data Conclusion: We found that conventional diffusion models had consistent performance at differentiating prostate cancer from benign tissue. Our results also indicated that post-processing decisions on DWI data can affect sensitivity and specificity when applied to radiological-pathological studies in prostate cancer., Level of Evidence: 1 TECHNICAL EFFICACY: Stage 3., (© 2021 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Background: With the development of new technologies and the changing patient profiles, cytopathology departments receive increasing numbers of adrenal gland cytology specimens. In this study, the authors analyzed archival adrenal gland cytology cases and attempted to implement a diagnostic reporting system., Design: Retrospective electronic medical record search was performed for adrenal gland cytology specimens in seven tertiary care centers. The cytology diagnoses were grouped in 7 categories: nondiagnostic, nonneoplastic, benign adrenal cortical elements (BACE), primary neoplasm of noncortical origin (NONC), atypia of undetermined significance (AUS), suspicious for malignancy (SM), and malignant (MAL). If available, histopathology results of concurrent and/or follow-up biopsies and/or resections were documented., Results: A total of 473 adrenal gland cytology cases were included. BACE cases comprised 21.8%, whereas MAL cases were 57.5% of all cases. For BACE and MAL categories, there were 100% and 98.9% correlation, respectively, in the cases with histopathology follow-up. Six of 10 NONC cases had histopathology diagnoses and there were 3 pheochromocytomas and 3 schwannomas. Twenty-one AUS cases had histology follow-up and 10 (47.6%) of them were malignant. Six cases of SM had histopathology follow-up, and all of them were malignant on the follow-up., Conclusions: The authors propose a 7-tier diagnostic scheme for adrenal gland cytology. The risk of malignancy was 98.9% in MAL cases (87/88) in the cohort. The only case with discordance was reported as "adrenal cortical adenoma with marked atypia"' on resection. There was no difference between endoscopic ultrasound-guided and percutaneous methods. Further studies are needed to validate and make this approach universal., (© 2022 American Cancer Society.)

Purpose: The clinical cell-cycle risk (CCR) score, which combines the University of California, San Francisco's Cancer of the Prostate Risk Assessment (CAPRA) and the cell cycle progression (CCP) molecular score, has been validated to be prognostic of disease progression for men with prostate cancer. This study evaluated the ability of the CCR score to prognosticate the risk of metastasis in men receiving dose-escalated radiation therapy (RT) with or without androgen deprivation therapy (ADT)., Methods and Materials: This retrospective, multi-institutional cohort study included men with localized National Comprehensive Cancer Network (NCCN) intermediate-, high-, and very high-risk prostate cancer (N = 741). Patients were treated with dose-escalated RT with or without ADT. The primary outcome was time to metastasis., Results: The CCR score prognosticated metastasis with a hazard ratio (HR) per unit score of 2.22 (95% confidence interval [CI], 1.71-2.89; P < .001). The CCR score better prognosticated metastasis than NCCN risk group (CCR, P < .001; NCCN, P = .46), CAPRA score (CCR, P = .002; CAPRA, P = .59), or CCP score (CCR, P < .001; CCP, P = .59) alone. In bivariable analyses, CCR score remained highly prognostic when accounting for ADT versus no ADT (HR, 2.18; 95% CI, 1.61-2.96; P < .001), ADT duration as a continuous variable (HR, 2.11; 95% CI, 1.59-2.79; P < .001), or ADT given at or below the recommended duration for each NCCN risk group (HR, 2.19; 95% CI, 1.69-2.86; P < .001). Men with CCR scores below or above the multimodality threshold (CCR score, 2.112) had a 10-year risk of metastasis of 3.7% and 21.24%, respectively. Men with below-threshold scores receiving RT alone had a 10-year risk of metastasis of 3.7%, and for men receiving RT plus ADT, the 10-year risk of metastasis was also 3.7%., Conclusions: The CCR score accurately and precisely prognosticates metastasis and adds clinically actionable information relative to guideline-recommended therapies based on NCCN risk in men undergoing dose-escalated RT with or without ADT. For men with scores below the multimodality threshold, adding ADT may not significantly reduce their 10-year risk of metastasis., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Genetic alterations involving NF2 occur at low frequencies in renal cell carcinoma across all of the major histologic subtypes and have been associated with adverse outcomes. To better characterize tumors harboring these alterations, we identified 14 cases with NF2 mutations that had been previously diagnosed as papillary renal cell carcinoma; renal cell carcinoma, unclassified; or translocation associated renal cell carcinoma. These tumors were characterized by a tubulopapillary architecture, sclerotic stroma, microscopic coagulative necrosis, and psammomatous calcifications. All the cases displayed eosinophilic cytology as well as a high nuclear grade (World Health Organization/International Society of Urological Pathology [WHO/ISUP] grade 3 to 4) in all but 1 case. A subset of cases shared features with the recently described biphasic hyalinizing psammomatous renal cell carcinoma. Next-generation sequencing demonstrated mutations involving NF2 gene in all cases. In 10 cases, this was paired with the loss of chromosome 22. Additional mutations involving PBRM1 were found in 5 cases that were associated with a more solid growth pattern. Eight patients presented with metastatic disease including all 5 with PBRM1 mutations. Despite the aggressive disease course seen in many of the patients in our series, 2 patients exhibited a dramatic response to immunotherapy. Our results support the existence of a distinct group of cases of renal cell carcinoma characterized by distinct although admittedly nonspecific morphology, an aggressive disease course, and NF2 mutations, often paired with the loss of chromosome 22., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Renal angiomyolipomas are benign tumors of the kidney that belong to the 'PEComa: perivascular epithelioid cell' family. Epithelioid AMLs (eAML) are a rare monotypic subtype with malignant potential, that can occur sporadically or be associated with tuberous sclerosis (TSC). Due to their epithelioid nature, eAMLs can closely resemble high-grade renal cell carcinoma (RCC), which may result in misdiagnosis. Multiple clinicopathologic parameters are predictive of worse outcomes for patients with eAML. Those can be used to stratify patients into groups with low, intermediate and high risk for disease progression. A high index of suspicion and a thorough immunohistochemical study are required to correctly diagnose eAML. Radiographically, eAMLs are also a diagnostic challenge as they share features with RCC on CT and MR imaging. Due to this close mimicry, the true incidence of eAML is thought to be much higher than 200 cases as reported in the literature. We report a series of four patients diagnosed with eAML and compare their clinical courses. We also report on the successful treatment of a patient with pulmonary metastasis from eAML using the mTOR inhibitor, everolimus. By identifying eAML and recognizing its high-risk features, it is possible mTOR inhibitors may have a meaningful role in the adjuvant treatment of these patients., Competing Interests: Conflict of interest The authors of this manuscript declare no conflicts of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: To validate prostate tissue composition measured using hybrid multi-dimensional MRI (HM-MRI) by comparing with reference standard (ground truth) results from pathologists' interpretation of clinical histopathology slides following whole mount prostatectomy., Materials and Methods: 36 prospective participants with biopsy-confirmed prostate cancer underwent 3 T MRI prior to radical prostatectomy. Axial HM-MRI was acquired with all combinations of echo times of 57, 70, 150, 200 ms and b-values of 0, 150, 750, 1500 s/mm 2 and data were fitted using a 3-compartment signal model using custom software to generate volumes for each tissue component (stroma, epithelium, lumen). Three experienced genitourinary pathologists independently as well as in consensus reviewed each histology image and provide an estimate of percentage of epithelium and lumen for regions-of-interest corresponding to MRI (n = 165; 64 prostate cancers and 101 benign tissue). Agreement statistics using total deviation index (TDI 0.9 ) was performed for tissue composition measured using HM-MRI and reference standard results from pathologists' consensus., Results: Based on the initial results showing typical variation among pathologists TDI 0.9  = 25%, we determined we will declare acceptable agreement if the 95% one-sided upper confident limit of TDI 0.9 is less than 30%. The results of tissue composition measurement from HM-MRI compared to ground truth results from the consensus of 3 pathologists, reveal that ninety percent of absolute paired differences (TDI 0.9 ) were within 18.8% and 22.4% in measuring epithelium and lumen, respectively. We are 95% confident that 90% of absolute paired differences were within 20.6% and 24.2% in measuring epithelium and lumen, respectively. These were less than our criterion of 30% and inter-pathologists' agreement (22.3% for epithelium and 24.2% for lumen) and therefore we accept the agreement performance of HM-MRI. The results revealed excellent area under the ROC curve for differentiating cancer from benign tissue based on epithelium (HM-MRI: 0.87, pathologists: 0.97) and lumen volume (HM-MRI: 0.85, pathologists: 0.77)., Conclusion: The agreement in tissue composition measurement using hybrid multidimensional MRI and consensus of pathologists is on par with the inter-raters (pathologists) agreement., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background Tissue estimates obtained by using microstructure imaging techniques, such as hybrid multidimensional (HM) MRI, may improve prostate cancer diagnosis but require histologic validation. Purpose To validate prostate tissue composition measured by using HM MRI, with quantitative histologic evaluation from whole-mount prostatectomy as the reference standard. Materials and Methods In this HIPAA-compliant study, from December 2016 to July 2018, prospective participants with biopsy-confirmed prostate cancer underwent 3-T MRI before radical prostatectomy. Axial HM MRI was performed with all combinations of echo times (57, 70, 150, and 200 msec) and b values (0, 150, 750, and 1500 sec/mm 2 ). Data were fitted by using a three-compartment signal model to generate volumes for each tissue component (stroma, epithelium, lumen). Quantitative histologic evaluation was performed to calculate volume fractions for each tissue component for regions of interest corresponding to MRI. Tissue composition measured by using HM MRI and quantitative histologic evaluation were compared (paired t test) and correlated (Pearson correlation coefficient), and agreement (concordance correlation) was assessed. Receiver operating characteristic curve analysis for cancer diagnosis was performed. Results Twenty-five participants (mean age, 60 years ± 7 [standard deviation]; 30 cancers and 45 benign regions of interest) were included. Prostate tissue composition measured with HM MRI and quantitative histologic evaluation did not differ (stroma, 45% ± 11 vs 44% ± 11 [ P = .23]; epithelium, 31% ± 15 vs 34% ± 15 [ P = .08]; and lumen, 24% ± 13 vs 22% ± 11 [ P = .80]). Between HM MRI and histologic evaluation, there was excellent correlation (Pearson r : overall, 0.91; stroma, 0.82; epithelium, 0.93; lumen, 0.90 [all P < .05]) and agreement (concordance correlation coefficient: overall, 0.91; stroma, 0.81; epithelium, 0.90; and lumen, 0.87). High areas under the receiver operating characteristic curve obtained with HM MRI (0.96 for epithelium and 0.94 for lumen, P < .001) and histologic evaluation (0.94 for epithelium and 0.88 for lumen, P < .001) were found for differentiation between benign tissue and prostate cancer. Conclusion Tissue composition measured by using hybrid multidimensional MRI had excellent correlation with quantitative histologic evaluation as the reference standard. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Muglia in this issue.

Unclassified renal cell carcinoma (RCC) accounts for ∼10% of renal tumors, and the most common histologic finding in these cases is eosinophilic cytoplasm. We previously demonstrated that a subset of eosinophilic renal tumors with heterogeneous morphology and immunohistochemical (IHC) staining harbored pathogenic mutations in tuberous sclerosis complex (TSC) or mammalian target of rapamycin (MTOR) as the primary defining mutation. We identified an additional 8 cases of eosinophilic tumors with unusual morphology that were originally diagnosed as chromophobe RCC (CHRCC) or CHRCC, eosinophilic variant. As a comparison, we included four classic CHRCC cases and one CHRCC, eosinophilic variant case. Gross examination revealed solid or solid and cystic patterns. The solid areas were composed of eosinophilic tumor cells divided by congested vessels, whereas the cystic areas were lined by cytologically bland eosinophilic cells with septae containing nests, ribbons, and single eosinophilic tumor cells. The tumor cells had abundant granular eosinophilic cytoplasm with round nuclei and inconspicuous nucleoli. IHC analysis demonstrated diffuse staining for CK7 and negative staining for CK20 and vimentin. Next-generation sequencing identified pathogenic variants in three genes: TSC1, TSC2, and MTOR. They also lacked significant copy number variations in contrast to our control cases. We have demonstrated with our expanded study that cases previously diagnosed as CHRCC or CHRCC, eosinophilic variant with discordant histology and IHC staining patterns may represent a separate subtype of RCC characterized by mutations in the TSC/MTOR pathway., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: High spectral and spatial resolution (HiSS) MRI is a spectroscopic imaging method focusing on water and fat resonances that has good diagnostic utility in breast imaging. The purpose of this work was to assess the feasibility and potential utility of HiSS MRI for the diagnosis of prostate cancer., Methods: HiSS MRI was acquired at 3 T from six patients who underwent prostatectomy, yielding a train of 127 phase-coherent gradient echo (GRE) images. In the temporal domain, changes in voxel intensity were analyzed and linear (R) and quadratic (R1, R2) quantifiers of signal logarithm decay were calculated. In the spectral domain, three signal scaling-independent parameters were calculated: water resonance peak width (PW), relative peak asymmetry (PRA), and relative peak distortion from ideal Lorentzian shape (PRD). Seven cancer and five normal tissue regions of interest were identified in correlation with pathology and compared., Results: HiSS-derived quantifiers, except R2, showed high reproducibility (coefficients of variation, 5%-14%). Spectral domain quantifiers performed better than temporal domain quantifiers, with receiver operator characteristic areas under the curve ranging from of 0.83 to 0.91. For temporal domain parameters, the range was 0.74 to 0.91. Low absolute values of the coefficients of correlation between monoexponential decay markers (R, PW) and resonance shape markers (PRA, PRD) were observed (range, 0.23-0.38)., Conclusion: The feasibility and potential diagnostic utility of HiSS MRI in the prostate at 3 T without an endorectal coil was confirmed. Weak correlation between well-performing markers indicates that complementary information could be leveraged to further improve diagnostic accuracy., (© 2021 International Society for Magnetic Resonance in Medicine.)

Background: Androgen deprivation therapy (ADT) improves outcomes in unfavorable-risk prostate cancer (PCa) treated with radiation therapy (RT). It was hypothesized that replacing luteinizing hormone-releasing hormone (LHRH) agonists with a 5-α-reductase inhibitor (5-ARI) would improve hormonal health-related quality of life (HRQOL) without differentially suppressing androgen-responsive (AR) gene expression., Methods: Patients with localized unfavorable-risk PCa, aged ≥70 years or Charlson Comorbidity Index score ≥2 were treated with oral ADT (oADT), consisting of 4 months of bicalutamide, a 5-ARI, and RT at 78 Gy. The primary end point was Expanded Prostate Cancer Index Composite HRQOL at 6 months ≤30%, and improvement compared with a synchronous standard of care (SOC) cohort receiving 4 months of bicalutamide and long-term LHRH agonist with RT. RNA sequencing was performed from matched pre-/post-ADT prostate tumor biopsies in a subset of men. Differential gene and pathway expressional changes were examined using gene set enrichment., Results: Between 2011 and 2018, 40 and 30 men were enrolled in the oADT and SOC cohorts, respectively. Median follow-up was 40 months. Those with ≤30% decline in hormonal HRQOL at 6 months was 97% (oADT) and 93% (SOC). The average 6-month hormonal decline was 1% (oADT) versus 12% (SOC; P = .04). The 4-year freedom from biochemical failure was 88% (oADT) versus 81% (SOC; P = .48). RNA sequencing (n = 9) showed similar numbers of downregulated and upregulated genes between the treatment groups (fold-change = 2; false-discovery rate-adjusted P ≤ .05). Both treatments comparably decreased the expression of 20 genes in canonical androgen receptor signaling., Conclusions: For men with PCa undergoing RT, oral versus standard ADT may improve 6-month QOL and appears to have a similar impact on androgen-responsive gene expression., (© 2021 American Cancer Society.)

Introduction: The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) specifies six categories with estimated risks of malignancy (ROM) and suggested management. The estimated ROM is 25% for Non-Diagnostic (ND) category, and 10% for Non-Neoplastic (NN). This study aimed to investigate histopathologic and clinical outcomes of MSRSGC categories ND and NN at the authors' institution., Materials and Methods: Cytopathology fine needle aspiration reports from 2008-2020 were searched for the word "salivary", "parotid", and "submandibular". Cases fitting Non-Diagnostic (ND) and Non-Neoplastic (NN) categories were identified. Follow-up cyto-/histopathologic and clinical data were extracted., Results: There were 43 ND and 46 NN cases. The average age was 58.3 years. Neoplastic lesions were found in 13 of 43 (30%) ND and 3 of 46 (6.5%) NN. The rate of malignancy in ND category was 14.0% (6/43) and 0% (0/46) in NN category. Four cases in ND (9.3%) and 6 (13.0%) in NN had no neoplasm and instead had an underlying reactive condition (e.g., chronic sialadenitis) or inflammatory lesion (e.g., lymphoepithelial cyst) on histologic follow-up. There was no follow-up pathology in 46.5% NDs (20/43) and 82.6% NNs (38/46); however, no lesions were apparent clinically with a mean follow-up of 3 years and 1.5 years, respectively., Conclusions: MSRSGC categories ND and NN are helpful for reporting salivary gland FNA results. With proper clinical and radiologic correlation, ROM of NN is low; however, ROM of ND remains significant. Repeat FNA after correlation for ND cases seems prudent as neoplasms and malignancies may have gone undetected., (Copyright © 2021 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

Objectives: While aberrations in the VHL gene and chromosome 3p resulting in clear cell renal cell carcinoma (CCRCC) are well established, we know that additional mutations in chromatin remodeling genes PBRM1, SETD2, and BRCA1-associated protein 1 (BAP1) contribute to pathogenesis in some cases. Given the known aggressive clinical behavior of BAP1-mutated CCRCC, we sought to define the pathologic phenotype of BAP1-mutated CCRCC., Methods: We identified 14 cases of molecularly proven BAP1-mutated CCRCC and investigated their clinicopathologic features., Results: BAP1-mutated CCRCC frequently showed papillary, tubulopapillary, or expanded nested architecture; demonstrated granular to diffusely eosinophilic cytoplasm with prominent eosinophilic globules; and contained high-grade nuclei. This morphology demonstrates significant overlap with Xp11 translocation renal cell carcinoma (RCC). Immunohistochemistry notably demonstrates loss of BAP1 expression in almost all tumors, in addition to strong p504S expression. A conventional CCRCC component was frequently present adjacent to the characteristic BAP1 areas and showed retained BAP1 expression and only patchy p504S. Approximately two-thirds of BAP1-mutated CCRCCs were stage pT3, renal vein invasion was common, and 50% developed metastases., Conclusions: Herein, we describe the histologic and immunohistochemical findings in BAP1-mutated CCRCC, which has important implications for utilization of molecular testing, prognosis, future therapeutics, and distinction from other RCC subtypes such as Xp11 translocation RCC., (© American Society for Clinical Pathology, 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aims: Translocation-associated renal cell carcinomas (RCCs) have been extensively subcharacterized in recent years, such that each is largely recognized by the 2016 World Health Organization as categorical neoplastic entities in the genitourinary tract. Those belonging to the t (6;11) family of tumors classically have a fusion between TFEB and MALAT1/α, and display a particular histomorphology. Specifically, they show a biphasic population of both small and large epithelioid cells, the smaller component of which surrounds basement membrane-type material. Despite this apt description, the tumors have variable morphology and mimic other RCCs including those with TFE3 translocations. Therefore, a high degree of suspicion is required to make the correct diagnosis., Methods: The 2 cases described in this article were of strikingly different appearance, and initially considered consistent with other non-translocation-associated renal tumors. These included clear cell RCC (CCRCC), perivascular epithelioid cell tumor (PEComa), and other eosinophilic RCCs (mainly papillary RCC type 2)., Results: Using RNA sequencing techniques, they were found to harbor distinct pathogenic rearrangements involving the TFEB gene, namely, fusions with CLTC and NEAT1 (the latter partnering heretofore never reported)., Conclusions: These alterations manifested in 2 notably dissimilar lesions, underscoring the importance of including this family of carcinomas in the differential of any renal neoplasm that does not display immunophenotypic characteristics consistent with its morphology.