Search

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: Levenes test, P

Purpose: Our study predictively maps epithelium density in magnetic resonance imaging (MRI) space while varying the ground truth labels provided by five pathologists to quantify the downstream effects of interobserver variability. Approach: Clinical imaging and postsurgical tissue from 48 recruited prospective patients were used in our study. Tissue was sliced to match the MRI orientation and whole-mount slides were stained and digitized. Data from 28 patients ( n = 33 slides) were sent to five pathologists to be annotated. Slides from the remaining 20 patients ( n = 123 slides) were annotated by one of the five pathologists. Interpathologist variability was measured using Krippendorffs alpha. Pathologist-specific radiopathomic mapping models were trained using a partial least-squares regression using MRI values to predict epithelium density, a known marker for disease severity. An analysis of variance characterized intermodel means difference in epithelium density. A consensus model was created and evaluated using a receiver operator characteristic classifying high grade versus low grade and benign, and was statistically compared to apparent diffusion coefficient (ADC). Results: Interobserver variability ranged from low to acceptable agreement (0.31 to 0.69). There was a statistically significant difference in mean predicted epithelium density values ( p < 0.001 ) between the five models. The consensus model outperformed ADC (areas under the curve = 0.80 and 0.71, respectively, p < 0.05 ). Conclusion: We demonstrate that radiopathomic maps of epithelium density are sensitive to the pathologist annotating the dataset; however, it is unclear if these differences are clinically significant. The consensus model produced the best maps, matched the performance of the best individual model, and outperformed ADC.

PurposeIn this study, the efficacy of transurethral prostate ablation in the presence of silica-shell ultrasound-triggered phase-shift emulsions (sUPEs) doped with MR contrast was evaluated. The influence of sUPEs on MR imaging assessment of the ablation zone was also investigated.MethodssUPEs were doped with a magnetic resonance (MR) contrast agent, Gd2 O3 , to assess ultrasound transition. Injections of saline (sham), saline and sUPEs alone, and saline and sUPEs with Optison microbubbles were performed under guidance of a prototype interventional MRI navigation platform in a healthy canine prostate. Treatment arms were evaluated for differences in lesion size, T1  contrast, and temperature. In addition, non-perfused areas (NPAs) on dynamic contrast-enhanced (DCE) MRI, 55°C isotherms, and areas of 240 cumulative equivalent minutes at 43°C (CEM43 ) dose or greater computed from MR thermometry were measured and correlated with ablated areas indicated by histology.ResultsFor treatment arms including sUPEs, the computed correlation coefficients between the histological ablation zone and the NPA, 55°C isotherm, and 240 CEM43 area ranged from 0.96-0.99, 0.98-0.99, and 0.91-0.99, respectively. In the absence of sUPEs, the computed correlation coefficients between the histological ablation zone and the NPA, 55°C isotherm, and 240 CEM43 area were 0.69, 0.54, and 0.50, respectively. Across all treatment arms, the areas of thermal tissue damage and NPAs were not significantly different (P = 0.47). Areas denoted by 55°C isotherms and 240 CEM43 dose boundaries were significantly larger than the areas of thermal damage, again for all treatment arms (P = 0.009 and 0.003, respectively). No significant differences in lesion size, T1 contrast, or temperature were observed between any of the treatment arms (P > 0.0167). Lesions exhibiting thermal fixation on histological analysis were present in six of nine insonations involving sUPE injections and one of five insonations involving saline sham injections. Significantly larger areas (P = 0.002), higher temperatures (P = 0.004), and more frequent ring patterns of restricted diffusion on ex vivo diffusion-weighted imaging (P = 0.005) were apparent in lesions with thermal fixation.ConclusionsT1 contrast suggesting sUPE transition was not evident in sUPE treatment arms. The use of MR imaging metrics to predict prostate ablation was not diminished by the presence of sUPEs. Lesions generated in the presence of sUPEs exhibited more frequent thermal fixation, though there were no significant changes in the ablation areas when comparing arms with and without sUPEs. Thermal fixation corresponded to some qualitative imaging features.

We report a comprehensive analysis of 412 muscle-invasive bladder cancers characterized by multiple TCGA analytical platforms. Fifty-eight genes were significantly mutated, and the overall mutational load was associated with APOBEC-signature mutagenesis. Clustering by mutation signature identified a high-mutation subset with 75% 5-year survival. mRNA expression clustering refined prior clustering analyses and identified a poor-survival "neuronal" subtype in which the majority of tumors lacked small cell or neuroendocrine histology. Clustering by mRNA, long non-coding RNA (lncRNA), and miRNA expression converged to identify subsets with differential epithelial-mesenchymal transition status, carcinoma in situ scores, histologic features, and survival. Our analyses identified 5 expression subtypes that may stratify response to different treatments.

Simple Summary: This study investigated whether quantitative MRI and histology of the prostate reveal differences between races that can affect diagnosis. The cancer signal enhancement rate (α) on dynamic contrast-enhanced MRI (DCE-MRI) was significantly higher for African Americans (AAs) compared to Caucasian Americans (CAs). The signal washout rate (β) was significantly lower in benign tissue in AAs and significantly elevated in cancers in AAs. However, no significant differences were found for ADC and T2. The ROC analysis showed that the apparent diffusion coefficient (ADC) and T2 are slightly less effective in AAs compared to CAs. 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 that cancers have a greater proportion of epithelium and lower lumen in AAs compared to CAs. This study shows that the different races have different quantitative MRI values and histologic makeup. Quantitative DCE-MRI is highly effective and improves PCa diagnosis in African Americans. 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. [ABSTRACT FROM AUTHOR]

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. The current study is the first to investigate the molecular characteristics of spindle cell carcinoid tumors. This rare subset of carcinoid tumors harbored unique cytologic, prognostic, and molecular features that may have significant diagnostic and clinical implications. [ABSTRACT FROM AUTHOR]

Despite the powerful tools provided by morphology and immunohistochemistry, 4% to 5% of renal cell carcinomas (RCCs) remain unclassified. (1) At our institutions, unclassified RCC represents 2% to 3% of [...], Context.--Cytogenomic analysis provides a useful adjunct to traditional pathology in the categorization of renal cell carcinomas (RCCs), particularly in morphologically ambiguous cases, but it has disadvantages, including cost. Objective.--To define the clinical scenarios in which this technology has direct clinical applications. Design.--DNA was isolated from paraffin-embedded tissue from 40 selected cases of RCC. Chromosome genomic array testing was performed using the OncoScan. Results.--Of 23 cases of unclassified renal tumors, 19 (83%) were reclassified with incorporation of cytogenetic and histologic features, including 10 as clear cell RCC, 2 as collecting duct carcinoma, 2 as papillary RCC, and 1 as novel TFEB-amplified tumor lacking TFEB translocation. Of 5 tumors with "hybrid" oncocytic features, 3 were reclassified as an eosinophilic variant of chromophobe RCC and 1 as oncocytoma. Appropriate staging in 2 patients was determined by identifying distinct, nonshared cytogenetic profiles. Of 11 cases of metastatic clear cell RCC, 7 (63%) had cytogenetic features associated with a poor prognosis. Conclusions.--We identified 5 scenarios in which chromosome genomic array testing has direct clinical utility: (1) to investigate unclassified RCCs, (2) to understand tumors with "hybrid" features and "collision" tumors, (3) to determine appropriate staging in questions of bilateral tumors and/or metastases, (4) to identify chromosomal aberrations in metastatic clear cell RCCs associated with a worse prognosis, and (5) to identify new entities. This has practical value in our institution, where a molecular profile diagnostically separating morphologically difficult to classify clear cell, papillary, chromophobe, and unclassified RCC influences treatment recommendations and clinical trial eligibility. (Arch Pathol Lab Med. 2019;143:494-504; doi: 10.5858/arpa.2018-0104-OA)

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. [ABSTRACT FROM AUTHOR]