Therapy with anti-PD-L1 immune check-point inhibitors is approved for several cancers, including advanced urothelial carcinomas. PD-L1 prevalence estimates vary widely in bladder cancer, and lack of ...correlation between expression and clinical outcomes and immunotherapy response may be attributed to methodological differences of the immunohistochemical reagents and procedures. We characterized PD-L1 expression in 235 urothelial carcinomas including 79 matched pairs of primary and metastatic cancers using a panel of four PD-L1 immunoassays in comparison with RNAscope assay using PD-L1-specific probe (CD274). The antibody panel included three FDA-approved clones (22C3 for pembrolizumab, 28.8 for nivolumab, SP142 for atezolizumab), and a commonly used clone E1L3N. Manual scoring of tissue microarrays was performed in each of 235 tumors (624 tissue cores) and compared to an automated image analysis. Expression of PD-L1 in tumor cells by ≥1 marker was detected in 41/142 (28.9%) primary tumors, 13/77 (16.9%) lymph nodes, and 2/16 (12.5%) distant metastases. In positive cases, high PD-L1 expression (>50% cells) was detected in 34.1% primary and 46.7% metastases. Concordant PD-L1 expression status was present in 71/79 (89.9%) cases of matched primary and metastatic urothelial carcinomas. PD-L1 sensitivity ranked from highest to lowest as follows: RNAscope, clone 28.8, 22C3, E1L3N, and SP142. Pairwise concordance correlation coefficients between the four antibodies in 624 tissue cores ranged from 0.76 to 0.9 for tumor cells and from 0.30 to 0.85 for immune cells. RNA and protein expression levels showed moderate to high agreement (0.72-0.87). Intra-tumor expression heterogeneity was low for both protein and RNA assays (interclass correlation coefficients: 0.86-0.94). Manual scores were highly concordant with automated Aperio scores (0.94-0.97). A significant subset of 56/235 (23.8%) urothelial carcinomas stained positive for PD-L1 with high concordance between all four antibodies and RNA ISH assay. Despite some heterogeneity in staining, the overall results are highly concordant suggesting diagnostic equivalence of tested assays.
BAP1-Mutated Clear Cell Renal Cell Carcinoma Gallan, Alexander J; Parilla, Megan; Segal, Jeremy ...
American journal of clinical pathology,
2021-Apr-26, Letnik:
155, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Abstract
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.
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.
Eosinophilic solid and cystic renal cell carcinomas (ESC RCC) is a rare, unique tumor type not yet included in the World Health Organization classification of renal neoplasia. Separately, RCCs found ...in patients with tuberous sclerosis complex (TSC) have recently been categorized into 3 morphologic groupsRCC with a tubulopapillary architecture separated by smooth muscle stroma, chromophobe-like, and eosinophilic-microcytic type. The third classification has been identified in ∼11% of TSC-associated RCC and have histology identical to ESC RCCs. The sporadic form of ESC RCC, not associated with TSC, have only been characterized on the cytogenetic level and the full molecular underpinnings have yet to be examined. Using next-generation sequencing we present 2 cases of sporadic ESC RCC in patients without clinical features of tuberous sclerosis, which demonstrate pathogenic somatic TSC2 gene mutations. These mutations are without other alterations in any other genes associated with RCC, suggesting that sporadic ESC RCC may be characterized by somatic tuberous sclerosis gene mutations (TSC2).
Primary rhabdomyosarcoma of the adult prostate is rare and associated with an aggressive clinical course. Given the limited number of cases reported about the prostate, little is known about the ...impact of molecular mutations on tumor biology and prognosis in adults. In this article, we present a case of primary embryonal rhabdomyosarcoma of the adult prostate with a complete molecular mutational profile of the tumor.
To analyze the diffusion and perfusion parameters of central gland (CG) prostate cancer, stromal hyperplasia (SH), and glandular hyperplasia (GH) and to determine the role of these parameters in the ...differentiation of CG cancer from benign CG hyperplasia.
In this institutional review board-approved (with waiver of informed consent), HIPAA-compliant study, 38 foci of carcinoma, 38 SH nodules, and 38 GH nodules in the CG were analyzed in 49 patients (26 with CG carcinoma) who underwent preoperative endorectal magnetic resonance (MR) imaging and radical prostatectomy. All carcinomas and hyperplastic foci on MR images were localized on the basis of histopathologic correlation. The apparent diffusion coefficient (ADC), the contrast agent transfer rate between blood and tissue (K(trans)), and extravascular extracellular fractional volume values for all carcinoma, SH, and GH foci were calculated. The mean, standard deviation, 95% confidence interval (CI), and range of each parameter were calculated. Receiver operating characteristic (ROC) and multivariate logistic regression analyses were performed for differentiation of CG cancer from SH and GH foci.
The average ADCs (× 10(-3) mm(2)/sec) were 1.05 (95% CI: 0.97, 1.11), 1.27 (95% CI: 1.20, 1.33), and 1.73 (95% CI: 1.64, 1.83), respectively, in CG carcinoma, SH foci, and GH foci and differed significantly, yielding areas under the ROC curve (AUCs) of 0.99 and 0.78, respectively, for differentiation of carcinoma from GH and SH. Perfusion parameters were similar in CG carcinomas and SH foci, with K(trans) yielding the greatest AUCs (0.75 and 0.58, respectively). Adding K(trans) to ADC in ROC analysis to differentiate CG carcinoma from SH increased sensitivity from 38% to 57% at 90% specificity without noticeably increasing the AUC (0.79).
ADCs differ significantly between CG carcinoma, SH, and GH, and the use of them can improve the differentiation of CG cancer from SH and GH. Combining K(trans) with ADC can potentially improve the detection of CG cancer.
http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.10100021/-/DC1.
To validate three previously identified quantitative image features across multiparametric magnetic resonance (MR) images acquired with imagers made by two different manufacturers to differentiate ...prostate cancer (PC) from normal prostatic tissue and to assess cancer aggressiveness.
This study was HIPAA-compliant and approved by the institutional review board. Preoperative 1.5-T multiparametric endorectal MR images of 119 PC patients (dataset A, 71 patients; dataset B, 48 patients) were analyzed, and 265 PC and normal peripheral zone regions of interests (ROIs) were identified through histologic and MR consensus review. The 10th percentile average apparent diffusion coefficient (ADC) value, average ADC value, and skewness of T2-weighted signal-intensity histogram were evaluated with area under the receiver operating characteristic curve (AUC). The image features were combined with a linear discriminant analysis classifier and evaluated both on the image dataset of each type of imager alone (leave-one-patient-out evaluation) and across the datasets (training on one dataset, testing on the other). Spearman correlation coefficient was calculated between the image features and ROI-specific Gleason scores.
AUC values of the image features combined were 0.95 ± 0.02 (standard error) and 0.88 ± 0.03 on dataset B and dataset A alone, respectively, and 0.96 ± 0.02 and 0.89 ± 0.03 when training on dataset A and testing on dataset B and vice versa, respectively. Spearman correlation coefficients between Gleason scores and the ADC features were between -0.27 and -0.34.
Consistently across images from datasets A and B, the 10th percentile ADC value, average ADC value, and T2-weighted skewness can distinguish PC from normal-tissue ROIs, and ADC features correlate moderately with ROI-specific Gleason scores.
MFAP5, a 25-kD microfibril-associated glycoprotein that is involved in elastic microfibril assembly, has been demonstrated to be significantly downregulated in tumor stroma by previous gene ...expression study. The aim of this study was to confirm the reduced expression of MFAP5 in colonic tumor stroma using immunohistochemistry and to explore the utility of MFAP5 as a marker to facilitate diagnosing an invasive component versus pseudoinvasion in colon polyps. In all 19 colon cancer resection cases evaluated, while there was intact MFAP5 immunoreactivity in the uninvolved normal connective tissue, there was marked reduction of MFAP5 immunoreactivity in the desmoplastic stroma surrounding the invasive component. The difference in MFAP5 expression levels was most pronounced within the tumor, while a more heterogeneous expression pattern was observed at the tumor invasive front. Reduction of MFAP5 staining was also observed in the stroma around mucin pools in 6 out of 9 sections from mucinous adenocarcinomas and in areas with high-grade dysplasia. For the polypectomy cases, intact expression of MFAP5 was seen in the stroma surrounding the displaced adenomatous glands in 9 out of 12 polyps with pseudoinvasion. Loss of expression of MFAP5 was observed in the stroma surrounding small foci of invasive adenocarcinoma in 8 of 10 malignant polyps. MFAP5 is a useful marker that may help distinguish normal connective tissue from stroma within invasive colonic adenocarcinoma. MFAP5 may facilitate the distinction between pseudoinvasion and true invasive cancer in colonic adenomatous polyps with a sensitivity of 80% (confidence interval 44–96%) and a specificity of 75% (confidence interval 43–93%) in this small cohort.
This study compares the performance of T2 maps in the detection of prostate cancer (PCa) in comparison to T2-weighted (T2W) magnetic resonance images.
The prospective study was institutional review ...board approved. Consenting patients (n = 45) with histologic confirmed PCa underwent preoperative 3-T magnetic resonance imaging with or without endorectal coil. Two radiologists, working independently, marked regions of interests (ROIs) on PCa lesions separately on T2W images and T2 maps. Each ROI was assigned a score of 1-5 based on the confidence in accurately detecting cancer, with 5 being the highest confidence. Subsequently, the histologically confirmed PCa lesions (n = 112) on whole-mount sections were matched with ROIs to calculate sensitivity, positive predictive value (PPV), and radiologist confidence score. Quantitative T2 values of PCa and benign tissue ROIs were measured.
Sensitivity and confidence score for PCa detection were similar for T2W images (51%, 4.5 ± 0.8) and T2 maps (52%, 4.5 ± 0.6). However, PPV was significantly higher (P = .001) for T2 maps (88%) compared to T2W (72%) images. The use of endorectal coils nominally improved sensitivity (T2W: 55 vs 47%, T2 map: 54% vs 48%) compared to the use of no endorectal coils, but not the PPV and the confidence score. Quantitative T2 values for PCa (105 ± 28 milliseconds) were significantly (P = 9.3 × 10
) lower than benign peripheral zone tissue (211 ± 71 milliseconds), with moderate significant correlation with Gleason score (ρ = -0.284).
Our study shows that review of T2 maps by radiologists has similar sensitivity but higher PPV compared to T2W images. Additional quantitative information obtained from T2 maps is helpful in differentiating cancer from normal prostate tissue and determining its aggressiveness.
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