Malignant mesothelioma of the testicular tunics is rare. About one third of cases are metastatic and carry a poor prognosis. This paper reviews the epidemiology, clinicopathologic features, ...treatment, and outcome of this entity.
Five years after the last prostatic carcinoma grading consensus conference of the International Society of Urological Pathology (ISUP), accrual of new data and modification of clinical practice ...require an update of current pathologic grading guidelines. This manuscript summarizes the proceedings of the ISUP consensus meeting for grading of prostatic carcinoma held in September 2019, in Nice, France. Topics brought to consensus included the following(1) approaches to reporting of Gleason patterns 4 and 5 quantities, and minor/tertiary patterns, (2) an agreement to report the presence of invasive cribriform carcinoma, (3) an agreement to incorporate intraductal carcinoma into grading, and (4) individual versus aggregate grading of systematic and multiparametric magnetic resonance imaging–targeted biopsies. Finally, developments in the field of artificial intelligence in the grading of prostatic carcinoma and future research perspectives were discussed.
•Germ cell neoplasia in situ is discussed.•Invasive types of germ cell tumor are discussed.•Immunostains are recommended in some cases.•The staging and differential diagnosis of germ cell tumors are ...discussed.
Germ cell neoplasia in situ (GCNIS) is the precursor of both seminomatous and non-seminomatous germ cell tumors. It consists of distended tubules that may have either intratubular seminoma or intratubular embryonal carcinoma cells. Many invasive non-seminomatous tumors contain a mixture of tumor types, which are reviewed here. Morphology, aided by a panel of immunostains, can determine the presence and percent of embryonal carcinoma, yolk sac tumor, choriocarcinoma, or teratoma in such tumors. Use of immunostains, required for diagnosis in perhaps 25% of testicular neoplasms, is reviewed. Changes of classification in the AJCC (8th edition) in 2016 are discussed, including the partitioning of two tumor types: the central role of chromosome 12p amplification allows both teratoma and yolk sac tumor to be divided into prepubertal types (lacking amplification) and post-pubertal types. Occasionally, sex cord-stromal tumors, hematolymphoid tumors, or epididymal adenomatoid tumors enter the differential diagnosis of germ cell neoplasms.
Recent epidemiologic, genetic, and molecular studies suggest infection and inflammation initiate certain cancers, including those of the prostate. The American Cancer Society, estimates that ...approximately 20% of all worldwide cancers are caused by infection. Mycoplasma, a genus of bacteria that lack a cell wall, are among the few prokaryotes that can grow in close relationship with mammalian cells, often without any apparent pathology, for extended periods of time. In this study, the capacity of Mycoplasma genitalium, a prevalent sexually transmitted infection, and Mycoplasma hyorhinis, a mycoplasma found at unusually high frequency among patients with AIDS, to induce a malignant phenotype in benign human prostate cells (BPH-1) was evaluated using a series of in vitro and in vivo assays. After 19 weeks of culture, infected BPH-1 cells achieved anchorage-independent growth and increased migration and invasion. Malignant transformation of infected BPH-1 cells was confirmed by the formation of xenograft tumors in athymic mice. Associated with these changes was an increase in karyotypic entropy, evident by the accumulation of chromosomal aberrations and polysomy. This is the first report describing the capacity of M. genitalium or M. hyorhinis infection to lead to the malignant transformation of benign human epithelial cells and may serve as a model to further study the relationship between prostatitis and prostatic carcinogenesis.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•A system for automatic histological grading of prostate cancer was developed.•The classifier was trained based on detailed annotations of six pathologists.•The inter-observer variability was ...addressed by adapting a crowdsourcing approach.•Novel features based on spatial statistics of the nuclei were proposed.•The performance of the classifier was within agreement levels among pathologists.
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Prostate cancer (PCa) is a heterogeneous disease that is manifested in a diverse range of histologic patterns and its grading is therefore associated with an inter-observer variability among pathologists, which may lead to an under- or over-treatment of patients. In this work, we develop a computer aided diagnosis system for automatic grading of PCa in digitized histopathology images using supervised learning methods. Our pipeline comprises extraction of multi-scale features that include glandular, cellular, and image-based features. A number of novel features are proposed based on intra- and inter-nuclei properties; these features are shown to be among the most important ones for classification. We train our classifiers on 333 tissue microarray (TMA) cores that were sampled from 231 radical prostatectomy patients and annotated in detail by six pathologists for different Gleason grades. We also demonstrate the TMA-trained classifier’s performance on additional 230 whole-mount slides of 56 patients, independent of the training dataset, by examining the automatic grading on manually marked lesions and randomly sampled 10% of the benign tissue. For the first time, we incorporate a probabilistic approach for supervised learning by multiple experts to account for the inter-observer grading variability. Through cross-validation experiments, the overall grading agreement of the classifier with the pathologists was found to be an unweighted kappa of 0.51, while the overall agreements between each pathologist and the others ranged from 0.45 to 0.62. These results suggest that our classifier’s performance is within the inter-observer grading variability levels across the pathologists in our study, which are also consistent with those reported in the literature.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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Eosinophilic Kidney Tumors: Old and New Iczkowski, Kenneth A; Czaja, Rebecca C
Archives of pathology & laboratory medicine (1976),
12/2019, Volume:
143, Issue:
12
Journal Article
Peer reviewed
Open access
Eosinophilic cytoplasm is the most common finding of difficult-to-classify kidney tumors. Morphology, cytogenetics, and immunohistochemical stains are discriminatory. This review compares ...well-recognized tumors such as granular clear cell carcinoma, papillary variants, chromophobe renal cell carcinoma, and oncocytoma and introduces newly described entities of hybrid oncocytic tumors, carcinomas defined by translocations, and carcinomas with deficiencies in the tricarboxylic acid cycle. The focus is on immunostaining, clinical correlations, and differential diagnoses. Representative examples of some entities are presented with elaboration on their workup.
To provide a review of the differential diagnoses for renal neoplasms with eosinophilic cytoplasm and elaborate on methods that may assist with correct identification.
Review of current literature on kidney tumors with eosinophilic cytoplasm, as well as the authors' personal experience.
Eosinophilic cytoplasm is a feature shared by many kidney tumors. Understanding the morphologic differences and the role of ancillary studies is key when encountering such a tumor.
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DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
One in eight men will be affected by prostate cancer (PCa) in their lives. While the current clinical standard prognostic marker for PCa is the Gleason score, it is subject to inter-reviewer ...variability. This study compares two machine learning methods for discriminating between cancerous regions on digitized histology from 47 PCa patients. Whole-slide images were annotated by a GU fellowship-trained pathologist for each Gleason pattern. High-resolution tiles were extracted from annotated and unlabeled tissue. Patients were separated into a training set of 31 patients (Cohort A, n = 9345 tiles) and a testing cohort of 16 patients (Cohort B, n = 4375 tiles). Tiles from Cohort A were used to train a ResNet model, and glands from these tiles were segmented to calculate pathomic features to train a bagged ensemble model to discriminate tumors as (1) cancer and noncancer, (2) high- and low-grade cancer from noncancer, and (3) all Gleason patterns. The outputs of these models were compared to ground-truth pathologist annotations. The ensemble and ResNet models had overall accuracies of 89% and 88%, respectively, at predicting cancer from noncancer. The ResNet model was additionally able to differentiate Gleason patterns on data from Cohort B while the ensemble model was not. Our results suggest that quantitative pathomic features calculated from PCa histology can distinguish regions of cancer; however, texture features captured by deep learning frameworks better differentiate unique Gleason patterns.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
AIMSTo evaluate the frequencies and types of disagreements in a contemporary urological second-opinion consult service in order to improve pathologist awareness. METHODSFor 7 years ending 30 October ...2021, records were kept of our department's total urologic outside consultation and disagreed-upon cases. Disagreements were categorized according to specimen type and nature of conflict. All grading and staging assignments used International Society of Urological Pathology (ISUP) criteria. Statistical analyses for each specimen type included the percent disagreement. Cohen's kappa analysis was done to measure interrater reliability on the prostate biopsies, prostatectomies, and the bladder biopsies/resections. In addition, for the prostate biopsies, the potential for change in treatment candidacy calculation (CTC), was assessed as sum of changes from cancer to non-malignant tissue or the reverse, plus changes from Gleason Grade group (GG)1 to GG ≥ 2 (3 +4 =7) or the reverse. RESULTSOverall mean disagreement rate for all specimens was 15.2%. The highest rate was among 1545 prostate biopsy cases, where 410 contained disagreements (26.5%). 118 (7.6%) met criteria for CTC: 10 cases were altered from cancer to non-cancer, 38 cases downgraded from GG≥ 2 to GG1, and 70 upgraded from GG1 to GG≥ 2. Second opinion downgraded the overall highest GG more often than it upgraded it, with downgrade:upgrade ratios of 64:37 for the GG1/GG2 threshold, 79:67 for the GG2/GG3, and 14:0 for the GG3/GG4. 146 specimen parts had disagreements as to cancer vs. suspicious vs. benign, with 85 undercalled and 61 overcalled. Other rates of disagreement included: prostatectomy 34/198 (17.2%); bladder resection or biopsy 68/591 (11.5%); kidney 27/175 (15.4%); and orchiectomy 9/82 (11.0%). In bladder specimens, overgrading was 6X more frequent than undergrading; and overstaging muscularis propria invasion was 6X more frequent than understaging. CONCLUSIONSThe review of uropathologic materials before definitive therapy can lead to changes that impact clinical decisions significantly. As an example, for prostate biopsies, candidacy for active surveillance versus definitive treatment hinges on GG1 versus 2 and this distinction constituted most CTC cases. The above findings highlight aspects of urological pathology to be emphasized to residents in training, and pathologists in practice.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZRSKP
Prostate‑derived calcitonin (CT) and its receptor induce tumorigenicity and increase metastatic potential of prostate cancer (PC). CT‑inducible genes in human prostate were identified by subtraction ...hybridization. Among these genes, zinc finger protein like 1 (ZFPL1) protein was interesting since it was abundantly expressed in malignant prostates but was almost absent in benign prostates. ZFPL1 expression was upregulated by CT and androgens, and ZFPL1 protein was secreted by prostate tumor cells through exosomal secretion. Serum levels of ZFPL1 in cancer patients were at least 4‑fold higher than those in the sera of cancer‑free individuals. Cell biology of ZFPL1 suggests its localization in Golgi bodies and exosomes, and its colocalization with chromogranin A and CD44. These results suggested that ZFPL1 is secreted by tumor cells of neuroendocrine (NE)/stem cell phenotype. The knockdown of endogenous ZFPL1 in (PC) cells led to a remarkable decrease in cell proliferation, and invasion while increasing their apoptosis. As expected, the overexpression of ZFPL1 in prostate cells had an opposite effect on these functions. The knockdown of ZFPL1 in PC cells also decreased Akt phosphorylation, suggesting the actions of ZFPL1 may be mediated through the PI3K‑Akt pathway. Moreover, the present results revealed that ZFPL1 is released by tumors cells of NE or androgen‑independent phenotype and its serum levels are significantly higher in cancer patients, suggesting that it may serve as a blood‑based non‑invasive biomarker of aggressive PC.
The New Realization About Cribriform Prostate Cancer Iczkowski, Kenneth A; Paner, Gladell P; Van der Kwast, Theodorus
Advances in anatomic pathology,
2018-January, 2018-Jan, 2018-01-00, 20180101, Volume:
25, Issue:
1
Journal Article
Peer reviewed
Data from the past 6 years have shown that the presence of any amount of cribriform (or more comprehensively, large acinar cribriform to papillary) pattern of invasive prostate cancer is associated ...with adverse pathologic features and leads to uniquely adverse outcomes. Sixteen papers and numerous abstracts have reached these conclusions concordantly. Not only does this justify removal of all cribriform cancer from Gleason grade 3, it shows that cribriform cancer has pathologic, outcome, and molecular features distinct from noncribriform Gleason grade 4. Suggestions for accommodating the presence of cribriform cancer into the 2014 Grade Group scheme are proposed.
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