Collagenous micronodules in prostate cancer revisited: are they solely associated with Gleason pattern 3 adenocarcinomas?
Mi J. KimMukul DivatiaJeong Ho LeeSteven S. ShenBrian J. MilesJun Hyun HwangAlberto G. AyalaJae Y. Ro
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Collagenous micronodules (CMs) are microscopic stromal nodular eosinophilic fibrillar collagen deposition of uncertain histogenesis seen in prostatic adenocarcinoma. Per the 2005 International Society of Urologic Pathology (ISUP) consensus conference, they are categorized as Gleason pattern 3. This study analyzes morphological and clinical features of CMs from a large series of radical prostatectomies. Hematoxylin and eosin stained slides for 129 radical prostatectomies for adenocarcinoma of prostate with CMs and for 93 prostatic adenocarcinoma cases without CMs as comparison were examined out of a total of 667 cases performed from January 2010 to December 2011 at Houston Methodist Hospital. CMs were identified in 19% of all radical prostatectomies (129/667 cases). Almost all tumors with CMs were located in the peripheral zone (98%) as single or multiple foci of prostatic cancer glands. The vast majority of cases (96%) were identified in association with mucinous secretion. A cribriform Gleason pattern 4 was associated in 86 cases (67%). The CMs were associated with glomerulation (42%) and amphophilic luminal secretion (59%). 88 cases (68%) showed tumor foci with Gleason pattern ≥ 4 in close association with CMs. Multivariate analysis revealed CMs of the prostatic adenocarcinoma are closely related to mucinous secretion, cribriform growth pattern, and Gleason pattern 4. This study suggests that CMs are more frequently associated with Gleason pattern 4 cancer warranting morphologic reappraisal of CMs, rather than the consensus assignment of Gleason pattern 3.Keywords:
Cribriform
Surgical pathology
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Histogenesis
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In surgical pathology, atypical small acinar proliferation is commonly detected in prostate biopsies. Most studies on atypical small acinar proliferation have examined morphological characteristics and the utility of immunohistochemical studies. However, these resources are not available to many pathology departments. We have found that examining additional sections is a simple and inexpensive method that allows better evaluation of focal prostatic glandular atypia.The present report compares the diagnostic utility of immunohistochemical techniques versus examining additional sections in prostate biopsies with focal glandular atypia.Thirty recently studied prostate biopsies with focal glandular atypia were selected. In each case, 3 additional levels were examined. An immunohistochemical study was performed on one level using an antibody against high-molecular-weight keratin (34BetaE12). Two additional sections were stained with hematoxylin and eosin.The diagnosis of focal carcinoma was established with only additional sections in 4 cases (13.3%). In 2 of these biopsies, additional areas of carcinoma were found that were not identified in the original sections. In 4 other cases, immunohistochemical analysis was the only useful method for diagnosing cancer. In 9 cases (30%), both methods were useful for classifying focal glandular atypia as carcinoma. In the remaining 13 cases,neither immunohistochemical analysis nor additional sections were useful in changing the diagnosis of focal glandular atypia.Focal glandular atypia in prostatic needle biopsies should be routinely examined with additional sections, particularly when immunohistochemical analysis is not possible. Some biopsies with atypical glandular proliferation may show focal carcinoma in additional sections, even if the immunohistochemical analysis did not provide a diagnosis of malignancy. Additional sections can also reveal areas of carcinoma that were not apparent in the original sections.
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Immunohistochemistry, a technique that microscopically detects cellular constituents via specific antibodies, has revolutionized the field of surgical pathology by tremendously empowering the hematoxylin and eosin (H&E) slide. In the investigation of the unknown primary, it enables detecting the origin of the tumor by use of tissue- or organ-specific antibodies as well as antibodies associated with minimal histogenetic differentiation. It has almost perfected the pathologist's ability to make specific diagnoses such as those of mesothelioma, melanoma, and neuroendocrine tumors. These diagnoses should be reached by interpreting the immunohistochemical results in the context of a detailed morphological analysis and differential diagnosis based on the H&E. Other important uses include detection of microinvasive and micrometastatic disease. Through the use of prognostic markers, immunohistochemistry can provide valuable information regarding tumor behavior and therapy. Lastly, immunohistochemistry serves a small but valuable role in highlighting microorganisms, particularly viruses.
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Collagenous micronodules (CMs) are microscopic stromal nodular eosinophilic fibrillar collagen deposition of uncertain histogenesis seen in prostatic adenocarcinoma. Per the 2005 International Society of Urologic Pathology (ISUP) consensus conference, they are categorized as Gleason pattern 3. This study analyzes morphological and clinical features of CMs from a large series of radical prostatectomies. Hematoxylin and eosin stained slides for 129 radical prostatectomies for adenocarcinoma of prostate with CMs and for 93 prostatic adenocarcinoma cases without CMs as comparison were examined out of a total of 667 cases performed from January 2010 to December 2011 at Houston Methodist Hospital. CMs were identified in 19% of all radical prostatectomies (129/667 cases). Almost all tumors with CMs were located in the peripheral zone (98%) as single or multiple foci of prostatic cancer glands. The vast majority of cases (96%) were identified in association with mucinous secretion. A cribriform Gleason pattern 4 was associated in 86 cases (67%). The CMs were associated with glomerulation (42%) and amphophilic luminal secretion (59%). 88 cases (68%) showed tumor foci with Gleason pattern ≥ 4 in close association with CMs. Multivariate analysis revealed CMs of the prostatic adenocarcinoma are closely related to mucinous secretion, cribriform growth pattern, and Gleason pattern 4. This study suggests that CMs are more frequently associated with Gleason pattern 4 cancer warranting morphologic reappraisal of CMs, rather than the consensus assignment of Gleason pattern 3.
Cribriform
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Not Otherwise Specified
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Chromophobe cell
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This review focuses on histopathological aspects of carcinoma of the prostate. A tissue diagnosis of adenocarcinoma is often essential for establishing a diagnosis of prostate cancer, and the foundation for a tissue diagnosis is currently light microscopic examination of hematoxylin and eosin (H&E)-stained tissue sections. Markers detected by immunohistochemistry on tissue sections can support a diagnosis of adenocarcinoma that is primary in the prostate gland or metastatic. Histological variants of carcinoma of the prostate are important for diagnostic recognition of cancer or as clinicopathologic entities that have prognostic and/or therapeutic significance. Histological grading of adenocarcinoma of the prostate, including use of the 2014 International Society of Urological Pathology (ISUP) modified Gleason grades and the new grade groups, is one of the most powerful prognostic indicators for clinically localized prostate cancer, and is one of the most critical factors in determination of management of these patients.
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Adenoid Cystic Carcinoma
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Prostate cancer treatment planning is largely dependent upon examination of core-needle biopsies. The microscopic architecture of the prostate glands forms the basis for prognostic grading by pathologists. Interpretation of these convoluted three-dimensional (3D) glandular structures via visual inspection of a limited number of two-dimensional (2D) histology sections is often unreliable, which contributes to the under- and overtreatment of patients. To improve risk assessment and treatment decisions, we have developed a workflow for nondestructive 3D pathology and computational analysis of whole prostate biopsies labeled with a rapid and inexpensive fluorescent analogue of standard hematoxylin and eosin (H&E) staining. This analysis is based on interpretable glandular features and is facilitated by the development of image translation-assisted segmentation in 3D (ITAS3D). ITAS3D is a generalizable deep learning-based strategy that enables tissue microstructures to be volumetrically segmented in an annotation-free and objective (biomarker-based) manner without requiring immunolabeling. As a preliminary demonstration of the translational value of a computational 3D versus a computational 2D pathology approach, we imaged 300 ex vivo biopsies extracted from 50 archived radical prostatectomy specimens, of which, 118 biopsies contained cancer. The 3D glandular features in cancer biopsies were superior to corresponding 2D features for risk stratification of patients with low- to intermediate-risk prostate cancer based on their clinical biochemical recurrence outcomes. The results of this study support the use of computational 3D pathology for guiding the clinical management of prostate cancer. SIGNIFICANCE: An end-to-end pipeline for deep learning-assisted computational 3D histology analysis of whole prostate biopsies shows that nondestructive 3D pathology has the potential to enable superior prognostic stratification of patients with prostate cancer.
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Histopathologic diagnosis of adenocarcinoma of the prostate is based on light-microscopic examination of hematoxylin-eosin-stained tissue sections. Multiple factors, including preanalytic and analytic elements, affect the ability of the pathologist to accurately diagnose prostatic adenocarcinoma. False-negative diagnosis, that is, failure to diagnose prostatic adenocarcinoma, may have serious clinical consequences. It is important to delineate and understand those factors that may affect and cause histopathologic false-negative diagnoses of prostatic adenocarcinoma.To review common factors involved in histopathologic underdiagnosis of prostatic adenocarcinoma, including the following: (1) tissue processing and sectioning artifacts, (2) minimal adenocarcinoma, (3) deceptively benign appearing variants of acinar adenocarcinoma, (4) single cell adenocarcinoma, and (5) treatment effects.Data sources included published, peer-reviewed literature and personal experiences of the senior author.Knowledge of the reasons for histopathologic false-negative diagnosis of adenocarcinoma of the prostate is an important component in the diagnostic assessment of prostate tissue sections. Diagnostic awareness of the histomorphologic presentations of small (minimal) adenocarcinoma; deceptively benign appearing variants including atrophic, foamy gland, microcystic, and pseudohyperplastic variants; single cell carcinoma; and treatment effects is critical for establishment of a definitive diagnosis of adenocarcinoma and the prevention of false-negative diagnoses of prostate cancer.
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