Advances In Anatomic Pathology最新文献

{"title":"Role of Surgical Pathologist for the Detection of Immuno-oncologic Predictive Factors in Non-small Cell Lung Cancers.","authors":"Sambit K Mohanty,&nbsp;Sourav K Mishra,&nbsp;Mahul B Amin,&nbsp;Abbas Agaimy,&nbsp;Florian Fuchs","doi":"10.1097/PAP.0000000000000395","DOIUrl":"https://doi.org/10.1097/PAP.0000000000000395","url":null,"abstract":"<p><p>Until very recently, surgery, chemotherapy, and radiation therapy have been the mainstay of treatment in non-small cell carcinomas (NSCLCs). However, recent advances in molecular immunology have unveiled some of the complexity of the mechanisms regulating cellular immune responses and led to the successful targeting of immune checkpoints in attempts to enhance antitumor T-cell responses. Immune checkpoint molecules such as cytotoxic T-lymphocyte associated protein-4, programmed cell death protein-1, and programmed death ligand (PD-L) 1 have been shown to play central roles in evading cancer immunity. Thus, these molecules have been targeted by inhibitors for the management of cancers forming the basis of immunotherapy. Advanced NSCLC has been the paradigm for the benefits of immunotherapy in any cancer. Treatment decisions are made based on the expression of PD-L1 on the tumor cells and the presence or absence of driver mutations. Patients with high PD-L1 expression (≥50%) and no driver mutations are treated with single-agent immunotherapy whereas, for all other patients with a lower level of PD-L1 expression, a combination of chemotherapy and immunotherapy is preferred. Thus, PD-L1 blockers are the only immunotherapeutic agents approved in advanced NSCLC without any oncogenic driver mutations. PD-L1 immunohistochemistry, however, may not be the best biomarker in view of its dynamic nature in time and space, and the benefits may be seen regardless of PD -L1 expression. Each immunotherapy molecule is prescribed based on the levels of PD-L1 expression as assessed by a Food and Drug Administration-approved companion diagnostic assay. Other biomarkers that have been studied include tumor mutational burden, the T-effector signature, tumor-infiltrating lymphocytes, radiomic assays, inflammation index, presence or absence of immune-related adverse events and specific driver mutations, and gut as well as local microbiome. At the current time, none of these biomarkers are routinely used in the clinical decision-making process for immunotherapy in NSCLC. However, in individual cases, they can be useful adjuncts to conventional therapy. This review describes our current understanding of the role of biomarkers as predictors of response to immune checkpoint molecules. To begin with a brief on cancer immunology in general and in NSCLC, in particular, is discussed. In the end, recent advancements in laboratory techniques for refining biomarker assays are described.</p>","PeriodicalId":7305,"journal":{"name":"Advances In Anatomic Pathology","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9276576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathology of Immunotherapy-induced Responses in Cutaneous Melanoma: Current Evidences and Future Perspectives.","authors":"Alice Indini,&nbsp;Maurizio Lombardo,&nbsp;Angelo Sidoni,&nbsp;Andrea Gianatti,&nbsp;Mario Mandalà,&nbsp;Daniela Massi","doi":"10.1097/PAP.0000000000000375","DOIUrl":"10.1097/PAP.0000000000000375","url":null,"abstract":"<p><p>Over the last years, immune checkpoint inhibitors (ICIs) have demonstrated remarkable anti-tumor activity and beneficial effects in patients with early and advanced melanoma. However, ICIs provide clinical benefit only in a minority of patients due to primary and/or acquired resistance mechanisms. Immunotherapy resistance is a complex phenomenon relying on genetic and epigenetic factors, which ultimately influence the interplay between cancer cells and the tumor microenvironment. Information is accumulating on the cellular and molecular mechanisms underlying the production of resistance and the resulting diminished therapeutic efficacy. In addition, current knowledge on predictors of response and toxicity to immunotherapy and on biomarkers that reliably identify resistant patients is in progress. In this review, we will focus on the tumor microenvironment changes induced by ICIs in melanoma, summarizing the available evidence of clinical trials in the neoadjuvant and metastatic setting. We will also overview the role of potential biomarkers in predicting disease response to ICIs, providing insight into current and future research in this field.</p>","PeriodicalId":7305,"journal":{"name":"Advances In Anatomic Pathology","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9279534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of Surgical Pathologist for Detection of Predictive Immuno-oncological Factors in Breast Cancer.","authors":"Mandy Berner,&nbsp;Arndt Hartmann,&nbsp;Ramona Erber","doi":"10.1097/PAP.0000000000000382","DOIUrl":"10.1097/PAP.0000000000000382","url":null,"abstract":"<p><p>Immune checkpoint inhibitors (ICIs) have changed therapy strategies in breast cancer (BC) patients suffering from triple-negative breast cancer (TNBC). For example, in Europe the anti-programmed cell death 1 ligand 1 (PD-L1) ICI Azetolizumab is approved for adult patients with locally advanced or metastasized TNBC (mTNBC), depending on the immunohistochemical (IHC) PD-L1 expression of immune cells in the tumor area [immune cell (IC) score ≥1%); the anti-programmed cell death 1 (PD-1) ICI pembrolizumab is approved for mTNBC if PD-L1 Combined Positive Score (CPS), that is PD-L1 expression on tumor and/or immune cells, is ≥10. For early TNBC, in contrast, neoadjuvant use of pembrolizumab is approved in the United States and Europe independent from PD-L1 IHC expression. The determination of PD-L1 expression in tumor tissue to predict response to ICI therapy requires sensitive immunostaining with appropriate primary antibodies and staining protocols and a standardized and meticulous assessment of PD-L1 IHC stained breast cancer tissue slides. For the selection of the test material and continuous quality control of the dyeing, high standards must be applied. The evaluation is carried out according to various evaluation algorithms (scores). Here, the role of PD-L1 in BC and the currently most relevant PD-L1 assays and scores for TNBC will be explained. Furthermore, other tissue-based biomarkers potentially predictive for ICI therapy response in BC, for example, tumor mutational burden (TMB), will be presented in this review.</p>","PeriodicalId":7305,"journal":{"name":"Advances In Anatomic Pathology","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9647976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Guiding Individualized Patient' Care: Emerging Roles of Pathology in the Era of Immune-oncological Therapy.","authors":"Abbas Agaimy,&nbsp;Mahul B Amin","doi":"10.1097/PAP.0000000000000384","DOIUrl":"10.1097/PAP.0000000000000384","url":null,"abstract":"","PeriodicalId":7305,"journal":{"name":"Advances In Anatomic Pathology","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9648019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gastrointestinal and Hepatobiliary Immune-related Adverse Events: A Histopathologic Review.","authors":"Zainab I Alruwaii,&nbsp;Elizabeth A Montgomery","doi":"10.1097/PAP.0000000000000401","DOIUrl":"https://doi.org/10.1097/PAP.0000000000000401","url":null,"abstract":"<p><p>Immune checkpoint inhibitors have been increasingly used to treat various malignant neoplasms. Despite their superior efficacy in treating certain ones, their global immune-activation effect leads to systemic side effects, referred to as immune-related adverse events. Immune-related adverse events affect a variety of organs, including the skin, gastrointestinal, hepatobiliary, and endocrine organs. Gastrointestinal tract immune-related adverse events present with a wide range of symptoms with variable severity, which may lead to treatment interruption and administration of immunosuppression therapy in many cases. Histopathologic changes are diverse, overlapping with many other conditions. Therefore, recognizing these changes is crucial in diagnosing immune-related adverse events. This review discusses the pathologic manifestations of gastrointestinal immune-related adverse events and discusses the primary differential diagnoses.</p>","PeriodicalId":7305,"journal":{"name":"Advances In Anatomic Pathology","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9276578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune-Checkpoint-Inhibitor Therapy-Principles and Relevance of Biomarkers for Pathologists and Oncologists.","authors":"Christopher Darr,&nbsp;Thomas Hilser,&nbsp;Claudia Kesch,&nbsp;Aykhan Isgandarov,&nbsp;Henning Reis,&nbsp;Milan Wahl,&nbsp;Isabel Kasper-Virchow,&nbsp;Boris A Hadaschik,&nbsp;Viktor Grünwald","doi":"10.1097/PAP.0000000000000373","DOIUrl":"10.1097/PAP.0000000000000373","url":null,"abstract":"<p><p>Immune-checkpoint-inhibitor (ICI) therapy has been one of the major advances in the treatment of a variety of advanced or metastatic tumors in recent years. Therefore, ICI-therapy is already approved in first-line therapy for multiple tumors, either as monotherapy or as combination therapy. However, there are relevant differences in approval among different tumor entities, especially with respect to PD-L1 testing. Different response to ICI-therapy has been observed in the pivotal trials, so PD-L1 diagnostic testing is used for patient selection. In addition to PD-L1 testing of tumor tissue, liquid biopsy provides a noninvasive way to monitor disease in cancer patients and identify those who would benefit most from ICI-therapy. This overview focuses on the use of ICI-therapy and how it relates to common and potential future biomarkers for patient-directed treatment planning.</p>","PeriodicalId":7305,"journal":{"name":"Advances In Anatomic Pathology","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9279533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Renaming Grade Group 1 Prostate \"Cancer\" From a Pathology Perspective: A Call for Multidisciplinary Discussion.","authors":"Gladell P Paner,&nbsp;Ming Zhou,&nbsp;Jeffry P Simko,&nbsp;Scott E Eggener,&nbsp;Theodorus van der Kwast","doi":"10.1097/PAP.0000000000000400","DOIUrl":"https://doi.org/10.1097/PAP.0000000000000400","url":null,"abstract":"<p><p>Despite the innovations made to enhance smarter screening and conservative management for low-grade prostate cancer, overdiagnosis, and overtreatment remains a major health care problem. Driven by the primary goal of reducing harm to the patients, relabeling of nonlethal grade group 1 (GG 1) prostate cancer has been proposed but faced varying degrees of support and objection from clinicians and pathologists. GG 1 tumor exhibits histologic (invasive) and molecular features of cancer but paradoxically, if pure, is unable to metastasize, rarely extends out of the prostate, and if resected, has a cancer-specific survival approaching 100%. Most of the arguments against relabeling GG 1 relate to concerns of missing a higher-grade component through the unsampled area at biopsy. However, the designation of tumor benignity or malignancy should not be based on the shortcomings of a diagnostic procedure and sampling errors. This review explores possible solutions, mainly the feasibility of renaming GG 1 in radical prostatectomy (RP) with ramifications in biopsy diagnosis, acceptable for both pathologists and clinicians. One workable approach is to rename GG 1 in RP with a cautious neutral or nonbenign non-cancer term (eg, acinar neoplasm) using \"defined criteria\" that will stop the indiscriminate reporting of every GG 1 in biopsy as carcinoma including eventual insignificant microtumors in RPs. Use of a corresponding noncommittal term at biopsy while commenting on the possibility of an undersampled nonindolent cancer, might reduce the pathologist's concerns about upgrading. Dropping the word \"carcinoma\" in biopsy preempts the negative consequences of labeling the patient with cancer, including unnecessary definitive therapy (the root cause of overtreatment). Renaming should retain the status quo of contemporary grading and risk stratifications for management algorithms while trying to minimize overtreatment. However, the optimal approach to find answers to this issue is through multidisciplinary discussions of key stakeholders with a specific focus on patient-centered concerns and their ramifications in our practices. GG 1 renaming has been brought up in the past and came up again despite the continued counterarguments, and if not addressed more comprehensively will likely continue to reemerge as overdiagnosis, overtreatment, and patient's sufferings persist.</p>","PeriodicalId":7305,"journal":{"name":"Advances In Anatomic Pathology","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2023-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9425292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Spectrum of Digestive Tract Histopathologic Findings in the Setting of Severe Acute Respiratory Syndrome Coronavirus-2 Infection: What Pathologists Need to Know.","authors":"Rana Shaker Al-Zaidi","doi":"10.1097/PAP.0000000000000398","DOIUrl":"https://doi.org/10.1097/PAP.0000000000000398","url":null,"abstract":"<p><p>Although the novel severe acute respiratory syndrome coronavirus-2 is known primarily to affect the respiratory system, current evidence supports its capability to infect and induce gastrointestinal tract injury. Data describing the histopathologic alterations of the digestive system in patients infected with severe acute respiratory syndrome coronavirus-2 are becoming more detailed, as the number of studies is increasing and the quality of our insight into the infection and the histopathologic findings is improving. This review highlights the range of pathologic findings that could be observed in gastrointestinal specimens from patients infected with coronavirus disease 2019 and the potential underlying pathogenetic mechanisms of this disease.</p>","PeriodicalId":7305,"journal":{"name":"Advances In Anatomic Pathology","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2023-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/37/03/pap-30-342.PMC10412085.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10341254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Highlighting Bone and Soft Tissue Pathology on Instagram.","authors":"Casey P Schukow, Scott E Kilpatrick","doi":"10.1097/PAP.0000000000000396","DOIUrl":"10.1097/PAP.0000000000000396","url":null,"abstract":"","PeriodicalId":7305,"journal":{"name":"Advances In Anatomic Pathology","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2023-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10857682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Conjunctivitis: A Primer on Conjunctival Biopsy and Approach to Histopathologic Diagnosis.","authors":"Curtis E Margo, Lynn E Harman","doi":"10.1097/PAP.0000000000000397","DOIUrl":"10.1097/PAP.0000000000000397","url":null,"abstract":"<p><p>Conjunctivitis, or inflammation of the mucosal covering the anterior third of sclera and inner eyelid, is a common clinical condition of varied causation. Most cases are self-limited due to infection or allergy and rarely necessitate biopsy. Inflammation of the conjunctiva, however, is one of the most common principal histopathologic diagnoses rendered when the tissue is biopsied. In the context of conjunctivitis, biopsy is usually performed when inflammation is chronic and recalcitrant to therapy, has clinically atypical features, or requires an etiologic diagnosis when one cannot be reached through other laboratory methods. The exclusion of ocular surface neoplasia in a chronically inflamed conjunctiva is a common justification for biopsy. When inflammation is the principal histopathology finding, it is desirable-whenever feasible-to establish the cause. This brief review provides a guide in how histologic findings of an inflamed conjunctiva can direct the clinical evaluation towards an etiologic diagnosis.</p>","PeriodicalId":7305,"journal":{"name":"Advances In Anatomic Pathology","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2023-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10857681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}