Journal•ISSN: 1072-4109
Advances in Anatomic Pathology
Lippincott Williams & Wilkins
About: Advances in Anatomic Pathology is an academic journal published by Lippincott Williams & Wilkins. The journal publishes majorly in the area(s): Medicine & Cancer. It has an ISSN identifier of 1072-4109. Over the lifetime, 1265 publications have been published receiving 40713 citations.
Topics: Medicine, Cancer, Carcinoma, Breast cancer, Internal medicine
Papers published on a yearly basis
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716 citations
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677 citations
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TL;DR: An update is provided on the pathogenesis and clinicopathologic features of these 2 types of serous carcinomas and addresses some of the diagnostic problems that are encountered in routine practice.
Abstract: Ovarian serous carcinomas have been graded using various systems. Recently, a 2-tier system in which tumors are subdivided into low-grade and high-grade has been proposed. This approach is simplistic, reproducible, and based on biologic evidence indicating that both tumors develop via different pathways. Low-grade serous carcinomas exhibit low-grade nuclei with infrequent mitotic figures. They evolve from adenofibromas or borderline tumors, have frequent mutations of the KRAS, BRAF, or ERBB2 genes, and lack TP53 mutations (Type I pathway). The progression to invasive carcinoma is a slow step-wise process. Low-grade tumors are indolent and have better outcome than high-grade tumors. In contrast, high-grade serous carcinomas have high-grade nuclei and numerous mitotic figures. Identification of a precursor lesion in the ovary has been elusive and therefore the origin of ovarian carcinoma has been described as de novo. More recently, studies have suggested that a proportion appear to originate from intraepithelial carcinoma in the fallopian tube. The development of these tumors is rapid (Type II pathway). The vast majority are characterized by TP53 mutations and lack mutations of KRAS, BRAF, or ERBB2. Although both types of serous carcinomas evolve along different pathways, rare high-grade serous carcinomas seem to arise through the Type I pathway. Immunohistochemical stains for p53, p16, and Ki-67 for distinction of low- from high-grade tumors are of limited value but can be helpful in selected instances. This review provides an update on the pathogenesis and clinicopathologic features of these two types of serous carcinomas and addresses some of the diagnostic problems that are encountered in routine practice.
538 citations
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University of Melbourne1, Université libre de Bruxelles2, Katholieke Universiteit Leuven3, St. Vincent's Health System4, University of Victoria5, La Trobe University6, Royal Melbourne Hospital7, Netherlands Cancer Institute8, University of California, San Diego9, Vanderbilt University10, Peter MacCallum Cancer Centre11, University of Antwerp12, University of Paris13, French Institute of Health and Medical Research14, Medical University of Vienna15, Cornell University16, University of Texas MD Anderson Cancer Center17, Mayo Clinic18, University of Queensland19, Royal Brisbane and Women's Hospital20, Harvard University21, Novartis22, Indiana University – Purdue University Indianapolis23, Fred Hutchinson Cancer Research Center24, University of Milan25, University of Auvergne26, Kansai Medical University27, Yeshiva University28, Yonsei University29, Brown University30, Rhode Island Hospital31, Curie Institute32, Charité33, Yale University34, University of British Columbia35, Garvan Institute of Medical Research36, Université Paris-Saclay37, Autonomous University of Madrid38, University of Ottawa39, National Institutes of Health40, New York University41, University of Adelaide42, Stanford University43, Anschutz Medical Campus44, University of Padua45, European Organisation for Research and Treatment of Cancer46, Medical University of Graz47, Hoffmann-La Roche48, Genentech49, MedImmune50, Merck & Co.51, Memorial Sloan Kettering Cancer Center52
TL;DR: Standardization of TIL assessment will help clinicians, researchers and pathologists to conclusively evaluate the utility of this simple biomarker in the current era of immunotherapy.
Abstract: Assessment of the immune response to tumors is growing in importance as the prognostic implications of this response are increasingly recognized, and as immunotherapies are evaluated and implemented in different tumor types. However, many different approaches can be used to assess and describe the immune response, which limits efforts at implementation as a routine clinical biomarker. In part 1 of this review, we have proposed a standardized methodology to assess tumor-infiltrating lymphocytes (TILs) in solid tumors, based on the International Immuno-Oncology Biomarkers Working Group guidelines for invasive breast carcinoma. In part 2 of this review, we discuss the available evidence for the prognostic and predictive value of TILs in common solid tumors, including carcinomas of the lung, gastrointestinal tract, genitourinary system, gynecologic system, and head and neck, as well as primary brain tumors, mesothelioma and melanoma. The particularities and different emphases in TIL assessment in different tumor types are discussed. The standardized methodology we propose can be adapted to different tumor types and may be used as a standard against which other approaches can be compared. Standardization of TIL assessment will help clinicians, researchers and pathologists to conclusively evaluate the utility of this simple biomarker in the current era of immunotherapy.
477 citations
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TL;DR: An elevated serum titer of immunoglobulin G4 (IgG4), the least common of the 4 subclasses of IgG, is a surrogate marker for the recently characterized IgG4-related sclerosing disease, which affects predominantly middle-aged and elderly patients, with male predominance.
Abstract: An elevated serum titer of immunoglobulin G4 (IgG4), the least common (3% to 6%) of the 4 subclasses of IgG, is a surrogate marker for the recently characterized IgG4-related sclerosing disease. The syndrome affects predominantly middle-aged and elderly patients, with male predominance. The patients present with symptoms referable to the involvement of 1 or more sites, usually in the form of mass lesions. The prototype is IgG4-related sclerosing pancreatitis (also known as autoimmune pancreatitis), most commonly presenting as painless obstructive jaundice with or without a pancreatic mass. Other common sites of involvement are the hepatobiliary tract, salivary gland, orbit, and lymph node, but practically any organ-site can be affected, such as retroperitoneum, aorta, mediastinum, soft tissue, skin, central nervous system, breast, kidney, prostate, upper aerodigestive tract, and lung. The patients usually have a good general condition, with no fever or constitutional symptoms. Common laboratory findings include raised serum globulin, IgG, IgG4, and IgE, whereas lactate dehydrogenase is usually not raised. Some patients have low titers of autoantibodies (such as antinuclear antibodies and rheumatoid factor). The disease often shows excellent response to steroid therapy. The natural history is characterized by the development of multiple sites of involvement with time, sometimes after many years. However, the disease can remain localized to 1 site in occasional patients. The main pathologic findings in various extranodal sites include lymphoplasmacytic infiltration, lymphoid follicle formation, sclerosis and obliterative phlebitis, accompanied by atrophy and loss of the specialized structures of the involved tissue (such as secretory acini in pancreas, salivary gland, or lacrimal gland). The relative predominance of the lymphoplasmacytic and sclerotic components results in 3 histologic patterns: pseudolymphomatous, mixed, and sclerosing. Immunostaining shows increased IgG4+ cells in the involved tissues (>50 per high-power field, with IgG4/IgG ratio >40%). The lymph nodes show multicentric Castleman disease-like features, reactive follicular hyperplasia, interfollicular expansion, or progressive transformation of germinal centers, with the unifying feature being an increase in IgG4+ plasma cells on immunostaining. The nature and pathogenesis of IgG4-related sclerosing disease are still elusive. Occasionally, the disease can be complicated by the development of malignant lymphoma and possibly carcinoma.
426 citations