Advances In Anatomic Pathology最新文献

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.

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.

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.

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.

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.

Salivary gland intraductal carcinoma (IDC) is a very uncommon group of neoplasms. Many names, variations in diagnostic criteria, and newly observed molecular findings (including NCOA4 :: RET , TRIM27 :: RET , HRAS point mutations, and PIK3CA pathway alterations) have generated further confusion in being able to recognize and categorize this group of tumors. Different histologic appearances and patterns of growth suggest there is more than one tumor category, with intercalated duct, apocrine, oncocytic, and hybrid features seen. Frankly destructive invasion further complicates the category, as the name "intraductal" would suggest an "in situ" neoplasm. Recent evidence on fusion-positive IDC demonstrates the same molecular underpinnings in both the ductal and the myoepithelial cells, which aids in further separating these tumors. This article summarizes the historical group of 183 neoplasms classified under the umbrella of IDC and highlights the unique histologic, immunohistochemistry, and molecular features that may further guide nomenclature standardization and harmonization.

The classification of poorly differentiated sinonasal carcinomas and their nonepithelial mimics has experienced tremendous developments during the last 2 decades. These recent developments paved the way for an increasingly adopted approach to a molecular-based or etiology-based refined classification of the many carcinoma variants that have been historically lumped into the sinonasal undifferentiated carcinoma category. Among these new achievements, recognition of carcinoma subtypes driven by defects in the Switch/Sucrose nonfermentable (SWI/SNF) chromatin remodeling complex represents a major highlight. This resulted in a new definition of 4 sinonasal entities driven solely or predominantly by Switch/Sucrose nonfermentable complex deficiency: (1) SMARCB1(INI1)-deficient sinonasal carcinoma (lacking gland formation and frequently displaying a non-descript basaloid, and less frequently eosinophilic/oncocytoid morphology, but no features of other definable subtypes), (2) SMARCB1-deficient sinonasal adenocarcinoma (with unequivocal glands or yolk sac-like pattern), (3) SMARCA4-deficient undifferentiated (sinonasal undifferentiated carcinoma-like) carcinoma (lacking glandular or squamous immunophenotypes), and (4) SMARCA4-deficient subset (~80%) of sinonasal teratocarcinosarcoma. Fortunately, diagnostic loss of all these proteins can be detected by routine immunohistochemistry, so that genetic testing is not mandatory in routine practice. This review summarizes the main demographic, clinicopathological, and molecular features of these new entities.

Thyroblastoma is a novel thyroid malignancy included in the 5th Edition WHO Classification of Endocrine and Neuroendocrine Tumours. The majority of tumors now classified as thyroblastoma were originally regarded to be malignant thyroid teratomas. However, these neoplasms were recently recognized as a separate entity based on a distinctive constellation of primitive multilineage elements, including immature thyroid epithelium, undifferentiated or rhabdomyoblastic spindle cell proliferations, and neuroepithelial blastema, as well as recurrent DICER1 hotspot mutations. Thyroblastoma is an aggressive tumor that leads to death from disease in ~50% of patients, making it essential to differentiate this entity from a wide range of other thyroid tumors that show overlapping histologic features or DICER1 mutations. This review aims to provide a practical overview of the background, clinicopathologic features, molecular underpinnings, and differential diagnosis of this recently-described and molecularly-defined entity.