Advances in Anatomic Pathology

The classification of thymoma continues to be a source of controversy in pathology. The difficulties in histologic classification are evident from the number of proposals that have been offered over the years, as well as for the continuous changes and modifications introduced by the World Health Organization to their classification system over the past 20 years. We analyze here some of the issues involved in the classification of these tumors and the difficulties encountered for practicing pathologists in deciphering the "letters and numbers" system devised by the World Health Organization...

Cervical cancer is the fourth most common cancer among women globally. Historically, human papillomavirus (HPV) infection was considered necessary for the development of both precursor and invasive epithelial tumors of the cervix; however, studies in the last decade have shown that a significant proportion of cervical carcinomas are HPV-independent (HPVI). The 2020 World Health Organization (WHO) Classification of Female Genital Tumors separates both squamous cell carcinomas (SCCs) and endocervical adenocarcinomas (ECAs) by HPV status into HPV-associated (HPVA) and HPVI tumors...

This article reviewed the identification of breast cancer in the distant metastatic setting through traditional immunohistochemical markers, such as mammaglobin and GATA3, compared with the novel immunohistochemical stain, Trichorhinophalangeal syndrome-1 (TRPS1). We review previous studies evaluating TRPS1 staining, which were conducted using cytology specimens, as well as our recently conducted study evaluating this stain using surgical tissue samples, both from primary and distant metastatic invasive breast carcinoma...

In response to recent clinical trials that demonstrate the clinical benefit of antibody-drug conjugate drug therapy in breast cancer (BC) with human epidermal growth factor 2 (HER2) immunohistochemical scores of 1+ or 2+ and negative in situ hybridization results, a new concept of "HER2-low BC" has emerged to describe this newly relevant therapeutic category of BC. Clinical recognition of HER2-low BC has caused a paradigm shift in the therapeutic landscape and management of patients with BC and resulted in rapid changes in clinical practice guidelines...

Fibroepithelial lesions of the breast encompass a broad spectrum of lesions from fibroadenomas and their variants to phyllodes tumors, including their clinical range of benign, borderline, and malignant. Classification of this spectrum of neoplasms has historically and currently been based purely on morphology, although the nomenclature has shifted over the years largely due to the significant histologic overlap that exists primarily within the cellular fibroadenomas to borderline malignant phyllodes tumor categories...

Large Language Models are forms of artificial intelligence that use deep learning algorithms to decipher large amounts of text and exhibit strong capabilities like question answering and translation. Recently, an influx of Large Language Models has emerged in the medical and academic discussion, given their potential widespread application to improve patient care and provider workflow. One application that has gained notable recognition in the literature is ChatGPT, which is a natural language processing "chatbot" technology developed by the artificial intelligence development software company OpenAI...

Social media use in pathology has continued to grow and become more mainstream among pathologists, trainees, and medical students over the past decade. Twitter has historically been (and still seems to be) a positive platform for the social media pathology community to engage with each other virtually (ie, PathTwitter). However, as a new era of Twitter leadership began to unfold in October 2022, a young platform called "Mastodon" began to gain notice within this community as the hashtag #PathMastodon became prevalent...

World Health Organization cytopathology reporting system systems have proposed for the pancreatobiliary tract, lung, lymph node, and soft tissue aligned with the updates in the World Health Organization classification of Tumor series. Among them, the pancreatobiliary tract and lung specimen reporting system have been published recently and are now a 7-tier and 5-tier category system, respectively, without any subcategorization. World Health Organization reporting systems also encourage the application of ancillary diagnostic tests like cell block preparation, immunocytochemistry, and rapid on-site evaluation for better categorization of specimens and further management, especially in indeterminate (atypical and suspicious for malignancy) and malignant cytology categories...

Mesotheliomas are rare and aggressive tumors that originate from mesothelial cells. Although exceedingly rare, these tumors may occur in children. Different from adult mesotheliomas, however, environmental exposures particularly to asbestos do not appear to play a major role in mesotheliomas in children, in whom specific genetic rearrangements driving these tumors have been identified in recent years. These molecular alterations may increasingly offer opportunities for targeted therapies in the future, which may provide better outcomes for these highly aggressive malignant neoplasms...

Primary pericardial mesothelioma (PM) is a rare tumor arising from the mesothelial cells of the pericardium. It has an incidence of <0.05% and comprises <2% of all mesotheliomas; however, it is the most common primary malignancy of the pericardium. PM should be distinguished from secondary involvement by the spread of pleural mesothelioma or metastases, which are more common. Although data are controversial, the association between asbestos exposure and PM is less documented than that with other mesotheliomas...

A remarkable amount of new information has been generated on peritoneal mesothelioma (PeM), ranging from nomenclature changes, including the removal of "malignant" when referring to this neoplasm and the use of the term "tumor" rather than "mesothelioma" to designate the neoplasm formerly known as "well-differentiated papillary mesothelioma", to the acknowledgment that PeMs can be associated with tumor predisposition syndromes or germline mutations. Although the disease is still more frequently seen in caucasian males, PeM is not uncommon in women...

Pleural mesotheliomas represent one of the most common diagnostic challenges in thoracic pathology. The diagnosis of pleural mesothelioma weighs heavily on clinical and radiologic information. In addition, in the past, before the era of immunohistochemistry, the diagnosis was aided with the use of special histochemical stains-PAS, D-PAS, and mucicarmine, which now very much have been replaced by immunohistochemical stains. In the era of immunohistochemistry, a combination of carcinomatous epitopes and positive mesothelioma markers has become paramount in the diagnosis of mesothelioma, and more recently the use of molecular techniques has become another ancillary tool in supporting such a diagnosis...

Common well-differentiated hepatocellular lesions include focal nodular hyperplasia, focal nodular hyperplasia-like lesions, large regenerative nodule, hepatocellular adenoma, dysplastic nodule, and hepatocellular carcinoma. The term atypical hepatocellular neoplasm/hepatocellular neoplasm of uncertain malignant potential can be used especially in needle core biopsies when a well-differentiated hepatocellular lesion is either histologically atypical (focal reticulin loss, focal cytologic/architectural atypia) or is clinically atypical (male sex or female >50 y) and cannot be confidently classified as adenoma or hepatocellular carcinoma...

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...

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...

Genitourinary malignancies include a broad spectrum of distinct tumor entities occurring in the kidney, the urinary tract, the prostate, the adrenal glands, the penis, and testicles. Each tumor entity presents with unique biological characteristics, especially in terms of immunobiology. The immune landscape of genitourinary malignancies differs between immunoreactive tumors like urothelial carcinoma or carcinomas of the kidney, for which several immunotherapeutic treatment options have been approved in the past years...

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...

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%...

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...

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...