Advances In Anatomic Pathology最新文献

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. The classification further indicates that, in contrast to endocervical adenocarcinomas, HPVI and HPVA SCCs cannot be distinguished by morphological criteria alone and suggests that HPV testing or correlates thereof are required for correct classification. Moreover, while HPVA SCC precursor lesions (ie, high-grade squamous intraepithelial lesion) are well known and characterized, precursors to HPVI SCCs have only been described recently in a small number of cases. We studied 670 cases of SCCs from the International Squamous Cell Carcinoma Project (ISCCP) to analyze the reproducibility of recognition of invasive SCC growth patterns, presence of lymphovascular space invasion, tumor grade, and associations with patient outcomes. Consistent with previous studies, we found histologic growth patterns and tumor types had limited prognostic implications. In addition, we describe the wide morphologic spectrum of HPVA and HPVI SCCs and their precursor lesions, including tumor growth patterns, particular and peculiar morphologic features that can lead to differential diagnoses, and the role of ancillary studies in the diagnosis of these tumors.

The standard of care for invasive cancers of the breast has been and continues to be to evaluate them for breast prognostic markers: estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 by immunohistochemistry. Over 2 decades ago, a study was the first to report on the molecular subtypes of breast cancer. Four main subtypes were reported. Since then there have been some changes in the molecular subtype classification, but overall many studies have shown that this subtyping has clinical prognostic and predictive value. More recently, molecular assays have been developed and studies have shown similar clinical prognostic and predictive value. We reviewed the literature for studies evaluating the clinical significance of all 3 of these methods of evaluation and the follow-up findings of that review are presented below.

As the leading cause of cancer morbidity and the second leading cause of cancer mortality among women, breast cancer continues to remain a major global public health problem. Consequently, significant attention has been directed toward early breast cancer detection and prevention. As a result, the number of image-detected biopsies has increased, and minimally invasive diagnostic procedures have almost replaced open surgical biopsies. Therefore, pathologists are expected to provide more information with less tissue and diagnose increasing numbers of atypical proliferative breast lesions, in situ lesions, and small breast carcinomas. This is a difficult task, as reflected by continuous reports highlighting the challenges associated with morphologic distinction between atypical ductal hyperplasia and low-grade ductal carcinoma in situ. The current interobserver variability among pathologists to accurately define these two entities often leads to silent overdiagnosis and overtreatment. Up to now, there are no reproducible morphologic features and/or any reliable biomarkers that can accurately separate the above-mentioned entities. Despite these reports, patients diagnosed with low-grade ductal carcinoma in situ are subject to cancer therapy regardless of the fact that low-grade ductal carcinoma in situ is known to be an indolent lesion. Studies have shown that low and high-grade ductal carcinoma in situ are genetically different forms of breast cancer precursors; however, the term ductal carcinoma in situ is followed by cancer therapy regardless of the grade and biology of the tumor. In contrast, patients with the diagnoses of atypical ductal hyperplasia do not undergo cancer therapy. In the current article, attempts are made to highlight the continuous dilemma in distinction between atypical ductal hyperplasia and low-grade ductal carcinoma in situ. Going forward, we suggest that low-grade ductal carcinoma in situ be referred to as ductal neoplasia. This alternative terminology allows for different management and follow-up strategies by eliminating the word carcinoma.

Pathology clinical practice has evolved by adopting technological advancements initially regarded as potentially disruptive, such as electron microscopy, immunohistochemistry, and genomic sequencing. Breast pathology has a critical role as a medical domain, where the patient's pathology diagnosis has significant implications for prognostication and treatment of diseases. The advent of digital and computational pathology has brought about significant advancements in the field, offering new possibilities for enhancing diagnostic accuracy and improving patient care. Digital slide scanning enables to conversion of glass slides into high-fidelity digital images, supporting the review of cases in a digital workflow. Digitization offers the capability to render specimen diagnoses, digital archival of patient specimens, collaboration, and telepathology. Integration of image analysis and machine learning-based systems layered atop the high-resolution digital images offers novel workflows to assist breast pathologists in their clinical, educational, and research endeavors. Decision support tools may improve the detection and classification of breast lesions and the quantification of immunohistochemical studies. Computational biomarkers may help to contribute to patient management or outcomes. Furthermore, using digital and computational pathology may increase standardization and quality assurance, especially in areas with high interobserver variability. This review explores the current landscape and possible future applications of digital and computational techniques in the field of breast pathology.

Some histologic special types of breast carcinoma harbor specific recurrent genetic alterations that are not seen in other types of breast carcinoma (no special type), namely adenoid cystic carcinoma, secretory carcinoma, and tall cell carcinoma with reversed polarity. These tumors have unique morphologic features, are triple-negative, that is, do not express hormone receptors or HER2, and are generally associated with a favorable prognosis. Adenoid cystic carcinoma, like its counterpart in other organs, shows a MYB-NFIB fusion gene that is the result of a recurrent t(6;9)(q22-23;p23-24) translocation. Other MYB alterations have been described that result in overexpression of MYB . Secretory carcinoma is characterized by an ETV6-NTRK3 gene fusion that is the result of recurrent (12;15);(p13;q25) translocation, which is also seen in mammary analog secretory carcinoma of the salivary gland. Tall cell carcinoma with reversed polarity shows IDH2 p.Arg172 hotspot mutations. Immunohistochemical antibodies have emerged that identify the underlying genetic alterations in these tumors and serve as useful diagnostic tools. This review will provide an update on the molecular features and diagnostic immunohistochemical markers that have become increasingly popular to aid in diagnosing these uncommon triple-negative breast tumors.

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. In addition the American Society of Clinical Oncology-College of American Pathologists (ASCO-CAP) recently updated their HER2 Guidelines Recommendations to specifically address HER2-low BC. A literature search in PubMed of peer-reviewed articles, regulatory communications, and relevant practice guidelines pertaining to HER2-low BC was conducted. In this review, we have summarized current published knowledge regarding the clinicopathologic and molecular features, diagnostic criteria, and most current guideline recommendations regarding HER2-low BC, and also highlight ongoing practical and diagnostic challenges when identifying HER2-low BC in routine clinical practice.

Because of the unique anatomic structure of the nipple, a few specific breast lesions occur only at this site. Large lactiferous sinuses may be involved by inflammatory conditions such as squamous metaplasia of lactiferous ducts and ductal ectasia or be the site of uncommon superficial epithelial neoplasms such as nipple adenoma or syringomatous tumor of the nipple. Paget disease of the nipple may be secondary to intraepidermal extension of ductal carcinoma in situ in the underlying lactiferous ducts or develop from malignant transformation of Toker cells. Invasive breast cancer may also arise primarily in the nipple. Most of these conditions present as a palpable mass and/or skin changes with or without nipple discharge. Due to the delicate location and often relatively small size of nipple lesions, biopsy specimens are often superficial and fragmented, and the interpretation is challenging. Knowledge of the morphologic and immunophenotypic features of nipple lesions is essential in making the correct diagnosis. Information on the molecular alterations underpinning nipple neoplasms is currently very limited.

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. A review of the current diagnostic challenge, proposed ancillary studied and their value in prognostic significance, is provided. This article highlights the most recent molecular and genetic findings as well as the limitations of the studies, in the context of practical and available applications for the diagnostician and managerial implications for the clinician.