Advances in Anatomic Pathology

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STK11 adnexal tumor is a novel malignant neoplasm of uncertain histogenesis frequently arising in a para-adnexal location and associated with Peutz-Jeghers syndrome in ∼50% of patients. Its broad morphologic spectrum and nonspecific immunohistochemical profile has resulted in misclassification in the past as a variety of other neoplasms including those of wolffian, sex cord-stromal, mesothelial, and epithelial derivation. This review focuses on the spectrum of adnexal neoplasms that may develop in Peutz-Jeghers syndrome, with particular emphasis on STK11 adnexal tumor and its differential diagnosis...

Very early onset inflammatory bowel disease (VEO-IBD) is a clinical term referring to IBD-like symptomatology arising in children younger than 6 years. VEO-IBD may be due to polygenic etiology in "pure" IBD (Crohn disease-CD and ulcerative colitis-UC), or it may be caused by primary immunodeficiency underlined by monogenic disease. Primary immunodeficiency monogenic diseases have a Mendelian inheritance and affect the immune system with multiorgan morbidity and possible effects on the gastrointestinal system...

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This manuscript provides a comprehensive overview of the application of artificial intelligence (AI) in lung pathology, particularly in the diagnosis of lung cancer. It discusses various AI models designed to support pathologists and clinicians. AI models supporting pathologists are to standardize diagnosis, score PD-L1 status, supporting tumor cellularity count, and indicating explainability for pathologic judgements. Several models predict outcomes beyond pathologic diagnosis and predict clinical outcomes like patients' survival and molecular alterations...

Immunohistochemical (IHC) staining represents a comparatively inexpensive testing method that is attractive as a potential alternative to molecular sequencing methods or fluorescence in situ hybridization for pulmonary biomarker testing. While a variety of IHC tests directed at actionable genetic alterations have been developed and evaluated since the advent of targeted therapy, specific antibody clones for anaplastic lymphoma kinase, ROS-1, and potentially neurotrophic tropmyosin receptor kinase have been the primary antibodies that provide sufficiently robust results to be utilized as either a primary testing or screening method to direct targeted therapy...

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This is the first systematic review and meta-analysis of The International System (TIS) for reporting serous fluid cytopathology. Our aims were to present the pooled malignancy rate of each TIS reporting category and the diagnostic accuracy of cytology using this system. Database search using a predefined strategy was followed by study selection, data extraction, study quality assessment, and statistical analysis. Data derived from 16 eligible studies were pooled. The pooled rates of malignancy were as follows: 27% (95% CI; 16%-41%) for "nondiagnostic" (ND), 11% (95% CI; 7%-18%) for negative for malignancy" (NFM), 49% (95% CI; 37%-61%) for "atypia of undetermined significance" (AUS), 90% (95% CI; 81%-95%) for "suspicious for malignancy" (SFM), and 100% (95% CI; 98%-100%) for "positive for malignancy" (MAL)...

We review the time honored but still frequently challenging features of ovarian sex cord-stromal tumors and also emphasize new developments, including unusual morphologic appearances that, despite the relative rarity of many of the tumors, result in a disproportionate number of differential diagnostic problems, variant immunohistochemical profiles, and specific molecular and syndromic associations. These neoplasms are also of historical interest as current knowledge is still based in significant part to the contributions of 2 giants of gynecologic pathology, Dr Robert Meyer and Dr...

In two separate reviews, we review the time-honored but still frequently challenging features of ovarian sex cord-stromal tumors, and also emphasize new developments including unusual morphologic appearances that, despite the relative rarity of many of the tumors, result in a disproportionate number of differential diagnostic problems, variant immunohistochemical profiles, and specific molecular and syndromic associations. These neoplasms are also of historical interest as current knowledge is still based in significant part on the contributions of 2 giants of gynecologic pathology, Dr Robert Meyer and Dr Robert E...

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Reproducibility of pulmonary invasive adenocarcinoma diagnosis is poor when applying the World Health Organization (WHO) classification. In this article, we aimed first to explain by 3-dimensional morphology why simple pattern recognition induces pitfalls for the assessment of invasion as applied in the current WHO classification of pulmonary adenocarcinomas. The underlying iatrogenic-induced morphologic alterations in collapsed adenocarcinoma in situ overlap with criteria for invasive adenocarcinoma. Pitfalls in seemingly acinar and papillary carcinoma are addressed with additional cytokeratin 7 and elastin stains...

The increasing incidence of multiple lung nodules underscores the need for precise differentiation between multiple primary lung cancers (MPLCs) and intrapulmonary metastases (IPMs). This distinction impacts patient prognosis and treatment strategies. The prevalence of multiple lung nodules, ranging from 19.7% to 55.5%, highlights the clinical significance of this challenge. Historically, the role of histopathology, particularly comprehensive histology assessment (CHA), has been pivotal in differentiating MPLCs and IPMs...

The diagnosis and reporting of prostatic adenocarcinoma have evolved from the classic framework promulgated by Dr Donald Gleason in the 1960s into a complex and nuanced system of grading and reporting that nonetheless retains the essence of his remarkable observations. The criteria for the "Gleason patterns" originally proposed have been continually refined by consensuses in the field, and Gleason scores have been stratified into a patient-friendly set of prognostically validated and widely adopted Grade Groups...

The NKX3.1 immunohistochemical stain is widely recognized as a highly sensitive and specific marker for prostate adenocarcinoma. Nevertheless, its expression has been documented in various nonprostatic tissues and malignancies. This review aims to provide an overview of NKX3.1 expression in diverse tumor types, with a specific focus on its aberrant expression in esophageal/gastroesophageal adenocarcinoma (E/GE-ADC). In our investigation, we explored the expression of NKX3.1 in a series of E/GE-ADC to shed light on its prevalence in this tumor category...

Papillary renal cell carcinoma classification has evolved as a result of attentive morphologic observations by pathologists coupled with specific immunohistochemical, molecular, and clinical data. Refinement of this relatively common diagnostic category of renal neoplasia has resulted in the parsing out of specific renal cell carcinoma subtypes that no longer belong in the papillary renal cell carcinoma category and can have distinct familial and prognostic implications (eg, fumarate hydratase (FH)-deficient renal cell carcinomas)...

Histologic grading of tumors is associated with prognosis in many organs. In the lung, the most recent grading system proposed by International association for the Study of Lung Cancer (IASLC) and adopted by the World Health Organization (WHO) incorporates the predominant histologic pattern, as well as the presence of high-grade architectural patterns (solid, micropapillary, and complex glandular pattern) in proportions >20% of the tumor surface. This system has shown improved prognostic ability when compared with the prior grading system based on the predominant pattern alone, across different patient populations...

Uterine smooth muscle tumors are a heterogeneous group of mesenchymal neoplasms with multiple histologic variants and distinct biological behaviors. Pathologic classification (benign, uncertain malignant potential, malignant) relies on the evaluation of mitotic index, necrosis, and degree of cytologic atypia, with different thresholds based on each subtype. Immunohistochemistry and other ancillary studies may be necessary to establish the diagnosis in a subset of cases, given the morphologic overlap with other mesenchymal neoplasms, including low-grade and high-grade endometrial stromal tumors, inflammatory myofibroblastic tumors, and PEComa...

Primary gastric leiomyosarcoma is an exceptionally rare disease. This review covers 41 post-gastrointestinal stromal tumor (GIST) era gastric leiomyosarcoma cases that are supported by immunohistochemistry markers. Other spindle cell lesions are also excluded through histological and immunohistochemistry evaluations. The patients range from 3 to 82 years old, with an average age of 54.6 years. The male-to-female ratio is 1.4:1, from diverse geographic areas. Patients may experience abdominal symptoms, and tumor sizes vary between 1 cm and 22 cm...

Uterine mesenchymal neoplasms are a challenging group of tumors that often show overlapping morphologic features and immunohistochemical profiles. The increasing use of molecular testing in these tumors has enabled a better appreciation of their pathobiology, resulting in a wave of emerging neoplasms and improved characterization of ones previously considered exceptionally rare. Identification of specific molecular alterations has permitted targeted therapy options in tumors that were typically unresponsive to conventional therapies, as well as recognition that a subset can have a hereditary basis...