Advances In Anatomic Pathology最新文献

Penile squamous cell carcinomas (pSCC) are broadly divided into two subgroups based on their etiopathogenesis: Human Papillomavirus (HPV)-associated and HPV-independent. HPV-associated pSCC is driven by high-risk HPV and commonly overexpresses p16 by immunohistochemistry (IHC), making it a widely used surrogate for HPV presence. HPV-associated pSCC encompasses multiple histologic subtypes, including basaloid, warty, mixed (warty-basaloid), clear cell, lymphoepithelioma-like, and medullary carcinomas. Although most of these have a distinct morphology, a "block" or "diffuse" staining pattern of p16 IHC is recommended for categorically classifying them as HPV-associated pSCC. Molecular diagnostics (e.g., HPV DNA or RNA assays) are rarely employed for the classification of pSCC. The prognostic relevance of HPV status and p16 overexpression remains under investigation, but preliminary findings suggest that HPV-associated / p16-positive tumors may have a more favorable prognosis, with better survival outcomes, and may also dictate the choice of therapy in advanced cases. Larger multicentric datasets from regions of higher incidence, harmonized criteria for p16 IHC interpretation, and standardized HPV detection methods are needed to further understand the utility of these biomarkers in pSCC. Finally, the relevance and impact of HPV vaccination on HPV-associated pSCC are not well documented, largely because male vaccination is not yet accepted globally.

Hereditary renal cancer syndromes account for approximately 5% to 8% of all renal cell carcinomas (RCCs) and are caused by germline alterations, mainly in tumor suppressor genes. Advances in molecular testing have led to the identification of new hereditary syndromes and expanded our understanding of the genetic landscape of renal neoplasia. This review summarizes both well-established and recently described hereditary renal cancer syndromes, highlighting their clinical, pathologic, and molecular features. Emphases are placed on genotype-phenotype correlations and the relationship between germline and somatic alterations in tumors. Understanding these correlations is critical for diagnosis, risk assessment, surveillance, and management and underscores the importance of a high index of clinical suspicion for early detection to optimize patient outcomes.

The Dublin ISUP Consensus Conference covered the proceedings on the best practice recommendations on nonurachal glandular lesions of the urinary bladder, bladder diverticular cancers, and molecular features of bladder and urachal glandular lesions. The conference proceedings on urachal neoplasms (except for their molecular features) are published elsewhere. The rationale for convening this conference was the lack of structured and consented pathologic recommendations in these rare lesions. Consensus by participants was reached on the following statements: (1) intestinal metaplasia with dysplasia is considered to be a precursor to primary bladder adenocarcinoma; (2) dysplasia arising from cystitis glandularis should be reported in terms of focality (focal or nonfocal) and grade (low or high); (3) the term "adenocarcinoma" should only be used for carcinomas showing pure (nonurothelial) morphology and should not be used interchangeably in urothelial carcinoma with "glandular differentiation" because of the pathobiological differences and management implications; (4) the different histologic subtypes of bladder adenocarcinoma should be specified in the report; (5) immunohistochemistry has an ancillary role in the work up of bladder adenocarcinoma versus gastrointestinal or Müllerian-type adenocarcinomas; (6) lymphovascular invasion should be included as a parameter when reporting bladder adenocarcinoma; (7) representative or targeted sampling will be sufficient for bladder diverticulum resection specimens; and (8) molecular analysis in genomic profiling should be performed only in advanced or metastatic bladder and urachal adenocarcinomas for targetable therapy. This report on glandular (nonurachal) lesions of the bladder from the Dublin ISUP consensus conference will serve as a best practice recommendation and as a guide for future research on these relatively rare lesions.

Pulmonary large cell neuroendocrine carcinoma (LCNEC) represents a controversial entity that has been associated with difficulties for diagnosis. The sources for these difficulties are multiple, including lack of stringent morphologic criteria, variable immunohistochemical profile, and variable molecular profile that share overlap with other tumors of the lung. There appears to exist a spectrum of lesions in the lung that have the potential to overlap with LCNEC, compounding the difficulties inherent in making a diagnosis for what is essentially a rare lesion that most general pathologists have limited experience with. Moreover, the broad definition of LCNEC by the World Health Organization (WHO) has the potential for classifying tumors that may not clearly belong in this group under this category. Herein we will discuss the criteria for light microscopic, immunohistochemical, and molecular diagnostic features of LCNEC along with a discussion of some of the problems encountered in the interpretation of these tumors. The differential diagnosis is also discussed, including tumors that may show similar neuroendocrine-like morphology.

DICER1 plays a crucial role in the biogenesis and maturation of microRNAs. Germline mutations in the DICER1 gene are associated with an increased risk of developing a wide range of benign and malignant neoplasms. The same tumors may also arise sporadically due to somatic DICER1 mutations. In syndromic patients, a germline loss-of-function DICER1 mutation is usually followed by a somatic hotspot mutation in the tumor as a second hit. In the gynecologic tract, DICER1 -associated neoplasms include most commonly embryonal rhabdomyosarcoma and moderately to poorly differentiated Sertoli-Leydig cell tumor, and less frequently pleuropulmonary blastoma-like peritoneal sarcoma, adenosarcoma, gynandroblastoma, juvenile granulosa cell tumor, and Sertoli cell tumor. Irrespective of the primary site of origin, DICER1 -associated neoplasms frequently share characteristic morphology, including primitive mesenchyme, fetal-type epithelium, fetal-type cartilage, rhabdomyoblastic and/or neuroectodermal differentiation, osteoid formation, and anaplasia. Recognition of these distinctive features in gynecologic tumors should prompt consideration of a DICER1 -associated neoplasm followed by genetic testing, thereby facilitating surveillance for patients and their families. As illustrated in this review, the morphologic spectrum of most DICER1 -mutant gynecologic neoplasms (eg, DICER1 -related Wilms-like uterine tumor) appears to be wider than that of any known type of sarcoma. Therefore, we propose that the term " DICER1 -related primitive polyphenotypic neoplasm" may be more inclusive of the diverse histologic features and thus more appropriate for these unique neoplasms.

The occurrence of spindle cell tumors of the pleural other than the conventional sarcomatoid mesothelioma or solitary fibrous tumor, is rather unusual. Clinically and radiologically, patients with these tumors may show similar features as those associated with the more common neoplasms of the pleura. Therefore, histopathologic assessment of those lesions is highly important. However, it is also important to highlight the role that immunohistochemistry plays in separating these tumors, as some of these neoplasms may show similar immunophenotype with mesothelioma. Even though in most of these cases, the use of immunohistochemistry can provide valid information to properly separate these tumors, in some more unusual circumstances, the use of molecular techniques may further aid in the characterization of these tumors. Nevertheless, it is highly important not only to acknowledge the existence of these tumors arising primarily in the pleura but also to keep them in the differential diagnosis of primary spindle cell neoplasms of the pleura.

Hemangioblastoma-like clear cell stromal tumor (HLCCST) of the lung is an exceptionally rare mesenchymal neoplasm that is generally considered benign. Current knowledge of this tumor remains limited. Histologically, HLCCST is defined by a hypervascular stroma with dilated blood vessels and is predominantly composed of epithelial-like cells arranged in solid sheets or nests with uniform morphology. Molecular genetic studies have identified YAP1::TFE3 gene fusions as a hallmark in most reported cases. To date, in addition to our case, a total of 19 HLCCST cases have been reported across 7 publications. Here, we present a comprehensive review of HLCCST, detailing its clinicopathologic features, key molecular alterations, and prognostic data of HLCCST. In addition, we emphasize the importance of accurate recognition and diagnosis of this rare tumor to ensure appropriate treatment and improved patient outcomes.

Laryngectomy margin assessment is an important part of patient care and can affect outcomes. There is no standard approach to grossing laryngectomy specimens, with variations in the published guidelines. A uniform approach to margin assessment may be helpful to improve patient care and future research. At the very least, sampling of all mucosal margins (arytenoid area, hypopharyngeal, and anterior epiglottis) and tracheal margin should be performed. Sampling of soft tissue margins may be delegated to the pathologist, and contingent on the tumor extent into soft tissue. If a tracheostomy is present, skin and soft tissue margins should be sampled from the stoma. This review provides a template for laryngectomy margin assessment and can be used as a guideline as to which margins should be assessed.

Steatotic liver disease (SLD) is now used as an overarching category encompassing five subcategories: metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic and alcohol related/associated liver disease (MetALD), alcohol-related/associated liver disease (ALD), SLD with specific etiology, and cryptogenic SLD. This review summarizes foundational and recent advances in the histologic evaluation of SLD, including common pathologic features across all subcategories, distinctions associated with different etiologies, scoring and grading systems, and the evolution of digital pathology techniques for SLD assessment.