CONTEXT.—: The pathologic diagnosis of pT1 substage in conventional transurethral resection of bladder tumor specimens is inaccurate and has low interobserver reproducibility owing to fragmentation and cauterization of the specimens. En bloc resection of bladder tumor is a novel surgical procedure that improves diagnostic feasibility and accuracy in the pathologic diagnosis of bladder cancer, including depth and extent of invasion. OBJECTIVE.—: To examine the prognostic value of multiple pT1 subclassification methods, using only en bloc resection specimens. DESIGN.—: We examined 106 patients with T1 bladder cancer who underwent en bloc resection. The pT1 substages were assigned by 3 different subclassification methods by using the muscularis mucosae or stalk of the papillary lesion as diagnostic landmarks or millimetric depth of invasion. Intergroup differences in progression-free survival and recurrence-free survival rates were analyzed. The prognostic values of clinicopathologic factors for progression/recurrence were analyzed by using multivariate analysis. RESULTS.—: The pT1 substage was evaluable in all cases. Tumors with invasion into/beyond the muscularis mucosae and those beyond the stalk of the papillary lesion were associated with worse progression-free survival (P = .002 and P = .01, respectively). Notably, no patient with invasion confined to the stalk had disease progression during the 23-month median follow-up period. Only the pT1 subclassification method using the muscularis mucosae was an independent prognosticator of progression in multivariate analysis (P = .03). CONCLUSIONS.—: Precise pathologic subclassification of invasion using en bloc resection specimens may enable accurate prognosis and assessment in patients with bladder cancer with suspicious shallow invasion.

CONTEXT.—: In 2021 the World Health Organization distributed a new classification of central nervous system tumors that incorporated modern testing modalities in the diagnosis. Although universally accepted as a scientifically superior system, this schema has created controversy because its deployment globally is challenging in the best of circumstances and impossible in resource-poor health care ecosystems. Compounding this problem is the significant challenge that neuropathologists with expertise in central nervous system tumors are rare. OBJECTIVE.—: To demonstrate diagnostic use of simple unsupervised machine learning techniques using publicly available data sets. I also discuss some potential solutions to the deployment of neuropathology classification in health care ecosystems burdened by this classification schema. DATA SOURCES.—: The Cancer Genome Atlas RNA sequencing data from low-grade and high-grade gliomas. CONCLUSIONS.—: Methylation-based classification will be unable to solve all diagnostic problems in neuropathology. Information theory quantifications generate focused workflows in pathology, resulting in prevention of ordering unnecessary tests and identifying biomarkers that facilitate diagnosis.

CONTEXT.—: Although the basic principles of intraoperative diagnosis in surgical neuropathology have not changed in the last century, the last several decades have seen dramatic changes in tumor classification, terminology, molecular classification, and modalities used for intraoperative diagnosis. As many neuropathologic intraoperative diagnoses are performed by general surgical pathologists, awareness of these recent changes is important for the most accurate intraoperative diagnosis. OBJECTIVE.—: To describe recent changes in the practice of intraoperative surgical neuropathology, with an emphasis on new entities, tumor classification, and anticipated ancillary tests, including molecular testing. DATA SOURCES.—: The sources for this review include the fifth edition of the World Health Organization Classification of Tumours of the Central Nervous System, primary literature on intraoperative diagnosis and newly described tumor entities, and the authors' clinical experience. CONCLUSIONS.—: A significant majority of neuropathologic diagnoses require ancillary testing, including molecular analysis, for appropriate classification. Therefore, the primary goal for any neurosurgical intraoperative diagnosis is the identification of diagnostic tissue and the preservation of the appropriate tissue for molecular testing. The intraoperative pathologist should seek to place a tumor in the most accurate diagnostic category possible, but specific diagnosis at the time of an intraoperative diagnosis is often not possible. Many entities have seen adjustments to grading criteria, including the incorporation of molecular features into grading. Awareness of these changes can help to avoid overgrading or undergrading at the time of intraoperative evaluation.

CONTEXT.—: Clinician feedback is an important source of information for laboratory quality improvement programs. OBJECTIVE.—: To pilot a program for nearly real-time solicitation and analysis of physician feedback regarding clinical laboratory services. DESIGN.—: Laboratories distributed either electronic or paper survey forms to physicians. Results were tabulated by College of American Pathologists staff. Free-text comments were shared promptly with the participating laboratories to facilitate follow-up. RESULTS.—: Forty-seven clinical laboratories participated in the study and submitted results for 987 physician surveys, including both paper and electronic forms. Of 694 responses submitted electronically within the study period, 460 (66.3%) included at least 1 free-text entry, for a total of 951 free-text comments. CONCLUSIONS.—: Point-of-service solicitation of physician feedback regarding clinical laboratory services is feasible and can provide a substantial quantity of potentially useful information regarding laboratory performance from the customer perspective.

CONTEXT: The World Health Organization classification of tumors of the breast recognizes several special type carcinomas and benign lesions with features comparable to those of salivary gland tumors. OBJECTIVE: To discuss the histologic, immunophenotypic, molecular, and clinical features of salivary gland-like carcinomas of the breast. These breast tumors are often negative for hormone receptors and human epidermal growth factor receptor 2 (HER2), that is, triple-negative, but they generally have a much better prognosis than triple-negative breast carcinomas of no special type. We compare the immunophenotypic, molecular, and clinical features of these breast tumors with their salivary gland counterparts, highlighting similarities and differences. We also discuss benign salivary gland-like breast tumors. Finally, we highlight recent developments in understanding the molecular pathogenesis of these breast tumors and novel ancillary studies that can be used to support their diagnosis. DATA SOURCES: A literature review was conducted, and papers were selected for further analysis and discussion by the authors of this review based on their novelty, applicability, and impact in the field. CONCLUSIONS: Breast tumors that exhibit morphologic overlap with salivary gland tumors have been recognized by pathologists for decades, but the similarities and differences in their molecular pathogenesis have not been understood until more recently. These developments have led to novel diagnostic tools and further knowledge of these rare breast lesions.

CONTEXT.—: Increasing implementation of whole slide imaging together with digital workflow and advances in computing capacity enable the use of artificial intelligence (AI) in pathology, including breast pathology. Breast pathologists often face a significant workload, with diagnosis complexity, tedious repetitive tasks, and semiquantitative evaluation of biomarkers. Recent advances in developing AI algorithms have provided promising approaches to meet the demand in breast pathology. OBJECTIVE.—: To provide an updated review of AI in breast pathology. We examined the success and challenges of current and potential AI applications in diagnosing and grading breast carcinomas and other pathologic changes, detecting lymph node metastasis, quantifying breast cancer biomarkers, predicting prognosis and therapy response, and predicting potential molecular changes. DATA SOURCES.—: We obtained data and information by searching and reviewing literature on AI in breast pathology from PubMed and based our own experience. CONCLUSIONS.—: With the increasing application in breast pathology, AI not only assists in pathology diagnosis to improve accuracy and reduce pathologists' workload, but also provides new information in predicting prognosis and therapy response.

CONTEXT.—: Breast pathology has many mimics and diagnostic pitfalls. Evaluation of malignant breast lesions, particularly in the biopsy setting, can be especially challenging, with diagnostic errors having significant management implications. OBJECTIVE.—: To discuss the pitfalls encountered when evaluating ductal carcinoma in situ and invasive breast carcinomas, providing histologic clues and guidance for appropriate use and interpretation of immunohistochemistry to aid in the correct diagnosis. DATA SOURCES.—: Data were obtained from review of pertinent literature of ductal carcinoma in situ and invasive breast carcinomas and from the experience of the authors as practicing breast pathologists. CONCLUSIONS.—: Awareness of the pitfalls in diagnosing breast cancers is important when creating a differential diagnosis for each breast lesion evaluated. This review will cover some of these scenarios to aid in the diagnostic process.

PURPOSE.—: To update the American Society of Clinical Oncology-College of American Pathologists (ASCO-CAP) recommendations for human epidermal growth factor receptor 2 (HER2) testing in breast cancer. An Update Panel is aware that a new generation of antibody-drug conjugates targeting the HER2 protein is active against breast cancers that lack protein overexpression or gene amplification. METHODS.—: The Update Panel conducted a systematic literature review to identify signals for updating recommendations. RESULTS.—: The search identified 173 abstracts. Of 5 potential publications reviewed, none constituted a signal for revising existing recommendations. RECOMMENDATIONS.—: The 2018 ASCO-CAP recommendations for HER2 testing are affirmed. DISCUSSION.—: HER2 testing guidelines have focused on identifying HER2 protein overexpression or gene amplification in breast cancer to identify patients for therapies that disrupt HER2 signaling. This update acknowledges a new indication for trastuzumab deruxtecan when HER2 is not overexpressed or amplified but is immunohistochemistry (IHC) 1+ or 2+ without amplification by in situ hybridization. Clinical trial data on tumors that tested IHC 0 are limited (excluded from DESTINY-Breast04), and evidence is lacking that these cancers behave differently or do not respond similarly to newer HER2 antibody-drug conjugates. Although current data do not support a new IHC 0 versus 1+ prognostic or predictive threshold for response to trastuzumab deruxtecan, this threshold is now relevant because of the trial entry criteria that supported its new regulatory approval. Therefore, although it is premature to create new result categories of HER2 expression (eg, HER2-Low, HER2-Ultra-Low), best practices to distinguish IHC 0 from 1+ are now clinically relevant. This update affirms prior HER2 reporting recommendations and offers a new HER2 testing reporting comment to highlight the current relevance of IHC 0 versus 1+ results and best practice recommendations to distinguish these often subtle differences. Additional information is available at www.asco.org/breast-cancer-guidelines.

CONTEXT.—: United States' clinical practice guidelines (CPGs) are often produced by professional societies and used worldwide in daily medical practice. However, studies in various medical specialties demonstrate underrepresentation of women and racial and ethnic minority groups in CPGs. The representation of authors by gender, race, and ethnicity of US pathology CPGs has not been previously evaluated. OBJECTIVE.—: To assess if women and individuals from racial and ethnic minority groups are underrepresented as authors of pathology CPGs. DESIGN.—: The gender, race, ethnicity, and terminal degrees of authors of 18 CPGs from the College of American Pathologists were coded by using photographs and other available information online and compared to their representation in academic pathology per Association of American Medical Colleges benchmark data. RESULTS.—: Two hundred seventy-five author positions (202 physician author positions) were analyzed. Women overall (119 of 275; 43.3%) and women physicians (65 of 202; 32.2%) held fewer positions than all men and men physicians. Women physicians were significantly underrepresented in physician author positions, while White men physicians were significantly overrepresented in all, first, senior, and corresponding authorship roles when compared to the proportion of women and White men physicians among pathology faculty, respectively. Asian men and women physicians were underrepresented as compared to their representation among pathology faculty. CONCLUSIONS.—: Men, particularly White men physicians, are overrepresented among pathology CPG author positions, while women physicians and some physicians from racial and ethnic minority groups are underrepresented. Further research is needed to understand the impact of these findings on the careers of underrepresented physicians and the content of guidelines.

CONTEXT.—: Health care providers were surveyed to determine their ability to correctly decipher laboratory test names and their preferences for laboratory test names and result displays. OBJECTIVE.—: To confirm principles for laboratory test nomenclature and display and to compare and contrast the abilities and preferences of different provider groups for laboratory test names. DESIGN.—: Health care providers across different specialties and perspectives completed a survey of 38 questions, which included participant demographics, real-life examples of poorly named laboratory orders that they were asked to decipher, an assessment of vitamin D test name knowledge, their preferences for ideal names for tests, and their preferred display for test results. Participants were grouped and compared by profession, level of training, and the presence or absence of specialization in informatics and/or laboratory medicine. RESULTS.—: Participants struggled with poorly named tests, especially with less commonly ordered tests. Participants' knowledge of vitamin D analyte names was poor and consistent with prior published studies. The most commonly selected ideal names correlated positively with the percentage of the authors' previously developed naming rules (R = 0.54, P < .001). There was strong consensus across groups for the best result display. CONCLUSIONS.—: Poorly named laboratory tests are a significant source of provider confusion, and tests that are named according to the authors' naming rules as outlined in this article have the potential to improve test ordering and correct interpretation of results. Consensus among provider groups indicates that a single yet clear naming strategy for laboratory tests is achievable.

CONTEXT.—: The nature and associations of gallbladder (GB) "adenomyoma" (AM) remain controversial. Some studies have attributed up to 26% of GB carcinoma to AMs. OBJECTIVE.—: To examine the true frequency, clinicopathologic characteristics, and neoplastic changes in GB AM. DESIGN.—: Cholecystectomy cohorts analyzed were 1953 consecutive cases, prospectively with specific attention to AM; 2347 consecutive archival cases; 203 totally embedded GBs; 207 GBs with carcinoma; and archival search of institutions for all cases diagnosed as AM. RESULTS.—: Frequency of AM was 9.3% (19 of 203) in totally submitted cases but 3.3% (77 of 2347) in routinely sampled archival tissue. A total of 283 AMs were identified, with a female to male ratio = 1.9 (177:94) and mean size = 1.3 cm (range, 0.3-5.9). Most (96%, 203 of 210) were fundic, with formed nodular trabeculated submucosal thickening, and were difficult to appreciate from the mucosal surface. Four of 257 were multifocal (1.6%), and 3 of 257 (1.2%) were extensive ("adenomyomatosis"). Dilated glands (up to 14 mm), often radially converging to a point in the mucosa, were typical. Muscle was often minimal, confined to the upper segment. Nine of 225 (4%) revealed features of a duplication. No specific associations with inflammation, cholesterolosis, intestinal metaplasia, or thickening of the uninvolved GB wall were identified. Neoplastic change arising in AM was seen in 9.9% (28 of 283). Sixteen of 283 (5.6%) had mural intracholecystic neoplasm; 7 of 283 (2.5%) had flat-type high-grade dysplasia/carcinoma in situ. Thirteen of 283 cases had both AM and invasive carcinoma (4.6%), but in only 5 of 283 (1.8%), carcinoma was arising from AM (invasion was confined to AM, and dysplasia was predominantly in AM). CONCLUSIONS.—: AMs have all the features of a malformative developmental lesion, and may not show a significant muscle component; (ie, the name "adeno-myoma" is partly a misnomer). While most are innocuous, some pathologies may arise in AMs, including intracholecystic neoplasms, flat-type high-grade dysplasia or carcinoma in situ and invasive carcinoma (1.8%, 5 of 283). It is recommended that gross examination of GBs include serial slicing of the fundus for AM detection and total submission if one is found.

CONTEXT.—: Noninvasive papillary urothelial carcinomas (PUCs) comprise most urinary bladder tumors. Distinction between low-grade (LG-PUC) and high-grade (HG-PUC) PUCs is pivotal for determining prognosis and subsequent treatment. OBJECTIVE.—: To investigate the histologic characteristics of tumors with borderline features between LG-PUC and HG-PUC, focusing on the risk of recurrence and progression. DESIGN.—: We reviewed the clinicopathologic parameters of noninvasive PUC. Tumors with borderline features were subcategorized as follows: tumors that look like LG-PUC but have occasional pleomorphic nuclei (1-BORD-NUP) or elevated mitotic count (2-BORD-MIT), and tumors with side-by-side distinct LG-PUC and less than 50% HG-PUC (3-BORD-MIXED). Recurrence-free, total progression-free, and specific invasion-free survival curves were derived from the Kaplan-Meier method, and Cox regression analysis was performed. RESULTS.—: A total of 138 patients with noninvasive PUC were included, with the following distribution: LG-PUC (n = 52; 38%), HG-PUC (n = 34; 25%), BORD-NUP (n = 21; 15%), BORD-MIT (n = 14; 10%) and BORD-MIXED (n = 17; 12%). Median (interquartile range) follow-up was 44.2 months (29.9-73.1 months). Invasion-free survival was different between the 5 groups (P = .004), and pairwise comparison showed that HG-PUC had a worse prognosis compared with LG-PUC (P ≤ .001). On univariate Cox analysis, HG-PUC and BORD-NUP were 10.5 times (95% CI, 2.3-48.3; P = .003) and 5.9 times (95% CI, 1.1-31.9; P = .04) more likely to invade, respectively, when compared to LG-PUC. CONCLUSIONS.—: Our findings confirm a continuous spectrum of histologic changes in PUC. Approximately a third of noninvasive PUCs show borderline features between LG-PUC and HG-PUC. Compared with LG-PUC, BORD-NUP and HG-PUC were more likely to invade on follow-up. BORD-MIXED tumors did not statistically behave differently from LG-PUC.

CONTEXT.—: Ankylosing spondylitis (AS) is an autoimmune disorder with a strong genetic risk, especially with HLA-B27. Clinical testing for HLA-B27 has been used to help diagnose patients with signs and symptoms of AS. Testing methods used by clinical laboratories for HLA-B27 fall into the broad categories of serologic/antibody- or molecular-based methods and have evolved over time. The College of American Pathologists (CAP) offers a proficiency testing survey for HLA-B27. OBJECTIVE.—: To analyze HLA-B27 testing trends and their performance in the past decade, using the proficiency testing survey data submitted to CAP. DESIGN.—: We analyzed the HLA-B27 CAP proficiency testing data from 2010 to 2020 for the method used, participant concordance, and error rates. Results from case scenarios to understand evolving scientific data around HLA-B27 risk alleles was also analyzed. RESULTS.—: Antibody-based flow cytometry is the most common method, though it has decreased from 60% in 2010 to 52% in 2020, with a corresponding increase in molecular methods. Among the molecular methods, real-time polymerase chain reaction has increased from 2% to 15%. Flow cytometry had the highest error rate (5.33%) and sequence-specific oligonucleotide (0%) is the most accurate (0%). Results of case scenarios demonstrated that most participants understood that allele-level HLA-B27 typing results inform clinical interpretation, for example HLA-B*27:06 is not associated with AS. CONCLUSIONS.—: These data demonstrated the changing trends for HLA-B27 testing during the past decade. HLA-B27 allelic typing provides a better understanding of AS association. This is possible by testing for the second field with methods like next-generation sequencing.

CONTEXT.—: Immunohistochemistry serves as an ancillary diagnostic tool for a wide variety of neoplastic and nonneoplastic disorders, including infections, workup of inflammatory conditions, and subtyping neoplasms of the pancreas/liver/gastrointestinal luminal tract. In addition, immunohistochemistry is also used to detect a variety of prognostic and predictive molecular biomarkers for carcinomas of the pancreas, liver, and gastrointestinal luminal tract. OBJECTIVE.—: To highlight an update on the role of immunohistochemistry in the evaluation of pancreatic/liver/gastrointestinal luminal tract disorders. DATA SOURCES.—: Literature review and authors' research data and personal practice experience were used. CONCLUSIONS.—: Immunohistochemistry is a valuable tool, assisting in the diagnosis of problematic tumors and benign lesions of the pancreas, liver, and gastrointestinal luminal tract, and also in the prediction of prognosis and therapeutic response for carcinomas of the pancreas, liver, and gastrointestinal luminal tract.

CONTEXT.—: Fine-needle aspiration (FNA) is a well-established procedure for the diagnosis and management of salivary gland lesions, despite challenges imposed by salivary gland tumor diversity, complexity, and cytomorphologic overlap. Until recently, the reporting of salivary gland FNA specimens was inconsistent among different institutions throughout the world, leading to diagnostic confusion among pathologists and clinicians. In 2015, an international group of pathologists initiated the development of an evidence-based tiered classification system for reporting salivary gland FNA specimens, the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC). The MSRSGC consists of 6 diagnostic categories, which incorporate the morphologic heterogeneity and overlap among various nonneoplastic, benign, and malignant lesions of the salivary glands. In addition, each MSRSGC diagnostic category is associated with a risk of malignancy and management recommendations. OBJECTIVE.—: To review the current status of salivary gland FNA, core needle biopsies, ancillary studies, and the beneficial role of the MSRSGC in providing a framework for reporting salivary gland lesions and guiding clinical management. DATA SOURCES.—: Literature review and personal institutional experience. CONCLUSIONS.—: The main goal of the MSRSGC is to improve communication between cytopathologists and treating clinicians, while also facilitating cytologic-histologic correlation, quality improvement, and research. Since its implementation, the MSRSGC has gained international acceptance as a tool to improve reporting standards and consistency in this complex diagnostic area, and it has been endorsed by the 2021 American Society of Clinical Oncology management guidelines for salivary gland cancer. The large amount of data from published studies using MSRSGC served as a basis for the recent update of the MSRSGC.

CONTEXT.—: Detection of human papillomavirus (HPV) in formalin-fixed, paraffin-embedded (FFPE) tissues may identify the cause of lesions and has value for the development of new diagnostic assays and epidemiologic studies. Seegene Anyplex II assays are widely used for HPV screening, but their performance using FFPE samples has not been fully explored. OBJECTIVE.—: To validate Anyplex II HPV HR Detection (Anyplex II, Seegene) using FFPE samples. DESIGN.—: We used 248 stored DNA extracts from cervical cancer FFPE samples collected during 2005-2015 and that tested HPV positive using the RHA kit HPV SPF10-LiPA25, v1 (SPF10, Labo Biomedical Products) HPV genotyping assay, manufacturer-validated for FFPE samples. RESULTS.—: Of the selected 248 samples, 243 were used in our analysis. Consistent with SPF10 genotyping results, Anyplex II detected all 12 oncogenic types and had an overall HPV detection rate of 86.4% (210 of 243 samples). Anyplex II and SPF10 showed very high agreement for the detection of the 2 most important oncogenic genotypes: HPV 16 (219 of 226; 96.9%; 95% CI, 93.7-98.75) and HPV 18 (221 of 226; 97.8%; 95% CI, 94.9-99.3). CONCLUSIONS.—: Overall results showed that both platforms produced comparable HPV genotyping results, indicating the suitability of Anyplex II for FFPE samples. The Anyplex II assay has the added convenience of being an efficient, single-well semiquantitative polymerase chain reaction assay. Further optimization of Anyplex II may enhance its performance using FFPE samples by improving the detection limit.

CONTEXT.—: The pathologic diagnosis of usual interstitial pneumonia (UIP) remains a challenging area, and application of histologic UIP guidelines has proved difficult. OBJECTIVE.—: To understand current practice approaches by pulmonary pathologists for the histologic diagnosis of UIP and other fibrotic interstitial lung diseases (ILDs). DESIGN.—: The Pulmonary Pathology Society (PPS) ILD Working Group developed and sent a 5-part survey on fibrotic ILD electronically to the PPS membership. RESULTS.—: One hundred sixty-one completed surveys were analyzed. Of the respondents, 89% reported using published histologic features in clinical guidelines for idiopathic pulmonary fibrosis (IPF) in their pathologic diagnosis; however, there was variability in reporting terminology, quantity and quality of histologic features, and the use of guideline categorization. Respondents were very likely to have access to pulmonary pathology colleagues (79%), pulmonologists (98%), and radiologists (94%) to discuss cases. Half of respondents reported they may alter their pathologic diagnosis based on additional clinical and radiologic history if it is pertinent. Airway-centered fibrosis, granulomas, and types of inflammatory infiltrates were considered important, but there was poor agreement on how these features are defined. CONCLUSIONS.—: There is significant consensus among the PPS membership on the importance of histologic guidelines/features of UIP. There are unmet needs for (1) consensus and standardization of diagnostic terminology and incorporation of recommended histopathologic categories from the clinical IPF guidelines into pathology reports, (2) agreement on how to incorporate into the report relevant clinical and radiographic information, and (3) defining the quantity and quality of features needed to suggest alternative diagnoses.

CONTEXT.—: Digital pathology using whole slide images has been recently approved for primary diagnosis in clinical surgical pathology practices. Here we describe a novel imaging method, fluorescence-imitating brightfield imaging, that can capture the surface of fresh tissue without requiring prior fixation, paraffin embedding, tissue sectioning, or staining. OBJECTIVE.—: To compare the ability of pathologists to evaluate direct-to-digital images with standard pathology preparations. DESIGN.—: One hundred surgical pathology samples were obtained. Samples were first digitally imaged, then processed for standard histologic examination on 4-μm hematoxylin-eosin-stained sections and digitally scanned. The resulting digital images from both digital and standard scan sets were viewed by each of 4 reading pathologists. The data set consisted of 100 reference diagnoses and 800 study pathologist reads. Each study read was compared to the reference diagnosis, and also compared to that reader's diagnosis across both modalities. RESULTS.—: The overall agreement rate, across 800 reads, was 97.9%. This consisted of 400 digital reads at 97.0% versus reference and 400 standard reads versus reference at 98.8%. Minor discordances (defined as alternative diagnoses without clinical treatment or outcome implications) were 6.1% overall, 7.2% for digital, and 5.0% for standard. CONCLUSIONS.—: Pathologists can provide accurate diagnoses from fluorescence-imitating brightfield imaging slide-free images. Concordance and discordance rates are similar to published rates for comparisons of whole slide imaging to standard light microscopy of glass slides for primary diagnosis. It may be possible, therefore, to develop a slide-free, nondestructive approach for primary pathology diagnosis.

CONTEXT.—: Inflammatory lesions of the breast are rare but not infrequently pose problems both clinically and morphologically, particularly on needle core biopsies. These lesions range from acute inflammatory conditions to chronic lymphoplasmacytic and lymphohistiocytic to granulomatous inflammatory diseases. OBJECTIVE.—: To provide a comprehensive overview of inflammatory lesions of the breast with etiopathogenesis and clinical, radiologic, and pathologic features, with differential diagnostic considerations, clinical management, and prognosis. DATA SOURCES.—: The existing literature in the English language, including original research articles and review articles describing inflammatory lesions of the breast. CONCLUSIONS.—: Inflammatory lesions of the breast are characterized by a wide variety of clinical, radiologic, and morphologic features. The histopathologic differential diagnosis often includes a neoplastic process requiring ancillary studies and correlation with clinical and radiologic findings. Although most specimens display nonspecific findings precluding a definitive pathologic diagnosis, pathologists have a unique opportunity to play a crucial role in identifying key histologic features suggestive of certain entities, such as cystic neutrophilic granulomatous mastitis, immunoglobulin (Ig) G4 mastitis, or squamous metaplasia of lactiferous ducts, in the right clinical and radiologic context, and thereby guiding optimal and timely clinical management. The information presented herein will be helpful to practicing anatomic pathologists and pathology trainees in becoming more familiar with specific morphologic features and overcoming differential diagnostic challenges related to pathology reporting of inflammatory lesions of the breast.

CONTEXT.—: Pediatric soft tissue tumors are one of the areas of pediatric pathology that frequently generate consult requests. Evolving classification systems, ancillary testing methods, new treatment options, research enrollment opportunities, and tissue archival processes create additional complexity in handling these unique specimens. Pathologists are at the heart of this critical decision-making, balancing responsibilities to consider expediency, accessibility, and cost-effectiveness of ancillary testing during pathologic examination and reporting. OBJECTIVE.—: To provide a practical approach to handling pediatric soft tissue tumor specimens, including volume considerations, immunohistochemical staining panel recommendations, genetic and molecular testing approaches, and other processes that impact the quality and efficiency of tumor tissue triage. DATA SOURCES.—: The World Health Organization Classification of Soft Tissue and Bone Tumors, 5th edition, other recent literature investigating tissue handling, and the collective clinical experience of the group are used in this manuscript. CONCLUSIONS.—: Pediatric soft tissue tumors can be difficult to diagnose, and evaluation can be improved by adopting a thoughtful, algorithmic approach to maximize available tissue and minimize time to diagnosis.