Archives of pathology & laboratory medicine最新文献

Context.—: Salivary gland neoplasms are rare lesions in the head and neck (H&N) pathology realm. There are more than 20 malignant and 15 benign salivary gland neoplasms in the 5th edition of the World Health Organization classification of H&N tumors. These neoplasms consist of heterogeneous groups of uncommon diseases that make diagnosis and treatment challenging for the clinical team. Using an algorithmic immunohistochemical approach-defined tumor origin and type has proven to be effective and advantageous. Immunohistochemistry may be used as sort of a "diagnostic looking glass," not as a positive or negative type tool, but as an indispensable complement to a hematoxylin-eosin morphologic pattern-based approach. Furthermore, the understanding of the novel discoveries of the salivary gland gene fusions and the molecular aspects of these tumors makes the process easier and improve the diagnosis as well as treatment aspects. This review reflects our experience with more recent diagnostic antibodies, which include MYB RNA, Pan-TRK, PLAG1, LEF1, and NR4A3. Each of these is linked with a specific type of neoplasm; for example, gene fusions involving the PLAG1 and HMGA2 oncogenes are specific for benign pleomorphic adenomas, and MYB is associated with adenoid cystic carcinoma.

Objective.—: To review these more recent antibodies, which highly enhance salivary gland neoplasm diagnosis.

Data sources.—: The study sources involved literature PubMed searches, including multiple review articles, case reports, selected book chapters, and Geisinger Medical Center cases.

Conclusions.—: Salivary gland tumors are a rare, varied group of lesions in H&N pathology. We need to have continuous readings and revisions of the molecular consequences of these fusion oncoproteins and their subsequent targets, which will eventually lead to the identification of novel driver genes in salivary gland neoplasms.

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.—: Tissue contaminants on histology slides represent a serious risk of diagnostic error. Despite their pervasive presence, published peer-reviewed criteria defining contaminants are lacking. The absence of a standardized diagnostic workup algorithm for contaminants contributes to variation in management, including investigation and reporting by pathologists.

Objective.—: To study the frequency and type of tissue contaminants on microscopic slides using standardized criteria. Using these data, we propose a taxonomy and algorithm for pathologists on "floater" management, including identification, workup, and reporting, with an eye on patient safety.

Design.—: A retrospective study arm of 1574 histologic glass slides as well as a prospective study arm of 50 slide contamination events was performed. Using these data we propose a structured classification taxonomy and guidelines for the workup and resolution of tissue contamination events.

Results.—: In the retrospective arm of the study, we identified reasonably sized benign tissue contaminants on 52 of 1574 slides (3.3%). We found size to be an important parameter for evaluation, among other visual features including location on the slide, folding, ink, and tissue of origin. The prospective arm of the study suggested that overall, pathologists tend to use similar features when determining management of potentially actionable contaminants. We also report successfully used case-based ancillary testing strategies, including fluorescence in situ hybridization analysis of chromosomes and DNA fingerprinting.

Conclusions.—: Tissue contamination events are underreported and represent a patient safety risk. Use of a reproducible classification taxonomy and a standardized algorithm for contaminant workup, management, and reporting may aid pathologists in understanding and reducing risk.

Context.—: A recent study demonstrated that NKX3.1-positive staining can uncommonly be seen in testicular Sertoli cell tumors (1 of 4 cases). Also, it was reported that 2 of 3 Leydig cell tumors of the testis showed diffuse cytoplasmic staining for P501S, although it was unclear whether it was specific granular staining that defines true positivity. However, Sertoli cell tumors do not typically pose a diagnostic dilemma with metastatic prostate carcinoma to the testis. In contrast, malignant Leydig cell tumors, which are exceedingly rare, can closely resemble Gleason score 5 + 5 = 10 prostatic adenocarcinoma metastatic to the testis.

Objective.—: To evaluate the expression of prostate markers in malignant Leydig cell tumors and steroidogenic factor 1 (SF-1) in high-grade prostate adenocarcinoma, as no data are currently published on these topics.

Design.—: Fifteen cases of malignant Leydig cell tumor were collected from 2 large genitourinary pathology consult services in the United States from 1991 to 2019.

Results.—: All 15 cases were negative immunohistochemically for NKX3.1, and all 9 with available additional material were negative for prostate-specific antigen and P501S and positive for SF-1. SF-1 was negative immunohistochemically in a tissue microarray with cases of high-grade prostatic adenocarcinoma.

Conclusions.—: The diagnosis of malignant Leydig cell tumor and its distinction from metastatic adenocarcinoma to the testis can be made immunohistochemically on the basis of SF-1 positivity and negativity for NKX3.1.

Context.—: Workup of the poorly differentiated or undifferentiated tumor remains a significant and challenging entity in the practice of anatomic pathology. Particularly in the setting of small biopsies and limited material, these cases demand a balanced approach that considers the patient's clinical and radiologic presentation, a basic assessment of tumor morphology, a reasonably broad immunohistochemical panel, and diligent preservation of tissue for prognostic and therapeutic studies.

Objective.—: To illustrate some of the new and emerging immunohistochemical markers in the evaluation of tumors with undifferentiated or poorly differentiated morphology, with a focus on the workup in limited tissue samples to raise awareness of the issues involved with the pathologic workup in these challenging tumors.

Data sources.—: A literature review of new ancillary studies that can be applied to cytologic specimens was performed.

Conclusions.—: Knowledge of the patient's history and communication with the patient's clinical team is essential in formulating a differential diagnosis that can appropriately limit the differential diagnosis based on morphology, especially in small specimens. This information, in conjunction with classifying the tumor morphology (eg, epithelioid, spindled, neuroendocrine, basaloid/biphasic, mixed) gives a logical approach to choosing an initial immunohistochemical panel. Fortunately, immunohistochemistry is evolving quickly in the wake of groundbreaking molecular studies to develop new and better markers to further classify these difficult tumors beyond where we traditionally have been able to go.

Context.—: Serology plays a vital role in celiac disease (CD) diagnosis, and the latest European guidelines advocate for biopsy-free diagnoses in patients with ≥10× the upper limit of normal (ULN) of anti-tissue transglutaminase (tTG) immunoglobulin A (IgA) antibodies.

Objective.—: To assess performance characteristics of a novel automated particle-based multianalyte technology (Aptiva) for anti-tTG and anti-deamidated gliadin peptide (DGP) antibody detection as compared to the traditional enzyme-linked immunosorbent assay (QUANTA Lite). Performance characteristics of the ≥10× ULN anti-tTG IgA criteria for serologic diagnosis of CD were also evaluated.

Design.—: Sera samples from 703 patients were tested for anti-tTG IgA, anti-tTG immunoglobulin G (IgG), anti-DGP IgA, and anti-DGP IgG antibodies on both platforms. In total, 127 patients had medical information and were classified as CD-positive (n = 58) and CD-negative (n = 69) based on biopsy results. Clinical performance characteristics were evaluated.

Results.—: Anti-tTG IgA detection showed equal clinical sensitivity and specificity of 91% sensitivity and 99% specificity on both platforms. Anti-tTG IgG resulted in moderate sensitivity of 69% and 72%, but high specificity of 100% and 94% on Aptiva and QUANTA Lite, respectively. Anti-DGP IgG displayed comparable sensitivity of 90% and 81%, and a specificity of 94% and 99%, on Aptiva and QUANTA Lite, respectively. Anti-DGP IgA demonstrated greater sensitivity on QUANTA Lite (83%) than Aptiva (69%) and similar specificities of 97% and 98% on QUANTA Lite and Aptiva, respectively. At ≥10× ULN levels for anti-tTG IgA, Aptiva displayed a sensitivity of 72% and a specificity of 100%, and QUANTA Lite showed a sensitivity of 69% and a specificity of 100%.

Conclusions.—: Aptiva is a reliable method to measure CD biomarkers with reduced hands-on necessity and high-throughput capabilities. This study supports the use of a ≥10× ULN anti-tTG IgA biopsy-free approach for serologic diagnosis of CD.

Context.—: Because of restrictions as a result of the COVID-19 pandemic, medical educators rapidly transitioned to an online curriculum for pathology resident education. The benefits and challenges of the shift to online learning, as well as strategies to maximize learning, are yet to be fully elucidated.

Objective.—: To assess learner perception and satisfaction with the move to online learning. Understanding the benefits of online learning will allow future curricular changes to most effectively incorporate online learning. Understanding the common challenges will allow our current learning strategies to rapidly adapt and ideally mitigate these challenges as online learning is incorporated into medical education.

Design.—: This was a survey-based study distributed by email to pathology residents nationwide in Canada in anatomic pathology, general pathology, neuropathology, and hematopathology. Thirty residents participated, from anatomic pathology (n = 23; 76%), from general pathology (n = 5; 16%), and 1 participant each from hematopathology and neuropathology.

Results.—: All participants indicated that their program had transitioned to online learning at least in part. The majority of participants (n = 16; 53%) did not feel their pathology education was negatively affected by the transition to online learning; however, a significant minority (n = 6; 20%) felt their education had been negatively affected. Convenience and less intimidation were rated as benefits of online learning. Negative effects included technical issues and decreased engagement; we identified a number of strategies used by programs and pathology residents to mitigate these negative effects.

Conclusions.—: Our survey points to a need to use adaptations and best-practice recommendations to maximize the benefits of online learning moving forward.

Context.—: An immunohistochemistry (IHC) assay developed to detect lymphocyte-activation gene 3 (LAG-3), a novel immune checkpoint inhibitor target, has demonstrated high analytic precision and interlaboratory reproducibility using a Leica staining platform, but it has not been investigated on other IHC staining platforms.

Objective.—: To evaluate the performance of LAG-3 IHC assays using the 17B4 antibody clone across widely used IHC staining platforms: Agilent/Dako Autostainer Link 48 and VENTANA BenchMark ULTRA compared to Leica BOND-RX (BOND-RX).

Design.—: Eighty formalin-fixed, paraffin-embedded melanoma tissue blocks were cut into consecutive sections and evaluated using staining platform-specific IHC assays with the 17B4 antibody clone. Duplicate testing was performed on the BOND-RX platform to assess intraplatform agreement. LAG-3 expression using a numeric score was evaluated by a pathologist and with a digital scoring algorithm. LAG-3 positivity was determined from manual scores using a 1% or greater cutoff.

Results.—: LAG-3 IHC staining patterns and intensities were visually similar across all 3 staining platforms. Spearman and Pearson correlations were 0.75 or greater for interplatform and BOND-RX intraplatform concordance when LAG-3 expression was evaluated with a numeric score determined by a pathologist. Correlation increased with a numeric score determined with a digital scoring algorithm (Spearman and Pearson correlations ≥0.88 for all comparisons). Overall percentage agreement was 77.5% or greater for interplatform and BOND-RX intraplatform comparisons when LAG-3 positivity was determined using a 1% or greater cutoff.

Conclusions.—: Data presented here demonstrate that LAG-3 expression can be robustly and reproducibly assessed across 3 major commercial IHC staining platforms using the 17B4 antibody clone.

Context.—: Pathology training is focused on the attainment of clinical, diagnostic, and administrative skills. Preparation for employment search and the interview process are often neglected. Given that a near majority of pathology trainees in the United States are graduates of foreign medical schools, training in the job search and interview process according to local customs, norms, and expectations has greater salience for individuals new to the United States.

Objective.—: To offer perspectives on 2 components of the job search process: (1) finding a suitable job opening in academic and private practice settings and (2) preparing for an interview. We have provided a set of common interview questions and suggested preparatory methodology. The differences in the process and expectations in academic settings and private practice operations are highlighted. Engaging in the job search process early and networking are emphasized. We have also suggested approaches for pathology teachers and mentors in guiding trainees in a job search and preparation for an interview.

Data sources.—: The information and opinions expressed in this communication are based on the personal experiences of 4 senior pathologists in academic and private practice settings.

Conclusions.—: Start networking early. Leverage contacts with teachers, attending pathologists, senior residents, and people at national meetings to locate appropriate job opportunities. Seek assistance from attending pathologists in preparing a curriculum vitae and cover letter. Prepare for the questions that may come up in an interview. A dress rehearsal for an interview is strongly recommended.

Context.—: Pancreatic ductal adenocarcinoma has some of the worst prognostic outcomes among various cancer types. Detection of histologic patterns of pancreatic tumors is essential to predict prognosis and decide the treatment for patients. This histologic classification can have a large degree of variability even among expert pathologists.

Objective.—: To detect aggressive adenocarcinoma and less aggressive pancreatic tumors from nonneoplasm cases using a graph convolutional network-based deep learning model.

Design.—: Our model uses a convolutional neural network to extract detailed information from every small region in a whole slide image. Then, we use a graph architecture to aggregate the extracted features from these regions and their positional information to capture the whole slide-level structure and make the final prediction.

Results.—: We evaluated our model on an independent test set and achieved an F1 score of 0.85 for detecting neoplastic cells and ductal adenocarcinoma, significantly outperforming other baseline methods.

Conclusions.—: If validated in prospective studies, this approach has a great potential to assist pathologists in identifying adenocarcinoma and other types of pancreatic tumors in clinical settings.