OBJECTIVES:To establish the occurrence of BRAF mutation in marginal zone lymphomas (MZLs) and study its impact on clinical presentation, pathologic features, and disease classification. METHODS:Conventional histology, immunohistochemistry, flow cytometry, and molecular methods were used. RESULTS:We identified 2 BRAF‑mutated MZL cases: a nodal MZL (NMZL) with BRAF V600E and partial morphologic/immunophenotypic overlap with hairy cell leukemia (HCL) and an extranodal MZL with a non-V600E BRAF mutation co‑occurring with TET2, KRAS, and TP53 variants. The NMZL case showed strong CD25 and CD123 expression and patchy cyclin D1 expression; together with the presence of a BRAF V600E mutation, these features overlapped with HCL. However, the absence of annexin A1 and CD103 expression, along with the remaining morphologic features in the lymph node, supported accurate classification as NMZL. CONCLUSIONS:These 2 cases expand the mutational spectrum of MZL and illustrate important diagnostic pitfalls. These observations underscore that BRAF V600E, while highly specific and clinically useful for HCL in the context of a B‑cell lymphoproliferative process involving blood and marrow, is not entirely pathognomonic and must be interpreted alongside morphology and a full immunophenotypic panel. Integrating BRAF testing into the workup of challenging small B‑cell lymphomas may refine diagnosis and reveal rare, potentially targetable MAPK pathway lesions.
OBJECTIVES:VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a rare adult-onset autoinflammatory disorder, caused by a single somatic UBA1 mutation. We report a novel case with 3 independent UBA1-mutated clones and compare its clinical, hematologic, and laboratory features with those of the only 3 previously reported cases harboring multiple UBA1 mutations. METHODS:Droplet digital polymerase chain reaction (PCR) and targeted next-generation sequencing of peripheral blood DNA were performed to assess UBA1 variants. Bone marrow specimens were evaluated for morphologic, immunophenotypic, and cytogenetic abnormalities. RESULTS:Clinical and hematologic features included neck swelling, headache, elevated inflammatory markers, leukopenia, macrocytic anemia, and thrombocytopenia. Bone marrow biopsy specimens showed no dysplasia, increased blasts, or cytoplasmic vacuolization. Droplet digital PCR detected atypical positive signals across multiple targets, and next-generation sequencing identified 3 presumed independent UBA1 variants: p.M41V, p.M41L, and c.118-2A > T. Comparison with 3 previously reported VEXAS cases carrying multiple UBA1 variants revealed diverse clinical manifestations, including systemic inflammation, polychondritis, venous thromboembolism, arthritis, and arthralgia, with variable hematologic findings ranging from no neoplasm to myelodysplastic syndrome or multiple myeloma, as well as co-occurring clonal hematopoietic variants. CONCLUSIONS:This report describes a novel VEXAS case with multiple UBA1 variants and highlights the clinical and hematologic heterogeneity among patients harboring multiple UBA1 mutations. It also emphasizes the technical challenges in detecting these variants and the importance of sequencing studies for definitive diagnosis in complex or equivocal cases, supporting early identification of UBA1 mutations and closer hematologic surveillance in patients with inflammatory symptoms and cytopenias.
OBJECTIVES:To review clinically important preanalytical variables in surgical pathology and their effects on diagnostic accuracy, ancillary testing, and patient safety. METHODS:A narrative review was developed from selected literature on surgical pathology preanalytics, fixation, specimen handling, histotechnology, immunohistochemistry, molecular testing, tissue contamination, and quality improvement. Emphasis was placed on practical variables that affect routine anatomic pathology workflows. RESULTS:The diagnostic value of a surgical pathology specimen is shaped before microscopic interpretation. Ischemia time, delayed or inadequate fixation, tissue thickness, container and transport problems, labeling discrepancies, poor orientation, grossing variability, histotechnical artifacts, and tissue contamination can compromise morphology, margin assessment, staging, biomarker interpretation, and molecular testing. These effects are especially consequential in small biopsy specimens and precision oncology specimens, in which the same limited tissue may be required for diagnosis, immunohistochemistry, fluorescence in situ hybridization, polymerase chain reaction-based testing, and next-generation sequencing. Gross examination is a particularly important pathology-controlled preanalytical step because block selection determines what can be assessed microscopically. CONCLUSIONS:Preanalytical control should be regarded as a diagnostic quality and patient safety process rather than a technical background activity. Standardized fixation, specimen tracking, communication, grossing protocols, histotechnical quality assurance, and tissue stewardship are essential to reliable surgical pathology practice.
OBJECTIVES:Erdheim-Chester disease (ECD) is one of 3 major types of histiocytic neoplasms, along with Rosai-Dorfman disease and Langerhans cell histiocytosis. It was first recognized as a neoplasm in the 2016 World Health Organization Classification of Haematolymphoid Tumours. About 80% to 90% of cases harbor MAPK pathway mutations. METHODS:We discuss the diagnosis of ECD using 3 illustrative cases, consider interpretative challenges, and present a diagnostic algorithm. RESULTS:Erdheim-Chester disease is a systemic disease that shows a characteristic pattern of organ involvement including bone, perinephric soft tissue, skin, heart, and central nervous system. Histologically, ECD shows a spectrum of xanthogranulomatous, lymphohistocytic, or fibrohistiocytic infiltrates. By immunohistochemistry, the neoplastic histiocytes have a macrophage phenotype with expression of CD163, negative to focal S100, and negative CD1a and langerin. These features alone are not specific and thus insufficient for diagnosis. Immunohistochemistry for cyclin D1 and BRAF V600E, correlation with clinical and imaging findings, and mutational analysis for MAPK pathway mutations all play important roles in establishing an ECD diagnosis. CONCLUSIONS:The diagnosis of ECD is often challenging due to its clinical and histologic overlap with reactive inflammatory processes. Correlation of histology features with clinical findings, immunohistochemistry, and genetic studies is essential for an accurate and timely diagnosis.
OBJECTIVE:We sought to assess how centrally reviewed radical prostatectomy (RP) Grade Group (GG), tumor volume (TV), prostate-specific antigen density (PSAD), pathologic stage, tumor topography, patient age, and race and ethnicity relate to regional lymph node metastasis (LN+). METHODS:We reviewed patient cases with treatment-naive RPs performed from 2013 through 2026. All specimens underwent centralized histologic review by 1 urologic pathologist. Grade Group was assigned from the highest-grade tumor, and its TV was measured. Tumor volume and PSAD were modeled on the log2 scale (odds ratios per doubling), and multivariable Firth penalized logistic regression assessed factors associated with LN+. RESULTS:No metastasis was seen in GG1 cases (n = 368). The final cohort comprised 3142 node-staged GG2 to GG5 RP specimens. Positive regional LNs were identified in 135 (4.3%) patients, with a median of 1 positive node (IRQ, 1-2 LNs; range, 1-17 LNs). Cases with LN+ disease had a median of 9 LNs (range, 1-31 LNs) examined compared with 5 LNs (range, 1-45 LNs) in cases without metastasis (P < .001). Grade Group 5 cancer was associated with a clinically significantly lower value for PSAD divided by TV (PSAD/TV) than for GG2 to GG4 cancers. In the augmented multivariable Firth model, PSAD, TV, GG, posterior or extensive bilateral topography, and pT3a/pT3b stage were independently associated with LN+. Age, race, and ethnicity were not independently associated. Anterior topography inversely correlated with LN+. CONCLUSIONS:In this centrally reviewed RP cohort, no LN+ was observed in GG1 cancer. Among GG2 to GG5 cancers, LN+ was associated with increasing GG, larger TV, higher PSAD, pT3a/pT3b stage, and posterior or extensive bilateral topography after adjustment for age, race, and ethnicity. Grade Group 5 cancers showed lower PSA production than did GG2 to GG4 cancers, indicating a different PSAD-TV relationship.
OBJECTIVES:Interpreting postmortem microbiological data is challenging, especially when enteric organisms are isolated. We evaluated whether virulence gene profiles could distinguish hospitalized decedents in whom Escherichia coli was adjudicated to be in the causal pathway to death from those in whom it was not. METHODS:We conducted a prospective autopsy study from 2016 through 2019 at 2 hospitals in northern Tanzania. Postmortem cultures were collected from multiple specimen types. The role of E coli in the causal pathway to death was adjudicated using clinical, microbiological, and histopathologic data. Separate from adjudication, whole-genome sequencing was performed on E coli isolates for classification as extraintestinal pathogenic E coli (ExPEC) vs non-ExPEC based on their virulence genes. Logistic regression assessed the odds of isolating ExPEC when E coli was adjudicated as being in the causal pathway to death. RESULTS:We identified 74 E coli isolates from 57 (26.4%) of the 216 decedents enrolled in our study. Among decedents with E coli growth in culture, median (IQR) age was 38 (24-61) years, 14 (24.6%) were female, and E coli was adjudicated as being in the causal pathway to death in 17 (29.8%). Of these 17 decedents, 13 (76.5%) had at least 1 isolate designated as ExPEC compared with 24 (60.0%) of 40 decedents for whom E coli was not deemed causative of death. The odds of isolating ExPEC when E coli was in the causal pathway to death was 2.78 (95% CI, 0.62-12.3; P = .18). CONCLUSIONS:No single genomic marker, including ExPEC status, was sufficient to establish the causal role of E coli in death.
OBJECTIVES:Helicobacter pylori infections result in significant global disease burden related to chronic gastritis, peptic ulcer disease, and gastric cancer. Optimal treatment requires knowledge of local resistance epidemiology. We characterized our patient population infected with H pylori in Washington, DC, United States, and evaluated the diagnostic utility of microbiology and surgical pathology approaches for H pylori diagnosis. METHODS:A retrospective, observational study was performed from April 2015 to March 2022, consisting of patients positive for H pylori. Review of the electronic medical record for patient demographics, clinical presentation, laboratory results, and clinical management was performed. RESULTS:Top clinical presentations in our patients with H pylori infections (n = 31, mean age 51 years) were abdominal pain (55%), gastroesophageal reflux disease (19%), and nausea/vomiting (10%), with most (84%) experiencing recurrent disease. Concordant findings (n = 105 specimens) between microbiology and surgical pathology were noted in 96% of patients. Microbiology testing provided a faster preliminary positive diagnosis by 3 days (P < .00001). For both approaches, antrum biopsy specimens demonstrated a 100% recovery rate (odds ratio [OR], 5.4). Active gastritis was the most common diagnosis (82%), which significantly increased the likelihood of H pylori seen in microbiology smears (OR, 1.7) and viable recovery of the organism (OR, 2.6) for further antimicrobial susceptibility testing. Our antibiogram revealed more than 55% resistance to first-line drugs, with 77% of our isolates being multidrug resistant. CONCLUSIONS:An accurate diagnosis of an H pylori infection is dependent on specimen site and disease severity. Appropriate biopsy collection and ordering of microbiology and surgical pathology tests maximize diagnostic utility. A local antibiogram is essential for guiding empiric therapy.
OBJECTIVES:Anaplastic thyroid carcinoma (ATC) is one of the most aggressive and lethal thyroid malignancies, with limited effective treatment options. We aimed to identify previously unreported gene alterations and evaluate the potential for clinically actionable targeted therapies in ATC using the largest single next-generation sequencing (NGS) cohort to date. METHODS:This retrospective genomic analysis included deidentified NGS data from 713 patients with ATC obtained from the FoundationCORE database. Pathogenic gene alterations were analyzed for frequency. A comprehensive review of the literature and genomic databases was performed to identify alterations not previously reported in ATC and to assess associated targeted therapies. RESULTS:Targeted sequencing of 713 ATC tumor specimens identified 250 genes with pathogenic or likely pathogenic alterations, including 108 not previously reported in ATC. Among these novel genes, 24 were altered in 5 or more cases, with MTAP (methylthioadenosine phosphorylase) showing the highest frequency (15.26%). MTAP was also co-deleted with CDKN2A/B at significantly higher rates than previously reported. Notably, 99.58% of cases harbored at least 1 gene alteration associated with a potentially actionable therapy. Among the 250 altered genes, 150 (60.0%) had at least 1 available corresponding targeted therapy, and 75.0% of drug categories demonstrated multiple-gene targeting capabilities. CONCLUSIONS:This largest single-cohort NGS data analysis identified 108 previously unreported genomic alterations in ATC, significantly expanding the understanding of the genomic landscape of this aggressive cancer. Moreover, these findings highlight a broad range of potentially actionable alterations and underscore the importance of identifying driver mutations and combination therapeutic strategies.
OBJECTIVES:Packed red blood cell (pRBC) units are tested before transfusion to confirm compatibility, safety, and quality. Segments are lengths of heat-sealed tubing from the pRBC unit that enable compatibility testing without compromising sterility. If the degree of hemolysis differs between the segment and the parent unit, hematologic or metabolic testing of segments may lead to inaccurate assessment of the corresponding unit. We directly compared hemolysis indices between paired pRBC units and their corresponding segments to assess the degree of hemolysis and possible association with pRBC unit characteristics. METHODS:Discarded pRBC units bearing at least 1 attached segment were obtained from a university hospital blood bank. Recorded characteristics included product expiration date, ABO/Rh type, and anticoagulant/additive solutions. Supernatant plasma was analyzed for hemolysis using the Roche cobas 8000 automated chemistry system H index. Associations between the H index and pRBC unit characteristics were also evaluated. RESULTS:A total of 42 paired pRBC units and corresponding segments were analyzed. The segment H index was statistically significantly higher than that of parent units (median [IQR], 309 [189-512] vs 98 [72-177]; Wilcoxon signed rank P < .001), with 39 of 42 (93%) paired samples demonstrating a higher H index in segments. The H index increased with the number of days past expiration both for segments (Spearman ρ = 0.69) and parent units (ρ = 0.61; both P < .001). No statistically significant association between H index and ABO blood group, Rh type, or additive solution type was identified. CONCLUSIONS:Our investigation revealed that pRBC segments had statistically significantly increased hemolysis compared with corresponding parent units. As a result, caution should be taken when using segments to assess hemolysis and other hematologic or metabolic testing.
OBJECTIVES:MECOM rearrangements (MECOM-r) are high-risk events in myeloid neoplasms often cryptic or incompletely characterized by conventional karyotype analysis. We used optical genome mapping (OGM) to define the frequency and spectrum of MECOM-r in an unselected, consecutively collected cohort of individuals with high-grade myeloid neoplasms (HGMNs) and compared these findings with standard cytogenetic approaches. METHODS:A total of 252 HGMN specimens, including 224 with definitive diagnoses of acute myeloid leukemia, were processed over a 2-year period using OGM, G-banded karyotyping and, in some cases, reflex fluorescence in situ hybridization (FISH) for the MECOM locus. Cases were retrospectively reviewed to determine whether the identification of MECOM-r by OGM refined diagnosis and/or prognosis. RESULTS:Our diagnostic workflow identified MECOM-r in 12 cases (4.7%), only 6 of which were identified by combined karyotype and FISH analyses, the latter for suspected chromosome 3 abnormalities. The remaining 6 cases were cryptic due to normal karyotypes, highly complex karyotypes lacking apparent chromosome 3 involvement, or culture failure and thus were identified by OGM and reflex FISH. Furthermore, OGM clarified complex architectures, resolved genetic alterations, and identified diverse partner loci, including GATA2, THADA, MYC, PHACTR1, MB21D2, XR_001744423.2, IL12A-AS1, TRIM59, CDK6, and MSI2. Detection of these structural alterations prompted diagnostic and/or risk reclassification in 5 cases. CONCLUSIONS:Optical genome mapping doubled the detection rate and improved the structural resolution of MECOM-r by identifying rearrangements incompletely resolved or missed by conventional cytogenetics. Implementation of OGM showed that MECOM-r can be cryptic and frequently overlooked, highlighting the value of high-resolution testing in HGMNs.
OBJECTIVES:The use of #pathology and #pathologist is increasing on TikTok, a short-form video platform with over 1 billion users. As of July 2024, #pathology had over 21 000 posts and 468 million views, while #pathologist had over 3000 posts. It could be a useful tool for education and recruitment if the content is accurate and engaging. METHODS:To assess the accuracy, engagement, and educational value of this growing content, we conducted a cross-sectional study analyzing 105 English-language TikTok videos identified using these keywords over a 72-hour period. Videos were evaluated using the Patient Education Assessment Tool for audiovisual material (PEMAT-AV) for audiovisual quality, the Global Quality Scale (GQS) for overall content quality, and a modified JAMA benchmark score for information accountability. Additionally, a harm-benefit score categorized educational impact. RESULTS:Statistical analysis revealed that educational content demonstrated significantly higher quality scores on GQS (P = .0001) and PEMAT-AV (P = .0007) than other content types. In contrast, medical profile type was associated with higher PEMAT-AV (P = .0147), JAMA (P = .0332), and harm-benefit (P = .0004) scores. CONCLUSIONS:While the volume of pathology-specific content is currently limited, the high average engagement metrics-298 100 followers, 1.5 million views, and 67 884 likes per video-indicate substantial user interest. The higher-quality scores for educational and medical content suggest that pathology content creators are generally knowledgeable and accurately represent the field on TikTok, highlighting TikTok's potential as a valuable platform for disseminating reliable pathology-related information.
OBJECTIVES:Chromosome 4q12 rearrangements are recurrent in hematologic malignancies, most frequently involving PDGFRA. Fluorescence in situ hybridization (FISH) is routinely used for detecting 4q12 rearrangements. This study aimed to clarify 4q12 rearrangements misdiagnosed by FISH and explore the transcriptomic profile of acute myeloid leukemia (AML) with CHIC2 rearrangements. METHODS:Fluorescence in situ hybridization with a PDGFRA/CHIC2/FIP1L1 probe set detected 4q12 rearrangements. RNA sequencing (RNA-seq) characterized fusion transcripts and compared transcriptomic profiles between CHIC2-rearranged AML and NPM1-mutated controls, identifying differentially expressed genes and enriched pathways. Previously reported PDGFRA-independent 4q12 cases were reviewed. RESULTS:RNA sequencing of 2 AML cases with FISH signals suggestive of PDGFRA rearrangement identified CHIC2 fusions instead: a novel CDK6::CHIC2 and a known ETV6::CHIC2. Integrating our cases with a systematic literature review, we identified 41 hematologic neoplasms with PDGFRA-independent 4q12 rearrangements, of which 38 (92.7%) were AML. The 4q12 breakpoints most frequently involved CHIC2 (27 cases, 65.9%), followed by GSX2, SCFD2, and intergenic regions. Among 15 cases assessed by both FISH and molecular methods, FISH misclassified 9 (60.0%; 9/15) as PDGFRA rearranged; subsequent molecular testing revealed rearrangements of genes adjacent to PDGFRA (eg, CHIC2, GSX2) or intergenic regions. Transcriptomic profiling of CHIC2-rearranged AML revealed a distinct expression signature with 492 differentially expressed genes, including PDGFRA upregulation. Pathway analysis showed significant enrichment for cytokine-cytokine receptor interaction and JAK-STAT signaling (false discovery rate <0.05). CONCLUSIONS:Molecular methods such as RNA-seq are effective for resolving cryptic 4q12 rearrangements in cases where FISH falsely suggests PDGFRA involvement. The distinct transcriptional profile of CHIC2-rearranged AML suggests dysregulated cytokine signaling and JAK-STAT activity in its pathogenesis.
OBJECTIVES:We sought to assess the real-world impact of the Genius Digital Diagnostics System (Genius Dx [Hologic, Inc]) on workload, efficiency, and turnaround time in a high-volume cervical cytology laboratory. METHODS:The laboratory information system was retrospectively queried for all Papanicolaou test cases performed between January 1, 2023, and March 31, 2025. A total of 512 177 cases (655 468 reviews) were included. Genius Dx was implemented on August 1, 2024, and cases were classified as preimplementation or postimplementation. Daily caseload, number of reviewers, number of cases per reviewer, and accession-to-sign-out times were compared using independent-samples t tests. Diagnostic distributions were compared using ꭓ2 tests. RESULTS:Average daily cytologist (CT) reviews were similar before and after Genius Dx (747.8 vs 758.4 cases) but required fewer CTs per day (10.4 vs 8.1; P < .001), increasing cases per CT per day from 74.5 to 94.7 (P < .001). Pathologist reviews per day increased (106.0 vs 145.3; P < .001) with fewer pathologists (4.4 vs 3.4; P < .001). Average daily CT case workload increased by 53.5% after implementation. Accession-to-sign-out times decreased for all diagnoses (P < .001). A small but statistically significant shift in diagnostic proportions was observed, with a decrease in negative results and an increase in atypical squamous cells of uncertain significance or higher (ASC-US+) findings with negligible effect size. CONCLUSIONS:Implementation of Genius Dx substantially increased reviewer efficiency and reduced turnaround times without compromising diagnostic performance. The increased detection of ASC-US+ findings observed in this study are in line with results from the Genius Dx clinical trial and other published literature.
OBJECTIVES:To evaluate the use of standardized protocols for reflexing to broad, multigene panels in non-small cell lung cancer (NSCLC) and identify barriers that limit timely pathologist‑ordered biomarker reflex testing. METHODS:A cross-sectional survey was administered to a national sample of health care professionals involved in NSCLC biomarker testing. RESULTS:Of 111 respondents in the dataset, 77.5% reported using an institutional standardized protocol for comprehensive biomarker testing (CBT), and 88.4% of these protocols included reflexing to a multigene panel. Most respondents with reflex protocols indicated that 80% or more of newly diagnosed patients with NSCLC received CBT; however, fewer respondents reported that results were available before the oncology visit to select first‑line treatment. Pathologists were the primary ordering providers in institutions with standardized protocols. Respondents agreed that pathologist‑ordered reflex biomarker testing improves cancer care and supported Centers for Medicare & Medicaid Services (CMS) recognition of pathologists as ordering physicians for broad biomarker panels. Despite protocol adoption, respondents cited persistent barriers-including reimbursement, insurance authorization delays, and the Medicare 14-day rule. CONCLUSIONS:Locally standardized protocols incorporating reflex multigene panel testing have been reported and are associated with high rates of CBT. Institutional and operational barriers delay the availability of results and limit the impact of these protocols on first‑line treatment decisions. Clarifying CMS guidance on pathologists as valid ordering physicians for broad biomarker panels, strengthening coordination with multidisciplinary teams, addressing workflow constraints, and educating the laboratories and payers on pathologists having ordering authority may enhance the effectiveness and adoption of reflex biomarker testing models.
OBJECTIVES:Fine-needle aspiration (FNA) is crucial for evaluating thyroid nodules, traditionally using conventional smears (CSs). Recently, liquid-based preparations (LBPs) have gained popularity. This study compared CS and LBP accuracy, combined and separately, in reducing nondiagnostic (Bethesda I) results and identified predictors associated with Bethesda I for both methods combined and separately. METHODS:A prospective comparison of thyroid FNA results in early 2024, using LBP alone vs LBP combined with CSs, was conducted. Retrospective data were collected from 2087 patients who underwent cytologic evaluation between 2020 and 2023, using CS alone and LBP combined with CSs. The study compared nondiagnostic results between the methods and adjusted for significant predictors. RESULTS:In a prospective analysis of 218 LBP samples, combining CSs improved diagnosis in 15 cases (7%), allowing diagnosis in 12 and upgrading the result in 3 cases compared with LBP alone. In the retrospective analysis (CS, 1126 samples; LBP and CS, 961 samples), nondiagnostic results occurred in 14.2% and 18.2% of the cases, respectively (P = .793). Higher nondiagnostic results were significantly associated with older age, comorbidities, and pure cysts (P = .001) for both methods. For CS only, significant associations were found with abnormal thyroid-stimulating hormone (TSH) levels (P = .050), macrocalcifications (P = .045), and heterogeneous cysts (P = .038). CONCLUSIONS:We did not demonstrate an additive effect for the LBP method. However, it may still be preferable in nodules with abnormal TSH levels, heterogeneous cystic features, or macrocalcifications. The prospective findings indicate a clinical advantage for CS analysis. Accordingly, we recommend performing aspiration for both techniques, using CS only if a nondiagnostic result is obtained for LBP.
OBJECTIVES:This study examines the cost of completing laboratory education programs across degree levels and evaluates the availability and use of financial resources for laboratory students. Its findings support advocacy to reduce student debt, inform federal and state policy, and help institutions strengthen recruitment and retention by addressing financial barriers. METHODS:This national cross-sectional study surveyed laboratory professionals, educators, and current or recent students across the United States and its territories. It was conducted in a collaboration among the American Society for Clinical Pathology's (ASCP's) Institute for Science, Technology, and Policy; the ASCP Evaluation, Measurement, and Assessment Department; and the ASCP Board of Certification. RESULTS:The cost of attending a laboratory education program generally falls at or below the lower end of national averages for educational expenses among students and working laboratory professionals. Respondents most often rely on self-funding, federal student loans, and private loans, with financing methods varying by enrollment period. Logistic regression showed that dependence on federal loans and younger age were the strongest predictors of student loan participation among laboratory professionals. CONCLUSIONS:Continued advocacy is essential to ensure that laboratory professionals remain included in federal and state scholarships, grants, and loan forgiveness programs. As policies governing educational funding evolve, it is increasingly important to engage stakeholders in championing financial support for laboratory professionals. Doing so will help reduce the burden of educational costs and strengthen pathways into laboratory careers, ultimately securing recruitment and retention.
OBJECTIVES:Surface low-grade papillary urothelial carcinoma with an invasive phenotype represents an understudied entity with its clinical behavior, therapeutic responses, and long-term outcomes remaining poorly defined. METHODS:We evaluated 17 patients from a single institution with histologically confirmed surface low-grade papillary urothelial carcinoma with an invasive phenotype, followed by longitudinal clinicopathologic analysis to delineate disease trajectories and treatment outcomes. RESULTS:Surface components of all tumors in this cohort demonstrated a low-grade papillary urothelial carcinoma phenotype. At the initial presentation, 53% of patients had invasive disease, while 47% were diagnosed with noninvasive disease. During follow-up, 37% of those with noninvasive disease appeared to progress to invasive disease within 1 year. At the point when invasive disease was diagnosed, pT1 disease was observed in 77% cases, and pT2-4 was observed in 23%. During subsequent follow-up, 77% of patients experienced recurrences, with 41% requiring therapeutic escalation to intravesical Bacillus Calmette-Guérin or systemic chemotherapy for disease progression. High-grade recurrence was identified in 23% patients. Distant metastases developed in 18% of patients, preferentially involving the lungs and bone. The median survival of the cohort was 66 months, and 1 patient died of disease. CONCLUSIONS:These findings underscore the variable and unpredictable course of this disease phenotype, emphasizing its potential for aggressive evolution despite surface low-grade tumor histology. Vigilant surveillance and early consideration of definitive treatment may be a prudent strategy to mitigate progression risks in this rare subset of patients.
OBJECTIVES:Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoma with limited curative treatment options. Carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) has recently been implicated in B-cell receptor signaling in MCL. We evaluated CEACAM1 expression by immunohistochemistry across MCL and other mature B-cell neoplasms, including small lymphocytic lymphoma (SLL), marginal zone lymphoma (MZL), diffuse large B-cell lymphoma (DLBCL), and multiple myeloma (MM). METHODS:We retrospectively analyzed 164 lymphoma cases, 35 MM cases, and 2 plasmacytomas. CEACAM1 expression was assessed on tissue microarrays by immunohistochemistry and scored using a prespecified dichotomous cutoff. In DLBCL, CEACAM1 status was correlated with cell-of-origin classification and targeted mutational data. RESULTS:CEACAM1 was expressed in 27 of 30 MCL cases (90%), higher than in the other lymphoma subtypes combined (35%; P < .0001). Expression was also seen in SLL (20/30, 67%), MM (23/35, 66%), MZL (8/22, 36%), and DLBCL (19/82, 23%). In DLBCL, expression was more frequent in germinal center B-cell subtype than activated B-cell subtype cases (30% vs 13%; P = .023). Within sequenced DLBCL cases, CEACAM1 expression was associated with BCL2 and TNFRSF14 mutations. In MM, CEACAM1 expression was not significantly associated with recurrent cytogenetic abnormalities, although a nonsignificant trend toward higher expression in t(11;14) cases (75% vs 53%, Fisher exact P = .28). CONCLUSIONS:CEACAM1 is frequently expressed in MCL and in subsets of other mature B-cell neoplasms and MM. These findings support further investigation of CEACAM1 as a biologically relevant marker and potential therapeutic target in selected lymphoid malignancies.
OBJECTIVES:Lacrimal gland adenoid cystic carcinoma (ACC) is a rare and lethal malignancy associated with a poor prognosis, with no known therapeutic targets. The clinical relevance of Myb, Sox4, c-Kit protein expression, and the MYB::NFIB fusion gene in lacrimal gland ACC is not well known. The current study aims to investigate the prognostic significance of Myb, Sox-4, c-Kit protein, and the MYB::NFIB fusion gene in lacrimal gland ACC. METHODS:A total of 30 histopathologically diagnosed lacrimal gland ACC cases were included in this study. Myb, Sox4, c-Kit expression, and MYB::NFIB gene fusion were evaluated by immunohistochemistry and fluorescence in situ hybridization, respectively. The results were correlated with clinicopathologic features and patient survival. RESULTS:Immunoexpression of Myb, Sox4, and c-Kit was observed in 70%, 63%, and 63% of ACC cases, respectively. Myb expression showed a significant association with the solid and cribriform histologic patterns, Sox-4 expression, and disease-free survival. On univariate analysis, Myb expression, solid histologic pattern, bone erosion, intracranial extension, and advanced tumor stage were indicators of poor prognosis. c-Kit expression showed a significant association with advanced tumor stage. MYB::NFIB fusion, detected in 47% of cases, was significantly associated with intracranial extension. CONCLUSIONS:Myb protein emerged as a prognostic indicator in the pathogenesis and clinical outcomes of patients with lacrimal gland ACC.
OBJECTIVES:While recent studies have estimated the carbon footprint of surgical pathology, they did not consider the many other impacts this activity has on the environment. We aimed to estimate the environmental impacts of the preparation of hematoxylin-phloxine-saffron (HPS) staining, Congo red (CR) staining, and immunofluorescence (IF) staining for a biopsy analysis. METHODS:We used a comprehensive life cycle assessment methodology of 18 environmental indicators. Life cycle assessment is a standardized and robust method for comprehensively assessing the various environmental impacts of a process throughout its entire life cycle. All contributing items (eg, materials, reagents, electricity) within the different technical steps in the surgical pathology department were considered. RESULTS:For the entire procedure (HPS + CR + IF), the electricity consumption of the cryostat for IF staining was the main contributing item for all indicators (from 19.4%-75.8%), except land use. The other most impactful contributing items were (1) single-use materials used during specimen grossing (second or third largest contributing item for 8 indicators), (2) electricity consumption during slide/block storage (second largest contributor for 6 indicators), (3) materials and consumables used during sample receipt (third largest contributor for 6 indicators), (4) materials used during cryostat section (third largest contributor for 6 indicators), and (5) reagents used during IF staining (second or third largest contributor for 5 indicators). Interestingly, for formalin fixation, the main environmental impacts were represented by global warming, fine particle matter formation, and human toxicity. CONCLUSIONS:These data allow us to better understand the environmental impacts of our activities and to propose more pertinent eco-design solutions.
