American journal of clinical pathology最新文献

Objective: β-Catenin-mutated hepatocellular adenomas (HCAs) carry an increased malignant transformation risk and are screened by interpreting glutamine synthetase (GS) and β-catenin by immunohistochemistry (IHC). Our study aims to assess GS and β-catenin interpretation guidelines for applicability and reproducibility in predicting high-risk HCA and other relevant molecular alterations.

Methods: Hematoxylin and eosin (H&E), β-catenin, GS, and CD34 stains from 75 HCAs were interpreted by three pathologists using Method A (GS interpretation: negative, perivenular patchy, map-like, diffuse, and indeterminate) and Method B criteria (similar GS interpretation scheme based on a recent publication, with and without CD34 expression patterns). Ease of application and interpretation confidence level were assessed. High-risk IHC was defined as nuclear β-catenin and/or diffuse homogeneous GS. Molecular testing was performed on a subset of HCAs and controls.

Results: There were 57 resections and 18 biopsy specimens examined. Methods A and B (GS only) were rated as easy to apply, with high interpretation confidence (≥90% using both methods). Consensus rate was comparable in biopsy specimens (100% for both methods) and resections (88% for Method A, 93% for Method B). While the same cases were stratified into high-risk GS categories using both systems, clinically significant genetic alterations (TERT promoter, EGFR, MTOR, and TP53) were identified in 25% of cases stratified as not high risk by IHC.

Conclusions: Both methods have a similar ease of application and level of interpretation confidence, and they also detected β-catenin mutations as expected. Other relevant molecular alterations associated with risk of neoplastic progression and/or bleeding were detected in 25% of HCAs with the non-high-risk IHC phenotype, suggesting the value of molecular testing in this subset.

Objective: Breast cancer is a leading malignancy among women worldwide. Mitotic regulation proteins such as POC1A and NUF2 have been linked to tumor aggressiveness.

Methods: This retrospective study evaluated the immunohistochemical expression of POC1A and NUF2 in 136 cases of invasive ductal carcinoma (IDC), 96 matched metastatic lymph nodes, and 48 adjacent normal breast tissues using Ki-67 as a supporting proliferation marker. Associations with clinicopathologic features were assessed, and survival analyses were conducted using Kaplan-Meier and Cox regression models.

Results: POC1A and NUF2 were significantly overexpressed in tumor tissues compared to normal tissues (P < .001). High expression levels were associated with larger tumor size, higher grade and stage, lymphovascular invasion, distant metastasis, hormone receptor negativity, triple-negative breast cancer (TNBC), and poor Nottingham Prognostic Index scores. Both markers were significantly associated with lymph node involvement. Ki-67 expression also correlated positively with POC1A and NUF2 coexpression (r = 0.574; 95% CI, 0.449-0.677; P < .001). Multivariate analysis identified POC1A as an independent predictor of poor overall survival (OS) (hazard ratio, 2.102; 95% CI, 1.41-3.13; P < .001). Coexpression of POC1A and NUF2 was linked to significantly worse prognosis.

Conclusions: High expression levels of POC1A and NUF2 were significantly associated with aggressive clinicopathologic features and poorer prognosis in IDC. Their correlation with Ki-67 and enrichment in TNBC highlight their potential as prognostic markers and predictors of nodal metastasis. Importantly, POC1A expression was independently associated with worse OS in IDC, including TNBC. While not yet directly actionable, our findings nominate POC1A as a promising independent prognostic biomarker that could potentially refine risk stratification in IDC, particularly for aggressive subtypes like TNBC. However, prospective validation in larger cohorts is mandatory before any clinical application.

Objective: To characterize the clinicopathologic, immunohistochemical, and molecular features of 2 new cases of xanthomatous giant cell renal cell carcinoma, a rare TSC2/MTOR-altered renal neoplasm.

Methods: Both tumors underwent histologic evaluation, immunohistochemical profiling, and DNA-based targeted next-generation sequencing. Fluorescence in situ hybridization for TFE3 rearrangement was performed in 1 case.

Results: Both patients were men (aged 27 and 64 years) with incidentally detected renal masses showing infiltrative growth and discohesive large cells with a xanthomatous-eosinophilic cytoplasm, basophilic stippling, vacuolization, and prominent nucleoli. Both tumors were positive for PAX8, CD10, vimentin, and GPNMB; keratin 20 was diffusely strong in 1 patient and isolated in the other. One case showed TFE3 and Melan-A coexpression without TFE3 rearrangement. Biallelic TSC2 mutations were identified in both cases, corroborated by loss of TSC2 protein expression. Both patients were disease-free at 15 and 40 months postsurgery.

Conclusions: Xanthomatous giant cell renal cell carcinoma represents a distinct morphologic variant of TSC/MTOR-altered renal neoplasms with indolent behavior despite aggressive histologic features.

Objective: This study aimed to determine reference intervals for immunoglobulin G (IgG), IgA, IgM, and IgE concentrations in the pediatric population using an immunonephelometric method. The reliability of the derived reference intervals was assessed by comparing them with results from the Canadial Laboratory Initiative on Pediatric Reference Intervals (CALIPER) study, which employed direct methods.

Methods: A total of 120 194 IgG, IgA, IgM, and IgE results from 2020 to 2023 were extracted from the hospital database. After applying the necessary exclusion criteria, 2 groups were formed: 1 with exclusions (n = 70 565) and 1 without (n = 69 435). Immunoglobulin results were partitioned by age and sex, where required, using the Harris-Boyd method. Reference intervals were calculated using the refineR and Kolmogorov-Smirnov Distance (kosmic) indirect reference interval calculation algorithms, with and without outlier exclusion, to assess the impact of outliers.

Results: A statistically significant difference between sexes was observed only for the IgM concentrations-specifically, in the age group of 1 month to 1 year. In both groups, with and without outlier exclusion, a difference was observed only for the IgE test in the group aged 1 to 18 years, where a higher frequency of pathologic results was observed. The reference intervals calculated using the kosmic and refineR algorithms were generally consistent with each other; however, substantial differences were observed for IgA in the group aged 2 to 3 years and for the IgE test. The patterns observed in the reference intervals were consistent with those reported in the CALIPER study.

Conclusions: This study successfully verified the CALIPER pediatric reference intervals for IgG, IgA, IgM, and IgE concentrations using the immunonephelometric method.

Objectives: Special AT-rich sequence binding protein 2 (SATB2) is a sensitive immunohistochemical marker of colorectal origin. Loss of SATB2 staining in colorectal cancer (CRC) has been associated with adverse outcomes, poor response to chemotherapy, and clinicopathologic features. This study summarizes the survival outcomes and clinicopathologic associations of SATB2 expression and CRC.

Methods: A literature search for studies of survival outcomes and clinicopathologic associations of SATB2 in CRC was undertaken. Meta-analysis with random-effects models was used to combine data.

Results: We analyzed 17 published studies comprising 7733 patients. SATB2 loss was seen in 19% of cases (risk ratio [RR], 0.19 [95% CI, 0.14-0.27]). SATB2 loss was associated with worse overall survival (RR, 0.76 [95% CI, 0.70-0.84]; P < .001) and worse disease-free survival (RR, 0.78 (95% CI, 0.72-0.86]; P < .001). SATB2 loss was associated with more advanced overall stage, nodal involvement, distant metastases, and right-sided tumor location. Loss was also associated with high-risk histologic features, including poor differentiation; lymphatic, venous, and perineural invasion; mucinous and signet ring histology; and tumor budding. SATB2 loss was also seen more commonly in microsatellite unstable and BRAF-mutated cases but was not associated with KRAS mutation.

Conclusions: Loss of SATB2 staining in CRC is associated with inferior survival outcomes and adverse clinicopathologic features.

Objective: To identify challenges, opportunities, and best practices for improving the communication of urgent and significant unexpected diagnoses in anatomic pathology, to enhance diagnostic excellence and patient safety.

Methods and results: The American Society for Clinical Pathology convened a group of eleven pathologists from diverse practice settings who discussed the challenges, opportunities, and best practices for improving communication of urgent and significant unexpected findings in anatomic pathology. Through structured discussions, the group identified the challenges such as variability in definitions of urgent and significant unexpected diagnoses and lack of standardized protocols. The group developed a set of best practices and strategies to support timely notification, clear documentation, and standardized communication processes within the healthcare teams to ensure appropriate patient management based on the communicated diagnoses.

Conclusions: Timely and effective communication of urgent and significant unexpected findings in anatomic pathology is essential for patient safety. Standardized definitions and protocols, combined with collaborative strategies, can improve diagnostic accuracy and clinical outcomes. Future research should focus on building an evidence base to support these practices and evaluate their impact on patient care.

Objective: Colorectal cancer surveillance recommendations rely on polyp counts to determine optimal intervals. This study aims to uncover discrepancies in polyp counts between colonoscopy and pathology reports and their clinical implications.

Methods: A retrospective review of 1293 polyp cases from October 1 to December 31, 2019, was performed, comparing the reported number of polyps removed to the number identified pathologically (gross and microscopic). Cases with discrepant polyp counts prompted additional reviews, including colonoscopy reports and glass slides. The potential impact on surveillance interval decisions was further assessed.

Results: Of the 1293 polyp specimens from 600 patients, 1072 (83%) contained a single polyp per container, with no discrepancies. However, in the remaining 221 (17%) specimens that had multiple polyps submitted per container, an exact polyp count was indeterminable in 54 (24%) of these 221 specimens. Among these, polyp count discrepancies in 15 patients potentially influenced surveillance intervals. Overall, the most common discrepancy was a higher number of fragments on gross description and/or glass slides compared to colonoscopy reports and/or a container designator.

Conclusions: Discrepancies in polyp counts more often occur when more than 1 polyp is submitted in a single container. These discrepancies may alter the recommended surveillance colonoscopy intervals. Therefore, close collaboration between pathology and colonoscopy providers-through improved endoscopic documentation, specimen handling, reporting strategies, and feedback-is essential to ensure accurate polyp counts and mitigate these effects. Adopting a single polyp per container approach in those cases where polyp count matters would significantly improve report accuracy and ensure the most appropriate surveillance intervals.

Objective: Differentiating between the repertoire of immunoglobulin rearrangements is important in guiding diagnoses and management of B-cell lymphoma processes. A subset of these disease entities, such as chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), can show distinct genomic profiles with a shared cell of origin. In this report, we describe a rare case in which differentiating between the immunoglobulin family of rearrangements (IGH, IGK, IGL) with optical genome mapping (OGM) helped revise the clinical suspicion of CLL.

Methods: We present a 50-year-old woman with a lymphoproliferative disorder. Her clinical laboratory genetics workup included chromosomal banding analysis, fluorescence in situ hybridization, next-generation sequencing, and OGM. Optical genome mapping was performed on the bone marrow specimen, starting with the ultra-high molecular weight DNA mapped on the Saphyr system. Structural variants with OGM were detected using rare variant analysis set to default parameters.

Results: In 2021, flow cytometry performed on the peripheral blood detected a monotypic CD5+/CD23+ B-cell population. A subsequent bone marrow in 2024 detected similar findings by flow with κ light chain restriction. Chromosomal banding analysis found a translocation between the long arms of chromosomes 11 and 22. Optical genome mapping demonstrated that this translocation involved the CCND1 locus juxtaposed to the regulatory immunoglobulin λ (IGL) gene cluster.

Conclusions: We present a case of CD5+/CD10- small B-cell lymphoma that immunophenotypically resembled CLL but showed positive immunostaining for cyclin D1. The combination of the clinicopathologic findings and the CCND1 translocation involving IGL, detected by OGM, supported a revised diagnosis of MCL.

Objective: Research on CD9 expression has been extensive in B lymphoblastic leukemia, with fewer studies focusing on acute myeloid leukemia (AML). We investigated the usefulness of CD9 in differentiating normal from abnormal myeloid progenitors, as well as expression in normal cell types and in AML.

Methods: Flow cytometry was used to assess the level of CD9 expression on normal and leukemic myeloid blasts and other normal bone marrow populations. Geometric mean fluorescence intensity levels and expression patterns were compared among cell types and AML subtypes.

Results: In normal subsets (n = 69), the level of CD9 expression was lowest in mature B cells, myeloid blasts, promyelocytes, and neutrophils, with intermediate expression in monocytes and highest in hematogones (stages 1 and 2). Committed myeloid progenitors (CMPs) had lower expression than hematopoietic stem cells (HSCs). CD9 typically has higher expression in AML (n = 58) compared to normal myeloid blasts and promyelocytes, and it is differentially expressed in AML, with the highest expression in PML::RARA AML.

Conclusions: Aberrant CD9 expression can be useful differentiating normal from abnormal myeloid progenitors, with the highest level of expression in AML with PML::RARA in our cohort. There was differential expression between HSCs and CMPs in the small numbers studied. Normal mature B cells can be used as an internal negative control in most cases.

Objective: We sought to investigate the frequency of diagnostic changes in hematopathology cases referred to the University of Michigan during a 3-year period and explore which parameters contribute to diagnostic change.

Methods: Pathology reports from hematology patients who came to the University of Michigan for a second opinion from 2017 to 2019 were reviewed. Diagnostic discrepancies were classified into major or minor. Specimen type, hematopathology board certification and practice time of the outside pathologists, referring practice type, and whether the second review was done at the referring institution were recorded too. Agreement in diagnosis by the above-listed specimen characteristics was analyzed.

Results: A total of 2786 cases were reviewed (2016 bone marrow and 770 tissue specimens). Disagreements in diagnosis were found in 263 cases (9.4% of total cases), and 163 (5.9%) were major disagreements. Among the major disagreements, 119 (73%) were in bone marrow specimens and 44 (27%) in tissue specimens. Among bone marrows, the most common revisions were myeloid neoplasm reclassifications (35.3%), whereas lymphoma subtype revisions comprised 70.4% of all changes in tissues. Univariate analysis showed that major disagreement rates were significantly higher in cases signed out by pathologists without hematopathology certification, those practicing for more than 10 years, and in cases from nonacademic institutions. When analyzing bone marrows and tissues separately, these differences remained significant only for bone marrows.

Conclusions: Second review of pathology material serves as an important quality assurance and patient safety measure. Lack of hematopathology training of the referring pathologists may contribute to the rate of diagnostic discrepancy.