Archives of pathology & laboratory medicine最新文献

Context.—: Apocrine differentiation and androgen receptor (AR) positivity represent a specific subset of triple-negative breast cancer (TNBC) and are often considered potential prognostic or predictive factors.

Objective.—: To evaluate the response of TNBC to neoadjuvant chemotherapy (NAC) and to assess the impact of apocrine morphology, AR status, Ki-67 labeling index (Ki-67LI), and tumor-infiltrating lymphocytes (TILs).

Design.—: A total of 232 TNBC patients who underwent NAC followed by surgical resection in a single institute were analyzed. The study evaluated apocrine morphology and AR and Ki-67LI expression via immunohistochemistry from pre-NAC biopsy samples. Additionally, pre-NAC intratumoral TILs and stromal TILs (sTILs) were quantified from biopsies using a deep learning model. The response to NAC after surgery was assessed based on residual cancer burden.

Results.—: Both apocrine morphology and high AR expression correlated with lower Ki-67LI (P < .001 for both). Apocrine morphology was associated with lower postoperative pathologic complete response (pCR) rates after NAC (P = .02), but the difference in TILs between TNBC cases with and without apocrine morphology was not statistically significant (P = .09 for sTILs). In contrast, AR expression did not significantly affect pCR (P = .13). Pre-NAC TILs strongly correlated with postoperative pCR in TNBCs without apocrine morphology (P < .001 for sTILs), whereas TNBC with apocrine morphology demonstrated an indeterminate trend (P = .82 for sTILs).

Conclusions.—: Although TIL counts did not vary significantly based on apocrine morphology, apocrine morphology itself was a more reliable predictor of NAC response than AR expression. Consequently, although apocrine morphology is a rare subtype of TNBC, its identification is clinically important.

Context.—: The Oncotype DX recurrence score (RS) is a widely used test that provides prognostic information on the likelihood of disease recurrence and predictive information on the benefit of chemotherapy in early-stage, hormone receptor-positive breast cancer. Despite its widespread use, quality assurance of the RS does not receive the same level of scrutiny as other tests, such as human epidermal growth factor receptor 2 (HER2) immunohistochemistry.

Objective.—: To use modified Magee equations to calculate Magee score (MS) as a quality check of RS.

Design.—: The MS is an easily accessible prognostic model that uses histopathologic and immunohistochemical criteria. We identified cases where the RS and MS differed by 10 points or more or were in different risk categories. These instances were considered significant discordances. MS was presented along with RS at multidisciplinary tumor boards and all discrepancies were discussed to determine clinical significance and appropriate next steps.

Results.—: Twenty-five of 155 cases (16.1%) had discrepancies between RS and MS. Of these 25 cases, 3 (12%) had problems with either the RS or the histopathologic interpretation. Among the cases with concordant RS and MS, no RS or interpretive problems were identified.

Conclusions.—: Use of the MS as a quality control check for the RS can help ensure appropriate treatment decisions in breast cancer patients. Pathologists can play a key role in ensuring the quality of molecular-based prognostic scores by using histopathologic models to ensure accurate risk stratification and improve clinical outcomes.

Context.—: Mesothelioma subtyping into epithelioid and nonepithelioid categories plays a crucial role in prognosis and treatment selection, with emerging recognition of the impact of various histologic patterns.

Objective.—: To investigate the prognostic implications of transitional and pleomorphic patterns in sarcomatoid mesothelioma.

Design.—: A total of 132 mesothelioma cases (87 biphasic, 45 sarcomatoid) were analyzed. Histologic slides were assessed, treatment data collected, and cases categorized into predominant epithelioid or sarcomatoid patterns. The sarcomatoid mesotheliomas were classified into usual, pleomorphic, and transitional patterns, with reticulin staining for the latter. Statistical analysis included Cox regression and Kaplan-Meier methods.

Results.—: Younger age (P = .02) and receiving therapy (P < .001) correlated with improved survival for both histotypes. Advanced stage was associated with shorter survival in sarcomatoid cases (P = .02). Predominant epithelioid pattern in biphasic cases led to longer survival (P < .001). Transitional and pleomorphic patterns were indicative of worse prognosis, with significantly lower survival in cases with both patterns than with usual sarcomatoid (P = .046). Multivariate analysis identified independent survival factors, including predominant epithelioid component in biphasic mesothelioma (P = .001) and chemotherapy (P < .001).

Conclusions.—: Histologic subtyping in mesothelioma plays a pivotal role in prognosis. Transitional and pleomorphic patterns, even in low percentages, indicate poorer outcomes. This study highlights the need for standardized diagnostic support and suggests the potential utility of histochemical staining in identifying more aggressive morphologic aspects. Recognizing the significance of these patterns can guide treatment decisions and patient care strategies.

Context.—: Unlike parotid fine-needle aspiration biopsy, standardized reporting for core needle biopsy (CNB) and incisional biopsy (IB) is not established.

Objective.—: To examine the value of risk stratification by a Milan System for Reporting Salivary Gland Cytopathology (MSRSGC)-like classifier for parotid CNB/IB.

Design.—: Five hundred ninety-two parotid biopsy records (CNB = 356, IB = 236) were retrieved (1994-2022) along with clinicopathologic data. Diagnoses were transformed to an MSRSGC-like classifier and compared with end points including risk of malignancy.

Results.—: Over time, CNB was progressively more used compared with IB. Overall malignancy call rate was 223 of 592 (37.7%). Common specific diagnoses included Warthin tumor, lymphoma subtypes, and metastatic squamous cell carcinoma for CNB and IB, in addition to pleomorphic adenoma for CNB. Descriptive diagnoses were still frequent. Nondiagnostic rates were higher in CNB (26 of 356; 7.30%) than IB (5 of 236; 2.12%; P <.001). Tissue volumes significantly influenced CNB adequacy, with minimum and optimal volumes of 4.76 mm³ (J index, receiver operating characteristic curve) and 12.92 mm³ (95th percentile of distribution), respectively. One hundred forty-four patients (112 CNBs) had follow-up resections; diagnoses were concordant for 66 of 73 adequate CNBs (90.41%). Our restructured risk grouping of MSRSGC categories performed robustly in terms of risk of malignancy (sensitivity = 85.5%, specificity = 100%, accuracy = 92.3%, area under the curve = 0.9677).

Conclusions.—: Although CNB and IB are amenable to a risk stratification system, there are some differences as compared with fine-needle aspiration biopsy, particularly given the high baseline prevalence of malignancy. Specific diagnoses are often feasible and concordant with resection. CNB tissue volume can inform optimal and minimal sampling recommendations for adequacy.

Context.—: In 2022, 2 distinct guidelines for the diagnosis of myeloid neoplasms became available: the 5th edition of the World Health Organization guideline (WHO2022) solely and the International Consensus Classification (ICC). Despite major overlap, there are important differences that can have important implications.

Objective.—: To explore the current opinions and diagnostic practices of hemato-oncologists and hematopathologists across the United States.

Design.—: An online anonymous survey was created using REDCap, and a secure link was shared via email to fellowship program leaderships and via posts on social media.

Results.—: A total of 310 responses were obtained. Only 33 of 309 respondents (10.7%) reported using solely the 2016 World Health Organization guideline to make diagnoses, whereas 167 of 309 (54%) supplemented it with other guidelines. The rest were either not sure (17; 5.5%), used WHO2022 solely (46; 14.9%), or used ICC solely (6; 1.9%). The choice of guideline was not related to region (P = .15), practice setting (P = .86), or hospital size (P = .22). More than 90% reported it is a source of confusion in clinical diagnosis, management, trial design, and other areas.

Conclusions.—: Overall, our study found that having 2 distinct guidelines could be a source of confusion for physicians and calls for a unified diagnostic language.

Context.—: Rapid advancements in the understanding and manipulation of tumor-immune interactions have led to the approval of immune therapies for patients with non-small cell lung cancer. Certain immune checkpoint inhibitor therapies require the use of companion diagnostics, but methodologic variability has led to uncertainty around test selection and implementation in practice.

Objective.—: To develop evidence-based guideline recommendations for the testing of immunotherapy/immunomodulatory biomarkers, including programmed death ligand-1 (PD-L1) and tumor mutation burden (TMB), in patients with lung cancer.

Design.—: The College of American Pathologists convened a panel of experts in non-small cell lung cancer and biomarker testing to develop evidence-based recommendations in accordance with the standards for trustworthy clinical practice guidelines established by the National Academy of Medicine. A systematic literature review was conducted to address 8 key questions. Using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach, recommendations were created from the available evidence, certainty of that evidence, and key judgments as defined in the GRADE Evidence to Decision framework.

Results.—: Six recommendation statements were developed.

Conclusions.—: This guideline summarizes the current understanding and hurdles associated with the use of PD-L1 expression and TMB testing for immune checkpoint inhibitor therapy selection in patients with advanced non-small cell lung cancer and presents evidence-based recommendations for PD-L1 and TMB testing in the clinical setting.

Context.—: Fondaparinux monitoring is not required among noncritically ill patients due to a predictable dose-response effect. However, this is debatable among critically ill patients, because fondaparinux bioavailability can be influenced by complicated medical conditions.

Objective.—: To investigate fondaparinux monitoring among the critically ill.

Design.—: Retrospective analysis of patients admitted in intensive care unit from February 2021 to December 2021, who received prophylactic fondaparinux and had anti-Xa activity tests.

Results.—: Of 156 anti-Xa values, 86 (55.1%) were within 0.10-0.50 μg/mL (the recommended prophylactic range), 38 (24.4%) were less than 0.10 μg/mL, 32 (20.5%) were greater than 0.50 μg/mL, demonstrating an unpredictable dose-response effect. Among 70 patients, thrombotic tendency was controlled in 32 (45.7%), thrombosis progressed in 22 (31.4%), bleeding events occurred in 16 (22.9%). Patients with progressed thrombosis had 17 of 54 (31.5%) anti-Xa less than 0.10 μg/mL, even though this proportion was greater than that of patients with controlled thrombotic tendency (11 of 72, 15.3%), it was similar to that of patients with bleeding (10 of 30, 33.3%), indicating a weak practicability of anti-Xa for monitoring fondaparinux efficacy. Thrombin-antithrombin complex showed a gradual decline among patients with controlled thrombotic tendency, but a bounce-back effect among patients with progressed thrombosis. Thrombelastography R value above the upper reference value occurred more frequently among patients with bleeding (4 of 6, 66.7%) compared to patients without bleeding (4 of 22, 18.2%) (P = .01).

Conclusions.—: The fondaparinux dose-response effect was unpredictable among the critically ill; anti-Xa activity combined with thrombin-antithrombin complex and thrombelastography can be helpful to guide a precise fondaparinux therapy in this population.

Context.—: Insulinoma-associated protein-1 (INSM1) is a recently developed immunohistochemical marker claimed to be highly specific and sensitive for the diagnosis of neuroendocrine malignancies. Recent studies, however, have demonstrated that this marker can also be expressed in non-neuroendocrine neoplasms including squamous cell carcinoma of the thymus.

Objective.—: To examine INSM1 expression in lymphoepithelial thymic carcinomas.

Design.—: Thirty-four cases of lymphoepithelial carcinoma of the thymus were examined by immunohistochemistry or in situ hybridization for INSM1, synaptophysin, chromogranin, CD5, CD117, Epstein-Barr virus-encoded small ribonucleic acid (EBER), and Ki-67. Basic clinical information was abstracted from the medical record.

Results.—: The patients were 14 women and 20 men, aged 20 to 85 years. The tumors arose in the anterior mediastinum without any previous history or evidence of malignancy at other sites. Immunohistochemical staining showed moderate to strong positivity of the tumor cells for INSM1 in 65% of cases (22 of 34), focal weak positivity in 20% (7 of 34), and negative staining in 5 cases. Chromogranin staining was focally and weakly positive in 1 case, and synaptophysin showed only focal weak positivity in scattered tumor cells in 12 cases. No significant correlation could be identified between the pattern and intensity of staining for INSM1 and staining for CD5, CD117, and Ki-67.

Conclusions.—: INSM1 positivity in lymphoepithelial carcinoma of the thymus may represent a pitfall for diagnosis, particularly in small biopsy samples. Awareness of this finding may be of importance to avoid misdiagnosis of neuroendocrine malignancy.

Context.—: Flow cytometry immunophenotypic analysis plays an important role in the diagnosis, classification, and disease monitoring of hematologic neoplasms. The interpretation of flow cytometry testing can be challenging.

Objective.—: To explore ways to improve diagnostic accuracy and in turn enhance the quality of patient care.

Design.—: A flow cytometry quality assurance (QA) program was developed. Cases from various complex flow cytometry panels were randomly selected and cross-reviewed. The outcomes of the QA review were categorized into 3 groups: complete agreement, minor discrepancy, and major discrepancy. Each discrepancy underwent a process of documentation, discussion, and resolution. Here we summarize our 3 years of experience with this program.

Results.—: In total, 6166 cases were evaluated; 6028 cases (97.7%) showed complete concordance, 120 cases (2.0%) showed minor discrepancies, and 18 cases (0.3%) showed major discrepancies. Among the top 5 panels evaluated, the panel evaluating mature T-cell abnormalities showed the highest rate of discrepancy, whereas the panel for evaluation of myelodysplastic syndromes showed the lowest discrepancy rate. When analyzing the trends of concordance and discrepancy over time, we observed a statistically significant decrease in discrepancy rate over time, from 4% at the beginning of the 6-month period to 1.5% in the final 6-month period.

Conclusions.—: The overall concordance rate was 97.7%. The remaining 2.3% of cases showed discrepancies that required a correction, underscoring the value and necessity of having a QA program. The overall discrepancy rates exhibited a gradual decline over time, indicative of the positive impact of the QA program on enhancing diagnostic competency and accuracy over time.