In 2014, the College of American Pathologists developed an evidence-based guideline to address analytic validation of immunohistochemical assays. Fourteen recommendations were offered. Per the ...National Academy of Medicine standards for developing trustworthy guidelines, guidelines should be updated when new evidence suggests modifications.
To assess evidence published since the release of the original guideline and develop updated evidence-based recommendations.
The College of American Pathologists convened an expert panel to perform a systematic review of the literature and update the original guideline recommendations using the Grading of Recommendations Assessment, Development and Evaluation approach.
Two strong recommendations, 1 conditional recommendation, and 12 good practice statements are offered in this updated guideline. They address analytic validation or verification of predictive and nonpredictive assays, and recommended revalidation procedures following changes in assay conditions.
While many of the original guideline statements remain similar, new recommendations address analytic validation of assays with distinct scoring systems, such as programmed death receptor-1 and analytic verification of US Food and Drug Administration approved/cleared assays; more specific guidance is offered for validating immunohistochemistry performed on cytology specimens.
The World Health Organization considers enterocolic mast cell aggregates with atypical morphologic and/or immunohistochemical features diagnostic of systemic mastocytosis mostly because published ...data are heavily influenced by inclusion of symptomatic patients with systemic disease. We occasionally encounter atypical mast cells in gastrointestinal biopsy samples from patients in whom systemic mastocytosis is not suspected. The aim of this study was to describe the clinicopathologic features and implications of atypical enterocolic mast cell aggregates in 16 patients without suspected or established systemic mastocytosis. Mast cell infiltrates were assessed for morphology, distribution, associated inflammatory cells, and CD117 and CD25 immunoexpression. Most (63%) patients were women; 15 underwent endoscopic examination for screening (n=7), abdominal pain (n=3), diarrhea (n=3), changing bowel habits (n=1), and dysphagia (n=1). Mast cell aggregates were detected in 1 colectomy specimen for cancer. Colonic involvement was most common (n=14) and resulted in polypoid (n=10), edematous (n=2), or normal (n=3) mucosae. All cases featured CD117/CD25, ovoid mast cells concentrated beneath the epithelium, or diffusely involving the entire mucosal thickness. Eosinophils were numerous and obscured mast cells in 63% of cases. Spontaneous resolution of symptoms occurred in all patients (mean follow-up54 mo), and asymptomatic patients remained symptom-free (mean follow-up17 mo). Of 4 patients evaluated for systemic mastocytosis, 3 had negative bone marrow biopsies and one lacked a KIT mutation in peripheral blood. We conclude that, although careful clinical assessment of patients with incidental enterocolic mast cell aggregates is reasonable, labeling them with a systemic hematologic disorder may not be justified.
Therapy targeted at human epidermal growth factor receptor 2 (HER2; also known as ERBB2) was used initially for breast and gastroesophageal carcinoma and has more recently been adopted for ...endometrial serous carcinoma (ESC) and colorectal carcinoma (CRC). There is evidence that predictive biomarker testing algorithms for HER2 must be tumor type specific and that an algorithm validated for one tumor type cannot be applied to another.
To describe current laboratory practices for HER2 assessment in ESC and CRC.
We surveyed laboratories participating in the 2021 College of American Pathologists (CAP) HER2 immunohistochemistry proficiency testing program.
The survey was distributed to 1548 laboratories and returned by 1195, of which 83.5% (998) were in the United States. For ESC, 24.0% (287) of laboratories reported performing in-house testing for HER2 by immunohistochemical staining and/or in situ hybridization; of these, 44.3% (127) performed it reflexively on all cases of ESC. The most common criterion for evaluating HER2 was the American Society of Clinical Oncology/CAP 2018 guideline for breast carcinoma (69.0%; 194 of 281), whereas only 16.0% (45) of laboratories used guidelines specific to ESC. For CRC, 20.2% (239 of 1185) of laboratories performed in-house HER2 testing, and 82.0% of these (196) did the test only at the clinician's request. A plurality (49.4%; 115 of 233) used gastroesophageal cancer guidelines when scoring CRC, 30.0% (70) used the CRC scoring system from the HERACLES trial, and 16.3% (38) used the American Society of Clinical Oncology/CAP 2018 guideline for breast carcinoma.
Laboratories vary in their approach to HER2 testing in ESC and CRC. Most laboratories did not report using tumor type-specific recommendations for HER2 interpretation. The lack of standardization could present a challenge to evidence-based practice when considering targeted therapy for these diseases.
Platinum-based chemotherapy with or without immunotherapy is the mainstay of treatment for advanced stage non-small cell lung cancer (NSCLC) lacking a molecular driver alteration. Pre-clinical ...studies have reported that pharmacological ascorbate (P-AscH-) enhances NSCLC response to platinum-based therapy. We conducted a phase II clinical trial combining P-AscH- with carboplatin-paclitaxel chemotherapy.
Chemotherapy naïve advanced stage NSCLC patients received 75 g ascorbate twice per week intravenously with carboplatin and paclitaxel every three weeks for four cycles. The primary endpoint was to improve tumor response per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 compared to the historical control of 20%. The trial was conducted as an optimal Simon's two-stage design. Blood samples were collected for exploratory analyses.
The study enrolled 38 patients and met its primary endpoint with an objective response rate of 34.2% (p = 0.03). All were confirmed partial responses (cPR). The disease control rate was 84.2% (stable disease + cPR). Median progression-free and overall survival were 5.7 months and 12.8 months, respectively. Treatment-related adverse events (TRAE) included one grade 5 (neutropenic fever) and five grade 4 events (cytopenias). Cytokine and chemokine data suggest that the combination elicits an immune response. Immunophenotyping of peripheral blood mononuclear cells demonstrated an increase in effector CD8 T-cells in patients with a progression-free survival (PFS) ≥ 6 months.
The addition of P-AscH- to platinum-based chemotherapy improved tumor response in advanced stage NSCLC. P-AscH- appears to alter the host immune response and needs further investigation as a potential adjuvant to immunotherapy.
•The study evaluated the efficacy of Pharmacological Ascorbate with platinum-based chemotherapy in advanced-stage NSCLC.•Pharmacological Ascorbate improved the response of NSCLC to platinum-doublet chemotherapy.•Cytokine and chemokines data suggest that protocol regimen elicited an immune response.•Patients with longer PFS had a greater fold increase in circulating activated effector CD8 T cells.•The combination of ascorbate and chemotherapy was safe and tolerable.
Objectives: The ongoing global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic necessitates adaptations in the practice of surgical pathology at scale. Primary diagnosis by ...whole-slide imaging (WSI) is a key component that would aid departments in providing uninterrupted histopathology diagnosis and maintaining revenue streams from disruption. We sought to perform rapid validation of the use of WSI in primary diagnosis meeting recommendations of the College of American Pathologists guidelines. Methods: Glass slides from clinically reported cases from 5 participating pathologists with a preset washout period were digitally scanned and reviewed in settings identical to typical reporting. Cases were classified as concordant or with minor or major disagreement with the original diagnosis. Randomized subsampling was performed, and mean concordance rates were calculated. Results: In total, 171 cases were included and distributed equally among participants. For the group as a whole, the mean concordance rate in sampled cases (n = 90) was 83.6% counting all discrepancies and 94.6% counting only major disagreements. The mean pathologist concordance rate in sampled cases (n = 18) ranged from 90.49% to 97%. Conclusions: We describe a novel double-blinded method for rapid validation of WSI for primary diagnosis. Our findings highlight the occurrence of a range of diagnostic reproducibility when deploying digital methods. Key Words: Whole-slide imaging; WSI validation; Digital pathology; Case management software; Primary digital diagnosis; SARS-CoV-2
The authors have identified an acute diarrheal syndrome that develops about 4 months after cord-blood hematopoietic stem-cell transplantation with the use of umbilical-cord blood. The disease is ...characterized by fever, watery diarrhea, and responsiveness to antibiotics.
Hematopoietic stem-cell transplantation (HSCT) with the use of umbilical-cord blood is effective in patients for whom a sibling or matched, unrelated donor is not available.
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Acute graft-versus-host disease (GVHD), a major cause of illness in patients undergoing HSCT, is less severe with cord-blood transplants than with adult donor transplants.
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However, cord-blood HSCT is associated with an increased risk of infection related to delayed immune reconstitution because of the infusion of naive immune cells with the graft.
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Acute GVHD and gastrointestinal infection are important causes of diarrhea after HSCT.
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Distinguishing between them is important because their treatment . . .
Abstract
Objectives
The ongoing global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic necessitates adaptations in the practice of surgical pathology at scale. Primary diagnosis ...by whole-slide imaging (WSI) is a key component that would aid departments in providing uninterrupted histopathology diagnosis and maintaining revenue streams from disruption. We sought to perform rapid validation of the use of WSI in primary diagnosis meeting recommendations of the College of American Pathologists guidelines.
Methods
Glass slides from clinically reported cases from 5 participating pathologists with a preset washout period were digitally scanned and reviewed in settings identical to typical reporting. Cases were classified as concordant or with minor or major disagreement with the original diagnosis. Randomized subsampling was performed, and mean concordance rates were calculated.
Results
In total, 171 cases were included and distributed equally among participants. For the group as a whole, the mean concordance rate in sampled cases (n = 90) was 83.6% counting all discrepancies and 94.6% counting only major disagreements. The mean pathologist concordance rate in sampled cases (n = 18) ranged from 90.49% to 97%.
Conclusions
We describe a novel double-blinded method for rapid validation of WSI for primary diagnosis. Our findings highlight the occurrence of a range of diagnostic reproducibility when deploying digital methods.
Diagnosis of Wilson disease (WD) can be difficult because of its protean clinical presentations, but early diagnosis is important because effective treatment is available and can prevent disease ...progression. Similarly, diagnosis of WD on liver biopsy specimens is difficult due to the wide range of histologic appearances. A stain that could help identify WD patients would be of great value. The goal of this study was to use mass spectrometry-based proteomics to identify potential proteins that are differentially expressed in WD compared to controls, and could serve as potential immunohistochemical markers for screening. Several proteins were differentially expressed in WD and immunohistochemical stains for two (metallothionein (MT) and cytochrome C oxidase copper chaperone (COX17)) were tested and compared to other methods of diagnosis in WD including copper staining and quantitative copper assays. We found diffuse metallothionein immunoreactivity in all liver specimens from patients with WD (n = 20); the intensity of the staining was moderate to strong. This staining pattern was distinct from that seen in specimens from the control groups (none of which showed strong, diffuse staining), which included diseases that may be in the clinical or histologic differential of WD (steatohepatitis (n = 51), chronic viral hepatitis (n = 40), autoimmune hepatitis (n = 50), chronic biliary tract disease (n = 42), and normal liver (n = 20)). COX17 immunostain showed no significant difference in expression between the WD and control groups. MT had higher sensitivity than rhodanine for diagnosis of WD. While the quantitative liver copper assays also had high sensitivity, they require more tissue, have a higher cost, longer turnaround time, and are less widely available than an immunohistochemical stain. We conclude that MT IHC is a sensitive immunohistochemical stain for the diagnosis of WD that could be widely deployed as a screening tool for liver biopsies in which WD is in the clinical or histologic differential diagnosis.
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