Anatomic Pathology Specimens Research Articles

Validating Whole Slide Imaging Systems for Diagnostic Purposes in Pathology.

The original guideline, "Validating Whole Slide Imaging for Diagnostic Purposes in Pathology," was published in 2013 and included 12 guideline statements. The College of American Pathologists convened an expert panel to update the guideline following standards established by the National Academies of Medicine for developing trustworthy clinical practice guidelines. To assess evidence published since the release of the original guideline and provide updated recommendations for validating whole slide imaging (WSI) systems used for diagnostic purposes. An expert panel performed a systematic review of the literature. Frozen sections, anatomic pathology specimens (biopsies, curettings, and resections), and hematopathology cases were included. Cytology cases were excluded. Using the Grading of Recommendations Assessment, Development, and Evaluation approach, the panel reassessed and updated the original guideline recommendations. Three strong recommendations and 9 good practice statements are offered to assist laboratories with validating WSI digital pathology systems. Systematic review of literature following release of the 2013 guideline reaffirms the use of a validation set of at least 60 cases, establishing intraobserver diagnostic concordance between WSI and glass slides and the use of a 2-week washout period between modalities. Although all discordances between WSI and glass slide diagnoses discovered during validation need to be reconciled, laboratories should be particularly concerned if their overall WSI-glass slide concordance is less than 95%.

Survey of Clinical and Anatomic Pathology Laboratory Infrastructure in Mozambique.

Pathology services are limited in most areas of sub-Saharan Africa. This study's aim was to survey anatomic and clinical pathology services and laboratory infrastructure in Mozambique. A survey was conducted from October-December 2018 across the four central hospitals of Mozambique to determine infrastructure and pathology services available. Most laboratory/pathology services in Mozambique are limited to the four central hospitals. Only 14 pathologists practice in the country despite a population of 29.5 million for the world's fifth worst workforce/population ratio. Approximately 35,000 anatomic pathology specimens are evaluated annually. Standard services across chemistry, hematology, microbiology, and blood bank are available at the four central hospitals. Esoteric laboratory testing and immunohistochemistry are generally only available in Maputo. While most pathology services are available in Mozambique, many are available only at the Maputo laboratory. Expansion of pathology services and infrastructure will improve provision of effective and efficient health care as access to timely and accurate clinical diagnoses increases in Mozambique.

Clinical Performance of Mycobacterial Immunohistochemistry in Anatomic Pathology Specimens.

Diagnosis of mycobacterial infections poses significant challenges in anatomic pathology. We recently described the use of antimycobacteria immunohistochemistry (IHC) as a sensitive, efficient diagnostic tool and now report the clinical performance of this assay among general, noninfectious disease pathology-trained anatomic pathologists. Over a 2-year period, all cases were retrospectively identified in which mycobacterial IHC was performed during routine diagnostic workup. From October 2017 to September 2019, mycobacterial IHC was evaluated for 267 cases, resulting in 58 (22%) positive stains. Compared with culture and molecular results, the sensitivity and specificity of IHC were 52% and 80%, respectively. IHC performed significantly better than acid-fast bacilli (AFB) staining (Ziehl-Neelsen) (P < .0001; sensitivity 21%, specificity 92%) but similarly to modified AFB staining (mAFB; Fite-Faraco) (P = .9; sensitivity 61%, specificity 84%). In cases with discordant IHC and mAFB staining, there were no differences in rates of culture or polymerase chain reaction-confirmed positivity. Mycobacterial IHC was well adopted with superior clinical performance to AFB and comparable performance to mAFB. These results support the use of IHC as an adjunctive tool in the diagnosis of mycobacterial infections and suggests its potential role as a rapid screening test for molecular testing.

An Analysis of the Effect of the COVID-19 Pandemic on Case Volumes in an Academic Subspecialty-Based Anatomic Pathology Practice

The recent COVID pandemic has had a major effect on anatomic pathology specimen volumes across the country. The effect of this pandemic on a subspecialty academic practice is presented. We used a data-driven approach to monitor the changing workloads in a granular fashion and dynamically adjust the scheduling of faculty and histology staff accordingly to minimize the number of people present on-site. At the peak of the pandemic locally, the main hospital in our health system had 450 COVID-positive inpatients. The surgical pathology specimen volume dropped to 13% of the pre-pandemic levels, and this occurred about 2 weeks before the peak of the inpatient census; cytology specimens (the majority of which are outreach gynecological) dropped to approximately 5% of the pre-pandemic volume, 4 weeks before the peak inpatient census. All of the surgical subspecialty services showed a significant decrease in volume, with hematopathology being the least affected (dropped to 30% of the pre-pandemic level). The genitourinary surgical subspecialty service (predominantly prostate and bladder biopsies) was the most affected (dropped to 1% of the pre-pandemic level) but was fastest to return as clinical operations began to return to normal. The only specimen type which showed a significant increase in turnaround time during the pandemic was our gynecologic cytology specimens and that occurred as the specimen volume returned. This was due to stay-at-home directives for the cytotechnologists and the fact that some of them were retasked to participate in our SARS-CoV-2 testing.

Targeting specimen misprocessing safety events with failure modes and effects analysis.

Targeting specimen misprocessing safety events with failure modes and effects analysis.

Decreasing Histology Turnaround Time Through Stepwise Innovation and Capacity Building in Rwanda.

PurposeMinimal turnaround time for pathology results is crucial for highest-quality patient care in all settings, especially in low- and middle-income countries, where rural populations may have limited access to health care.MethodsWe retrospectively determined the turnaround times (TATs) for anatomic pathology specimens, comparing three different modes of operation that occurred throughout the development and implementation of our pathology laboratory at the Butaro Cancer Center of Excellence in Rwanda. Before opening this laboratory, TAT was measured in months because of inconsistent laboratory operations and a paucity of in-country pathologists.ResultsWe analyzed 2,514 individual patient samples across the three modes of study. Diagnostic mode 1 (samples sent out of the country for analysis) had the highest median TAT, with an overall time of 30 days (interquartile range [IQR], 22 to 43 days). For diagnostic mode 2 (static image telepathology), the median TAT was 14 days (IQR, 7 to 27 days), and for diagnostic mode 3 (onsite expert diagnosis), it was 5 days (IQR, 2 to 9 days).ConclusionOur results demonstrate that telepathology is a significant improvement over external expert review and can greatly assist sites in improving their TATs until pathologists are on site.

The Utility of Immunohistochemistry in Mycobacterial Infection: A Proposal for Multimodality Testing.

Mycobacterium species are slow growing bacteria that cause significant morbidity and mortality worldwide. Because of the relative rarity of mycobacterial infections, potential for detection of nonpathogenic environmental contaminants, and substantial costs associated with molecular diagnostics, effective screening methods are needed to identify samples most suitable for molecular testing. While anatomic pathology specimens can be utilized to identify characteristic histologic inflammatory patterns and to directly visualize mycobacteria through histochemical (acid fast bacilli [AFB]) stains, the utility of immunohistochemistry (IHC) in this setting is unknown. A cohort of 121 cases previously referred for mycobacterial sequencing, including 12 Mycobacterium tuberculosis (MTB), 42 nontuberculosis mycobacteria (NTM), and 67 cases negative for mycobacteria by polymerase chain reaction (PCR), were stained with an antimycobacteria antibody, and the results were compared with histology, AFB stains, PCR, and cultures. IHC was positive in 50% MTB, 81% NTM, and 49% of cases negative for mycobacteria by sequencing, with excellent (>90%) concordance with AFB stains. Organisms were identifiable by IHC using a 10× objective in the majority of cases. Negative PCR with positive IHC was attributed to paucity of organisms in 30/33 cases, and positive PCR with negative IHC was most often associated with MTB. IHC is highly sensitive for NTM but has a lower sensitivity for MTB, suggesting that cases with a high clinical and histologic suspicion for MTB should be sent for PCR even when AFB and IHC are negative. Incorporation of IHC into a screening algorithm for molecular testing has the potential for significant savings of cost and time.

Introducing 3-Dimensional Printing of a Human Anatomic Pathology Specimen: Potential Benefits for Undergraduate and Postgraduate Education and Anatomic Pathology Practice.

Three-dimensional (3D) printing, a rapidly advancing technology, is widely applied in fields such as mechanical engineering and architecture. Three-dimensional printing has been introduced recently into medical practice in areas such as reconstructive surgery, as well as in clinical research. Three-dimensionally printed models of anatomic and autopsy pathology specimens can be used for demonstrating pathology entities to undergraduate medical, dental, and biomedical students, as well as for postgraduate training in examination of gross specimens for anatomic pathology residents and pathology assistants, aiding clinicopathological correlation at multidisciplinary team meetings, and guiding reconstructive surgical procedures. To apply 3D printing in anatomic pathology for teaching, training, and clinical correlation purposes. Multicolored 3D printing of human anatomic pathology specimens was achieved using a ZCorp 510 3D printer (3D Systems, Rock Hill, South Carolina) following creation of a 3D model using Autodesk 123D Catch software (Autodesk, Inc, San Francisco, California). Three-dimensionally printed models of anatomic pathology specimens created included pancreatoduodenectomy (Whipple operation) and radical nephrectomy specimens. The models accurately depicted the topographic anatomy of selected specimens and illustrated the anatomic relation of excised lesions to adjacent normal tissues. Three-dimensional printing of human anatomic pathology specimens is achievable. Advances in 3D printing technology may further improve the quality of 3D printable anatomic pathology specimens.

A multidisciplinary, multifaceted improvement initiative to eliminate mislabelled laboratory specimens at a large tertiary care hospital

ObjectivesTo sustainably reduce the rate of mislabelled laboratory specimens through implementation of a series of interventions as led and coordinated by a multidisciplinary performance improvement team.MethodsThe quality improvement project was...

A Multiplex Technology Platform for the Rapid Analysis of Clinically Actionable Genetic Alterations and Validation for BRAF p.V600E Detection in 1549 Cytologic and Histologic Specimens

Current clinicopathologic assessment of malignant neoplastic diseases entails the analysis of specific genetic alterations that provide diagnostic, prognostic, or therapy-determining information. To develop and validate a robust molecular method to detect clinically relevant mutations in various tissue types and anatomic pathology specimens. Genes of interest were amplified by multiplex polymerase chain reaction and sequence variants identified by liquid bead array cytometry. The BRAF assay was fully characterized by using plasmids and genomic DNA extracted from cell lines, metastatic colorectal cancer formalin-fixed, paraffin-embedded (FFPE) tissues, and thyroid nodule fine-needle aspirates. Qualitative multiplex assays for 22 different mutations in the BRAF, HRAS, KRAS, NRAS, or EGFR genes were established. The high signal-to-noise ratio of the technology enabled reproducible detection of BRAF c.1799T>A (p.V600E) at 0.5% mutant allele in 20 ng of genomic DNA. Precision studies with multiple operators and instruments showed very high repeatability and reproducibility with 100% (98.7%-100%) qualitative agreement among 292 individual measures in 38 runs. Evaluation of 1549 representative pathologic specimens in 2 laboratories relative to independent reference methods resulted in 99.0% (97.6%-99.6%) agreement for colorectal FFPE tissues (n = 416) and 98.9% (98.2%-99.4%) for thyroid fine-needle aspiration specimens (n = 1133) with an overall diagnostic odds ratio of 10 856 (2451-48 078). The multiplex assay system is a sensitive and reliable method to detect BRAF c.1799T>A mutation in colorectal and thyroid lesions. This optimized technology platform is suitable for the rapid analysis of clinically actionable genetic alterations in cytologic and histologic specimens.

In Situ Hybridization for rRNA Sequences in Anatomic Pathology Specimens, Applications for Fungal Pathogen Detection

Fungal infections are a frequent occurrence in medical practice due to increasing numbers of immunosuppressed patients. New antifungal medications have been developed and it has become evident that different fungi require different treatments as some are intrinsically resistant to these drugs. Thus, it is imperative that pathologists recognize the limitations of histopathologic diagnosis regarding speciation of fungal infections and advocate for the use of different techniques that can help define the genus and species of the fungus present in the specimen they are studying. In this review we present the use of in situ hybridization as an important adjunct for the diagnosis of fungal diseases, the different techniques that have been used for fungal identification, and the limitations that these techniques have.

Utilization of Silicone Polymer Plastination to Preserve and Enhance the Educational Value of Anatomic Pathology Specimens

Utilization of Silicone Polymer Plastination to Preserve and Enhance the Educational Value of Anatomic Pathology Specimens

Partial elective nephrectomy

IntroductionPartial nephrectomy is widely accepted as a therapeutic modality in renal cell carcinoma (RCC) in patients with single kidney, bilateral tumor or deteriorated renal function. Currently, long-term survival studies have consolidated partial nephrectomy as the treatment of choice for RCC in selected patients with normal contralateral kidney. Material and methodsBetween July 1990 and January 2008, a total of 102 partial nephrectomies were performed on 100 patients with pre-operative ultrasonography diagnosis of renal carcinoma in 94 cases and complex renal cysts in 6 cases. The pre-operative ultrasonography size varied from 1.5 to 10cm with an average of 4.85cm. ResultsTumor size was correlated with the pathological stage, finding tumors in stage pT1 with sizes smaller than and greater than 4cm in 74% and 64%, respectively, and in stage pT2 of 3.7% and 5.4%. Tumor size measured by pre-operative computed tomography (CT) scan was compared with the definitive size of the pathology specimen in 93 cases (56≤4cm and 37>4cm, according to the CT scan). We found high concordance; however, in the larger tumors, there was a tendency of the CT scan to overestimate the size. A post-operative gamma scintigraphy with DMSA (Dimercaptosuccinic Acid) was performed in 40 patients. The values in the tumors≤4cm (21 patients) were 12–77% (average 43.3%). In tumors between 4 and 7cm (17 patients), the values were 13.8–53.3% (average 37.6%) and in 2 cases of tumors>7cm the post-operative DMSA showed 47.5% and 51%. ConclusionsPartial nephrectomy is currently accepted as elective treatment in incidental kidney tumors smaller than 4cm and it is indicated increasingly more frequently in larger tumors and of central localization. The finding of benign pathology in the anatomic-pathology specimen in up to 20% of the incidental renal tumors and low potential of malignancy of the possible satellite lesions in the remnant kidney also support nephron-spearing surgery in these tumors.

Nefrectomía parcial electiva

IntroductionPartial nephrectomy is widely accepted as a therapeutic modality in renal cell carcinoma (RCC) in patients with single kidney, bilateral tumor or deteriorated renal function. Currently, long-term survival studies have consolidated partial nephrectomy as the treatment of choice for RCC in selected patients with normal contralateral kidney. Material and methodsBetween July 1990 and January 2008, a total of 102 partial nephrectomy were performed on 100 patients with pre-operative ultrasonography diagnosis of renal carcinoma in 94 cases and complex renal cysts in 6 cases. The pre-operative ultrasonography size varied from 1.5 to 10cm with an average of 4.85cm. ResultsTumor size was correlated with the pathological stage, finding tumors in stage pT1 with sizes less than and greater than 4cm in 74% and 64%, respectively, and in stage pT2 of 3.7% and 5.4%. Tumor size measured by pre-operative CT scan was compared with the definitive size of the pathology specimen in 93 cases (56<4cm and 37>4cm, according to the CT scan). We found high concordance, however in the larger tumors, there was a tendency of the CT scan to overestimate the size. A post-operative gamma scintigraphy with DMSA was performed in 40 patients. The values in the tumors<4cm (21 patients) were 12-77% (average 43.3%). In tumors between 4 and 7cm (17 patients), the values were 13.8-53.3% (average 37.6%) and in 2 cases of tumors>7cm the post-operative DMSA showed 47.5 and 51%. ConclusionsPartial nephrectomy is currently accepted as elective treatment in incidental kidney tumors less than 4cm and it is indicated increasingly more frequently in larger tumors and of central localization. The finding of benign pathology in the anatomic-pathology specimen in up to 20% of the incidental renal tumors and low potential of malignancy of the possible satellite lesions in the remnant kidney also support nephron-spearing surgery in these tumors.

Patient Misidentification in Laboratory Medicine: A Qualitative Analysis of 227 Root Cause Analysis Reports in the Veterans Health Administration

Abstract Context Mislabeled laboratory specimens are a common source of harm to patients, such as repeat phlebotomy; repeat diagnostic procedure, including tissue biopsy; delay in a necessary surgical procedure; and the execution of an unnecessary surgical procedure. Mislabeling has been estimated to occur at a rate of 0.1% of all laboratory and anatomic pathology specimens submitted. Objective To identify system vulnerabilities in specimen collection, processing, analysis, and reporting associated with patient misidentification involving the clinical laboratory, anatomic pathology, and blood transfusion services. Design A qualitative analysis was performed on 227 root cause analysis reports from the Veterans Health Administration. Content analysis of case reports from March 9, 2000, to March 1, 2008, was facilitated by a Natural Language Processing program. Data were categorized by the 3 stages of the laboratory test cycle. Results Patient misidentification accounted for 182 of 253 adverse events, which ...

Patient Misidentification in Laboratory Medicine: A Qualitative Analysis of 227 Root Cause Analysis Reports in the Veterans Health Administration

Mislabeled laboratory specimens are a common source of harm to patients, such as repeat phlebotomy; repeat diagnostic procedure, including tissue biopsy; delay in a necessary surgical procedure; and the execution of an unnecessary surgical procedure. Mislabeling has been estimated to occur at a rate of 0.1% of all laboratory and anatomic pathology specimens submitted. To identify system vulnerabilities in specimen collection, processing, analysis, and reporting associated with patient misidentification involving the clinical laboratory, anatomic pathology, and blood transfusion services. A qualitative analysis was performed on 227 root cause analysis reports from the Veterans Health Administration. Content analysis of case reports from March 9, 2000, to March 1, 2008, was facilitated by a Natural Language Processing program. Data were categorized by the 3 stages of the laboratory test cycle. Patient misidentification accounted for 182 of 253 adverse events, which occurred in all 3 stages of the test cycle. Of 132 misidentification events occurring in the preanalytic phase, events included wrist bands labeled for the wrong patient were applied on admission (n = 8), and laboratory tests were ordered for the wrong patient by selecting the wrong electronic medical record from a menu of similar names and Social Security numbers (n = 31). Specimen mislabeling during collection was associated with "batching" of specimens and printed labels (n = 35), misinformation from manual entry on laboratory forms (n = 14), failure of 2-source patient identification for clinical laboratory specimens (n = 24), and failure of 2-person verification of patient identity for blood bank specimens (n = 20). Of 37 events in the analytic phase, relabeling all specimens with accession numbers was associated with mislabeled specimen containers, tissue cassettes, and microscopic slides (n = 27). Misidentified microscopic slides were associated with a failure of 2-pathologist verification for cancer diagnosis (n = 4), and wrong patient transfusions were associated with mislabeled blood products (n = 3) and a failure of 2-person verification for blood products before release by the blood bank (n = 3). There were 13 events in the postanalytic phase in which results were reported into the wrong patient medical record (n = 8), and incompatible blood transfusions were associated with failed 2-person verification of blood products (n = 5). Patient misidentification in the clinical laboratory, anatomic pathology, and blood transfusion processes were due to a limited set of causal factors in all 3 phases of the test cycle. A focus on these factors will inform systemic mitigation and prevention strategies.

Interpretation of Dermatopathology Specimens Is within the Standard of Care of Dermatology Practice

Laws have been passed in New York, California, New Jersey, Nevada, Louisiana, and Rhode Island and were recently tabled in South Carolina to prohibit providers from billing for pathology services provided by other physicians. The Ohio proposal included language stating that only board-certified pathologists be able to directly bill for anatomic pathology services. Dermatologists, however, have extensive training in dermatopathology and frequently bill anatomic pathology codes. To determine if interpretation of cutaneous pathology falls within the standard of care of dermatology practice. We used Medicare part A and B claims data from the Medicare Current Beneficiary Survey, 1992 to 2000. We identified surgical pathology claims by Current Procedural Terminology (CPT) code 88305 and those related to skin disease by the associated International Classification of Disease, 9th Revision (ICD-9), code. Weights were applied to obtain nationally representative estimates. The number of physicians in each specialty was obtained from American Medical Association estimates. Pathologists, independent laboratories and group practices, and dermatologists submitted 59%, 26%, and 13% of total claims, respectively. For skin-related diagnoses, pathologists, dermatologists, and independent laboratories and group practices performed 34.5%, 31.2%, and 32.8% of cases, respectively. Assuming that independent laboratory and group practice claims were performed entirely by pathologists, dermatologists and pathologists submitted 1,047 and 1,154 cases/physician, respectively. Dermatologists have extensive training in dermatopathology and interpret a large proportion of cutaneous specimens. Interpretation of anatomic pathology, in particular, skin and subcutaneous pathology specimens, falls within the scope of dermatology practice.

The Cost-Effectiveness of Immunohistochemistry

Abstract Objective.—To evaluate the cost-effectiveness of immunohistochemistry. Design.—Using a theoretical decision analytic model, the cost-effectiveness of immunohistochemistry was evaluated in different scenarios depicting the beneficial use of immunohistochemistry. Data regarding the effectiveness of immunohistochemistry were obtained from the medical literature and costs were obtained from Allegheny General Hospital. Settings.—The scenarios depicted both private practice and university patients from which anatomic pathology specimens were obtained. Immunohistochemistry was subsequently performed on these specimens. Main Outcome Measures.—Cost, life expectancy, diagnostic certainty, ability to predict prognosis, and cost-effectiveness were evaluated. Results.—In all scenarios, immunohistochemistry was cost-effective at very low efficacies. Assuming a per-antibody cost of $50 and use of a 5-antibody panel, immunohistochemistry was cost-effective if it resulted in a 1-year gain of population life expec...

The cost-effectiveness of immunohistochemistry.

To evaluate the cost-effectiveness of immunohistochemistry. Using a theoretical decision analytic model, the cost-effectiveness of immunohistochemistry was evaluated in different scenarios depicting the beneficial use of immunohistochemistry. Data regarding the effectiveness of immunohistochemistry were obtained from the medical literature and costs were obtained from Allegheny General Hospital. The scenarios depicted both private practice and university patients from which anatomic pathology specimens were obtained. Immunohistochemistry was subsequently performed on these specimens. Cost, life expectancy, diagnostic certainty, ability to predict prognosis, and cost-effectiveness were evaluated. In all scenarios, immunohistochemistry was cost-effective at very low efficacies. Assuming a per-antibody cost of $50 and use of a 5-antibody panel, immunohistochemistry was cost-effective if it resulted in a 1-year gain of population life expectancy in 1 or more of every 200 cases in which it was applied. Alternatively, if the gain in diagnostic certainty by using immunohistochemistry was 10% and the value placed on a percentage gain in diagnostic certainty was $1000, immunohistochemistry was cost-effective if it produced this increase in certainty in 1 of every 40 tests. If a life-year was valued at $50 000, immunohistochemistry was cost-effective if it resulted in a change in patient prognosis of 0.5 years in 1 of every 100 tests. Using theoretical modeling, immunohistochemistry is extremely cost-effective. These data have implications in an era of managed care when providers attempt to trim laboratory services. Additional studies are needed to evaluate the actual practice efficacy of immunohistochemistry.

Discordance in the histopathologic diagnosis of melanoma and melanocytic nevi between expert pathologists

The reliability of a diagnostic test depends on the reproducibility of the result. Many clinical diagnostic tests can be quantified with established ranges and standard deviations. Other tests are more subjective, such as those that depend on analysis of a visual image with an increased possibility of variance in the result. To study this variance, the authors analyzed the performance of expert pathologists in the interpretation of cutaneous melanocytic tumors. A panel of expert pathologists was convened to review anatomic pathology specimens from melanocytic tumors. Each pathologist submitted five specimens, from which 37 were selected for review. Only one slide was used for each case. All specimens were interpreted by each pathologist without consultation with each other. In addition to standard diagnostic terms, each specimen was designated as benign, malignant, or indeterminate. Statistical analysis was used to determine the degree of concordance. The combined κ statistic for the eight observers and three possible outcomes (benign, malignant, or indeterminate) was 0.50. A κ statistic of this magnitude is defined as being moderate. In 62% of the specimens, there was unanimous agreement or only one discordant designation. Thirty-eight percent had two or more discordant interpretations. No single pathologist had a disproportionate number of discordant designations. This study mimics the consultation practice of anatomic pathology and shows the variability and discordance in diagnostic language and designation of biological behavior. The results suggest the criteria for the diagnosis of melanomas and melanocytic nevi need to be refined and more consistently applied.