Editor: Frederick L. Kiechle, MD, PhD
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Q. Immunofluorescence microscopy results for antinuclear antibodies (ANAs) are reported as a titer. How can we best comply with CAP checklist requirement IMM.34120 Daily QC—Nonwaived Tests for ANA testing?
A. October 2024—CAP checklist requirement IMM.34120 indicates that one negative and one positive control specimen with graded or titered reactivity should be run at least daily and that serial dilutions are not required. Laboratory directors have considerable latitude in how to interpret the requirement for running a graded or titered positive specimen. To satisfy this checklist requirement for ANA testing, the laboratory should run at least one specimen with a defined or expected degree of positivity. It can use a commercial control included in a kit, a commercial control purchased separately, or a control prepared in-house. The lab must establish the expected titer or degree of positivity of one or more titer control specimens. It is not sufficient to accept a positive result without defining the degree of positivity. Conversely, serial titers are not required. For example, a specimen with a known titer of 1:160 does not need to be assayed at twofold dilutions starting at 1:40 and continuing to 1:640.
Laboratories can implement any of several quality control approaches. For example, laboratories can use a single daily positive control with a known titer that is appropriate for the test and that can be tracked over time. Using this approach, labs can employ a control specimen that has a 1:80 reactive ANA titer and allow results of 1:80 plus or minus one dilution—i.e. 1:40, 1:80, or 1:160—to be in control. If the lab’s accumulated control data demonstrate a narrower range of acceptability (for example, if the control results are 1:40 or 1:80 in 95 percent of the runs), then a result of 1:160 would be out of control.
Alternatively, laboratories can use a semiquantitative grading parameter. For example, a control specimen with a defined titer of 1:80 that is expected to be graded as trace or 1+ positive warrants evaluation for failing control expectations if it is graded as negative or 2+ positive. This is analogous to the requirements for titered rapid plasma reagin (RPR) and Venereal Disease Research Laboratory (VDRL) agglutination tests for syphilis that report semiquantitative results, in which nonreactive, weakly reactive, and strongly reactive controls are used in assays that report semiquantitative results (CAP checklist requirement IMM.34170 Weakly Reactive Controls).
Some laboratories may instead choose to run a control only at the threshold of positivity (known as an endpoint control) or choose additional controls with dilutions that titer to above or below that threshold. For example, a control specimen with a known titer of 1:80 as an endpoint can also be run at dilutions of 1:40 and 1:160 to establish the range of variation at the cutoff. This latter approach might be particularly useful when evaluating a new reagent or lot of reagents to establish that the new reagent has performance characteristics similar to those of the previous reagent lot.
Quality control methods for semiquantitative or titered tests are not as well standardized as quality control methods for quantitative tests. Nevertheless, laboratories must use an approach that optimizes the reproducibility of the titer results they report.
College of American Pathologists. IMM.34120 Daily QC—nonwaived tests. In: Immunology checklist. Aug. 24, 2023.
College of American Pathologists. IMM.34170 Weakly reactive controls. In: Immunology checklist. Aug. 24, 2023.
Process control—quality control for qualitative and semiquantitative procedures. In: World Health Organization. Laboratory Quality Management System: Handbook. World Health Organization; 2011:91–100.
Pum JKW. Evaluation of analytical performance of qualitative and semi-quantitative assays in the clinical laboratory. Clin Chim Acta. 2019;497:197–203.
Mark H. Wener, MD
Professor, Department of Laboratory Medicine and Pathology
Adjunct Professor
Division of Rheumatology
University of Washington School of Medicine
Seattle, Wash.
American College of Rheumatology Liaison, CAP Diagnostic Immunology and Flow Cytometry Committee
Rebecca Treger, MD, PhD
Director, Clinical Immunology Laboratory
Assistant Professor
Department of Laboratory Medicine and Pathology
University of Washington School of Medicine
Seattle, Wash.
Member, CAP Diagnostic Immunology and Flow Cytometry Committee
Q. Is there a standard of care for anatomic pathology reporting? The CAP document “How to Read Your Pathology Report” states that pathologists “always perform the microscopic evaluation of a specimen, even if the final pathology report does not include a written description.” Must the testing pathology laboratory provide the patient with the microscopic description if it is requested and not included in the pathology report?
A. The pathology report conveys important information, such as prognosis, to patients and clinicians and guides treatment. The content of a pathology report must be presented efficiently and accurately.
The CAP Surgical Pathology Committee has published recommendations delineating the required, preferred, and optional elements of anatomic pathology reports. The diagnosis field of the report contains the pathologic diagnosis and incorporates information that may also be detailed in the gross description, intraoperative consultation, and microscopic description sections. However, a specific microscopic description is not required as part of the report. The testing pathology laboratory is not obligated to generate a separate microscopic description since the microscopic findings are used to generate the overall diagnosis.
The pathologist’s name and contact information is always on the pathology report. He or she can address questions and provide clarity for patients who are seeking information about their diagnoses.
For more resources on how pathologists can interact directly with patients who have questions about their pathology reports, see the CAP’s Steps to Start a Patient-Pathologist Consultation Program (https://bit.ly/cap_patient-path-prog) and www.yourpathologist.org.
Goldsmith JD, Siegal GP, Suster S, Wheeler TM, Brown RW. Reporting guidelines for clinical laboratory reports in surgical pathology. Arch Pathol Lab Med. 2008;132(10):1608–1616.
Rosai J, Bonfiglio TA, Corson JM, et al. Standardization of the surgical pathology report. Mod Pathol. 1992;5(2):197–199.
Sue Chang, MD
Associate Clinical Professor
Department of Pathology
Associate Chief Medical Information Officer
City of Hope
Duarte, Calif.
In collaboration with the CAP Professional and Community Engagement Committee