Frozen section biopsies provide clinicians with critical data about an organ’s health. Biopsy assessment facilitates accurate patient diagnosis, and it can inform the direction of treatment.
Frozen section analysis gets data fast. This is essential for time-sensitive procedures, like organ transplants.
Unfortunately, relevant clinical specialists are not always available on site. The time-crunch can push hospitals to seek evaluations from available non-specialists.
But non-specialist assessments can have harmful consequences. For example, 20% of transplantable organs are erroneously discarded due to inaccurate evaluation by non-specialist physicians.
Fortunately, you can reach specialist physicians at all times, regardless of your location. Telepathology solutions make quick, accurate frozen section analyses possible over long distances. To maximize the accuracy of frozen section analysis, implement these eight best practices.
Optimize Frozen Section Technique
To learn how to improve from section results, first master and optimize your sectioning technique. The textbook A Practical Guide o Frozen Sectioning Technique offers pragmatic strategies to optimize every stage of sectioning. Chapters cover techniques relevant to:
- Maintaining the cryostat
- Embedding tissue
- Cutting the section
- Variables that impact the tissue’s cuttability
- Fixation and staining
- Coverslipping
- Microscopic interpretation
A Practical Guide to Frozen Sectioning Technique is a professional resource by Stephen Peters, a board-certified pathologist.
It offers precise advice regarding biopsy tools, like the ideal brushes and grip. That would be 3/16 (#1) and 1/4 inch (#2) flat or bright bristle brushes, cut at an angle. The guide also describes how to alter techniques and tools to account for variables among different types of tissues.
Dr. Peters regularly updates his recommendations at Pathology Innovations. Pathology Innovations is a website dedicated to optimizing frozen sectioning and cryoembedding. Peters has published twenty-nine studies on biopsies and techniques in PubMed—most recently in 2019.
Implement Telepathology Solutions for Immediate Consultation
Digital pathology, or telepathology, improves the accuracy of diagnosis by enabling instant consultation. The efficacy of pathological verification has been supported in studies since 2002. That year, the U.S. Army Medical Department tested the validity of consultations through telepathology.
In the study, 120 long-distance specialist pathologists diagnosed frozen sections. The pathologists manipulated a robotic microscope over an internet connection to observe the sample. Then, they made assessments.
Different specialists diagnosed the same specimens in-person under glass slides. Researchers observed intraobserver agreement across the board. Digital pathologists came to a 100% diagnostic agreement for a “wide variety” of specimens.
This experiment was one of the first to validate frozen section results determined with telemedical devices.
Later, in 2016, researchers set out to quantify the utility of frozen section analysis. Specifically, how useful is it when diagnosing early-stage ovarian cancer?
The meta-analysis determined 91% of ovarian cancer diagnoses from frozen sections—both positive and negative—were ultimately correct. But, 9% of diagnoses were false positives or false negatives.
Researchers discovered discordant reporting of borderline tumors significantly factored into misdiagnosis. Borderline tumor reporting is not standardized. Standardization would improve accuracy.
Until standards are established, it’s in the best interest of patients to seek multiple specialist reports and assessments when sections include borderline tumors. Telepathologists can provide an expert second opinion when there is only one ovarian cancer specialist available on site.
Require Specialized Pathologist Evaluation for Potential Transplant Organs
Organ procurement poses some unique challenges to pathologists. Each organ has a set cold ischemia time (CIT) and warm ischemia time (WIT).
WIT is the amount of time an organ stays warm (body temperature) after it stops receiving oxygenated blood. This limit forces transplant clinicians to work quickly. They must obtain and cool the organ within its WIT-time limit.
CIT is the amount of time a cold organ can remain viable before being warmed again (re-connected to blood supply). Transplant practitioners must determine if a given organ is suitable for transplant within the time limits.
Frozen section biopsies are appealing in this regard, as they are rapid tests. Often, the typical frozen section result speed is under two hours.
Unfortunately, non-specialists who evaluate frozen sections erroneously discard transplantable organs. Up to 20% of viable kidneys are disposed of by non-specialists who determine non-viability from frozen sections.
To prevent inappropriate discard, make sure specialists in the organ in question evaluate the frozen section. For example, frozen kidney biopsy sections should be evaluated by renal pathologists, not general practitioners.
Perform Multiple Biopsies on Donor Organs
To evaluate a donor organ’s suitability, perform multiple biopsies. A 2020 study explored how often deceased donor kidney biopsies could be reproduced with verifiable results. In the study, biopsies from deceased donor kidneys were evaluated for:
- Glomerulosclerosis
- Vascular disease
- Interstitial fibrosis
Each donor kidney was biopsied twice. The study found poor agreement between the first and second biopsies. Moreover, a single biopsy did not improve the recipients’ rates of allograft survival.
However, the second biopsy was associated with better allograft survival. Optimal histology, as determined via the second biopsy, improved post-transplant outcomes when accounting for other factors.
Thus, it is wise to conduct multiple biopsies on donor organs. Kidney recipients, specifically, benefit from organs with two or more biopsies with optimal histology.
Emphasize Proactive Communication
Proactive communication is critical to getting accurate results. This is particularly true when you’re working with specialists virtually to determine the telepathology results of your sections.
The School of Pathology and Laboratory Medicine at UC Davis underscores the importance of context. Contextual information informs a pathologist’s diagnosis based on the frozen section. Therefore, it is particularly urgent to inform digital pathologists about:
- The anatomic location of the sample in the organ
- The orientation (angle) of the sample
- The clinical history of the patient or donor
- Information about the sample’s margin status
Margin status describes the edges of a tissue sample. Negative margin status means there are no observable tumors at the edge of the section. The reported margin status of a frozen section is less accurate regarding diffuse tumors and duodenal specimens.
The patient or donor’s clinical history affects the appearance of the sample. The pathologist can factor in traits—like altered appearance due to a history of radiation therapy—when they make observations. Likewise, the location of the sample determines whether a given microscopic feature is typical, or if it indicates some malignancy.
Communication should be as objective and quantifiable as possible. Suture lengths, suture colors, and clips can reliably indicate orientation.
Account for Artifacts
Artifacts are abnormalities in a frozen section. These abnormalities occur due to accidents during the sectioning process. They do not exist in the tissue itself.
Artifacts present a challenge to pathologists. It’s critical to account for the presence of artifacts in a sample before making your determination.
In 2018, histapoathologists published a comprehensive review of common artifacts. The review includes steps pathologists can take to remediate damaged samples. Researchers categorize artifacts by the process stage that damaged the tissue:
- Prefixation artifacts
- Fixation artifacts
- Artifacts related to bone tissue
- Tissue-processing artifacts
- Artifacts related to microtome
- Artifacts related to floatation and mounting
- Staining artifacts
- Mounting artifacts
While remediating artifacts is possible, preventing them is better.
Frozen sectioning can create artifacts particular to its process. For example, shatter artifact creates parallel, horizontal grooves in the tissue. If the biopsy cuts calcified tissue, or if it gets too cold when it freezes, the tissue develops shatter artifact.
Ice-crystal artifact is another type of damage caused by freezing. Air-drying artifacts can occur when there’s a delay between cutting the sample and fixing it.
The best way to account for artifacts is to study them. Learn what they look like in contrast to optimal samples.
Mandate Quality Assurance (Microscopic Classification)
Quality assurance practices are vital. To get the best possible outcome, laboratories and hospitals must require quality assurance. For frozen sections, this means verify microscopic classifications.
Microscopic misclassification causes half of all frozen section errors. Errors result in discordance between interoperative consultations, which slows down the diagnostic process.
One 2017 study concluded misclassification errors may be eliminated with an automated classification tool. The tool imposes a standardized method to classify elements among diverse organs and organ systems.
Quality assurance systems may track agreement between an initial section assessment and subsequent re-review. These types of systems allow labs to home in on procedures that need improvement. Potential improvements may be systemic, or they may be individual.
Verify Malignancy Diagnosis with Additional Section(s)
Finally, it’s best to verify diagnoses of cancer or malignant tumors with additional sections. For these conditions, there’s a limit to the diagnostic utility of frozen sections. The frozen section’s degree of sensitivity and specificity is lower than that of a permanent section.
So, though frozen section biopsies are useful, they should not be the sole method of diagnosing malignant tumors. Other permanent section methods should be used as well. Paraffin sections offer a lower risk of misdiagnosing malignancy than frozen sections.
Digital Pathology and More Telemedical Solutions
At Specialists Direct, we specialize in telepathology solutions. Our portable scanning microscope enables long-distance consultation in real time. Whether you’re an organ procurement organization, a hospital, or a rural healthcare facility, we can improve the accuracy of your frozen section analysis—instantly.
Our board-certified specialist pathologists offer a wide range of medical imagine insights. If your organization needs digital pathology, telecardiology, or teleradiology solutions, contact us today.
