Elevating Histology: Rethinking Clinical Laboratory Regulations for Modern Diagnostic Demands

Histology is the science dealing with the structure and analysis of cells and their formation into tissues and organs. The profession is responsible for the preparation of all pathological tissue samples removed and collected from the human body for the microscopic detection of tissue abnormalities for disease diagnosis and treatment. Despite advances in immunohistochemistry, molecular diagnostics, and digital pathology, the US Clinical Laboratory Improvements Amendments (CLIA) regulations from 1988 have not evolved to reflect histology’s scientific demands, including performing complex diagnostic tasks essential to patient care. Elizabeth Chlipala from Premier Laboratory (LLC), Longmont, Colorado and colleagues argue for a national certification requirement and regulatory oversight for histologists. Citing current problems including quality issues, workforce shortages, and the need for standardized practices, these experts argue that recognizing histologists under CLIA would elevate the profession, ensure competency, and improve patient outcomes, challenging the current position of the College of American Pathologists.

The Clinical Laboratory Improvement Amendments of 1988 (CLIA) regulate laboratory testing and require clinical laboratories to be certified by the Centers for Medicare and Medicaid Services (CMS) before accepting human samples for diagnostic testing. Despite the critical role histologists play in preparing tissue samples used for diagnosis and treatment, their work is not formally recognized under CLIA as high complexity testing.

Ms Chlipala and colleagues explore this gap in oversight, highlighting how core histological activities such as preparing haematoxylin and eosin (H&E) stains, special stains, and immunohistochemistry (IHC) assays directly support clinical diagnosis. These tasks, while foundational to patient care, do not currently require national certification or licensure. The researchers aim to outline why histology, as practiced today, meets the characteristics of high complexity testing and should be evaluated as such within the CLIA framework.

Technological Advances Redefining Histology

Histotechnology has advanced significantly in the past two decades. Ms Chlipala notes that automation, once intended primarily to improve throughput, now plays a central role in enhancing quality and standardization. Automated staining systems have become standard, utilizing validated reagents and protocols that are often established and maintained by histologists.

The field has also witnessed the evolution of IHC from a diagnostic adjunct to a tool used to guide targeted therapy decisions. For instance, the introduction of the DAKO Hercep test in 1998 marked a turning point by enabling companion diagnostics. IHC now frequently produces quantitative and qualitative outputs that guide clinical management. Despite this, the regulatory classification of IHC methodologies under CLIA has not changed.

Ms Chlipala and colleagues further point to molecular methods such as in situ hybridization (ISH), fluorescent ISH (FISH), as well as whole slide imaging and computational image analysis, which are becoming integral to modern diagnostics. These tools depend on the accuracy of tissue preparation processes performed by histologists, reinforcing the need for competent oversight.

Regulatory Gaps and Professional Parity

Ms Chlipala raises the issue that when CLIA was last updated in 1992, many histological tasks were categorized as simple, low risk procedures that did not require a histologist to produce an independent result. Consequently, these processes were not included in CLIA’s oversight. Since then, the complexity and importance of histological work have grown considerably. Histologists oversee the pre-analytical and analytical phases of tissue analysis, requiring sample preparation through processes that include:

• Collection, Fixation, and Sampling — Tissue specimens taken from routine surgical cases, autopsies, or other scientific investigations are examined, described, and trimmed to proper size; preserved by placing them in solutions designed to prevent decomposition
• Tissue processing — prepares tissue samples by removing water and replacing it with paraffin to preserve cell microstructures
• Embedding — involves placing the processed tissue into a paraffin block to allow precise sectioning
• Sectioning — uses a microtome to cut very thin slices of the paraffin-embedded tissue for mounting on slides and analysis, eg. microscopy
• Staining — the application of dyes (eg. H&E and special stains) to highlight and differentiate between tissue structures
• IHC & ISH Assays — determines cell types, identifies specific markers for diagnosis, prognosis, and therapeutic treatments
• Whole Slide Imaging & Analysis — generating a digital scan of the slide used for quantitative assessment

These responsibilities require an understanding of chemistry, molecular biology, and scientific technique. However, under current regulations, histologists are not required to hold national certification. In contrast, Medical Laboratory Scientists, who often use fully automated instruments, are recognized as personnel performing high complexity testing.

Ms Chlipala and colleagues suggest that this regulatory imbalance contributes to professional disparities. Similarities in responsibilities and knowledge between Medical Laboratory Scientists and histologists highlight the need for a reassessment of histology’s classification under CLIA.

Quality Considerations in Histopathology

The challenges with quality in histopathology are persistent. Error rates in IHC assays have remained at 10 to 30 percent over the past 20 years. Contributing factors include inconsistent fixation, uneven staining, and variability in sectioning — all of which occur during histological processing. These problems can compromise accurate diagnosis, as they can distort tissue appearance, obscure critical diagnostic markers, and compromise the clarity of cellular structures, making precise interpretation by pathologists more difficult.

While the College of American Pathologists (CAP) maintains that current oversight is sufficient, Ms Chlipala notes that literature reviews and error reports suggest otherwise. The authors acknowledge the importance of automation but emphasize that instruments rely on skilled personnel to ensure valid outcomes. Histologists are responsible for optimizing and validating protocols, interpreting control results, and troubleshooting performance issues: functions that align with high complexity testing under CLIA’s criteria.

Ms Chlipala and colleagues clarify that their objective is not to criticize existing oversight models but to advocate for broader dialogue about aligning regulations with current practice. Their concern is not limited to laboratory quality but includes patient safety, workforce training, and diagnostic integrity.

Considering a ‘Total Test Perspective’

Ms Chlipala and colleagues support Dr Clive Taylor’s ‘total test’ approach, which recognizes that diagnostic outcomes depend on all steps of testing, from tissue acquisition and preparation to interpretation. Within this model, histology is a central component.

Histologists apply judgment at multiple points during sample preparation, including selection of antigen retrieval methods, antibody dilution, and control samples. These decisions impact the interpretability and reliability of diagnostic results. According to Ms Chlipala, this complexity is sufficient to qualify histology for classification as high complexity testing.

Furthermore, the lack of national licensure or certification requirements means that individuals without formal qualifications may handle irreplaceable tissue samples. Ms Chlipala and colleagues underscore the importance of developing professional standards that reflect the responsibilities and scientific expertise required in histotechnology today.

What does the future hold: reengaging with CAP and CLIA Policy

Ms Chlipala and colleagues agree with the National Society for Histotechnology’s (NSH) call for a revaluation of histology’s regulatory standing under CLIA. NSH’s intent is not to impose burdensome regulation, but to engage CAP, CMS, and other stakeholders in an open discussion about how histology fits within the evolving landscape of laboratory medicine.

Agreeing with NSH, they emphasize that increased recognition would help address long-standing workforce shortages by elevating the profession, offering clearer career trajectories, and improving training and compensation. Ms Chlipala invites collaboration to ensure that histologists are supported and that diagnostic processes continue to evolve in the best interest of patient care.

By outlining the scientific demands, technological complexity, and quality implications of histological practice, these experts aim to foster constructive dialogue about aligning regulatory frameworks with current laboratory realities.