Automation in the histology department

Introduction

Transforming a tissue specimen from fixed material to stained sections is a multiple step process which began as separate manual tasks. Indeed, histology in the last century has been the slowest of the laboratory medicine departments to innovate and keep pace with the speed required for a modern dynamic hospital. Whereas the availability of high-throughput analyzers has made same-day results the expected norm in the blood sciences, histology, with its labor-intensive preparations and processes usually sees result turnaround time (TAT) for biopsies and surgical samples being counted in days or weeks rather than hours or minutes.

Historically the lengthy TATs of the histopathology laboratory have been unavoidable due to the technical requirements and the multiple manual stages involved from tissue handling through to the preparation of slides. However, alongside the demands of modern medicine many laboratories have introduced new semi and fully automated processes and tracking systems designed to enable rapid, accurate and safe histopathology reporting.

The modern manipulations to deliver these tissue handling steps are covered in the various chapters of this book, but increasingly this is an automated and standardized reality. Histology automation is perceived as a relatively recent movement, but examples began to be seen as far back as 1945 ( ). This chapter will deal with various components of laboratory activity and the automation which currently exists. Whilst there are many companies and systems to facilitate these automated solutions to histology laboratory practice, only some illustrative examples are given and the discussion cannot be all-encompassing. Indeed, one must look at this evolving technology arena regularly in order to to keep up to date with the companies which serve this aspect of laboratory practice and their equipment.

The drivers for change

Drivers for the automation of histology processing are various, but principally hinge on two elements: financial budgets (generally constrained) and the need for rapid sample analysis (patient and clinician led). The increase and availability of preventative medicine such as screening protocols, and the development of specific testing for personalized medicine within an aging population, have all contributed to an increase in histology workload. Globally, laboratories are expected to be more efficient than ever. The trend being seen in terms of economies of scale and diagnostic national and international guidelines has pushed towards a minimum number of samples for laboratory efficiency. There are fewer, larger laboratories processing thousands of specimens per month.

The changing nature of laboratory accreditation is another driver to the introduction of automation. The required standards for an accredited laboratory have been expanded to include the validation and verification of all processes, as well as standardizing the equipment and reagents used. The innate production of this type of process normalization and audit information is one of the strengths of an automated procedure.

Technology now exists which, combined with adaptations to work practices, allows results to be available within 24 hours of a biopsy being taken for small and straightforward samples. This should lead to an improved clinical response and patient outcome without an increase in cost. The goal of introducing a more automated process into histology is to enable a leaner, more efficient process which benefits staff, patients and the service user/s.

Finally there are subsidiary drivers to be considered. For example, looking at processing, one can appreciate that tissue samples needing to move from fixative to paraffin wax requires transfer between multiple solvents and impregnation periods at each stage; this normally takes several hours. Automation of this stage reduces the requirement for manual intervention and allows the process to occur faster or overnight, assisting TATs. Other beneficial outcomes to these systems include the increased safety of the user as the process occurs in an enclosed environment with minimal reagent handling. This has significant health and safety benefits.

Barcode technology and automated sample tracking

A laboratory’s responsibility for a specimen (and the laboratory’s TAT) begins as soon as the tissue has been removed from the patient. It is from here automation and tracking can begin. Systems such as the Menerini Tissue SAFE are available. These record the time the specimen was taken, when formaldehyde was added and the temperature at which the specimen was transported to the laboratory, therefore maintaining standardization. This allows comprehensive verifiable data on the pre-analysis handling of the specimen ( ).

Sample tracking continues once the specimen is received and passes through all the laboratory processes, ultimately producing a diagnostic report and recording both the disposal of excess material, and specimen storage. The production of an audit trail and the associated chain of custody can be a labor intensive process both to complete and interrogate. Indeed, this mundane task of the completion of an audit trail can account for a significant portion of the departmental workload, the majority of which is the responsibility of the laboratory staff.

In many laboratories the creation of this audit trail has been constructed piecemeal over a period of time, with each step often recorded in a different format and the records often stored in separate physical locations within the laboratory. As a result, laboratories have a plethora of different systems in use including (but not limited to) colored slides and beads, lists of specimens, log books, worksheets and initials here, there and everywhere! This approach arises as a result of the different requirements for the histology material as the specimen moves through the histology process. It is not easy to capture all the required information in a centralized location and there has been a lack of computer software designed specifically for this task.

A comprehensive computer system which records key aspects of the process, such as who has booked in, dissected, embedded, trimmed, cut and checked a specimen can be a useful information management tool.

Barcoding specimens on receipt and integrating this into the laboratory information management system (LIMS) can help facilitate tracking through the laboratory processes. Printing corresponding barcodes onto all of the forms, blocks and slides associated with the specimen and scanning at every station in the laboratory process can provide a comprehensive tracking system from the time a specimen enters the laboratory, right up to the time the sample analysis is concluded. Using purpose-built software with user identification, this kind of minute-by-minute, station-to-station tracking can also provide a detailed record of the personnel involved at each step, detailed data on which equipment was used (where applicable), and the overall laboratory efficiency.

Not only does this automation create the audit trail with a fraction of the user time currently required, it also integrates this information and displays it in an easy-to-use dashboard format. This information can easily and quickly be interrogated to provide workflow, error identification and quality indication information. This is simply not possible with conventional manual systems.

The other advantage of barcode technology is that it enables the automation of the transcription of information from one medium to another. For example, slides can be automatically printed with the laboratory accession number, patient name and stain generated by the LIMS system and driven directly from the block barcode. This makes the process much faster, safer and more reliable than error-prone manual transcription by humans. At the same time the audit trail attached to the block can be automatically updated with details such as the microtome used and microtomist performing the task.

Many laboratories currently manually transcribe tens of thousands of digits per day and the potential adverse impact of any transcription error necessitates several checks to ensure that the manual transcription of information is correct. The appeal of automating this step wherever possible can be readily appreciated. Providers claim that the correct use of a proprietary system of this kind can reduce the chance of transcription error to almost zero ( ).

Implementation of these error reducing automated steps can significantly minimize the risk of adverse events reducing reliance on vigilance at each process step. This permits streaming of the complex array of double and triple checks, thereby significantly improving productivity. There is also an improvement in the ability to access relevant information at each point in the workflow from block or slide.

Automated sample transcription and tracking can either be achieved via in-house development or purchased as whole tracking systems, such as the Leica CEREBRO system, Dako’s True Positive ID or VENTANA/Roche’s VANTAGE. Some of the advantages and disadvantages associated with each method are outlined in Table 11.1 .

Dissection/grossing

Dissection remains a hands-on area of the laboratory with knowledge and training the main requirements for best practice. However, the implementation of macroscopic photography and videography equipment can assist in both of these aspects.

Photographs can be used to store images of forms, blocks and pot labeling and other relevant information e.g. where certain blocks have been taken from a macro specimen. These images can be stored and annotated, improving the record of the macroscopy and dissection of complex specimens. The images can then be made available to the pathologist at the time of reporting and during future discussions, e.g. multidisciplinary team (MDT) meetings.

Their use allows dissection images to be taken which can be used as training tools, to write standard operating procedures (SOP’s) in a video format, or to live stream an unusual case for pathologists to discuss. Their use can also allow for remote pathology, with real-time guidance given to the dissector by off-site pathologists viewing the dissection over a video link or web-based systems.

Many systems now exist which fulfill this role and can be permanently mounted over the dissection table. Examples currently include the Menerini MACROpath and Cirdan’s Pathlite Macro Camera Station.