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The Cost of Reprocessing

Herbert Skip Brown
Herbert Skip Brown M. Div., HT(ASCP), Director of Education & Training, Lab Management Consultants

One of the most fundamentally critical elements of diagnostic histopathology is first the ability to suspend all cellular activity in tissue and prevent egradation, and secondly to process that specimen in a manner that facilitates subsequent steps such as microtomy and staining. When these essential factors are not optimally met, a progressive decline results in the quality of tissue oftentimes resulting in an un-diagnosable specimen and attempts to ‘reprocess’ specimens correctly. There is a cost associated with reprocessing in workload, and more directly in laboratory costs per patient. Moreover, the reprocessed tissue never renders the diagnostic quality of optimal processing, thus compromises the pathologist’s ability to make accurate diagnoses. Every event of reprocessing compromises patient care and must be addressed and resolved to avoid reoccurrence.

Learning Objectives

  1. Understand the histochemical process of fixation and processing on tissues
  2. Illustrate the physical, diagnostic, and monetary cost to reprocessing
  3. Outline quality assurance and operational imperatives essential and necessary to eliminate the incidence of reprocessing

Webinar Transcription


The next slide is our course objectives. The first bulleted objective is to understand the histochemical process of fixation and processing on tissues. To understand what is happening when you need to reprocess, you must understand molecularly what is going on with the tissue and how that is affecting the tissue at a molecular level.


The next bulleted objective is to illustrate the physical, diagnostic, and monetary cost to reprocessing. There is a cost that is involved with physical changes, diagnostic changes, and complications, and the monetary cost to reprocessing. The third bullet is to outline the quality assurance and operational imperatives essential and necessary to eliminate the incidence of reprocessing. If you are having some incidence of reprocessing even occasionally, we will address what operational things you can look at to eliminate or at least minimize your risk or your possibility of having those events occur.

The next slide is a statement I want to make: One of the most fundamentally critical elements of diagnostic histopathology is first the ability to suspend all cellular activity in tissues and prevent degradation, and secondly, to process that specimen in a manner that facilitates subsequent steps such as microtomy and staining. When these essential factors are not optimally met, a progressive, and this is important, a progressive decline results in the quality of tissue, oftentimes resulting in an un-diagnosable specimen and attempts to “reprocess” the specimen correctly. There is a cost associated with reprocessing in workload, and more directly in laboratory cost per patient. This last part is important: Moreover, the reprocessed tissue never renders the diagnostic quality of optimal processing, thus compromising the pathologist’s ability to make accurate diagnoses. Every event of reprocessing compromises patient care and must be addressed and resolved to avoid reoccurrence.

I say this because we are so skilled at what we do as histology professionals, that when we have a tissue that is not optimally processed, we just fix the problem because particularly in patient care, we want to give the doctor something to diagnose because of the patient. In the U.S., there is a 24-hour turnaround time from the time that the patient goes into surgery to diagnosis. If we can get a diagnosable slide to the doctor, even if it is not optimal, so that he can make that diagnosis for the patient, we are going to do that, but this compromises the doctor’s ability to make that diagnosis and compromises patient care.


This next slide exhibits three different areas of comprehensive cost, looking first at diagnostic. This slide shows a block of tissue with a center that looks different. While the pathologists only interpret what they see, the histology professionals shed light and bring revelation to the pathology, to the disease state. If we don’t do our professional job optimally, then the pathologist will never have a clear picture or that light to see. This is diagnostic cost, and the animation represents acute cost, or the immediate cost to the patient. On the lower left is a block showing incomplete penetration where the solutions were not in fixation long enough or they were not in processing cycles long enough, and the solutions for fixation and for processing had not penetrated to the center of the tissue. We will talk about penetration time and penetration rate, or the rate of solutions such as formaldehyde to reach the center of the tissue, which is largely determined by the thickness of the tissue. The tissue on the right is an undifferentiated tumor; this is un-diagnosable because it did not have ample time to penetrate. The block would be very difficult for the doctor to diagnose causing him to go back and do a reprocessing.

The second area of comprehensive cost is financial. The first bullet is operational workload costs, which is the cost in time and manpower allocations. The time refers to the time allocated to go back and reprocess; the manpower refers to allocation of stopping current activities to return the tissues and melt them down. We are not addressing the time involved; we are looking at the cost involved in that patient’s specimen being hung up, to have to go back and be reprocessed.

The second bullet on this slide represents productivity measures, the justification for full-time employees and part-time employees. In productivity and management, we must justify the number of both full-time and part-time employees. One way to look at this number is by the amount of work that you have. The time involved in wasting a lot of our day going back to reprocess could be justified towards having another full-time employee, or maybe not having another full-time employee. It affects our productivity, and it is a long-term cost.

The third bullet represents laboratory operation cost, the cost in reagents, materials, and time: tissue is run back through, and reprocessing costs include reagents being utilized again; the materials; and the time involved. These three are chronic costs which are long-term. We rarely see this cost because we fix the problem, and we move on, but the cost to the laboratory is substantial over weeks and months.

The third area of comprehensive cost is in patient care. This is the trust and integrity that we have from the patient to us. The first bullet is confidence in lab testing quality and competency, followed by competence in hospital patient care abilities, and confidence in the patient care ethics of the hospital and health system. Competency in us being able to do basic lab testing and in our staff falls if diagnosis is not optimized. If a hospital is unable to optimize tissue specimens, its competence level is seen as lower and patients may avoid going to that facility. Confidence in patient care ethics can be undermined via word-of-mouth when a healthcare facility falls short of optimizing diagnosis and studies.


The next slide looks at histochemistry. To understand the diagnostic cost, we have to look at how the tissues are compromised at a molecular level. The two methods of fixation in tissues involve a disruption of the secondary and tertiary molecular structures, or a cross-linking of protein groups. Disruption of structure may include a jostling of polar and nonpolar amino acids in aqueous phase; during processing, water molecules migrate out and away from the polar phase. In fixation, particularly using alcohol fixatives, removal of bound water results in brittle tissue. Tissues become overly dehydrated when they are not processed or fixed optimally.

The next slide shows cross-linking of protein groups. Formalin is utilized most often in basic hospital histopathology. Formaldehyde plus reactive hydrogen on tissue results in formation of a reactive hydroxy methyl compound, the additive compound of formalin. Formalin enlarges a tissue molecule. A methylene crosslink bridge is formed, with cross-linking of protein groups and release of water. This process continues: tissue molecules will link on with other tissue molecules in the presence of formalin.

Prior to working in immunohistochemistry, we never had to worry about this cross-linking. But in the early 1980s, we discovered that these cross-linking methylene bridges can block epitope sites and impede them from binding with their antibodies. Thus, false negative results can be seen in histochemistry studies. This is another example of activity at the molecular level, and with most laboratories using formalin, this actually occurs on a day-to-day basis. We must use antigen retrieval steps to break the methylene bridge and free up that epitope site.

From the molecular level, we will address two other topics. The next slide shows penetration rate versus binding time. Penetration rate can significantly affect the infiltration of the tissues, the spreading of the solution or the penetration of the solution into the tissues to create optimal fixation all throughout the tissue, not just on the outer perimeter. With penetration rate, we know that the initial penetration rate is rapid at 1-2 cell layers initially. Following this, penetration rate progressively decreases with time as it continues to sit in a fixative such as formalin in the absence of agitation. Lastly, the variability due to thickness and density of tissues affects the penetration rate. Thus, for good penetration we need to make sure in our laboratories that we have optimal time for fixation or that we do agitation or physical inducement.

Penetration rate is one factor, and the other is binding time to penetrate the tissues. The penetration requires ample time to penetrate the tissues. Yet, we rarely talk about binding time: even when tissues are sliced optimally thin, 3 mm, there is a certain amount of time involved for stabilization of proteins that I just showed you for cross-linking and disruption of secondary and tertiary structures. Events involved in binding time include: stabilization of proteins; formalin is chemically linked to tissue molecule; tertiary structure of the molecule is altered; and a gel-like precipitate is formed. A binding time must occur even with optimally gross tissues. You still need an optimal amount of time for this molecular or chemical reaction to occur at a molecular level.

The next slide shows a quote from the HistoNet net server in 2002, which says that even though thin slices of tissues would be penetrated faster and in thicker slices, it would seem that the binding time is the limiting factor for tissues stabilization. Hewlett is saying that this is more significant than penetration rate, which is equally significant if not more significant.

The next slide is another quote by Hewlett: Failure to recognize the importance of formaldehyde binding time is the leading cause of a tremendous intra- and inter-laboratory variability in performance. This is what led to the College of American Pathologists to develop its CAP safety guidelines in 2005 for ER/PR/ HER2. Cancer specimens must be handled in uniform manner in ER/PR/ HER2 studies with breast cancer specimens. While this data has changed, the guidelines state that ER/PR needs to be handled for 6-72 hr fixation time; HER2 studies for 6-48 hr fixation time, to cover the low level expressors; and clinical lab considerations must be made, such as for weekend processing. The ER/PR and the HER2 studies are now the same; there is no differentiation between the 6 hr and 72 hr, and the 6 hr and the 42 hr. Binding time is a key topic related to working with the tissues.


After looking at all these different factors, take a step back and look at what type of risk we have in our laboratory that might cause reprocessing. If you are having any kind of incidence, take a step back to assess how we are doing things and look at areas that could cause us to frequently have reprocessing.

Here are three common causative variables associated with risk assessment which could lead to frequent reprocessing. The first risk area is tissue preparation; the second risk area is reagent management, or how we are changing our solutions; and the third area is fixed time schedules, or ensuring that the time protocol is validated and adhered to every day, without compromise such as changing time protocol to meet a courier deadline, which ultimate winds up compromising patient care.

Here is a graphic which shows how, for instance, we receive a sample of an infra-axillary breast tissue for preparation, while the next slide shows polyps, ovary and breast tissue, the types of samples we want to receive. But our nightmare type sample shows tissue here sectioned off into three parts: this hunk of tissue, looking at the left-hand sample, is very thick and thus will compromise the penetration rate and thus the ability to fix the tissue in the center. We do not have control over what we receive, but one area of risk requires us to carefully determine whether the tissues are being grossed properly.

Turning to the risk area of reagent management, common causative variables include: solutions not rotated or changed on a regular/routine basis; rushing; accuracy and proficiency in daily solution change/rotations; and irregular and non-consistent load and start times for tissue processors. This final item presents a challenge to a manager: processors must start at a certain time every day to finish in a timely manner, and tissues removed at a certain daily time to meet courier schedules. Courier schedules are subject to occasional schedule deviations, leading to possible altered tissue prep time, which can compromise fixation and processing of tissues. Administrators have told me to simply adjust to the courier schedules, but I disagree: we are talking about patient care, so this is an area that needs to be fixed, not at the histology and management level but rather at the administrative level. Courier companies should be held accountable. The bottom line is these tissues must be delivered at a certain time to maintain processing schedules.

The third risk area is cleaning cycles: if a lab is rushed, someone may forget to hit the cleaning cycle, which can ultimately compromise the tissues because the processor has not been cleaned. The tissue thus runs through a dirty cycle. Your ability to do a clean processing cycle is compromised.

This next slide shows colon tissue preparation which has resulted from suboptimal fixation. While the nuclear and other detail is still intact and may be deemed diagnosable, you can see in the lower center portion a bleaching-out of the stain. During processing, a solution likely was not changed when it should have been changed: the alcohols were not as clean as they should have been, or the xylene was not changed. We would continue with such a sample since the doctor made the diagnosis, but this shows why we need to have a quality insurance check. For example, maybe 10% of slides in every tray of slides that goes out should be reviewed under the microscope prior to going out to the pathologist.

The next slide addresses risk management: gross room intervention. Lab assistants require monitoring by supervisors for correct cassette usage, for example, using a regular cassette for large specimens rather than a biopsy cassette, as well as monitoring for correct tissue processor usage, for example, having familiarity with the LIS system that it will inadequately protocol, and process one big polyp in the same way that it processes biopsy tissues. Reprocessing will thus be needed for the one cassette with the polyp. Supervisory oversight is needed for lab assistants and pathology group in the gross room. Monthly progress measures should be performed and posted reviewing pertinent incidents. Finally, lab assistants should be included in the histology staff meetings to maintain a team environment.

Lab assistants do make certain decisions. These next slides show a Turbo Flow cassette which was specially designed for optimal fluidic flow for breast and colon tissues or other thick specimens which might be compromised. Such cassettes may decrease the risk of reprocessing even when grossing is not done optimally.

This slide addresses reagent management, the second area of risk management. This CAP quality assurance standard, which is specifically written for each respective laboratory, basically designates how solutions are to be changed and rotated, and defines what change and rotation mean, such that all lab personnel understand and adhere to this process.

This slide addresses fixed time schedules, the third segment of risk management. Relevant factors include validated tissue processor cycles, mandatory start times, and universal consistency. Validated tissue processor cycles used for each tissue type, be it breast, colon, or another, must be run every day with mandatory start times to maintain universal consistency, thereby reducing risk. The next slide exemplifies this fixed time schedule factor, using three validated protocols, routine, biopsy, and breast, which list mandatory start cycles and processing times as defined in the validated procedures.

Cost Analysis

Turning now to the actual cost analysis, this slide shows Workload Cost Calculator. The facets used for this study include the American Society of Clinical Pathology, or ASCP, Wage Survey which determined what technicians are earning across regions; and the National Society of Histotechnology Task Force on Productivity which determined the amount of time required to perform each step in a laboratory, for instance, embedding a specimen or sectioning a specimen, both used to reach a workload differential and a time differential. The annual ASCP Wage and Vacancy Survey looks at the salary of technicians and others such as histotechnologist and supervisor; considers the size and type of laboratory under consideration, be it a hospital lab, physician office lab, or reference lab; factors in the geographical region of the laboratory; and determines the average salary based on these factors.

The second element of the study, the NSH Productivity Task Force 2004, was a nationwide test model that considered 25-30 different laboratories. The Task Force looked at both average workload, including number of personnel and daily workload volume, as well as average time to complete each task in routine slide production, including embedding, microtomy, and staining and coverslipping. Workload recording variables, based on a salary of $18.00/hour, show an average time to complete each step which allows for a breakdown into unit dollar cost for each task performed within the lab. Tasks include: unload tissue, embed, cool block, face off block, section block, problematic block, slide drying, stain (automated), and coverslip (manual).

Here, we look at workload recording variables, namely looking at time and cost for reprocessing. When all steps are added together, just the total reprocessing steps seen here at the bottom add another six hours, 37 minutes, and eight seconds, plus an additional $119.40 workload value. This value does not address what the technicians are doing but rather looks at the cost of that specimen being delayed during this time, and the workload cost associated with that workload.

Thus, basic workload cost based on $18.00/hour salary would be $20.23 for one hour, seven minutes, and 37 seconds time, while the reprocessing steps alone would be six hours, 37 minutes, and eight seconds, with the additional $119.40. So eight hours, 49 minutes, and five seconds is the total time required to start a specimen, go back and reprocess it, then finish it, with total unit dollar cost of $158.85. The workload cost increase from regular processing with standard results, to processing results that require reprocessing, is $138.53. That is a 681.5% workload increase, a nearly 700% workload increase every time reprocessing of tissues is required.

When workload cost is added up for reprocessing done once or twice a week, once or twice a month, six months, this cost is very significant to the laboratory. But this cost is invisible to administrators because we never see it; we just fix the problem. I encourage each manager and supervisor to show this data to your administrators because we need to fix these gaps, determine the reasons for reprocessing even on a small scale, and analyze what reprocessing is costing the laboratory.


As we come to the end of the presentation, this slide shows optimal results on four different slides with good nuclear staining, good eosinophilic counterstaining in the cytoplasm, and so forth.

When looking at our references, I will close by saying it is very important not to overlook this problem simply because things got diagnosed. We need to have some kind of QA check to critically look at 10% of slides that are going out every day, to ensure integrity of staining and so forth, and to ensure optimal processing. When problematic issues arise, we must look at why such issues occur, be it in the gross room, the processing room, then we need to fix such problems because they cost the lab a lot over a six-month or 12-month timeframe.

It has been an honor and pleasure to be here to present this material to you. We went beyond our allotted time. We will make room for Q&A now. I commend you all for continuing to grow and develop as histology professionals because it is very important in what we do: the patient depends on us to be the professionals that we are. Thank you very much for allowing me to do what I love to do. I want to thank Leica Biosystems, and also Rick for being the facilitator on this session. Thank you very much.


Q. Do you have any advice for labs that process intermittently, maybe once or twice a week, or do very low volumes per day with respect to processor solution management?

A. Yes, that is determined basically by the supervisor or the manager. It is difficult for me, not being involved in the laboratory, to know what specimens you are running through and how often you are using the processors. If the processor is being used only 1-3 times a week, but you are running colon and breast tissues, and so on, that would be different from if you are running biopsy specimens. You must determine if you are running thick specimens, I would say that every time that you run the processor, you need to at least have a rotation where you remove the dirtiest solution, you rotate it down, and you replace it with a clean cycle. If you are doing smaller normal, regular tissues, you could probably have two days go by before you do rotations. But this is something that you must determine and validate, and once validation is made, you must set that up in your standards for your laboratory and write it into your laboratory workbook or manual. If you need further discussion, my email address is available for you to send a follow-up question.

Q. Sometimes the needle biopsy fails to reach the desired nodule and the tissue type is the wrong tissue, or inadequate for further diagnoses. How quickly is the tissue typically recognized?

A. Assuming that they mean that it is the wrong tissue and not further in, typically, the pathologist would not have been involved in assisting in fine needle aspiration and biopsy, the pathologist or the ultrasound technician is determining whether they have gone in far enough. We get the specimen out, we might do a rapid analysis of it very quickly, and they can tell from the cellular structure whether the pathology is there or not. So basically, from a morphologic examination of the cells, they will be able to determine if they have gone in far enough or if they need to go deeper or they did not get the right portion of the tissue or the nodule. They should be able to look at that and tell morphologically under the scope. A lot of times when you are assisting, you will have a scope immediately available that the doctor can consider when you do rapid staining.

If I understand the question correctly, I think that is how I would respond to that. As I said before, please send in follow-up questions and concerns to my email address, and if you did not get a chance to ask a question, I am very good at responding to emails. Identify that you were in this session and ask your question.

About the presenter

Herbert Skip Brown , M. Div., HT(ASCP), Director of Education & Training, Lab Management Consultants

Skip Brown has 39 years of experience in the field of Histotechnology, over 30 of which being at the supervisory and management levels. He has managed some of the most progressive clinical and research institutions such as Kaiser Permanente of Southern California and Northwestern University Pathology Core Facility.

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