Surgical Pathology

Enabling digital intraoperative pathology consultations

Dominik Gerber
Dominik Gerber

CEO PreciPoint

Birgit Müller
Birgit Müller

Head of Business Development

Overview

To facilitate the readability of this article, we would like to point out to our readers that we use the generic masculine when referring to people. However, we make no distinction between the sexes and refer to all genders in our texts.

What is surgical pathology?

Surgical pathology is an area of practice in anatomical pathology. It consists of the evaluation by a pathologist of a surgical specimen – a tissue or fluid sample removed from the human body during a surgical operation. This assessment involves the gross inspection of the specimen and the microscopic examination of the fluid sample or of a tissue section prepared from the specimen. This process is called an intraoperative pathology consultation.

The rapid assessment takes place during surgery to provide the surgeon with the information he needs to take the necessary surgical steps. For example, a first benign vs. malignant evaluation, or the evaluation of the resection margins in case of a resection.

An accurate diagnosis is done after surgery using permanent FFPE slides. Depending on the clinical question, the final report can take up to a few days. 

What are the different types of surgical specimens?

Depending on the type of surgery or disease, different types of pathology specimens may be collected during a surgical procedure for submission to a pathologist. 

Tissue biopsies

Here is an overview of the most common types of tissue biopsies and surgical methods used to perform the biopsy during an operative procedure. This table intends to help the general understanding and does not claim to be exhaustive.

Type of biopsy Surgical methods Biopsied sites
Endoscopic biopsies
Endoscopic biopsies
Hollow organs
e.g. nose, sinus, digestive tract, bronchi
Incisional biopsies
Minimally invasive biopsies
e.g. thoracic, abdominal and pelvic organs
Core biopsies (needle biopsies)
Core needle biopsies
Solid organs
e.g. bone marrow, breast
Fine needle biopsies, also called:
fine needle aspiration (FNA)
e.g. bone marrow, thyroid,
breast, neurological samples (cerebrospinal fluid)
Excisional biopsies
Any organ

Surgical resections

Surgical resection is a surgical method whereby as much tumor tissue as necessary and possible is removed. The Mohs surgery is a modern resection method used primarily in skin cancer surgical procedures.

Unlike biopsies, which are done for evaluation purposes, resections are indicated when a malignant tumor has already been detected.

Cytology specimens

Here is an overview of the most common types of surgical methods used to remove cytology specimens. This table intends to help the general understanding and does not claim to be exhaustive. 

Cytology specimens Methods Sites
Fine needle aspiration (FNA)
Bone marrow, any tumor
Test of body fluids
Body cavities
Scrape of brush cytology
(example: pap smear)
Cervix, esophagus, stomach, bronchi and mouth

Surgical pathology glossary of terms

Surgical management designates the various activities and that are necessary to perform efficient surgery. Surgery management includes the medical, surgical, and nursing activities, as well as other tasks related to the surgery such as facility management, patient administration and billing. Surgery management can be specific to a pathology, for example surgical management of appendicitis.
The surgical pathology report, also pathology report or pathologist report is a document that contains the findings of the pathologist after macroscopic and microscopic examination of the specimen removed during surgery. For intraoperative procedures, the pathologist usually communicates immediate information by telephone to the operating surgeon.
Cell or tissue sample removed from the human body during a surgical intervention for examination by a pathologist. The main purpose of a biopsy is to evaluate whether the tissue is healthy or not. In the case of a rapid intra-operative assessment of a biopsy, further necessary surgical steps can be initiated. In the case of a final biopsy assessment, patient treatment can be initiated or adjusted.
Intraoperative pathologist consultation is a pathology service whereby a pathologist examines a cell or tissue sample, such as a so-called frozen section, removed from a surgery patient. The primary purpose of the consultation is to provide the surgeon with rapid information that directly influences the course of the surgery, for example, whether the resection margins are positive or negative.
Cryosection is the technical name for frozen section. It is a procedure in which a tissue sample is shock-frozen in a so-called cryostat and sectioned to prepare it for microscopic examination by a pathologist during an intraoperative consultation.
Shock-frozen, stained, unfixed biopsy tissue in the 5–10um range of thickness used for microscopic examination by a pathologist during intraoperative consultation. Colloquially, the frozen section also refers to the entire intraoperative examination.
Rapid on-site evaluation (ROSE) is the rapid pathology assessment of FNA smears or small tissue specimen to provide real-time feedback and guidance during a biopsy operation. One of the main objectives of ROSE is the assessment of sampling adequacy. Source: Rapid On-Site Evaluation (ROSE) A Practical Guide, Guoping Cai, Adebowale J. Adeniran
Lesion or tumor tissue removed from the human body during a surgical intervention. The purpose of a resection is to remove as much as necessary and possible of the lesion.
In the case of a malignant tumor, the margins of healthy tissue around the malignant cells of the resection or biopsy. The resection margin is used as an approximating assessment of whether all malignant cells have been removed. The pathologist assesses the margins microscopically to determine whether they are sufficient (negative) or not (positive).
Single cells and small clusters of cells removed from the human body during a surgery for examination by a pathologist.

What is an intraoperative pathology consultation?

An intraoperative pathology consultation, or intraoperative procedure, is a quality assurance service provided by a pathologist during a surgery. It consists in the rapid evaluation of a surgical specimen (tissue biopsy, surgical resection, or cytology specimen).

It is sometimes also referred to as rapid on-site evaluation (ROSE), although technically speaking ROSE refers to the live evaluation of FNA smears and small specimens by a pathologist to guide the surgeon in real-time during a surgery.

Intraoperative consultations are mainly practiced in oncological surgery but are not limited to it.

The primary objective is to provide the operating surgeon with rapid pathological information according to which can be decided how the surgery proceeds.

Is the tumor cancerous or not (malign vs. benign evaluation)

For the removal of a biopsy, tell whether the right area has been targeted and evaluate the specimen adequacy.

For a resection, has the lesion or tumor been fully removed or does more tissue need to be taken out? In this case, the pathologist evaluates under the microscope whether the resection margins are clear of residual cancer or not.

The final objective of intraoperative consultations is to avoid follow-up surgeries and improve treatment outcomes for the patient. In terms of hospital care, intraoperative consultations contribute to improving surgery management and overall surgical patient management. 

What is the difference between surgical and clinical pathology?

Unlike routine clinical pathology, surgical pathology consultations are performed under high time pressure while the patient is in the operating theater. Therefore, intraoperative pathology workflows are significantly faster than routine pathology workflows. 

Overall intraoperative process time is critical

Surgical Pathology Overall Workflow
The journey of a surgical specimen from the operating room to pathology

Swift intraoperative pathology workflows are very important. When the patient is lying on the operating table, every minute counts.Today, an intraoperative frozen section is usually performed within 20 minutes after the delivery of the specimen in the pathology lab.

Reduced slide preparation time is possible because the frozen section protocol uses different, more rapid cutting and fixation techniques than in routine clinical histopathology. Once the slide is under the microscope, the pathologist may provide his feedback within minutes.However, some factors greatly influence the overall time it takes to perform an intraoperative consultation such as a frozen section.In many countries, the lack of pathologists or the uneven regional distribution of pathologists within a country are significant constraints and may even challenge the feasibility of a consultation.

For example, intraoperative procedures may not systematically be carried out, or are not carried out at all for non-critical surgeries, which may increase the chance of follow-up surgery.Additionally, when the operating room and the pathology lab are geographically distributed, or when the hospital does not have a full-time pathologist, the specimens have to be transported to a pathology lab or the pathologist needs to travel to the hospital. Not only does it represent a logistic challenge, but it also lengthens the overall time to examination and increases the costs of consultations.

Permanent vs. frozen sections

Due to the time sensitivity during surgeries, the protocol used to prepare frozen sections is different to the FFPE protocol used for permanent sections in routine pathology.

The frozen section method mostly involves manual tasks which must be performed very accurately under high time pressure. Therefore, frozen sections are usually prepared by trained and experienced technical medical assistants or technicians. For comparison, the main steps of each protocol are shown the following graphic.  

Cryosection

Overview of Cryosection vs. FFPE protocols
Overall comparison of sample preparation techniques

The technical name for a frozen section is cryosection. During a frozen section workflow, the cryosection process follows the macroscopic evaluation and sampling of the specimen.

Here are the most important steps of the cryosection:

Step 1: The tissue sample is placed in a special container and embedded with a gel or embedding agent (OCT).

Step 2: The tissue block is quickly frozen and placed in a cryostat. This step hardens the tissue block and makes it suitable for sectioning. 

Step 3: The frozen block is sliced with a microtome into very thin sections.

Step 4: The sections are placed onto glass slides and manually stained. 

The techniques used to prepare a frozen section allow for sample preparation within minutes. However, frozen section microscopy slides are of lower quality than permanent slides. 

Why are frozen section slides of lower quality than permanent slides?

Usually, frozen section slides are not as plane as permanent slides and contain more artifacts.

Sections obtained from cutting frozen blocks are not as smooth and plane as sections obtained from FFPE blocks. In addition, when freezing, the water contained in the tissue can disturb the morphology of the cells. This is due to the so-called ice crystal artifact. Other artifacts such as overlapping tissue, dirt, or air inclusions can be introduced when manually cutting the frozen tissue, placing it onto the glass slide and staining.

Under the microscope, frozen sections are more challenging to assess than regular FFPE slides. They usually require experienced pathologists in the respective specialty.

Frozen section microscopy is also limited in scope and accuracy to the rapid delivery of information for surgery guidance. Frozen section slides are not adequate for a specific final diagnosis, nor can they be archived or stored longer term. 

Can a frozen section slide be digitized?

As discussed above, frozen section slides are not plane. Though technically speaking uneven slides can be digitized, there are a couple of important considerations to be aware of in the context of intraoperative consultations. 

Why are frozen section slides not plane?

In microscopic terms, frozen section slides can be very ‘bumpy’ compared to permanent slides prepared according to the FFPE protocol.

Unlike permanent slides, tissue blocks for frozen sections are not fixated, quickly embedded and shock frosted. The sections obtained from cutting such blocks are not as smooth and plane as permanent sections.

Frozen sections are also vulnerable to freezing artifacts and other artifacts resulting from manual preparation, making them even more inconsistent.

Even though it is possible to digitize ‘bumpy’ slides, the process of digitization / digital image generation takes significantly longer than routine pathology slide. 

Why does it take longer to scan a ‘bumpy’ slide?

Let’s look at how a whole slide image (WSI) is created. The scanner sets an automatic focus point. The camera travels along the horizontal focus plane through hundreds of x-y positions, taking a picture at each position. All the pictures are then put together (stitching) to create one single image or whole slide image. For a regular permanent slide, this process usually takes a couple of minutes.

When scanning difficult slides such as a bone marrow smear or a frozen section, a different scanning process is used to generate a high-resolution digital representation of the tissue section: Not only does the camera travel horizontally through hundreds of x-y positions, but it also moves vertically, taking a picture at various z-axis positions for each x-y position. The sharpest picture at each z position is first identified and then used for stitching. This process takes much longer than for regular scans. In the case of a frozen section consultation, it must be repeated for each frozen section slide during the consultation (in average about 4 slides per consultation).

What takes just a few minutes for permanent slides often takes 5 to 10 minutes on average for a frozen section slide. As the overall frozen section workflow, including cryosection and microscopic assessment should not take longer than 15 to 20 minutes (depending on protocols), scanning a single frozen section slide will consume a large portion of the time available for the whole process. 

Why are WSIs generated from frozen section slides often of lower quality?

Lower quality WSI are caused by the various artifacts commonly found in frozen section slides, such as ice crystal artifacts, cutting artifacts, overlapping, dirt, or air inclusions.

These artifacts cause certain areas of the WSI generated from frozen sections, or sometimes the entire slide, to be less sharp. This makes a microscopic assessment more challenging or impossible. 

Why digitize intraoperative procedures?

If you want to drive the digitization of intraoperative consultations, you should be able to clearly communicate how everyone involved can benefit. Based on these 5 reasons, you can build a strong case. 

1. Reduce Care Gap

The lack of pathologists is a global problem with extreme regional disparities. Patients from remote or developing parts of the world are often less likely to benefit from intraoperative procedures. The situation can be severe in densely populated, developing countries. According to our interview with Dr. Rabia Ali, Consultant Pathologist in Karachi, surgeries are done daily throughout Pakistan, but only very few pathology centers in the large cities offer intraoperative services.

Digital frozen sections can connect surgery departments to pathology centers across any distance and regional borders, potentially improving the feasibility of many procedures from a logistical and financial standpoint. 

2. Improve patient care

The patient benefits of rapid microscopic assessment during intraoperative procedures are well researched: Studies show that in breast cancer reoperating rates were reduced by 70% from 48.9% to 14.9% using frozen sections1 and in prostate cancer 22% of cases found positive margins during frozen section, of which 92,3% of positive margins could be removed2. Therewith, significantly lower probabilities for reoperation are possible, which is a huge benefit to patients.

By connecting the specialists around a patient’s case during surgery, digital frozen sections can make intraoperative pathology services more readily available. As a result, more cancer patients could have access to the intraoperative procedure and benefit from improved surgical care and more individualized treatment plans. 

*American Journal of Clincal Pathology Author manuscript; available in PMC 2014 Apr 16.   Intraoperative frozen section analysis of margins in breast conserving surgery significantly decreases reoperative rates: one year experience at an ambulatory surgical centerJulie M. Jorns, M.D., Daniel Visscher, M.D., Michael Sabel, M.D., Tara Breslin, M.D., M.S., Patrick Healy, M.S., Stephanie Daignaut, M.S., Jeffrey L. Myers, M.D., and Angela Wu, M.D. 

**Source: Journal of Urology 2013 Aug;190(2):515-20.doi: 10.1016/j.juro.2013.02.011. Epub 2013 Feb 13., Intraoperative frozen section of the prostate decreases positive margin rate while ensuring nerve sparing procedure during radical prostatectomyChristian von Bodman 1 , Marko Brock, Florian Roghmann, Anne Byers, Björn Löppenberg, Katharina Braun, Jobst Pastor, Florian Sommerer, Joachim Noldus, Rein Jüri Palisaar   https://www.auajournals.org/doi/10.1016/j.juro.2013.02.011

3. Cut Total Procedure Time

Despite their time-sensitive nature, intraoperative procedures are usually very time-consuming. The simple reason is that the pathologist is seldom at point-of-care. Either they must commute to the lab next to the surgical arena, where the intraoperative assessment takes place, or the fresh surgical specimens from the operating theater are rushed to the nearest pathology lab for rapid evaluation. Very often, time for transportation, commuting, or waiting is the most time-consuming part of the procedure. 

Total Intraoperative Turnaround Time
Pic. 1: Intraoperative Procedures Total Turnaround Time

By enabling remote consultations, digital frozen sections may eliminate the need for travel or transport, saving very precious time while the patient is lying under anesthesia. However, decision makers should be aware that a reduction in the total procedure time may not always be achieved. This highly depends on the type of technology used. In paragraph 8, we review the various image acquisition technologies available to enable remote diagnostics. 

4. Enable Second Opinion

Frozen section interpretations necessitate knowledge and expertise in the relevant specialty or sub-specialty. When the expert is not locally available, it is virtually impossible to organize the second opinion of a qualified remote specialist within the consultation time.

Digital frozen sections can enable access to a remote second opinion from a much wider pool of specialists as an immediate support to the on-site pathologist. 

REMOTE CONSULTATIONS
Pic. 2: Remote cooperation across locations and geographical sites

5. Cut Procedure Costs

Getting a surgical specimen into the hands of a pathologist involves traveling or transport, which inevitably drives up the overall procedure costs. High procedure costs have direct consequences on the accessibility to intraoperative pathology services.

From the point of view of a pathologist, and especially of a lab owner, intraoperative work is often a loss-making business line due to the time spent traveling and away from actual clinical work. Yet, intraoperative consultations need to be offered as a service to customers, so as to secure the far bigger volume of work stemming from routine pathology consultations. Offering intraoperative consultations can therefore be an opportunity for lab owners to increase their customer base.

Digital frozen sections can eliminate the travel costs related to a frozen section consultation. Pathologists can deliver their services more efficiently, driving up the number of cases they can see in the same amount of time. 

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*PreciPoint GmbH is the owner of the content of this webpage. PreciPoint provides solutions and services for the digitization of laboratory and microscopy workflows. As such, we want to provide our website visitors with useful information pertaining to digitalization, our products and solutions. However, we cannot guarantee that the information contained herein is always fully exhaustive and up to date. Neither do we intend to make any medical statements or recommendations.