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10 Handling Surgical Specimens toDecrease Errors inPathology
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This frequently results in putting the wrong sample in the wrong container leading,
at best, to confusion and inefciency, and at worst to a mismatch between site and
diagnosis. The acquisition of advanced hospital information systems that rely heavily on barcodes and proper identication in order to minimize human error has
helped in that respect. It may, however, lead to overreliance on the accuracy of the
system, encouraging sloppy practices that will lead to mistakes irrespective of the
advances and advantages that medical software provides. For instance, a barcode on
the wristband of the patient leading to the opening of the appropriate electronic
medical chart and printing of the appropriate labels will not prevent an inattentive
healthcare worker from putting the wrong specimen in the wrong container.
Specimen containers should therefore be carefully checked for proper identication and labeling just as carefully as when a phlebotomist draws blood on a patient
and puts it in a tube for further testing [11].
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Communication Between Clinician andPathologist
Lack of adequate communication between clinicians and pathologists and between
clinicians themselves has affected the healthcare system for decades and continues
to play a major role in potential diagnostic and management errors, and in adverse
outcomes on multiple medical and non-medical levels [12–14]. We should be cognizant of the fact that patients are acutely aware of—and highly sensitive to—the
lack of sufcient communication between members of the medical teams in charge
of their care. In the absence of general patient satisfaction, it is doubtful that stateof- the-art medical procedures and knowledge can, by themselves, amount to optimal medical care and outcome. The absence of sufcient communication between
the clinician/surgeon and the pathologist is as detrimental as any instance of insufcient communication among medical teams and can manifest in any number of
ways. Most frequently, it consists of inadequate sharing of relevant clinical information, or unclear communication of the needed ancillary diagnostic modality [14].
Moreover, in the highly complex and intricate medical ecosystem that has evolved
over the recent decades, a surgical procedure may serve the sole purpose of diagnosis, therefore requiring specialized ancillary studies such as molecular testing, ow
cytometry, specic predictive immunohistochemical markers, etc. Resections may
be therapeutic, or palliative. Resection margins may or may not be relevant, and
which margins are especially relevant may not be apparent. A lesion may or may not
be grossly visible and may be isolated or one of several. Localization devices may
or may not have been inserted to identify the site of the tumor. The information that
can be, or needs to be, gleaned from a surgical specimen varies tremendously from
one specimen to the other and from one patient to the other. It is the surgeon’s solemn responsibility to inform the pathologist of the relevant information and the
henceforth-needed diagnostic and clinical tests for the appropriate evaluation and
management of the patient.
Another important aspect of proper communication between clinician and
pathologist relates to making the pathologist aware of special circumstances
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F. Boulos and M. Attieh
associated with a specic tissue sample. These include urgency of the sample,
scheduling at odd times when the pathologist and needed ancillary staff may not be
readily available, and samples requiring special handling, special media, and
unusual diagnostic tests. This frequently not only applies to hematolymphoid and
pediatric tumors, but also to a growing number of adult solid neoplasms.
We should remember that most communication occurring between clinician and
pathologist takes place on the requisition sheet or within the electronic laboratory
information system. Because many hospitals have not yet transitioned to an electronic ordering system and still rely on handwritten requisition sheets, it is important to emphasize the legibility of the information provided on the requisition, be it
clinical history, nature of specimen, physician information, among others. An example of poorly written requisition sheets is shown in Fig.10.1.
Fig. 10.1 Examples of poorly written notes
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159
Clinical History
This section—pertaining to clinical history—naturally overlaps with the preceding
section that discusses communication between pathologist and clinician. But herein
we will discuss the importance of including relevant and accurate clinical history,
especially if the surgeon/clinician may not be available for immediate inquiry and
clarication. The lack of adequate clinical history has affected most practicing
pathologists to some extent during their careers. Receiving a specimen with little to
no information and no real indication as to the purpose of the surgical procedure can
leave a pathologist in a precarious position, vulnerable to unwarranted mistakes.
The faith that surgeons often put in a pathologist’s ability to make the correct diagnosis or take the appropriate diagnostic measures based on gross and histopathologic features alone is exaggerated, and stems from poor understanding of the
intrinsic limitations of the discipline of pathology. Histopathology does not sit in a
vacuum, far from the clinical characteristics of the patient in question. It is therefore
paramount to reinforce the idea that microscopic changes peculiar to, or characteristic of, a certain condition, may be seen in a number of other conditions as well,
and can only be accurately interpreted within the proper clinical context. This is
especially relevant when patients undergo surgical resections for recurrent tumors
that have not been mentioned as part of the patient’s clinical or surgical history. The
amount of work, time, and stress that personnel may experience because of a specimen devoid of clinical background is great [15]. The more widespread use of electronic medical records and the accessibility of a patient’s clinical information has
decreased the amplitude of this problem. However, when patients come in for a
surgical procedure after having been managed and treated at other hospitals, and
while a clinic note may guide the pathologist toward what the clinician is looking
for, the information included in such notes often ends up being rudimentary.
What follows is an actual example from our pathology department. An open
biopsy from an abdominal mass was received on a 57-year-old woman. The biopsy
harbored an undifferentiated carcinoma. A large panel of immunohistochemical
stains was performed with variable nonspecic staining of some markers. A nal
diagnosis more precise than undifferentiated carcinoma could not be rendered.
After many days of working the case up, consulting colleagues, and not being able
to contact the surgeon (who was out of the country), examination of the chart
revealed, buried within one of the notes, a photocopy of an outside pathology report
detailing the ndings in a total abdominal hysterectomy procedure that revealed
ovarian carcinoma. While this instance did not pose a direct danger of misdiagnosis,
and was resolved positively, withholding important information from the pathologist resulted in a waste of time and resources and could have easily ended up with a
misinterpretation of the nonspecic ndings in the open biopsy, with potential mismanagement of the patient. In another instance, a patient undergoing decortication
of diffuse pleural thickening because of metastatic sarcomatoid renal cell carcinoma
was misdiagnosed with sarcomatoid mesothelioma because the clinicians omitted
the prior history of a malignant renal neoplasm. Understandably, the prognosis in
this latter instance may not be signicantly altered, but one can easily envision
instances where both prognosis and management are signicantly compromised by
inaccurate or inadequate clinical history.
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Another aspect of delivering accurate and complete clinical history includes providing the pathologist with relevant previous material for review. Instances where
the patient is undergoing resection of a recurrent tumor, be it locally or at a distant
site, are common. Comparing the original to the recurrent/metastatic tumor is very
important in order to condently differentiate a recurrence from a new primary. It is
commonly assumed that immunohistochemical staining will provide unequivocal
answers as to the type and site of origin of all tumors. This is, however, idealistic, as
many tumors share overlapping morphologic and immunohistochemical features,
yet carry entirely different management and prognostic characteristics.
In addition, there are many historical elements that may alter the morphology of a
resected specimen, or require ancillary testing or more vigilant examination, that may
be considered irrelevant by the clinician. These include, but are not limited to, HIV
status, EBV infection, administration of steroids in hematolymphoid neoplasms, prior
radiation therapy or chemotherapy, exposure to infectious organisms such as tuberculosis or leishmania, travel to possibly endemic areas, etc. Some of these situations may
not be intuitive to the clinician, but many are both intuitive and important, yet remain
frequently omitted from the clinical information paragraph on the requisition sheet.
F. Boulos and M. Attieh
Tissue Identification andOrientation
A pathologist cannot overemphasize the importance of stating the exact source of a
specimen in order to reach a correct diagnosis. Neighboring organs spawn distinctly
different types of neoplastic proliferation. The morphologic overlap between some
of these distinct tumors is, however, sufcient to issue a false diagnosis because of
incorrect information about the origin of the specimen. It matters if something is
renal or suprarenal, rectal or perirectal, gastric or from the gastro-esophageal junction, etc. Naturally, this applies more readily to core biopsies and small surgical
specimens lacking the benet of gross identication, but the principle of accurate
designation is not to be taken lightly under any circumstance.
Although laterality will not affect the accuracy of a pathology diagnosis, it
remains very important to mention for documentation and medico-legal purposes.
In the same vein, a large surgical specimen requiring orientation for adequate evaluation of landmarks and margins should be oriented via three axes, by sutures or
special ink applied by the surgeon him/herself. Although sutures are probably the
more prevalent method of orienting a specimen, at least in our experience, we
believe that a suture marking a single spot does not adequately represent an entire
surface as applying ink to it would. The limitation of using sutures is augmented by
the distortion an exvivo specimen may be subjected to following settling, manipulation, and xation in transportation containers. We do understand, however, that the
surgeon may perceive the inking of specimens as cumbersome and may consider the
pathologist better suited for such techniques. When knowing exactly which margin
is positive and how this positivity will inuence further surgical management, an
extra effort requiring a rather simple methodology toward a better clinical outcome
remains warranted.
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Tissue Preservation
The entire discipline of pathology is based on the examination of the architecture
and cellular details of tissue excised from the human body. This is only possible if
the excised tissue is preserved and prevented from undergoing the otherwise
unavoidable degradation process. Formaldehyde is the most commonly used and
ubiquitously accepted chemical that accomplishes this function. Once tissue is
soaked in formaldehyde, its constituent proteins are cross-linked, and soluble proteins are xed to structural proteins in a way that maintains tissue integrity, gives
mechanical strength, and renders it somewhat resistant to enzymatic digestion and
degradation [16, 17]. In other words, it becomes resistant to autolysis. It becomes,
therefore, possible to take sections from this tissue and embed them in parafn. This
is then followed by taking thin parafn tissue sections and putting them on glass
slides and staining them with hematoxylin and eosin. If the xation process is inadequate, then the microscopic detail is lost, and with it, any chance of a reliable or
complete diagnosis. This happens most frequently in specimens that sit overnight,
either in the surgical suite or in the receiving area, without being transported
promptly to surgical pathology. Specimens that are especially sensitive to autolysis
are ones that have a mucosal surface, due to the high susceptibility of the mucosa to
ischemic damage. Any specimen type can undergo autolytic degeneration to some
extent if not properly and promptly handled. Examples of autolysis as seen in hematoxylin and eosin preparations are shown in Fig.10.2.
Moreover, xation has become extremely important for adequate pathological
assessment, beyond morphologic preservation for histopathologic evaluation. Many
tumors, most notably breast cancer, require an array of immunohistochemical stains
to adequately predict response to targeted therapies such as hormonal therapy and
anti-Her2/neu treatment, among others that will likely be available in the near
Fig. 10.2 Examples of autolysis as seen on hematoxylin and eosin preparations. The cells appear
detached and oating in an empty space. In the sections from breast specimens, the pathologist can
hardly determine the grade of the invasive cells or distinguish between in situ carcinoma and lymphatic invasion
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future. Such predictive markers are tightly regulated to ensure accuracy and reproducibility of results [18]. As an example, the American Society for Clinical
Oncology (ASCO), in conjunction with the College of American Pathologists, have
since 2007 issued several reports detailing both testing and scoring requirements
based on the available evidence exactly for the purposes of standardization and
reproducibility across laboratories, testing facilities, and pathologists. In all of their
issued reports, the ASCO/CAP experts have mandated that the tissue be placed in
xative no later than 1h following surgical resection. This is referred to as cold
ischemic time (not to be confused with cold ischemia time, which relates to the
disconnection and reconnection of an organ from the systemic vasculature during a
surgical procedure) [19, 20]. It may seem like the 1-h threshold of cold ischemic
time is quite easy to achieve in the setting of a modern hospital milieu. The real
question, however, is how long it takes the xative to reach the tissue of interest and
preserve it for adequate staining and evaluation [21].
As stated above, the xative that is most widely used and on which all the standard recommendations are based is formaldehyde, in the form of 10% buffered
formalin, which is a combination of formaldehyde and a buffer. Formalin inltrates
tissue according to a formula that dictates a decremental rate of penetration reaching approximately 1mm per hour after the fourth hour. This rate is sufcient for
needle biopsies. However, when it comes to larger resection specimens with a tumor
in the center of the specimen, several centimeters away from the surgical margin, it
is remarkably slow. We bypass this limitation by immediately handling large specimens and sectioning them into multiple 0.5–1cm slabs in order to expose the maximum surface area possible to formalin and to avoid the all-but-guaranteed ensuing
poor xation and autolysis following delayed exposure to formalin [22].
Another aspect of formalin xation that is not well known among non- pathologists
is the amount of formalin required for the proper xation of a tissue sample.
Appropriate xation requires an equal volume-to-volume amount of formaldehyde
for the xative to accomplish its function. Given that the formalin used in labs is
signicantly diluted (10% buffered formalin) the approximate amount of formalin
needed for proper xation is roughly 10 times the volume of the tissue resected. In
other words, if an appendix that has a volume of approximately 6cm3 is to be properly xed, it will need approximately 60mL of formalin. In the case of small specimens and the small containers housing them, this is not a problem. However, when
dealing with larger specimens placed within barely large enough containers with
hardly any formalin, the issue becomes problematic. The very small amount of formalin barely surrounding the tissue will add to the problem of slow formalin inltration into the resected surgical specimen.
It is standard practice that specimens removed after-hours will sit overnight in
the refrigerator in the operating suite. Refrigeration is an important surrogate for
xation because it delays the degradation of tissue. However, when it comes to the
reliability of immunohistochemical markers, refrigeration might not be sufcient to
counteract the loss of antigenicity and tissue degradation with ensuing decreased
immunoreactivity for the predictive markers, and subsequent high rates of falsenegative results [23–25].
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The recommendation is to deal with any resected specimen, especially tumor
resections, with utmost care and urgency in order to provide the highest quality of
service to patients. Appropriately sized containers with a sufcient amount of formalin should be available and should receive the specimen as quickly following
excision as possible. This is especially relevant with procedures that take many
hours and may result in a specimen sitting on the shelf devoid of proper xative for
longer than necessary. One must, however, note that when it comes to very large
specimens, it would be a practical impossibility to surround the resected tissue with
formalin 10 times the volume of the tissue itself, which would require a container
almost the size of a barrel. However, ensuring that the resected specimen is surrounded by at least the same volume of formalin to allow for proper supercial xation until the specimen is received in the lab and properly handled, is vital [26, 27].
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Tissue Transportation
Serious errors can also occur while the specimen is transported from the surgical
suite to the pathology laboratory. These include specimen loss, misplacement of the
specimen in a location that exposes it to extremes of temperature leading to tissue
deterioration or destruction, and delivering the specimen to sites other than surgical
pathology (microbiology, chemistry, or cytogenetics) where it may remain unaccounted for, or subjected to unintended processing procedures that will render the
tissue unsuitable for further surgical pathology examination. Such events can be
damaging to the medical care and welfare of the patient, especially given that surgical specimens are usually unique and impossible to replace [28].
Notes onIntraoperative Consultation
Although the source of errors related to intraoperative frozen section diagnosis are
by far secondary to analytic concerns such as sampling and interpretation, there are
rare instances where a frozen section is requested on a small amount of tissue without proper justication of the intraoperative consultation. This may lead to exhaustion of valuable diagnostic material without reaching a nal diagnosis, or to
subjecting the tissue to freezing artifacts therefore compromising adequate histomorphologic assessment [29]. Such artifacts are magnied by placing the specimen
in an aqueous solution, where tissue is likely to absorb signicant amounts of uid,
therefore increasing freezing-related changes. Alternatively, putting small pieces of
tissue in a completely dry container may cause desiccation of the tissue and may
compromise histomorphologic detail. We believe the best practice is to make sure
the tissue is in a moderate state of moisture, with a small amount of surrounding
saline. A specimen received in formalin, especially if small and quickly affected by
the xative, will be challenging to freeze, as frozen xed tissue loses the ability to
adhere to glass slides. Non-technical issues pertaining to intraoperative consultation
include the importance of having a physician or physician-in-training bring the
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specimen to surgical pathology in order to alert laboratory staff that an intraoperative consultation is requested, and to ensure that the pathologist is aware of the
surgeon’s specic question, in order to appropriately handle the specimen and provide the needed intraoperative diagnosis.
F. Boulos and M. Attieh
Interventions andPossible Solutions
Reading through this chapter might leave one with the impression that the process
of collecting tissue, processing it, and issuing a diagnosis is nothing short of walking through a mineeld. This may be true to some extent, although achieving excellent results with minimal errors is certainly possible if appropriate measures are
taken. The traditional approach to problem-solving has often consisted of identifying and incriminating the culprit instead of analyzing the circumstances that lead to
the error and responding appropriately to prevent it from recurring. Undoubtedly,
many have witnessed a circulation employee drop off a specimen for frozen section,
leaving it on the receiving desk without alerting laboratory staff, and being squarely
blamed for the incident, while in reality they were covering for a coworker, and
were not aware of what a frozen specimen entailed. Rather than attaching blame on
an individual, a systems approach emphasizes the process as a whole with respect
to the handling and transport of specimens, and policies and procedures formed
within a systems approach focus on the precautions that can diminish the risk of
errors. The inclusion of a full requisition form accompanying all specimens delivered to the pathology or laboratory department is necessary, especially in the
absence of an electronic ordering system. Appropriate training and instructions to
ll all the required elds within the requisition sheet is also key. The following
information should be completed on the form: patient’s name; patient’s healthcare
facility identication number; patient’s unit and/or room number; clinical diagnosis; surgeon’s name; source of specimen to include anatomical location where the
specimen was removed, side, type of tissue, date and time of collection in the operating room; study requested, for example, frozen section, culture, lymphoma,
molecular, etc.; other pertinent clinical information; and the name of circulator who
completed documentation and preparation of the specimen for transport to the
pathology department. Another very important component of the systems-based
approach to decrease errors is chain of custody. Chain of custody tracking needs to
be established within the system for handling specimens. The chain of custody process should include the smallest possible number of hand-offs, each of which represents a potential source of error. The pathology, laboratory, and surgery departments
should establish a xed and predictable schedule for transport of surgical specimens
for permanent evaluation. Redundancy is an important component of the quality
check mechanisms that should be in place. By redundancy we mean repeatedly
making sure that all the steps that need to be followed have been followed. We also
mean repetitiveness of tasks by the same qualied and adequately trained personnel.
Many of the problems discussed in the previous sections can also be circumvented
through the use of electronic medical information systems. Relying on software will
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eliminate the problem of illegibility and will decrease the chances of incompletely
lled requisitions by potentially forcing the requesting physician to enter information in the different elds. Unfortunately, forcing a physician to enter a value within
the eld does not guarantee the accuracy and reliability of the entered value. The
single most important intervention toward decreasing the number of errors within
pathology is to infuse healthcare workers in charge of every step of the process with
a sense of ownership and responsibility, without which all attempts to improve quality and enhance result accuracy stand to fail. As long as automation is partial and
human intervention and contribution is an intrinsic part of laboratory and diagnostic
processes, focusing on the quality and reliability of the healthcare worker will
remain key. Establishing systems to identify weak links and systematic breakdowns
in order to effect appropriate modications is therefore crucial [30].
Conclusion
In the previous paragraphs, we’ve described many potential sources of error in the
handling of specimens prior to receipt within the surgical pathology laboratory.
Many of these errors result in inefciencies and wastage of resources, but the vast
majority culminate in a correct nal diagnosis. Despite this, procedural inefciencies and unjustied expenditures on unnecessary tests can easily fall under the
scrutiny of a dissatised customer and serve as fodder for medico-legal claims. As
stated earlier, scientic accuracy is paramount, but its importance is diminished in
the wake of patient dissatisfaction. We should therefore consistently strive toward
excellence, excellence of both procedure and results, for one cannot materialize
without the other. The smallest details will always be where the devil lies, either
leading us condently toward an outstanding product, or throwing us of course
into a tempest of nger pointing, impending mediocrity, unsatisfactory patient
care, and ultimate breakdown of the standards we have dedicated our careers
to uphold.
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