Science
What May the Future Hold for Histotechnologists?
Michael Titford, HTL(ASCP)HT, and Blythe Bowman, MD
ABSTRACT
The hospital-based histology laboratory experienced several changes
in the 1960s and 1970s when cryostats, enclosed tissue processors,
plastic cassettes, and disposable knives were introduced. Other than
the emergence of immunohistochemistry in the 1980s, few major
changes have occurred. But now, driven by costs, higher expectations,
and a desire for faster turnaround times, these laboratories are on
the brink of changes that will involve additional new duties for the
pathologist and the histotechnologist.
“Prediction is very difficult, especially about the
future,” the physicist Niels Bohr is reputed to have
joked. Nowhere is prediction more difficult than in
the hospital laboratory. Hospital clinical laboratories
constantly improve their equipment, technologies,
and tests; however, these types of changes haven’t
touched the histology laboratory in recent years. Now,
the histology laboratory is poised for change. But what
changes will occur? All predictions by their very nature
are speculative; those who work in the field cannot help
but wonder what will happen. Those who have worked
in the field for a few years will remember the promise
of glycolmethcrylate sections for small diagnostic
biopsies, the Specimen Management System offered
by one major company,1 and alternatives to formalin
DOI: 10.1309/LMXB668WDCBIAWJL
Abbreviations
FISH, fluorescence in situ hybridization; IHC, immunohistochemistry;
H&E, hematoxylin and eosin; CAP, College of American Pathologists;
ACIS, Automated Cellular Imaging System; JCAHO, Joint Commission
on Accreditation of Healthcare Organizations; CMS, Centers for
Medicare and Medicaid Services; CLIA, Clinical Laboratory
Improvement Amendments; TATs, turnaround times; UPMC, University
of Pittsburgh Medical Center; ER/PR, estrogen receptor/progesterone
receptor; HER2, human epidural growth factor receptor 2; PSA,
prostate-specific antigen; CA, carbohydrate antigen
Pathology Department, University of South Alabama, Mobile
*To whom correspondence should be addressed.
E-mail: MTitford@usouthal.edu
www.labmedicine.com Fall Supplement 2012 |  Lab Medicine e5
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New techniques, some already in use in some hospitals, will involve
flow cytometry, fluorescence in situ hybridization (FISH), DNA and
genetics studies, proteomics, telepathology, and digital imaging. New
antibodies in immunohistochemistry and new biomarkers will assist
in diagnoses. Accrediting agencies will raise their standards to meet
the new challenges. Although no one really knows what will happen in
the future, this article reviews the new changes that will likely occur in
hospital histology, based on present predictions and technology.
Keywords: Future, histotechnology, pathology, immunohistochemistry,
molecular pathology
fixation, for instance, which have been all but
abandoned in the histology laboratory. This article
examines possible avenues of change that may occur
in patient-care histology laboratories based on present
predictions and technology.
History
Seasoned histotechnologists have seen many
changes in the laboratory, including carbon dioxide
cooled microtomes replaced with cryostats and the
introduction of plastic cassettes, enclosed tissue
processors, and the advent of immunohistochemistry
(IHC) in the 1980s.1,2 Still, these changes have been
gradual: the field of histology has traditionally been
a veritable backwater compared with the rest of
the hospital laboratory. Working with solid tissues
from patients, tissue processors, and paraffin
wax, the histology laboratory is unique compared
with the clinical laboratory. Computerization, for
example, followed in the technological wake of its
adoption in rest of the laboratory. A second wave
of computerization included computer-generated
slide labels and work logs, use of bar codes, and
electronic record transfer. Whereas pathologists
previously pushed to gain the maximum information
from histochemically stained slides and electron
microscopy, interest has waned in those areas; instead,
pathologists now focus on new IHC antibodies and
molecular pathology tests.
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Who Will Be Affected?
The amount of change experienced by
histotechnologists will depend on their work settings.
Laboratories in smaller or community-based hospitals
will see lesser, slower change than in larger medical
centers, busy commercial laboratories, and teaching
hospitals.
A crucial factor will be the type of specimen a histology
laboratory receives. Small biopsies, such as those from
the cervix, skin, and gastrointestinal tract, usually only
require routine hematoxylin and eosin (H&E) staining.
Other tissue samples may not be processed at all.
Uterus with leiomyoma, gallbladders and appendix may
merely be examined on a gross level by the surgeon or
pathologist and then discarded.
Presently, much of the attention and new techniques
are directed at the diagnosis and management of
cancer. Because cancer is the second-leading cause
of death in the United States3, the entire medical
community is anxious to improve patient outcomes
through earlier diagnosis. Insurance companies and
hospitals will want to prepare proper care for the aging
Baby Boomer generation.
What Will Drive the Change?
Physicians and other clinicians want the best available
treatments for their patients and expect the newest,
most sensitive laboratory tests to result in accurate
diagnoses. They also want their test results as soon
as possible. The laboratory wants to produce these
results as quickly and as inexpensively as possible. The
rising cost of health care will apply increasing pressure
on the laboratory to provide more for less. Insurance
companies, Medicare, and Medicaid will play a larger
role in the treatment of patients by dictating what tests
they will and will not pay for. Insurance companies may
contract with histology laboratories directly, dictating
to which laboratory a patient’s specimen is submitted.
Hospitals want to continue to attract physicians and
the patients they bring to the hospital.
Larger academic medical centers want to have the
best, most current diagnostic tests available to
attract excellent teaching physicians, residents, and
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fellows. More histology laboratories will work 2 or 3
shifts to continue to produce slides for evaluation and
diagnosis. Hospital administrators will want histology
laboratories to run like hematology or chemistry
laboratories, handling racks of specimens 24 hours
a day and using Lean and Sigma Six managerial
principles.
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The commoditization of the laboratory will continue,
with investors seeing the hospital laboratory as an
investment opportunity. Hospitals will want to contract
out laboratory services, thus removing this running
cost from their budgets. Some well-known reference
labs (LabCorp, its offshoot DIANON Systems,
Ameripath, etc) are publicly traded companies anxious
to enlarge their market share.4
The College of American Pathologists (CAP), aware
of the coming changes, has sponsored several
Futurescape of Pathology conferences; papers
presented have been published in its journal, the
Archives of Pathology and Laboratory Medicine. In
2008, several authors describe scenarios5 including
a world without microscope slides and paraffin6
and further computerization of the histopathology
laboratory7. Another author8 predicts that areas of
change will include early health models, the rise
of molecular medicine, greater emphasis on early
diagnosis, increased pressure for cost-effectiveness,
the merger of pathology and radiology, use of multiple
biomarkers to improve prediction, and increased use of
digital tools in pathology.
New Duties for the Pathologist
Future medical professionals will expect the surgical
pathology report to include gross and microscopic
photographs of the specimen. For tumor specimens,
the report may also include results based on flow
cytometry, DNA studies, proteomics, and the
Automated Cellular Imaging System (ACIS), as well
as references from the literature.9 Instead of handling
predominantly surgical pathology and cytology reports,
the pathologist will be able to collect the various
laboratory reports on surgical pathology specimens
and generate a consolidated report that gathers and
interprets all the results for the clinicians. This is
already happening at some medical centers.10 Such
detailed molecular pathology reports will aid the

health care professional in selecting which treatment
or chemotherapy regimen to provide to the patient for
maximum effect.
New Duties for the
Histotechnologist
The role of the histotechnologist is closely aligned with
that of the pathologist; as the latter changes, so will
the former. New procedures first draw the attention
of pathologists, chief technologists, and laboratory
administrators; however, once those individuals
become acquainted with a new procedure, those
duties are delegated to the workers who implement
them on a daily basis, namely, histotechnologists.
In most hospital settings, the pathologist is assisted
by the histology laboratory, which is the first party to
receive fresh tissue samples removed from patients
during operations or procedures. The histotechnologist
will no doubt become responsible for the routine
submission of tumor samples for flow cytometry,
FISH, DNA studies, and other types of studies, as well
as for sending samples to the correct section of the
laboratory or to a reference laboratory.
Accreditation
Increased requirements by accrediting agencies such
as the CAP and the Joint Commission on Accreditation
of Healthcare Organizations (JCAHO) will drive changes
in the laboratory. These agencies meet approval
to certify that a laboratory has reached standards
required by the Federal Government’s Centers for
Medicare and Medicaid Services (CMS), including
the articles of the Clinical Laboratory Improvement
Amendments (CLIA). Laboratories will need to be
certified to receive compensation for their services.
These changes will affect all histology laboratories
regardless of size, workload, or the type of specimens
they handle. The CAP will most likely continue to raise
its standards, more closely following those of the
quality management and safety programs organized
by the International Organization for Standardization.
The ISO 9000 family of standards focuses on 18 areas
of the laboratory with an emphasis on more-detailed
manuals, closer attention to equipment, and Good
Laboratory Practice. Presently, research laboratories
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working for pharmaceutical companies follow these
more stringent requirements as they perform extensive
tests on new medications.
Faster Turnaround Times
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A major change for histology laboratories will be an
increased desire for faster turnaround times (TATs).
Because patients occupy expensive hospital beds after
an operation or procedure, physicians will want biopsy
results back the same day so they can start treatments
immediately; physicians of outpatients will want to send
their patients home with a diagnosis and treatment
plan. This requirement for cost effectiveness has been
described by one author as a “huge macroforce.”8
Telepathology and Digital
Imaging
New information systems in histopathology are
not limited to computer accessioning, bar codes,
reporting, and faxing of reports. New high-definition
slide scanners are available to scan slides (in their
entirety or partially) in as little time as 30 seconds.11
The definition of the images is so improved that
diagnosis can be made solely from these images. The
images are then stored or can be sent electronically
anywhere in the world for diagnosis or consultation.
In a similar development, radiology departments
are contracting with companies such as NightHawk
Radiology12 to read X-ray images submitted to them
electronically during off hours, such as overnight,
weekends, and holidays. Microscope slides present
technical challenges; still, technology is improving and
costs are decreasing. Storage cost is estimated at US
$0.25 per slide; however, those costs will decrease as
technology improves11 and images are able to be filed
electronically.
Advances in telepathology will also help smaller,
isolated hospitals. A recent article13 described a
histotechnologist at Ketchikan General Hospital in
Alaska preparing a frozen section with the surgeon and
the consultant pathologist in Bellingham, Washington
viewing the procedure by live video. The frozen section
was then scanned and the image diagnosed by the
pathologist over that long distance. A Norwegian
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hospital conducted a similar study with the same
results.14 Small hospitals in the future may not have
a full-time pathologist on staff and may routinely
use telepathology processes for frozen sections and
consultations.
The University of Pittsburgh Medical Center (UPMC)
has taken a lead role in telepathology and digital
imaging. UPMC has recently signed an agreement with
a large independent medical diagnostic laboratory in
China that serves more than 6000 hospitals and clinics
to provide second-opinion pathology consultations;
this service will involve telepathology.15
Computers programmed for pattern recognition will be
used to microscopically determine changes in tissues.
Researchers have studied the use of computerized
image analysis to score estrogen-receptor and
progesterone-receptor biomarkers in invasive ductal
carcinoma.16 Whereas that study was developed to
improve inter- and intraobserver reproducibility, it
seems only a small step to score other tumors and
disease conditions, possibly in H&E-stained sections.17
New Histology Laboratory
Technologies
For several years a new breed of tissue processors
has captured the attention of pathologists and
histotechnologists alike. These new processors use
thin slices of tissue and process them in little over an
hour. Some of these instruments run continuously;
some use old technology with faster schedules
and others use new technologies and proprietary
solutions. The Sakura Finetek Tissue Tek Xpress ×50
and Xpress ×120 processors (Sakura Seiki Co, Ltd,
Nagano, Japan) use a xylene-free schedule, low-
energy microwaves, and proprietary solutions. These
processors can be continually loaded and unloaded
throughout the day. The Leica Peloris II and ASP 6025
processors (Leica Microsystems GmbH, Wetzlar,
Germany) use heat in place of microwaves; use of
xylene is optional. In the newer LOGOS processor
from Milestone Srl (Sorisole, Italy), tissues are
processed directly from isopropyl alcohol to paraffin
wax assisted by heat. The STP 420ES from Thermo
Fisher Scientific Inc (Waltham, MA) uses a tilted
chamber and conventional or proprietary solutions,
assisted by heat; it processes samples in an hour.
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An optional attachment to the Sakura Xpress
processors is the Autotec embedding center, in
which the preoriented tissue blocks are hardened in
sectionable plastic cassettes. On some instruments,
printouts monitor processing solutions, indicating when
solutions should be changed. Other instruments can be
connected electronically to the manufacturer, which will
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contact your laboratory or your on-call employee if a
problem occurs during processing.
Other new technologies now available include
automated H&E staining, histochemistry and IHC
stainers. These methods represent an improvement
on the “dip and dunk” instruments of earlier days. The
automation of these processes provides consistent
results in a timely fashion. Quicker turnaround times
ultimately benefit the patient. But what about lost
blocks? Passive radio-frequency identification (RFID)
tags containing bar-code information can be included
in the cassettes during processing, sectioning, and
subsequent storage; the block can be located later if
it becomes misplaced, or “lost.”18 Synoptic reporting
and speech-recognition dictation facilities aid in gross
descriptions of tissues. Typing of these reports will
occur off site to reduce expense.
New Antibodies
Much attention is being given to the field of tumor
diagnosis as the medical community realizes that
early discovery, diagnosis, and treatment of cancer
increases the life span and quality of life of the
patient; this is known as the early health model.8 New
antibodies for use in IHC for the diagnosis of tumors
and other conditions are continually being evaluated
and identified, with algorithms showing which proteins
are most likely to be expressed by which tumors.
Some antibodies are sensitive to the technologies used
in processing and sectioning and only work reliably
when the techniques of the laboratorian are consistent.
In the future, we will see increased attention to
standardization of these new techniques as is the case
now for fixation time in formalin for estrogen receptor/
progesterone receptor (ER/PR), human epidural growth
factor receptor 2 (HER2)/neu, and Ki67 antibodies.
This technology may change in the future. Aptamers,
a new class of human-made oligonucleotides, may
take the place of antibodies prepared from laboratory

animals; the clinical applications of aptamers are still
being studied. Aptamers would be easy to produce,
have greater stability, have longer shelf life, and may
cost as little as US$0.002 per assay.19
Proteomics and Biomarkers
The field of proteomics is still in its infancy: prostate-
specific antigen (PSA) is the only widely used
biomarker studied at this time, to our knowledge.
Other tumor markers studied include α-fetoprotein,
carbohydrate antigen CA 19-9, CA 15-3, estrogen
receptors, progesterone, and HER2/neu. Putting
tumor markers to another use, the ACIS (Agilent
Technologies, Inc, Santa Clara, CA) uses HER2/neu
staining to quantify the disease in breast-cancer tissue
sections.
The field has tremendous potential, as researchers
continue to identify new biomarkers from neoplasms,
which they then link to genes; their studies focus on
the proteins encoded by the neoplastic cells. When
identified, antibodies can be used to identify those
proteins in tissue sections; pharmaceutical companies
will want to develop medications to interfere with the
production and behavior of those proteins.
Specialist Laboratories
With rapidly changing technology in histology
laboratories, it will be more cost-effective for some
to send samples out for low-volume tests. In this
scenario, it is not hard to imagine the evolution of
specialist IHC laboratories that stock a wide range of
IHC antibody reagents and controls. Other tests, for
DNA, flow, genetics, FISH, etc, may be sent out. Again,
the histotechnologist will be the most likely person to
handle the specimen and to make sure it is delivered
to the correct specialist laboratory. These laboratories
may function like the present-day Athena Diagnostics
and Mayo Clinic laboratories, or there may be smaller
laboratories servicing a group of hospitals or a certain
geographic area.
An important factor dictating the future of the
laboratory will be reimbursement by insurance
programs, Medicare, and Medicaid. If Medicare, for
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example, declines to pay for a certain laboratory
procedure, laboratories may decide to no longer
handle those specimens. Some examples that come
to mind are gross only–type specimens, such as those
associated with orthopedic devices, and certain other
specimens, such as uterine leiomyoma, gallbladder,
and appendix. The surgeon’s report of the operative
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procedure and their removal may be the only record for
the patient.
Autopsies
The number of autopsies will likely continue to
decrease for several reasons. First, newer imaging
methods and laboratory tests better inform health
care professionals of the reasons for a patient’s death.
Another factor is that there is no reimbursement for
autopsies, and as a result, pathologists are not anxious
to give up large amounts of time for such procedures.
In the future, we will witness virtual autopsies,10 in
which the deceased receive a CAT scan or similar
imaging method to visualize their bodies. Fine-needle
aspiration will be used to examine any tissue or lesion
requiring microscopic examination. Nevertheless, there
will always be a need for complete or partial autopsies
for patients with complicated disease processes.
Conclusion
The next few years will bring several changes in
histology laboratories, including faster turnaround times
requested by physicians eager to make diagnoses
and start treatments and improved capabilities of
the histology laboratory and surgical pathology
areas stemming from new types of equipment. The
discovery of new biomarkers will enlarge the field
of proteinomics and add new immunohistochemical
tests. For these new tests to be accepted by the
medical community, histology laboratories in different
hospitals will need to collaborate to standardize their
processes. Telepathology processes will be used for
consultation and diagnosis; however, laboratorians will
need confidence that a slide prepared in one location,
scanned, and sent to another location for diagnosis
has met certain criteria. For this to occur, specimen
collection, fixation, and processing will need to be
consistent between laboratories.20 Telepathology
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techniques and equipment will also be used to assist
patients in less-developed countries.
The amount of change a histology laboratory
experiences will depend on its type and size. Larger
laboratories, those in large academic medical centers,
and large commercial laboratories will experience
the greatest changes. There may be false starts;
new technologies will be tried and then put aside.
Pathology groups will look to new staff, recently
graduated from residency programs, to modernize their
services. Histotechnologists will be expected to be
knowledgeable about new techniques and instruments.
No one knows precisely what changes will occur in the
histology laboratory in the future. However, this article
has attempted to illustrate the changes that will occur if
present predictions come true. LM
Conflicts of interest: None reported.
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