THE USE OF TISSUES IN PATHOLOGY WORKFLOW
The study of human tissues procured through invasive
procedures for diagnostic and treatment purposes
constitutes one of the most important functions of pathology
departments worldwide. These tissues are processed using
complex techniques in order to provide the necessary
products that will allow diagnosis, prognostication and
further understanding of the disease process through
education and research. Different products emerge during
their processing to allow them to be analyzed pathologically
and their subsequent archiving and preserving. It is possible to categorize these products in three different groups based
on the material used and the effort spent: 1- fresh or frozen
tissues that have not undergone substantial processing, 2-
tissues that are processed and made suitable for diagnosis
and long-term preservation (paraffin blocks, fixed tissues),
3- tissues that are made suitable for diagnostic studies
using special stains and chemical analyses through complex
processing (slides, immunohistochemistry and molecular
analyses). One of the most important factors in the
categorization of these groups is processing and analyses
of tissues by experts using materials and methods that can only be found in a modern pathology laboratory. Although
minimum material and effort are used in the first category
of products, the use of extensive material and expert effort
are required to achieve the products in the third category.
The third category of products provides valuable diagnostic
and often prognostic information through the use of
technology by the experts in a pathology department. Thus,
an added is created by processing the tissue obtained from
patients, which in turn provides the critical information for
disease diagnosis and management.
The information obtained from the analysis of the tissues
should be delivered to the patients and the treating
physicians as soon as possible. Many countries have
enacted laws that regulate how this information should
be transferred as well as who has legal access to this
information. For example, Health Insurance Portability
and Accountability Act (HIPAA) which has been in effect
since 1996 in the US regulates the privacy and the secure
use of individual’s health information. HIPAA aims to
avoid and eliminate conflicts that may occur during the
use, distribution and storage of the healthcare information
that belong to patients. Such information, often referred
to as protected health information (PHI) includes any
information about health status, provision of health care,
or payment for health care that can be linked to a specific
individual. This is interpreted rather broadly and includes
any part of a patient’s medical record or payment history
and must be kept confidential. Every information that
can be determined to belong to a private person under
reasonable conditions must be considered within the scope
of this law and should be protected. Since the regulations
are only concerned with PHI, the actual tissues and material
and their possession is beyond the scope of HIPAA.
DEFINING THE PROBLEM
A series of questions emerge during the processing and
use of tissues mentioned above with the workflow of a
pathology department. The most critical questions within
the scope of our article are:
1) Who owns the tissues obtained from patients and are
subsequently embedded in paraffin blocks and processed
using special techniques in pathology departments?
2) Who owns the information and PHI related to these
tissues?
3) How should the information obtained from these
tissues be shared with the patient, physicians and other
legal entities for the purpose of healthcare? What are
the rights of the hospital, pathology department and
patients regarding this information?
4) Who should authorize the use of pathology material for
health education and research purposes?
While these questions may appear simple, they pose serious
dilemmas and the answers can lead to significant social
and legal problems in many countries today. Naturally, the
answers to these questions have serious implications for
all kinds of tissues or information obtained from patients
in addition to those submitted to pathology departments.
However, due to the unique nature of the tissues submitted
to pathology department and these questions should be
answered specifically for pathology and not be generalized.
For practical reasons, certain issues relating to pathology
material should be examined separately while answering
these questions. First and foremost, pathology materials
should be classified according to certain categories such as
the following: 1- Tissues that are minimally processed and
require mostly for archiving and storage expenses (fresh
or frozen, tissues), 2- tissues that are made suitable for
long-term archiving using special procedures and material
(paraffin blocks or polymer-embedded tissue), 3- tissues
that are processed for diagnostic purposes by using special
stains and molecular methods (immunohistochemistry, in
situ hybridization, histochemical stains, etc.).
The problems relating to the use of tissue for purposes of
1) Patient Care 2) Healthcare Education and 3) Research
are concepts that should also be discussed and evaluated
separately. Questions relating to all three areas have critical
importance in improving the healthcare in our country.
EXAMPLES FROM THE WORLD AND EXPERIENCES
The ethical and legal problems created by the four questions
mentioned above have been the subject of many books
and articles. Most of these resources are relate to the
duration of storage of pathology material as tissue blocks
and microscopic slides. However, many countries have
developed or are in the process of developing regulations
that deal with the above questions. It appears that two
diametrically opposite points of view exists, one suggests
that the pathology materials are not different than organs
and tissues as a whole, whereas the other suggests that they
are a part of the clinical records2.
Property Rights of the Tissues
The property rights of tissues obtained from patients and
analyzed in pathology departments are not clear in many
countries. For example, in Cornelio v. Stamford Hospital,
the Connecticut Supreme Court decided that the pathology
material that consisted of glass slides was the property of the
hospital3. The court also stated that the Papanicolau (Pap) smear slides were part of the medical records of the hospital
and found against the plaintiff3. The Supreme Court’s
majority decision stated that the pathology slides were a part
of patient’s permanent records and the hospital is charged
with the preservation of all original material including the
material that cannot be duplicated. The Supreme Court also
reaffirmed the responsibility of the pathology departments
in the storage and safe keeping of pathology material within
the period stated by the existing rules and regulations. The
decision of the Connecticut Supreme Court effectively
separates the patient from the control and property rights
of tissues removed from that patient. Connecticut State
legislation also identifies the material that cannot be
duplicated as the permanent property of the hospital and
that patients cannot claim property rights to such material.4. In Moore v. UC Regents, the California Supreme Court
decided that the organs removed from patients surgically
for treatment purposes no longer belong to the patient5. The California Supreme Court decision has set a very
significant precedence for all US State Legislation and
courts.
The United Kingdom, a constitutional monarchy, has
enacted the Human Tissue Act (HTA) (applicable in
England, Wales and Northern Ireland) which regulates the
procurement, use and disposal of tissues obtained from
live or deceased patients which commenting on any issue
relating to property rights6. The HTA had been revised
in 2004 following a major scandal. Between 1988 and
1995, more than 2.000 organs that were removed during
autopsy (850 of these from newborns) were kept without
authorization at the Liverpool Alder Hey Children’s
Hospital. The revelation of unauthorized use of so many
tissues prompted a revision of the original HTA that had
been in effect since 1961. The Human Tissue Authority
created by the revised HTA was charged with resolving the
conflicts relating to the property rights of tissues as well as
other issues relating to the use of human tissue6. Scotland
is not included within the scope of this law and this country
has enacted a similar law independently. The HTA covers
all tissues that contain human cells except for hair, nail
gamete, embryos and cell cultures. According to this law,
analysis of human DNA from tissue without approval is a
crime, but the use of existing DNA extracts are not subject
to authorization or approval. These changes increased the
anxieties of the medical researchers and educators due to
added restraints on the use of human tissue.
In Australia, the Supreme Court has also accepted that
once removed out of the body for treatment or diagnostic
purposes, the tissues are no longer considered the property of individual and the property rights remained with the
medical institution7.
Possession of Patient Related Information
To the extent of our investigations, the property right of
tissues obtained from patient are considered separately
from the information obtained from their analyses and
patient information in most countries. This fact implies that
the patients have the ultimate authority to allow or request
the analysis of their pathology material. In all countries
where we found sufficient information, the patients have
unfettered rights to access their medical records as well
as information from pathological analysis. In addition,
patients have the right to request review of their material
by other pathologists or experts, although rules and
regulations on this issue are quite variable2. Furthermore,
all pathology laboratories have the legal responsibility to
provide the pathology information when requested by the
patient or his/her legal guardian2. This fact does not
mean that the pathology laboratories need to relinquish
the property rights to the material, but to the information.
In the State of New York, medical institutions are required
to provide copies of all radiographic studies, medical and
laboratory records to patients or their legal representatives.8. This rule does not necessitate the hospital to relinquish
the original pathology material. However, on the contrary,
the State of Connecticut legislation require that the medical
institutions provide the original blocks and slides when
the copies are deemed not to be adequate. The State of
Connecticut laws also allow the laboratories to charge a
reasonable fee to cover the cost of duplicating the material
or records4. The State law also requires that the person
who receives the pathology material be responsible for its
preservation and safe return. The hospitals or the medical
institutions are not held liable in case the original material
is damaged or lost4.
As the principal legislation that governs the use of patient
information or PHI, HIPAA does not contain any stipulation
regarding the property rights of the tissues removed from
the patient2. HIPAA ensures the confidentiality and
security of the health information of the individual that can
in any way of form be used to reveal the patient’s identity.
The HIPAA regulates who can access this information,
how they can be used and when this information can be
shared. All electronic and non-electronic information that
can easily identify the patient’s identity are within the scope
of this law. Legislators in European countries and Australia
have also adopted many provisions of the HIPAA.
In summary, the common practice identified in all
references reviewed during this study hands over the control of the information obtained from the pathology material
to the patients and protects the patients’ right to choose
their physician and treatment. We believe that the property
rights of the tissue should be considered separately from
the property rights of the information obtained from the
tissue in legislative initiatives in our country as well.
The Use of Information Obtained from the Tissues for
Healthcare Purposes
The information obtained from the patient’s tissues is
often accompanied with other clinical and demographic
information. The use of tissues obtained from patients
during invasive procedures is not subject to further or
separate consent for diagnostic procedures. Laws in effect
in both European countries and the HIPAA in the U.S.
stipulate that the use of human tissues for patient care
purposes do not require any additional consent. The same
legislations also require that the pathology material and
the obtained information be shared with every authorized
staff for healthcare purposes subject to the patient’s
permission. According to the guidelines established by the
U.S. Ministry of Health under the scope of the HIPAA,
protected health information must be secured and can only
be given to the patient, to legal representatives or guardians
or to third party payers legally authorized to utilize this
information with limited scope9. HIPAA provides
detailed instructions on the use and share of PHI in regular
as well as exceptional circumstances1. HIPAA and its
amendments explicitly identifies the necessity of obtaining
consent for access to these information by others than the
healthcare personnel directly responsible for the patient’s
diagnosis and treatment. HIPAA also includes rules that
are also applicable in exceptional circumstances during
medical care.
The Use of Pathology Material for the Purpose of Health
Education and Research
Hospitals and pathology departments carry the
responsibility of preserving and disposing of pathology
material according to legislative requirements. During this
storage period, pathology materials play a critical role as
material for medical education and research. Furthermore,
some pathology material is too valuable to discard and
is kept within pathology departments for much longer
periods to be used in education and research. Countless
discoveries and innovations have been made possible with
the use of pathology material in recent decades. Pathology
material also plays a critical role in the training of medical
students and healthcare staff. Therefore, the pathology
departments are also charged with organizing the tissues obtained for clinical purposes for subsequent use in medical
education and research. Without the use of these material it
becomes virtually impossible to conduct any translational
research in any pathology department. Some countries
have laws that regulate the usage of pathology material for
the purposes of training and research. HTA enacted in the
United Kingdom includes stipulations that regulate such
issues. The revised HTA of 2004 has replaced the guidebook
containing ethical principles and procedures published by
the Medical Research Council in the same country. The use
of the tissues for research in the U.S.A. is regulated partly
by the HIPAA and partly by the local and Supreme Court
decisions that set the precedence regarding these issues.
The case of Moore v. UC Regents and the decision of the
Supreme Court in this case constitutes one of the most
important precedence in matters of tissue property rights.
The above mentioned case involved the use of an organ taken
from the plaintiff for research purposes and producing cell
cultures from these tissues with subsequent financial gain
in the form of a patent and shares. The California Supreme
Court rejected the patient’s property rights claim on the cell
culture produced from his tissue and the associated patents
arising from this discovery. The Supreme Court stated the
lack of regulations and experiences regulating the property
rights of human tissue and the uncertainty on how tissues
should be disposed. In addition, the court also stated that
the product formed by processing the tissue no longer
carried the original characteristics and therefore should be
considered different and a product of human creativity.
Sections of the HIPAA law regulate the usage of patient
information for research. In accordance with these rules,
institutions should require the completion of consent
forms aiming to keep health information confidential
and containing comprehensive information related to the
specific research project. Consent forms must comply
with the legal requirements, clearly identify how and by
whom the information will be used and should be signed
by the patient. Some studies have reported that the cost
and quality of medical research have been negatively
influenced by the bureaucratic procedures required by
HIPAA. For example, in a study by Michigan University,
follow up surveys conducted after a heart attack showed a
decrease in the participation rate from 96% to 34% due to
the application of the HIPAA confidentiality rule10. The
investigators conducting this study accepted the importance
of the confidentiality, but stated that these rules should
not make medical research and innovation difficult. The
College of American Pathologists (CAP) made a number
of suggestions about the use of human tissue in research, education and quality control. These recommendations
are intended to balance the privacy requirements with the
necessity of conducting research in everyday life.
While pathology material from patient can be used for
healthcare purposes without the patient’s consent, the
commercial use of these tissues pose an entirely different
challenge. The American Medical Association (AMA) has
adopted the following ethical principles in the document
published under the name of “commercial use of human
tissue”:1 Informed consent must be obtained from
patients for the use of organs or tissues in clinical research,2 Potential commercial applications must be disclosed to
the patient before a profit is realized on products developed
from biological materials,3 Human tissue and its products
may not be used for commercial purposes without the
informed consent of the patient who provided the original
cellular material,4 Profits from the commercial use of
human tissue and its products may be shared with patients,
in accordance with lawful contractual agreements,5 The
diagnostic and therapeutic alternatives offered to patients
by their physicians should conform to standards of good
medical practice and should not be influenced in any way
by the commercial potential of the patient’s tissue12.
In the Moore v. UC Regents case, the tissues obtained from
the patient generated a significant commercial profit. In
this case, the high court decided that the patient does not
have a right to profit from the tissue’s commercial use. The
Supreme Court clearly stated that cells obtained for any
purpose in medical institutions should not be accepted as
the property of the patient. This legal case is the only and
the most critical precedence regarding the profits that can
be obtained following research on patients’ tissues.
Many organizations and experts recommend certain
principles to avoid such conflicts that may occur during or
following research with pathology material. For example,
Mohapatra et al. made a series of suggestions in order to
prevent pathologists from facing such problems. They
state that the pathologists may wish to get assurances of
the following: 1) Patients have been informed of the risks
and benefits, (2) Patients have given consent to use of the
sample for research (3) Patients have been informed of any
possible commercial interests in this research (4) Tissues
already stored by the laboratory are made anonymous or
granted institutional review board (IRB) waivers2.
Many studies contend that it should be possible to perform
research on pathology material leftover from diagnostic
or therapeutic procedures with only institutional ethical
and scientific approval and without a special consent from the patient. In addition, all consent forms used for the
surgery and invasive initiatives should specify whether the
tissues obtained from the patient will be used for research
purposes. The patients should be informed and should be
told that they have the right to reject if they want13. If
obtaining consent is not practical or possible, the consent
of an IRB committee should be enough13.
REQUIREMENTS REGARDING THE POSSESSION
AND USE OF PATHOLOGY MATERIAL IN OUR
COUNTRY
Undoubtedly as in all other countries, there is a dire need for
legislation that regulates the possession and use of pathology
material in our country. The purpose of these laws should
be the delivery of healthcare services in an uninterrupted
manner and in accordance with modern standards,
while providing the most fertile environment for sensible
research and medical education that can set an admirable
precedence. It is critically important to resolve the problems
that may emerge from the uncertainties in legislation that
regulates property rights of pathology material in addition
to creating the most conducive environment for scientific
progress and discovery. The purpose of the new laws
should be to determine the property rights, conditions of
use, storage and appropriate disposal of human organs and
tissues and specifically pathology material13. Future laws
should balance patient rights with the rights and welfare of
the society and promote public health, medical education
and scientific research.
In summary, the basic principles that should be adopted in
future legislation can be summarized as follows:
1. Pathology material obtained from patients and
subsequently created paraffin embedded tissues and
glass slides should be considered to be the property of
the hospital or the governing healthcare organization.
2. The information that relates to the aforementioned
tissues and products created from these tissue should be
the property of the patient, legal representative or the
legal guardian of the patient.
a. The pathology department should be responsible
for preserving the confidentiality of information
belonging to these patients or related diagnostic and
prognostic information obtained from these tissues.
b. The use of this information should be dependent on
the consent of the patient except for circumstances
where such use is related to direct patient care.
c. In cases when an informed consent cannot be
obtained, the use of these tissues for research
purposes should be dependent on IRB approval.
3. The information that has been created or that can be
obtained from these tissues should be shared with any
healthcare personnel who is directly responsible for the
care of that patient without the necessity of obtaining
informed consent.
a. The information that will be used for the care of
the patient should only be given to the persons
responsible for the care of the patient.
b. Healthcare personnel who are not responsible for
the patient’s care should obtain an informed consent
from the patient or the patient’s legal representative
in order to access PHI.
c. Sharing of patient information for any other purpose
should be dependent on the informed consent of the
patient or the legal representative.
4. The authority to use the pathology material for education
or research purposes should be given to the healthcare
institution, which should be executed by the pathology
departments. The decisions on the use of pathology
material for education or research purposes should be
subject to IRB approval.
a. IRBs should only require a signed informed consent
when this is practically possible or for prospective
research trials.
b. The general informed consent obtained from the
patient before surgery or invasive procedures should
be sufficient for the use of this material for educational
and research purposes after IRB approval.
c. The requirements for informed consent and the
rules and regulations of IRBs should be based on
national standards or legislation. The principles
and procedures followed by IRBs should also be
determined within the national context.
d. The use of pathology material for the purpose of
education and research should not depend on
the permission of any physician or staff who was
responsible for that patient’s care.
e. The use of pathology material for commercial
purposes should be under the responsibility of the
hospital administration or its governing organization.
The hospitals and their governing organizations
should also regulate the rules of sharing profits that
may be gained through commercialization of the
research products.