Imaging-guided biopsies: Is there a preferred strategy to choose?
Author: Dror Nir, PhD
The most stressful period in a cancer patients’ pathway is from the moment they fail a screening test or present with suspicious symptoms to the moment they are diagnosed. Today’s medical guidelines require histopathology findings as the only acceptable proof: positive results mean you are a cancer patient, negative results mean, well…maybe you are and maybe you are not. You now enter into what might be a very long period, sometime years, of uncertainty regarding your health and prospects. And why?
Because the substance for histopathology is acquired by biopsies, and biopsies are known to be inaccurate. For example, breast and prostate biopsies fail to find 25% to 35% of the cancer lesions at the first biopsy session.
Therefore, it is not surprising that from the beginning of this procedure, medical practitioners look for ways to incorporate imaging into the workflow. In the last decade, significant progress has been made in the introduction of imaging-guided biopsies. The most common modalities were ultrasound and CT/mammography. Recently, as the industry solved the issues of magnetic field compatibility for biopsy needles and the introduction of open MRI systems, MRI-guided biopsies were also made possible.
Ultrasound-guided biopsies are by far the most commonly used procedure. Why? Because they can be often performed as an office-based procedure. Here are some interesting links to YouTube videos describing such procedures:
- Prostate
Prostate Ultrasound and Prostate Biopsy by Dr. Neil Baum
Transrectal ultrasound (Trus) Biopsy of the prostate
- Breast
Ultrasound-Guided Breast Biopsy
Breast Tissue Biopsy
The main advantages: they are easily accessible, low cost and quick. The disadvantages of these procedures are that they are very much operator dependent, rather than standardized, and there are no quality assurance guidelines attached. Efforts to standardize ultrasound-based biopsies and increase their efficiency are evident by recent introductions of ultrasound systems into the market , which support real-time guided biopsies and ultrasound applications that perform real-time biopsy tracking. But these systems are still far from being widely available. I will touch on this issue in my upcoming posts as I am part of these efforts.
CT and Mammography guided biopsies require more sophisticated equipment and well-trained operators. As an example:
Breast Biopsy – What To Expect
The main advantage: if you return to the same operator, the process is likely to be reproducible. The disadvantages are identical to that of ultrasound-based biopsies. It is worthwhile to note that, recently, radiologists who perform biopsies are required to go through a certification process. Still, such certification demands vary between the various radiology societies.
MRI-guided biopsies are an even more sophisticate and complex procedure:
- Prostate:
DynaTRIM Video
DynaTRIM Intervention
An interesting quote from Dr. Hashim U. Ahmed, M.D., MRCS, Division of Urology Department of Surgery, University College of London (https://mail.google.com/mail/u/1/?shva=1#label/Work%2FLinks%2FAuntMinnie/139d9c5bc6bda842): “Advocating the widespread use of MRI before biopsy in a population of men with risk parameters for harboring prostate cancer has a number of advantages, which might ultimately benefit the care these men undergo. Increasing the detection of prostate cancer that requires treatment while avoiding biopsy – and hence unnecessary treatment – in those with insignificant or no cancer are compelling arguments for this approach.”
- Breast
MRI Breast Biopsy – Diagnostic and Biopsy Services for Breast Evaluation
I recommend reading the following article regarding the use of Open MRI to guide freehand biopsies of breast lesions. Especially interesting is the discussion where the authors give a good description of the difficulties in breast biopsies they are trying to overcome in order to achieve good lesion sampling.
MR-guided Freehand Biopsy of Breast Lesions in a 1.0-T Open MR Imager with a Near-Real-time Interactive Platform: Preliminary Experience Frank Fischbach, MD, et. al
The question remains: which biopsy procedure is the best? And does this question have one coherent answer, i.e. one that will satisfy the patients, the doctors and the health-care insurers? Will the answer to this question remain the subject of endless uncoordinated clinical studies?
If anyone who reads this post knows on methodological scientific or regulatory initiatives aimed at answering this question on a level of global guide lines I would appreciate his comment.
Written by: Dror Nir, PhD.
I have been away from surgical pathology for some years, but I visit my colleague Marguerite Pinto at Bridgeport Hospital-Yale New Haven Health not infrequently. I think that the Cancer Review Board has established a guideline, but they have always referred back to the National Guidelines, The Am Col Radiology, and the Coll Amer Pathologists. I can search for how much variation there is across institutions. I have a relative by marriage who is at UCSF and is Chief of Imaging and Nationally Recognized in Computational Radiology. My second cousin is founder and Editor of Pathology Outlines, the most popular site for pathology information. In radiology for prostate cancer they may send a dozen biopsies in separate tubes for identification of location. This is under review for billing change because each specimen is billable as a procedure. My colleague made a change in staining procedure that brought her criticism because it involved two stains, and required a second visit. She worked out a double stain on a single slide (we looked at it together), so that the second visit is avoided.
Well Larry, that’s exactly how I know the situation: almost caos! not only that the way of acquiring the specimen is opn to “a lot of individual interpretation” also the way you read and report it is not at all standardised.
When I wanted to conduct a regourus study in order to evaluate the performance of HistoScanning in detection of prostate cancer I had to develop a very complicated (and expensive) pathology protocol and to insist on central pathology that was done at Bostwick laboratories in London.
I have witnessed many prostate and breast biopsy sessions accross Europe and the USA; never seen the same thing twice.
I also atended breast biopsy training at RSNA; did not see anyone fail…
The most crucial influence on the succes of a biopsy is the the person performing the procedure. Ask your practitioner how good they are at performing biopsies…… do they audit their own performance? Have they undertaken a recognised training course? Do they do a minimum number per year to maintain their competence? Most national professional (radiology) organisations set minumum training and performance standards…. choose a practitioner that meets these standards….
Thanks Anne-Marie for your reply. The point I was trying to make in my post is exactly about that: it’s all operator dependant. Mind you the word “all” refers not only to the performance of the biopsy itself, but also to the choice of system, needle, method and speciment processing. Reporting the histology is anothe big issue!
What I whanted to raise is the need for “opinion leaders” and “leading organisations” to create a unified and stndardised methodology! after all, a patient usualy doesn’t “choose” the practitioner. Patients’ get who ever is available!
Excellent post, Dr. Nit.
The discussion is germane and raises most critical issues involved in specimen collection procedure, documentation of findings and follow ups.
Your own effort in making a contribution to the development of Standards along the entire workflow of screening for detection is and will be a significant contribution to Health care management and disease prevention.
A personal story, in 1953, in Bucharest, Romania, my own Mother, underwent a breast biopsy that missed the tumor, in 1955 she underwent a mastectomy and radiation therapy, 9/1956 – she died at age 41, myself at age 6 1/2, my sister, Prof. Pnina Abir-Am, see Contributor’s Biographies, on this site, was 9 years old. My Father was widowed at 43.
In 2006 in Palo Alto, CA, my best woman friend since 1970 when we were students at HUJ, under care for Breast cancer at Stanford Medical Center, better care than in 1956 in Eastern Europe 1956, yet, Hava, died of CA at age 56. Fifty years after my major loss at age 6 1/2, no cure for CA, though great advancement in Science and Research, treatment and successes, no cure.
PUT IT IN CONTEXT OF CANCER CELL MOVEMENT
The contraction of skeletal muscle is triggered by nerve impulses, which stimulate the release of Ca2+ from the sarcoplasmic reticuluma specialized network of internal membranes, similar to the endoplasmic reticulum, that stores high concentrations of Ca2+ ions. The release of Ca2+ from the sarcoplasmic reticulum increases the concentration of Ca2+ in the cytosol from approximately 10-7 to 10-5 M. The increased Ca2+ concentration signals muscle contraction via the action of two accessory proteins bound to the actin filaments: tropomyosin and troponin (Figure 11.25). Tropomyosin is a fibrous protein that binds lengthwise along the groove of actin filaments. In striated muscle, each tropomyosin molecule is bound to troponin, which is a complex of three polypeptides: troponin C (Ca2+-binding), troponin I (inhibitory), and troponin T (tropomyosin-binding). When the concentration of Ca2+ is low, the complex of the troponins with tropomyosin blocks the interaction of actin and myosin, so the muscle does not contract. At high concentrations, Ca2+ binding to troponin C shifts the position of the complex, relieving this inhibition and allowing contraction to proceed.
Figure 11.25
Association of tropomyosin and troponins with actin filaments. (A) Tropomyosin binds lengthwise along actin filaments and, in striated muscle, is associated with a complex of three troponins: troponin I (TnI), troponin C (TnC), and troponin T (TnT). In (more ) Contractile Assemblies of Actin and Myosin in Nonmuscle Cells
Contractile assemblies of actin and myosin, resembling small-scale versions of muscle fibers, are present also in nonmuscle cells. As in muscle, the actin filaments in these contractile assemblies are interdigitated with bipolar filaments of myosin II, consisting of 15 to 20 myosin II molecules, which produce contraction by sliding the actin filaments relative to one another (Figure 11.26). The actin filaments in contractile bundles in nonmuscle cells are also associated with tropomyosin, which facilitates their interaction with myosin II, probably by competing with filamin for binding sites on actin.
Figure 11.26
Contractile assemblies in nonmuscle cells. Bipolar filaments of myosin II produce contraction by sliding actin filaments in opposite directions. Two examples of contractile assemblies in nonmuscle cells, stress fibers and adhesion belts, were discussed earlier with respect to attachment of the actin cytoskeleton to regions of cell-substrate and cell-cell contacts (see Figures 11.13 and 11.14). The contraction of stress fibers produces tension across the cell, allowing the cell to pull on a substrate (e.g., the extracellular matrix) to which it is anchored. The contraction of adhesion belts alters the shape of epithelial cell sheets: a process that is particularly important during embryonic development, when sheets of epithelial cells fold into structures such as tubes.
The most dramatic example of actin-myosin contraction in nonmuscle cells, however, is provided by cytokinesisthe division of a cell into two following mitosis (Figure 11.27). Toward the end of mitosis in animal cells, a contractile ring consisting of actin filaments and myosin II assembles just underneath the plasma membrane. Its contraction pulls the plasma membrane progressively inward, constricting the center of the cell and pinching it in two. Interestingly, the thickness of the contractile ring remains constant as it contracts, implying that actin filaments disassemble as contraction proceeds. The ring then disperses completely following cell division.
Figure 11.27
Cytokinesis. Following completion of mitosis (nuclear division), a contractile ring consisting of actin filaments and myosin II divides the cell in two.
http://www.ncbi.nlm.nih.gov/books/NBK9961/
This is good. I don’t recall seeing it in the original comment. I am very aware of the actin myosin troponin connection in heart and in skeletal muscle, and I did know about the nonmuscle work. I won’t deal with it now, and I have been working with Aviral now online for 2 hours.
I have had a considerable background from way back in atomic orbital theory, physical chemistry, organic chemistry, and the equilibrium necessary for cations and anions. Despite the calcium role in contraction, I would not discount hypomagnesemia in having a disease role because of the intracellular-extracellular connection. The description you pasted reminds me also of a lecture given a few years ago by the Nobel Laureate that year on the mechanism of cell division.
PUT IT IN CONTEXT OF CANCER CELL MOVEMENT
The contraction of skeletal muscle is triggered by nerve impulses, which stimulate the release of Ca2+ from the sarcoplasmic reticuluma specialized network of internal membranes, similar to the endoplasmic reticulum, that stores high concentrations of Ca2+ ions. The release of Ca2+ from the sarcoplasmic reticulum increases the concentration of Ca2+ in the cytosol from approximately 10-7 to 10-5 M. The increased Ca2+ concentration signals muscle contraction via the action of two accessory proteins bound to the actin filaments: tropomyosin and troponin (Figure 11.25). Tropomyosin is a fibrous protein that binds lengthwise along the groove of actin filaments. In striated muscle, each tropomyosin molecule is bound to troponin, which is a complex of three polypeptides: troponin C (Ca2+-binding), troponin I (inhibitory), and troponin T (tropomyosin-binding). When the concentration of Ca2+ is low, the complex of the troponins with tropomyosin blocks the interaction of actin and myosin, so the muscle does not contract. At high concentrations, Ca2+ binding to troponin C shifts the position of the complex, relieving this inhibition and allowing contraction to proceed.
Figure 11.25
Association of tropomyosin and troponins with actin filaments. (A) Tropomyosin binds lengthwise along actin filaments and, in striated muscle, is associated with a complex of three troponins: troponin I (TnI), troponin C (TnC), and troponin T (TnT). In (more ) Contractile Assemblies of Actin and Myosin in Nonmuscle Cells
Contractile assemblies of actin and myosin, resembling small-scale versions of muscle fibers, are present also in nonmuscle cells. As in muscle, the actin filaments in these contractile assemblies are interdigitated with bipolar filaments of myosin II, consisting of 15 to 20 myosin II molecules, which produce contraction by sliding the actin filaments relative to one another (Figure 11.26). The actin filaments in contractile bundles in nonmuscle cells are also associated with tropomyosin, which facilitates their interaction with myosin II, probably by competing with filamin for binding sites on actin.
Figure 11.26
Contractile assemblies in nonmuscle cells. Bipolar filaments of myosin II produce contraction by sliding actin filaments in opposite directions. Two examples of contractile assemblies in nonmuscle cells, stress fibers and adhesion belts, were discussed earlier with respect to attachment of the actin cytoskeleton to regions of cell-substrate and cell-cell contacts (see Figures 11.13 and 11.14). The contraction of stress fibers produces tension across the cell, allowing the cell to pull on a substrate (e.g., the extracellular matrix) to which it is anchored. The contraction of adhesion belts alters the shape of epithelial cell sheets: a process that is particularly important during embryonic development, when sheets of epithelial cells fold into structures such as tubes.
The most dramatic example of actin-myosin contraction in nonmuscle cells, however, is provided by cytokinesisthe division of a cell into two following mitosis (Figure 11.27). Toward the end of mitosis in animal cells, a contractile ring consisting of actin filaments and myosin II assembles just underneath the plasma membrane. Its contraction pulls the plasma membrane progressively inward, constricting the center of the cell and pinching it in two. Interestingly, the thickness of the contractile ring remains constant as it contracts, implying that actin filaments disassemble as contraction proceeds. The ring then disperses completely following cell division.
Figure 11.27
Cytokinesis. Following completion of mitosis (nuclear division), a contractile ring consisting of actin filaments and myosin II divides the cell in two.
http://www.ncbi.nlm.nih.gov/books/NBK9961/
This is good. I don’t recall seeing it in the original comment. I am very aware of the actin myosin troponin connection in heart and in skeletal muscle, and I did know about the nonmuscle work. I won’t deal with it now, and I have been working with Aviral now online for 2 hours.
I have had a considerable background from way back in atomic orbital theory, physical chemistry, organic chemistry, and the equilibrium necessary for cations and anions. Despite the calcium role in contraction, I would not discount hypomagnesemia in having a disease role because of the intracellular-extracellular connection. The description you pasted reminds me also of a lecture given a few years ago by the Nobel Laureate that year on the mechanism of cell division.