Specimen provenance complications

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Specimen provenance complications (SPCs) result from instances of biopsy specimen transposition, extraneous/foreign cell contamination or misidentification of cells used in clinical or anatomical pathology. If left undetected, SPCs can lead to serious diagnostic mistakes and adverse patient outcomes.

Contents

Causes

According to recent reports from the American Cancer Society, an estimated 12.7 million cases of cancer were diagnosed in 2008, and that number is expected to rise to more than 20 million by 2030 due to population growth and aging alone. The problem will likely be further exacerbated by the widespread adoption of certain lifestyle factors (smoking, poor diet, physical inactivity, etc.) that increase the risk of developing the disease. [1]

The process of collecting and evaluating the biopsy specimens used to render these cancer diagnoses involves nearly 20 steps and numerous medical professionals from the time the sample is originally taken from the patient to the time it is received by pathology for analysis. [2] With such a complex process executed at a large scale, the potential for a variety of Specimen Provenance Complications is a serious concern for both physicians and patients.

While enforcement of strict protocols and procedures for the handling of samples helps to minimize error, identification issues in anatomic and clinical pathology labs still occur. The most common error is a mislabeled or unlabeled specimen. Another potential complication is the presence of a contaminant tissue fragment - commonly referred to as a floater - that does not belong to the patient being evaluated. Floaters can be introduced in the laboratory during tissue sectioning, processing or gross dissection, or potentially in a clinical setting as well when the biopsy is being performed. [3] If one of these floaters is from a malignant specimen, a healthy patient could be falsely diagnosed as having cancer.

Frequency of occurrence

Medical research, reports from respected news organizations and real-life cases document the existence of Specimen Provenance Complications in the diagnostic testing cycle for cancer. One such report from the Wall Street Journal indicates that three to five percent of specimens taken each year are defective in some way, whether that be from insufficient extraction of tumor cells, a mix-up of patients’ samples or some other issue. [4] A study published in the Journal of Urology in 2014 concluded that more than 1 in every 200 prostate biopsy patients is misdiagnosed due to undetected specimen provenance complications. [5]

A study conducted by the College of American Pathologists extrapolated that reported misidentification errors from 120 pathology labs would result in more than 160,000 adverse patient outcomes per year. [6] The study further cautioned that the true incidence of both errors and resulting adverse events would be much higher than can be presently measured since the research results were based solely on errors that were actually detected.

To determine an estimate for the rate of occult Specimen Provenance Complication occurrence, researchers at Washington University School of Medicine conducted prospective analysis of approximately 13,000 prostate biopsies performed as part of routine clinical practice. Published in the American Journal of Clinical Pathology , this study classified biopsy misidentification errors into two segments: a complete transposition between patients (Type 1) and contamination of a patient’s tissue with one or more unrelated patients (Type 2). The frequency of occult Type 1 and Type 2 errors was found to be 0.26% and 0.67% respectively, or a combined error rate of 0.93%. However, each case involves at least two individuals, so this error rate actually underestimates the percentage of patients potentially affected by incidents of biopsy misidentification. Furthermore, the study demonstrated that errors occur across a variety of practice types and diagnostic laboratories, indicating no one setting is immune from this problem. [7]

Additionally, in a study published in the American Journal of Clinical Pathology in 2015, the researchers at Washington University’s School of Medicine Genomics and Pathology Services center in St Louis, MO, determined that 2% of tissue samples received in their lab for next generation sequencing were contaminated by another person’s DNA to an extent to be clinically significant (i.e. greater than 5% of the sample was contaminated). [8]

As data substantiates, SPCs are an under-recognized problem in clinical practice that warrants further investigation and consideration of additional safety measures such as required DNA testing to confirm the identity of biopsy samples. [9]

Outcomes

In terms of outcomes, diagnostic mistakes due to Specimen Provenance Complications can have devastating results for both patients and the medical professionals involved in their care. One patient may receive an unnecessary treatment that significantly affects his or her quality of life, while the other patient’s cancer remains undiagnosed, and thus continues to advance.

An example of the consequences of SPCs is the story of a Long Island, New York woman who underwent an unnecessary double mastectomy due to a misidentification error that caused her biopsy test results to be switched with those of another patient. Consequently, necessary treatment was delayed for the woman who did have breast cancer. [10] In another case, a young Australian woman received an unnecessary radical hysterectomy, leaving her infertile and dependent on hormone replacement therapy, after her biopsy sample was contaminated with malignant tissue from another patient. [11]

To ensure diagnostic accuracy of pathology lab results and prevent these types of adverse outcomes, a DNA Specimen Provenance Assignment (DSPA) also known as DNA Specimen Provenance Assay test can be performed to confirm that surgical biopsies being evaluated belong exclusively to the patient being diagnosed and that they are free from contamination.

Related Research Articles

<span class="mw-page-title-main">Pathology</span> Study of the causes and effects of disease or injury, and how they arise

Pathology is the study of disease and injury. The word pathology also refers to the study of disease in general, incorporating a wide range of biology research fields and medical practices. However, when used in the context of modern medical treatment, the term is often used in a narrower fashion to refer to processes and tests that fall within the contemporary medical field of "general pathology", an area that includes a number of distinct but inter-related medical specialties that diagnose disease, mostly through analysis of tissue and human cell samples. Idiomatically, "a pathology" may also refer to the predicted or actual progression of particular diseases, and the affix pathy is sometimes used to indicate a state of disease in cases of both physical ailment and psychological conditions. A physician practicing pathology is called a pathologist.

<span class="mw-page-title-main">Anatomical pathology</span> Medical specialty

Anatomical pathology (Commonwealth) or anatomic pathology (U.S.) is a medical specialty that is concerned with the diagnosis of disease based on the macroscopic, microscopic, biochemical, immunologic and molecular examination of organs and tissues. Over the 20th century, surgical pathology has evolved tremendously: from historical examination of whole bodies (autopsy) to a more modernized practice, centered on the diagnosis and prognosis of cancer to guide treatment decision-making in oncology. Its modern founder was the Italian scientist Giovan Battista Morgagni from Forlì.

<span class="mw-page-title-main">Cytopathology</span> A branch of pathology that studies and diagnoses diseases on the cellular level

Cytopathology is a branch of pathology that studies and diagnoses diseases on the cellular level. The discipline was founded by George Nicolas Papanicolaou in 1928. Cytopathology is generally used on samples of free cells or tissue fragments, in contrast to histopathology, which studies whole tissues. Cytopathology is frequently, less precisely, called "cytology", which means "the study of cells".

<span class="mw-page-title-main">Biopsy</span> Medical test involving extraction of sample cells or tissues for examination

A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a disease. The tissue is then fixed, dehydrated, embedded, sectioned, stained and mounted before it is generally examined under a microscope by a pathologist; it may also be analyzed chemically. When an entire lump or suspicious area is removed, the procedure is called an excisional biopsy. An incisional biopsy or core biopsy samples a portion of the abnormal tissue without attempting to remove the entire lesion or tumor. When a sample of tissue or fluid is removed with a needle in such a way that cells are removed without preserving the histological architecture of the tissue cells, the procedure is called a needle aspiration biopsy. Biopsies are most commonly performed for insight into possible cancerous or inflammatory conditions.

<span class="mw-page-title-main">Fine-needle aspiration</span> Diagnostic medical procedure

Fine-needle aspiration (FNA) is a diagnostic procedure used to investigate lumps or masses. In this technique, a thin, hollow needle is inserted into the mass for sampling of cells that, after being stained, are examined under a microscope (biopsy). The sampling and biopsy considered together are called fine-needle aspiration biopsy (FNAB) or fine-needle aspiration cytology (FNAC). Fine-needle aspiration biopsies are very safe minor surgical procedures. Often, a major surgical biopsy can be avoided by performing a needle aspiration biopsy instead, eliminating the need for hospitalization. In 1981, the first fine-needle aspiration biopsy in the United States was done at Maimonides Medical Center. Today, this procedure is widely used in the diagnosis of cancer and inflammatory conditions. Fine needle aspiration is generally considered a safe procedure. Complications are infrequent.

<span class="mw-page-title-main">Liver biopsy</span>

Liver biopsy is the biopsy from the liver. It is a medical test that is done to aid diagnosis of liver disease, to assess the severity of known liver disease, and to monitor the progress of treatment.

<span class="mw-page-title-main">Prostate biopsy</span>

Prostate biopsy is a procedure in which small hollow needle-core samples are removed from a man's prostate gland to be examined for the presence of prostate cancer. It is typically performed when the result from a PSA blood test is high. It may also be considered advisable after a digital rectal exam (DRE) finds possible abnormality. PSA screening is controversial as PSA may become elevated due to non-cancerous conditions such as benign prostatic hyperplasia (BPH), by infection, or by manipulation of the prostate during surgery or catheterization. Additionally many prostate cancers detected by screening develop so slowly that they would not cause problems during a man's lifetime, making the complications due to treatment unnecessary.

<span class="mw-page-title-main">Gleason grading system</span> Score given to a prostate cancer based on its microscopic appearance

The Gleason grading system is used to help evaluate the prognosis of men with prostate cancer using samples from a prostate biopsy. Together with other parameters, it is incorporated into a strategy of prostate cancer staging which predicts prognosis and helps guide therapy. A Gleason score is given to prostate cancer based upon its microscopic appearance. Cancers with a higher Gleason score are more aggressive and have a worse prognosis. Pathological scores range from 2 to 10, with higher numbers indicating greater risks and higher mortality. The system is widely accepted and used for clinical decision making even as it is recognised that certain biomarkers, like ACP1 expression, might yield higher predictive value for future disease course.

<span class="mw-page-title-main">Surgical pathology</span> Area of practice for anatomical pathologists

Surgical pathology is the most significant and time-consuming area of practice for most anatomical pathologists. Surgical pathology involves gross and microscopic examination of surgical specimens, as well as biopsies submitted by surgeons and non-surgeons such as general internists, medical subspecialists, dermatologists, and interventional radiologists.

Gastrointestinal pathology is the subspecialty of surgical pathology which deals with the diagnosis and characterization of neoplastic and non-neoplastic diseases of the digestive tract and accessory organs, such as the pancreas and liver.

<span class="mw-page-title-main">Medical laboratory</span> Principles of management with special reference to medical science

A medical laboratory or clinical laboratory is a laboratory where tests are conducted out on clinical specimens to obtain information about the health of a patient to aid in diagnosis, treatment, and prevention of disease. Clinical medical laboratories are an example of applied science, as opposed to research laboratories that focus on basic science, such as found in some academic institutions.

<span class="mw-page-title-main">Automated tissue image analysis</span>

Automated tissue image analysis or histopathology image analysis (HIMA) is a process by which computer-controlled automatic test equipment is used to evaluate tissue samples, using computations to derive quantitative measurements from an image to avoid subjective errors.

<span class="mw-page-title-main">PCA3</span> Non-coding RNA in the species Homo sapiens

Prostate cancer antigen 3 is a gene that expresses a non-coding RNA. PCA3 is only expressed in human prostate tissue, and the gene is highly overexpressed in prostate cancer. Because of its restricted expression profile, the PCA3 RNA is useful as a tumor marker.

FNA mapping is an application of fine-needle aspiration (FNA) to the testis for the diagnosis of male infertility. FNA cytology has been used to examine pathological human tissue from various organs for over 100 years. As an alternative to open testicular biopsy for the last 40 years, FNA mapping has helped to characterize states of human male infertility due to defective spermatogenesis. Although recognized as a reliable, and informative technique, testis FNA has not been widely used in U.S. to evaluate male infertility. Recently, however, testicular FNA has gained popularity as both a diagnostic and therapeutic tool for the management of clinical male infertility for several reasons:

  1. The testis is an ideal organ for evaluation by FNA because of its uniform cellularity and easy accessibility.
  2. The trend toward minimally invasive procedures and cost-containment views FNA favorably compared to surgical testis biopsy.
  3. The realization that the specific histologic abnormality observed on testis biopsy has no definite correlation to either the etiology of infertility or to the ability to find sperm for assisted reproduction.
  4. Assisted reproduction has undergone dramatic advances such that testis sperm are routinely used for biological pregnancies, thus fueling the development of novel FNA techniques to both locate and procure sperm.
<span class="mw-page-title-main">Breast biopsy</span> Surgical procedure

A breast biopsy is usually done after a suspicious lesion is discovered on either mammography or ultrasound to get tissue for pathological diagnosis. Several methods for a breast biopsy now exist. The most appropriate method of biopsy for a patient depends upon a variety of factors, including the size, location, appearance and characteristics of the abnormality. The different types of breast biopsies include fine-needle aspiration (FNA), vacuum-assisted biopsy, core needle biopsy, and surgical excision biopsy. Breast biopsies can be done utilizing ultrasound, MRI or a stereotactic biopsy imaging guidance. Vacuum assisted biopsies are typically done using stereotactic techniques when the suspicious lesion can only be seen on mammography. On average, 5–10 biopsies of a suspicious breast lesion will lead to the diagnosis of one case of breast cancer. Needle biopsies have largely replaced open surgical biopsies in the initial assessment of imaging as well as palpable abnormalities in the breast.

DNA Specimen Provenance Assignment (DSPA) also known as DNA Specimen ProvenanceAssay, is a molecular diagnostic test used to definitively assign biopsy specimen identity and establish specimen purity during the diagnostic testing cycle for cancer and other histopathological conditions. The term first appeared in the 2011 scientific paper, “The Changing Spectrum of DNA-Based Specimen Provenance Testing in Surgical Pathology,” published in the American Journal of Clinical Pathology, which built upon concepts described in an earlier paper published in the Journal of Urology.

<span class="mw-page-title-main">Molecular diagnostics</span> Collection of techniques used to analyze biological markers in the genome and proteome

Molecular diagnostics is a collection of techniques used to analyze biological markers in the genome and proteome, and how their cells express their genes as proteins, applying molecular biology to medical testing. In medicine the technique is used to diagnose and monitor disease, detect risk, and decide which therapies will work best for individual patients, and in agricultural biosecurity similarly to monitor crop- and livestock disease, estimate risk, and decide what quarantine measures must be taken.

Anne Louise Rosenberg is an American surgical oncologist retired from practice in Cherry Hill, New Jersey.

Urinary cell-free DNA (ucfDNA) refers to DNA fragments in urine released by urogenital and non-urogenital cells. Shed cells on urogenital tract release high- or low-molecular-weight DNA fragments via apoptosis and necrosis, while circulating cell-free DNA (cfDNA) that passes through glomerular pores contributes to low-molecular-weight DNA. Most of the ucfDNA is low-molecular-weight DNA in the size of 150-250 base pairs. The detection of ucfDNA composition allows the quantification of cfDNA, circulating tumour DNA, and cell-free fetal DNA components. Many commercial kits and devices have been developed for ucfDNA isolation, quantification, and quality assessment.

<span class="mw-page-title-main">Piflufolastat F-18</span> Chemical compound

Piflufolastat F-18, sold under the brand name Pylarify among others, is a radioactive diagnostic agent used for positron emission tomography (PET) imaging. It is given by intravenous injection.

References

  1. ↑ "Cancer Facts & Figures 2012" (PDF). American Cancer Society.
  2. ↑ Bronner, M (2006). "DNA fingerprint analysis for specimen identification". Cleveland Clinic Clinical and Translational Pathology Research (Fall): 5–7.
  3. ↑ Harada, S; Gocke C (2010). "Specimen identity testing using deoxyribonucleic acid analysis in clinical and surgical pathology setting". Pathol. Case Rev. 15 (4): 116–120. doi:10.1097/pcr.0b013e3181e69af3.
  4. ↑ "Hospitals move to cut dangerous lab errors". Wall Street Journal. June 14, 2006.
  5. ↑ Wojno, K; Hornberger J; Schellhammer P; Dai M; Morgan T (2014). "The clinical and economic implications of specimen provenance complications in diagnostic prostate biopsies". The Journal of Urology. 193 (4): 1170–1177. doi:10.1016/j.juro.2014.11.019. PMID   25463992.
  6. ↑ Valenstein, PN; Raab SS; Walsh MK (2006). "Identification error involving clinical laboratories: a College of American Pathologists Q-probes study of patient and specimen identification errors at 120 institutions". Arch. Pathol. Lab. Med. 130 (8): 1066–1113. doi:10.5858/2006-130-1106-IEICL. PMID   16879009.
  7. ↑ Pfeifer, J. D.; Liu, J. (2013). "Rate of occult specimen provenance complications in routine clinical practice". American Journal of Clinical Pathology. 139 (1): 93–100. doi:10.1309/ajcp50wezhwifciv. PMID   23270904.
  8. ↑ Sehn, Jennifer; Spencer, D.; Pfeifer, J.; Bredemeyer, A.; Cottrell, C.; Abel, H.; Duncavage, E. (2015). "Occult Specimen Contamination in Routine Clinical Next-Generation Sequencing Testing". American Journal of Clinical Pathology. 144 (4): 667–674. doi: 10.1309/AJCPR88WDJJLDMBN . PMID   26386089.
  9. ↑ Marberger, M; McConnell JD; Fowler I (2011). "Biopsy misidentification identified by DNA profiling in a multicenter trial". J Clin Oncol. 29 (13): 1744–1749. doi:10.1200/jco.2010.32.1646. PMC   3107764 . PMID   21444877.
  10. ↑ Celizic, Michael (October 4, 2007). "Cancer-free woman underwent double mastectomy because of lab mix-up". Today. Archived from the original on January 4, 2013.
  11. ↑ Medew, J (September 5, 2009). "The lab blunder that stole a woman's fertility". The Age.
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