Biopsy Sample Size Research Articles

A Randomized Trial Comparing the Diagnostic Yield of Rigid and Semirigid Thoracoscopy in Undiagnosed Pleural Effusions

Thoracoscopic pleural biopsy increases the diagnostic yield of pleural effusions undiagnosed after thoracentesis and is superior to closed pleural biopsy. Medical thoracoscopy can be performed using the rigid thoracoscope or the semirigid thoracoscope (pleuroscope). In this randomized trial, we compare the efficacy and safety of the 2 thoracoscopes. Subjects with undiagnosed exudative pleural effusions were randomly assigned to undergo pleural biopsy with either the rigid or the semirigid thoracoscope. The primary outcome was the diagnostic yield of the procedure, while the secondary outcomes were requirement of sedative/analgesic agents, scar size, biopsy sample size, and the operator's view of the procedure. Of the 145 screened subjects with exudative pleural effusions, 90 were randomized to undergo thoracoscopy with the 2 thoracoscopes (n = 45 each). The diagnostic yield of rigid thoracoscopy was superior to semirigid thoracoscopy (97.8% vs 73.3%, P = .002) on an intention-to-treat analysis but was similar (100% vs 94.3%, P = .18) in those with successful biopsy. The requirement of sedative/analgesic agents was higher in the rigid thoracoscopy arm. The scar size was slightly larger (mean ± SD, 23.1 ± 4 vs 18.7 ± 3.2 mm, P = .0001), whereas the biopsy sample size was distinctly larger in the rigid arm (mean ± SD, 13.9 ± 4.4 vs 4.4 ± 1.4 mm, P = .001). The operator-rated visual analog scale score for the ease of taking a biopsy sample was significantly higher with the rigid instrument (mean ± SD, visual analog scale 86 ± 12 vs 79 ± 12 mm, P = .01), while the quality of image was superior in the semirigid arm (mean ± SD, visual analog scale 88 ± 7 vs 92 ± 5 mm, P = .002). The number of complications were similar in the 2 groups. Rigid thoracoscopy was found to be superior to semirigid thoracoscopy overall, but the diagnostic yield was similar if pleural biopsy could be successfully performed. Due to the small sample size, a larger study is required to define the usefulness and choice between the 2 procedures. (ClinicalTrials.gov registration NCT01726556).

Utility and Diagnostic Accuracy of Ureteroscopic Biopsy in Upper Tract Urothelial Carcinoma

Ureteroscopic biopsy is the gold standard for the histopathologic diagnosis of urothelial carcinoma of the upper urinary tract. To assess the accuracy of endoscopically obtained biopsy samples in diagnosing, grading, and staging urothelial carcinoma and correlate diagnostic findings to biopsy sample size. We retrospectively reviewed endoscopic biopsies of the ureter, renal pelvis, and ureteropelvic junction from 2008 to 2011. Biopsy diagnoses that were discordant with follow-up pathology and/or ureteroscopic impression were re-reviewed and samples were immunohistochemically analyzed. Endoscopic biopsies (n = 118) yielded a sensitivity of 85.4% for the ureter (n = 79), 77.8% for the renal pelvis (n = 37), and 100% for the ureteropelvic junction (n = 2). A specificity of 100% for all locations and a diagnostic accuracy of 98.3% were identified. The median sample size was 0.3 cm for true positives, 0.3 cm for true negatives, and 0.2 cm for false negatives with no statistical significance. We found that 87.1% of tumors diagnosed on biopsy had concordant grade and 60.0% had concordant pT stage with follow-up surgical resections (n = 43) and biopsies (n = 24). Biopsy samples with concordant tumor grades (mean = 0.6 cm) compared with follow-up resection were larger than biopsy samples with discordant grades (mean = 0.3 cm) (P = .04). Though highly specific, endoscopic biopsy does provide a significant false-negative rate owing to both sampling and diagnostic errors when assessing the upper urinary tract for urothelial carcinoma. Tumor grading is accurate, particularly with larger tissue samples, but tumor staging is unreliable.

Use of Research Biopsies in Clinical Trials: Are Risks and Benefits Adequately Discussed?

Although the incorporation of research biopsies into clinical trials is increasing, limited information is available about how study protocols and informed consents integrate and describe their use. All therapeutic clinical trials in which image-guided research biopsies were performed from January 1, 2005, to October 1, 2010, were identified from an interventional radiology database. Data from study protocols and informed consents were extracted and analyzed. Procedural complications were recorded. A total of 57 clinical trials were identified, of which 38 (67%) contained at least one mandatory biopsy. The analysis of the research biopsy tumor tissue was a study end point in 95% of trials. The primary indication for a research biopsy was for integral biomarker analysis in 32% and for correlative science in 68% of trials. A statistical analytic plan for the correlative science research biopsy tumor tissue was mentioned in 26%, described as exploratory in 51%, and not mentioned in 23% of trials. For studies with mandatory biopsies, biopsy was an eligibility criterion in 71% of trials, and a statistical justification for the research biopsy sample size was present in 50% of trials. A total of 745 research biopsies were performed on 576 patients. Overall and major complication rates were 5.2% (39 of 745 biopsies) and 0.8% (six of 745 biopsies), respectively. Complication rates for intrathoracic and abdominal/pelvic solid organ biopsies were 17.1% (36 of 211 biopsies) and 1.6% (three of 189 biopsies), respectively. Site-stratified research biopsy-related risks were discussed in five consents. A better representation of the risks and benefits of research biopsies in study protocols and informed consents is needed.

The rate of melanoma transection with various biopsy techniques and the influence of tumor transection on patient survival

Depth of melanoma invasion is critical because it dictates patient treatment and prognosis. Recent reports indicate melanoma transection with initial biopsy does not impact patient survival; however, tumor transection can lead to misdiagnosis and inaccurate staging. This study assessed the rate of melanoma transection with various biopsy techniques and the impact of tumor transection on patient survival. We conducted a retrospective review of all melanoma cases at our institution between 2000 and 2008. Of the 490 melanoma cases identified, 479 met inclusion criteria for the study. The transection rates of biopsy techniques were determined. Cases of transected tumors were matched with nontransected cases in a retrospective case-control fashion to evaluate survival. The rate of melanoma transection was 1.5% for excisional biopsies, 4.1% for punch biopsies, and 9.0% for saucerization biopsies. The means of disease-free survival for the control and transected groups were 911 days and 832.7 days, respectively (P value .67). Overall survival for the control group was 1073.7 days versus 1012.4 days for the transected group (P value .72). The study used a select population. The sample size of transected biopsies was limited, in turn limiting the power of the study. Residents performed the majority of biopsies. Punch and saucerization biopsies were more likely to transect tumors than excisional biopsies. The transection of melanoma did not affect overall disease-free survival or mortality in the population studied.

New insights from breast pathology: should we consider low grade DCIS NOT a cancer?

Distinction between atypical ductal hyperplasia (ADH) and low grade DCIS remains a diagnostic challenge in the everyday practice of breast pathology [1]. Reported studies including a highly cited article by Dr. Rosai in 1991 continue to highlight the significant inter-observer variability even among experienced breast pathologists. This issue is compounded by the increasing number of tissue sampling by core needle biopsy as a consequence of screening mammography. The small sample size of core needle biopsies and tissue fragmentation contributes to the complexity of an accurate diagnosis of DCIS. It is important to recognize that assessment of core needle biopsy is different from circumstances under which the various diagnostic criteria were originally defined by reviewing multiple histologic sections obtained from surgical excisions [2,3]. The real challenge is how to minimize the occurrence of overdiagnosis of DCIS and how to balance the scope of therapy based on the biology and the extent of this disease. Ductal carcinoma in situ is a heterogenous disease characterized by neoplastic proliferation of epithelial cells within a breast duct with no ability to metastasize [4]. DCIS is considered a precursor lesion with a variable rate of progression into invasive breast cancer. Based on nuclear grade, presence or absence of necrosis and the pattern of morphologic features, DCIS is stratified into different grades and types. High nuclear grade lesions are associated with rapid growth and early progression to an invasive cancer and are easier to diagnose [5]. In contrast, low nuclear grade lesions remain indolent and even when they progress to invasive cancer the tumor is frequently low grade and well differentiated. Low grade DCIS and high grade DCIS represent two genetically distinct entities that lead to different forms of invasive cancer. Low grade DCIS share similar morphologic and biologic features with ADH, which raises the question of whether these two lesions represent different spectrums of the same entity [6,7]. Up to now, suggested terminologies of mammary intraepithelial neoplasia (MIN) by Dr. Rosai and ductal intraepithelial neoplasia (DIN) by Dr. Tavassoli have not been fully embraced by the pathology community. This is despite the fact that the unifying concept of mammary intraepithelial neoplasia may eliminate the use of the term “In Situ Carcinoma” and may reduce the chances of over treatment [1,8]. Interestingly, in 1978, Haagensen proposed the term of “lobular neoplasia” for the spectrum of lobular proliferations when he

The Impact of Partial Biopsy on Histopathologic Diagnosis of Cutaneous Melanoma

To compare partial and excisional biopsy techniques in the accuracy of histopathologic diagnosis and microstaging of cutaneous melanoma. Prospective case series. Tertiary referral, ambulatory care, institutional practice. Patients Consecutive cases from 1995 to 2006. Interventions Partial and excisional biopsy. Other factors considered were anatomic site, physician type at initial management, hypomelanosis, melanoma subtype, biopsy sample size, multiple biopsies, and tumor thickness. Histopathologic diagnosis (false-negative misdiagnosis-overall or with an adverse outcome-and false-positive misdiagnosis) and microstaging accuracy. Odds ratios (ORs) and 95% confidence intervals (CIs) obtained from multinomial logistic regression. Increased odds of histopathologic misdiagnosis were associated with punch biopsy (OR, 16.6; 95% CI, 10-27) (P < .001) and shave biopsy (OR, 2.6; 95% CI, 1.2-5.7) (P = .02) compared with excisional biopsy. Punch biopsy was associated with increased odds of misdiagnosis with an adverse outcome (OR, 20; 95% CI, 10-41) (P < .001). Other factors associated with increased odds of misdiagnosis included acral lentiginous melanoma (OR, 5.1; 95% CI, 2-13) (P < .001), desmoplastic melanoma (OR, 3.8; 95% CI, 1.1-13.0) (P = .03), and nevoid melanoma (OR, 28.4; 95% CI, 7-115) (P < .001). Punch biopsy (OR, 5.1; 95% CI, 3.4-7.6) (P < .001) and shave biopsy (OR, 2.3; 95% CI, 1.5-3.6) (P < .001) had increased odds of microstaging inaccuracy over excisional biopsy. Tumor thickness was the most important determinant of microstaging inaccuracy when partial biopsy was used (odds of significant microstaging inaccuracy increased 1.8-fold for every 1 mm increase in tumor thickness; 95% CI, 1.4-2.4) (P < .001). Among melanoma seen at a tertiary referral center, histopathologic misdiagnosis is more common for melanomas that have been assessed with punch and shave biopsy than with excisional biopsy. Regardless of biopsy method, adverse outcomes due to misdiagnosis may occur. However, such adverse events are more commonly associated with punch biopsy than with shave and excisional biopsy. The use of punch and shave biopsy also leads to increased microstaging inaccuracy.

Experimental Study on Biopsy Sampling Using New Flexible Cryoprobes: Influence of Activation Time, Probe Size, Tissue Consistency, and Contact Pressure of the Probe on the Size of the Biopsy Specimen

Cryoextraction is a procedure for recanalization of obstructed airways caused by exophytic growing tumors. Biopsy samples obtained with this method can be used for histological diagnosis. The objective of this study was to evaluate the parameters influencing the size of cryobiopsies in an in vitro animal model. New flexible cryoprobes with different diameters were used to extract biopsies from lung tissue. These biopsies were compared with forceps biopsy (gold standard) in terms of the biopsy size. Tissue dependency of the biopsy size was analyzed by comparing biopsies taken from the lung, the liver, and gastric mucosa. The effect of contact pressure exerted by the tip of the cryoprobe on the tissue was analyzed on liver tissue separately. Biopsy size was estimated by measuring the weight and the diameter. Weight and diameter of cryobiopsies correlated positively with longer activation times and larger diameters of the cryoprobe. The weight of the biopsies was tissue dependent: lung < liver < stomach. Only little tissue dependency was found for the biopsy diameter. The biopsy size increased when the probe was pressed on the tissue during cooling. Cryobiopsies can be taken from different tissue types with flexible cryoprobes. The size of the samples depends on tissue type, probe diameter, application time, and pressure exerted by the probe on the tissue. Even the cryoprobe with the smallest diameter can provide larger biopsies than a forceps biopsy in lung. It can be expected that the same parameters influence the sample size of biopsies in vivo.

Variability of Liver Biopsy Assessment in Hepatitis C

The decision to treat hepatitis C virus (HCV) infection is based mostly on the degree of histologic damage seen on liver biopsy. However, data suggest that the accuracy of histologic assessment can be affected by variations in biopsy sample size (JW Gastroenterol Oct 25 2005) and interpretation by the pathologist. Although this variability has been evaluated in HCV treatment trials, it has not been assessed in a community setting. To address the issue, researchers …

Alanine aminotransferase‐based algorithms of liver stiffness measurement by transient elastography (Fibroscan) for liver fibrosis in chronic hepatitis B

The aim of this study is to know the liver stiffness measurement (LSM) cutoffs for different stages of liver fibrosis in chronic hepatitis B (CHB) and to investigate the effect of alanine aminotransferase (ALT) on LSM. We prospectively studied consecutive CHB patients undergoing liver biopsy and transient elastography examinations. Diagnostic performance of LSM for different degrees of liver fibrosis was evaluated. One hundred and sixty-one CHB patients with adequate liver biopsy sample size were studied. Area under receiver operating characteristics curves of LSM for no fibrosis (F0 vs F1-4), bridging fibrosis (F0-2 vs F3-4) and liver cirrhosis (F0-3 vs F4) was 0.80 (95% CI: 0.68-0.92), 0.87 (95% CI: 0.82-0.93) and 0.93 (95% CI: 0.89-0.97) respectively. For liver cirrhosis, these optimal cutoff values were 8.4 kPa (98% sensitivity), 9.0 kPa (maximum sum of sensitivity and specificity), 13.4 kPa (94% specificity) and 13.4 kPa (maximum diagnostic accuracy, 85%) respectively. Patients with the same fibrosis staging but higher ALT levels tend to have higher LSM, and the diagnostic performance for low stage fibrosis was most seriously affected when ALT was elevated. Different LSM cutoff values and algorithms were derived for normal and elevated ALT levels. Based on these algorithms, liver biopsy can be avoided in 62% and 58% of patients with normal and elevated ALT respectively. In conclusion, transient elastography is a reasonable noninvasive tool to substitute liver biopsy among the lowest and highest risk patients for the assessment of liver fibrosis.

Endobiliary Biopsy with Larger Forceps in Extrahepatic Biliary Strictures

Backgrond & Aim: Endoscopic retrograde biliary biopsy is safe and effective to diagnose biliary stricture. However, the sample of biliary biopsy is frequently too small and inadequate, where histological interpretation is difficult. We evaluated the usefulness of larger forceps in terms of endobiliary biopsy for extrahepatic biliary strictures. Methods: In this prospective study, patients with biliary stricture underwent three attempts of biliary biopsy with larger forceps at one ERCP session. Studied forceps were following: (a) 2.2 mm M00515361 (Boston Scientific, USA), (b) 2.45 mm FB-230U (Olympus, Japan), (c) 2.3 mm E022-G (Endo-flex, Germany). In each patient, biopsies were attempted three times by three different forceps. The turn of the biopsy was randomly decided. The tissue samples were reviewed in a blind fashion by one co-author (MI) for the following parameters: overall surface area (mm2), adequacy of the specimens for histological diagnosis, and inclusion of muscle tissue. These results were compared with 129 biopsy samples previously taken from the biliary stricture with 1.8mm forceps ((d) FB-39Q, Olympus) in 44 patients (pancreatic cancer, 24; gallbladder cancer, 4; bile duct cancer, 4; metastasis, 1; benign, 11) over the last three years. Strictures in ampullary region or after metallic stent placement were excluded from this study. Results: 25 patients underwent endobiliary biopsy with larger forceps (pancreatic cancer, 11; bile duct cancer, 9; gallbladder cancer, 1; metastasis, 2; benign stricture, 2). In these patients, 75 attempts of biliary biopsy were performed. The biopsy sample size by larger forceps ((a) 1.51 mm2, (b) 1.70 mm2, (c) 1.40 mm2) were significantly greater than 1.8 mm forceps (d) 0.72 mm2) (p < 0.0001). However, there is no difference in size among three larger forceps. Adequacy of the specimen for histological diagnosis were (a), 92%; (b), 80%; (c), 92%; (d), 79.8%. There is no difference among them. Muscle tissue was included (a), 60%; (b), 56%; (c), 52%; (d), 23%. Muscle tissue was more frequently observed in specimen by larger forceps ((a) vs. (c), p = 0.0021; (b) vs. (d), p = 0.0071; (c) vs. (d), p = 0.0208)) There has been no complication as to taking biopsy in each group. Sensitivity per each specimen was (a) 43.5%, (b) 34.8%, (c) 43.5%, (d) 34%. Conclusions: With respects to endobiliary biopsy, larger biopsy forceps yielded biopsy specimens of larger size and deeper depth as compared to specimens obtained by the smaller forceps. Larger biopsy forceps might be safe and effective diagnostic procedure. For further assessment in their diagnostic value, a prospective randomized study compared with smaller forceps is required.

A Comparison of Wedge and Needle Hepatic Biopsy in Open Bariatric Surgery

Morbidly obese patients, despite normal laboratory tests and no clinical evidence of liver disease, present a high prevalence of hepatic histological changes. Liver biopsy is able to provide the diagnosis, staging and assessment of follow-up of hepatic disease, thus helping to define clinical management. There is no agreement on which biopsy technique provides better material for analysis. Considering that subcapsular fibrosis is a common finding, sampling from deeper sites is necessary to achieve an adequate histological assessment. A study was done in 264 consecutive morbidly obese patients who underwent open Roux-en-Y gastric bypass between July 2001 and Sept 2004, in whom an intraoperative liver biopsy was taken. The first 107 were wedge biopsies, and the last 157 were needle biopsies. The histological degree of steatosis, presence of fibrosis and adequacy of material from the 2 biopsy techniques were compared. Degree of steatosis in both sampling techniques showed no statistical difference (P=0.132). The presence of fibrosis in wedge biopsies (46.1% fibrosis, n 41) was significantly higher than in needle biopsies (13.7% fibrosis, n 20), P<0.001. As expected, sample size of needle biopsies was smaller than that obtained by the wedge technique (P<0.001), but there was no difference in the quality of material obtained (P=0.95). Needle biopsies were as effective as wedge biopsies in assessing the degree of steatosis in morbidly obese patients. More important, the presence of subcapsular fibrosis in needle biopsies was less than in wedge biopsies, suggesting an adequate tissue sample by the less invasive technique.

Variability in testis biopsy interpretation: implications for male infertility care in the era of intracytoplasmic sperm injection

To determine whether center to center discrepancies in the ability to locate sperm in infertile testes with abnormal histology stems in part from inconsistencies in pathologists' readings of testis biopsies. Prospective cohort study. Academic male infertility practice. Consecutive series of azoospermic men referred with testis biopsy slides between 1998 and 2003. Testis biopsy histologies on azoospermic patients referred for infertility care were re-reviewed by a single pathologist blinded to the original reading. Subsequent infertility care was guided by the findings from the second histologic reading. Agreement between the outside and in-house review of testis biopsy readings was assessed with the kappa statistic. Pregnancy outcomes that resulted from clinical decisions informed by the second histologic readings were also assessed. Among 113 histologic specimens, re-review was complicated by fixation artifacts in 18 cases (16%) and insufficient biopsy sample size in 13 cases (12%). The kappa score for interobserver agreement in readings was 0.43 (95% CI 0.32-0.054). Mixed histology patterns in particular were underappreciated by outside pathologists (13% of cases on original reading, 36% of cases on review). In 27% of all cases, the differences in biopsy readings had a significant impact on clinical management. A correlation between independent testis histology readings in azoospermic men demonstrates frequent inconsistencies. These differences contribute to inaccurate phenotyping of male infertility and can significantly impact the direction of infertility care. These findings highlight the need for a standardized approach to testis histologic review.

The importance of sample size in the interpretation of the renal biopsy.

The number of abnormal glomeruli present in a renal biopsy can be viewed as a binomial distribution. Recognition of this fact permits a quantitative assessment of the effect of biopsy sample size in renal biopsy interpretation. If the percent of glomerular involvement in a biopsy is used to determine the severity of a focal glomerular lesion, a small biopsy sample size will lead to considerable misclassification of disease severity. In addition, a small biopsy sample size will make the exclusion of focal disease difficult.

Effect of suction on biopsy sample size.

Effect of suction on biopsy sample sizeMG Hueftle and Haaga, JRAudio Available | Share

Minimum sample size of kidney biopsies for semiquantitative and quantitative evaluation.

The minimum sample size for semiquantitative and quantitative evaluation of interstitial tubular and glomerular parameters is calculated. For the majority of parameters a renal cortex area of 2 mm2 or 7 glomeruli (adults) or 13 glomeruli (children) is sufficient. Larger biopsies or more glomeruli are necessary for the evaluation of the area density of interstitium patent and obsolescent glomeruli as well as the numerical density of obsolescent glomeruli. The most sensitive parameters are those concerning crescents which require biopsies of 11-19 glomeruli in adults and 40 glomeruli in children. In summary, biopsies of usual size (10 mm2) containing about 20 glomeruli are sufficient for qualitative and quantitative evaluation.