False-negative Rate Of Biopsy Research Articles

Role of Doppler US and elastography prior to biopsy to identify candidates for avoidance of surgery following neoadjuvant chemotherapy for breast cancer.

This study aimed to evaluate the role of Doppler ultrasound (US) and elastography to identify residual breast cancer for patients showing near complete response following chemotherapy on magnetic resonance imaging (MRI). Between September 2016 and January 2018, 40 breast cancer patients who showed near complete response (either tumor size ≤0.5 cm or lesion-to-background parenchymal signal enhancement ratio ≤1.6) on MRI following neoadjuvant chemotherapy were prospectively enrolled. After excluding seven women who did not undergo Doppler US and elastography, 33 women (median age, 49 years; range, 32 to 67 years) were analyzed. On the day of surgery, women underwent Doppler US and elastography for tumor bed prior to US-guided core needle biopsy. Histopathologic results of biopsy and surgery were evaluated. Negative predictive value (NPV) and false negative rate (FNR) of biopsy and the combined Doppler US and elastography were analyzed, respectively. After surgery, nine women had residual cancers and 24 women had pathologic complete response. The NPV and FNR of biopsy were 92% (24 of 26) and 22% (2 of 9), respectively. The NPV and FNR of combined Doppler US and elastography were 100% (14 of 14) and 0% (0 of 9), respectively. All of nine women with residual cancers had positive vascularity or elasticity. Two women with false-negative biopsy results, having 0.3 cm or 2.5 cm ductal carcinoma in situ at surgery, showed positive vascularity or elasticity. Tumor bed showing positive vascularity or elasticity indicates residual breast cancer for patients showing near complete response on MRI following chemotherapy.

Effect of Quantitative and Semi-quantitative Elastography Methods for the Management of Borderline Lesions on Ultrasonography.

Elastography (strain or shear-wave) is a method that estimates tissue stiffness. The aim of this study is to evaluate the quantitative and semi-quantitative ultrasound elastography methods for the diagnosis of BI-RADS 4a and BI-RADS 3 lesions, which are borderline for biopsy and follow-up. 175 consecutive women with 193 ultrasound-visible breast lesions were classified on Conventional B-mode Ultrasonography (CUS) according to the BI-RADS scoring system. Quantitative and semiquantitative values from ultrasound elastography in the form of strain Elastography Ratio (SER), shear Wave Elastography (SWE) and Shear Wave Elastography Ratio (SWER) were obtained. The lesions categorized as BI-RADS 4a and BI-RADS 3 on ultrasound were subsequently re-categorized according to the elastography values. Except for the 13 BI-RADS 2 lesions, the remaining 180 lesions were biopsied. Pathology showed 83 lesions to be benign and 97 to be malignant. The sensitivity and specificity of the CUS were 96.9% and 75.0%, respectively with an accuracy of 86.0%. Cut-off points calculated based on ROC curves were 56.8 kPa for SWE, 3.53 for SWER and 3.81 for SER. When we downgraded BIRADS 4a lesions based on elastography results, the specificity (CUS+SER 96.9%, CUS+SWE 91.7%, and CUS+SWER 90.6%) and the accuracy (CUS+SER 95.3%, CUS+SWE 92.7%, and CUS+SWER 92.2%) were shown to be better than CUS. When we upgraded BI-RADS 3 lesions based on elastography results, the sensitivity of combined sets of SWE (99,0%) and SWER (100,0%) was better than CUS. The rate of false-negative biopsies can be decreased with the combined use of elastography and ultrasonography.

Performance of a 31-gene expression profile (GEP) test for metastatic risk prediction in cutaneous melanomas (CM) of the head and neck.

9576 Background: Accurate prognostication of distant metastatic risk using sentinel lymph node (SLN) biopsy for CM can be challenging in melanomas of the head and neck due to a higher false negative rate compared to other anatomical areas. A GEP signature that predicts metastatic risk based on primary tumor biology, providing a binary outcome of Class 1 (low risk of metastasis) or Class 2 (high risk), was previously described. The prognostic capabilities of the GEP independently and in combination with SLN status in a cohort of patients with primary head and neck CM are assessed here. Methods: All samples and clinical data were collected under an IRB-approved multicenter protocol. qPCR analysis was used to assess expression of the gene signature (Class 1 vs. Class 2). Distant metastasis-free survival (DMFS) and melanoma-specific survival (MSS) were assessed. Results: 157 subjects with primary CMs in the head and neck region were identified. 110 of 157 subjects had a SLN biopsy performed. Median age was 65 years (range 25-89) and median Breslow depth was 1.6 mm (range 0.2-15.0 mm). In 71 SLN-negative patients, 18 of 27 (67%) distant metastatic events were GEP Class 2. Overall, 73% (47 of 64) distant metastases, and 88% (22 of 25) deaths due to CM were called Class 2. By comparison, sensitivities for DMFS and MSS were 41% (26 of 64) and 52% (13 of 25), respectively, using SLN biopsy alone, and increased to 80% (51 of 64) and 88% (22 of 25), respectively, when combining the SLN status and GEP class. Kaplan-Meier 5-year DMFS and MSS rates based on SLN status alone or in combination with GEP are shown in the table. Conclusions: These data support the ability of the GEP test to accurately identify low- and high-risk cases of head and neck melanoma. The results strongly support the role of GEP testing to enhance current staging by better predicting the risk of distant metastasis and death for patients with melanoma in an anatomic region that is associated with a higher SLN biopsy false negative rate. [Table: see text]

Who may benefit from preoperative breast MRI? A single-center analysis of 1102 consecutive patients with primary breast cancer.

Several authors question the potential benefit of preoperative magnetic resonance imaging (MRI) against the background of possible overdiagnosis, false-positive findings, and unnecessary resections in patients with newly diagnosed breast cancer. In order to reveal a better selection of patients who should undergo preoperative MRI after histological confirmed breast cancer, the present analysis was implemented. We aimed to evaluate the influence of preoperative breast MRI in patients with newly diagnosed breast cancer to find subgroups of patients that are most likely to benefit from preoperative MRI by the detection of occult malignant foci. A total of 1102 consecutive patients who underwent treatment for primary breast cancer between 2002 and 2013 were retrospectively analyzed. All patients underwent triple assessment by breast ultrasound, mammography, and bilateral breast MRI. MRI findings not seen on conventional imaging that suggested additional malignant disease was found in 344 cases (31.2 %). Histological confirmed malignant foci were found in 223 patients (20.2 %) within the index breast and in 28 patients (2.5 %) in the contralateral breast. The rate of false-negative biopsies was 31 (2.8 %) and 62 (5.6 %), respectively. Premenopausal women (p = 0.024), lobular invasive breast cancer (p = 0.02) as well as patients with high breast density [American College of Radiology (ACR) 3 + 4; p = 0.01] were significantly associated with additional malignant foci in the index breast. Multivariate analysis confirmed lobular histology (p = 0.041) as well as the co-factors "premenopausal stage" and "high breast density (ACR 3+4)" (p = 0.044) to be independently significant. Previous studies revealed that breast MRI is a reliable tool for predicting tumor extension as well as for the detection of additional ipsilateral and contralateral tumor foci in histological confirmed breast cancer. In the present study, we demonstrate that especially premenopausal patients with high breast density as well as patients with lobular histology seem to profit from preoperative MRI.

MR imaging-guided vacuum-assisted breast biopsy: Reduction of false-negative biopsies by short-term control MRI 24–48 h after biopsy

To evaluate whether another contrast-enhanced (CE) magnetic resonance imaging (MRI) examination 24-48h after MRI-guided vacuum-assisted breast biopsy (MRI-VAB) can reduce the rate of false-negative cases. The study included 252 patients who underwent MRI-VAB for the clarification of 299 lesions. The success of MRI-VAB was assessed at interventional MRI and another CE MRI 24-48h after the intervention. In cases of successful MRI-VAB (complete or partial lesion removal) and benign histological results, follow-up breast MRI was performed. In cases of unsuccessful biopsy (unchanged lesion), tissue sampling was repeated. False-negative cases were calculated to assess the diagnostic value of MRI follow-up within 2 days after intervention. Ninety-eight malignant (32.8%) and 201 (67.2%) benign lesions were diagnosed using MRI-VAB. At immediate unenhanced control MRI, all lesions were assessed as successfully biopsied. In 18 benign cases (6%), CE MRI after 24-48h showed an unsuccessful intervention. Further tissue sampling revealed another 13 cancers in these patients. This results in a false-negative rate of 11.7%. Follow-up MRI of the benign lesions presented no further malignancy. MRI-VAB with immediate unenhanced control offers a success rate of 94%. The rate of false-negative biopsies (11.7%) could be reduced to zero by using short-term follow-up MRI. Therefore, a further CE breast MRI 24-48h after benign MRI-VAB to eliminate missed cancers is recommended.

False-negative Prostate Needle Biopsies: Frequency, Histopathologic Features, and Follow-up

Little is known about the frequency, histopathologic characteristics, and clinical consequences of false-negative prostate biopsies, that is, biopsies classified as benign but containing adenocarcinoma or atypical suspicious glands [atypical small acinar proliferations (ASAP)]. Objective of this study was to evaluate false-negative prostate biopsy in a prostate cancer screening setting. Prostate biopsy sets of 196 participants of a screening trial, which had been reported as "benign" at initial diagnosis, followed by a diagnosis of adenocarcinoma in a subsequent screening round were reviewed by 2 urologic pathologists. Adenocarcinoma was identified in 19 biopsy cores corresponding to 16 (8.2%) patients and ASAP in 24 cores, corresponding to 19 patients (9.7%). All missed prostate cancers were Gleason score 6 (3+3). After correction for patient selection, the overall false-negative biopsy rate was estimated to be 2.4%; 1.1% for prostate cancer; and 1.3% for ASAP. Clinicopathologic features at the time of initial biopsy and of subsequent prostate cancer diagnosis did not differ between patients with a false-negative or true benign biopsy. Relatively low number of atypical glands (<10 glands), intense intermingling with preexistent glands or lack of architectural disorganization were the most prominent risk factors for a false-negative diagnosis. Another potential pitfall was the presence of prostate cancer variants, as 1 adenocarcinoma was of foamy gland type and 3 of pseudohyperplastic type. Routine examination of at least 1 level of prostate biopsy sets at high magnification and awareness of histologic prostate cancer variants might reduce the risk of missing or misinterpreting a relevant lesion at prostate biopsy evaluation.

EXAMINATION OF THE 3 MOLECULAR FORMS OF SERUM PROSTATE SPECIFIC ANTIGEN FOR DISTINGUISHING NEGATIVE FROM POSITIVE BIOPSY: RELATIONSHIP TO TRANSITION ZONE VOLUME

We evaluated the relative usefulness of total, free and complexed serum prostate specific antigen (PSA), and their ratios for distinguishing positive from negative biopsy of prostates in a university referral practice. We compared 90 consecutive men who had 2 sets of 6 negative systematic biopsies with 70 who had at least 5 mm. of prostate cancer in systematic biopsies during the same period at our institution. Total prostate and transition zone volumes were determined by transrectal ultrasound. The Bayer, DPC and Hybritech assays were performed to measure total, free and complexed serum PSA. Receiver operating characteristics curves were constructed for all forms of serum PSA and their ratios as well as prostate size to distinguish true positive (sensitivity) from false-positive (1 minus specificity) fractions. Complexed PSA was only marginally better than total serum PSA. Free-to-total, complexed-to-total and prostate size had highly significant areas under the curves of greater than 80%. Free PSA only was better than complexed or total PSA. When factored by prostate volume, total PSA performed as well as the PSA ratios, and transition zone volume was consistently better than total prostate volume. DPC free-to-total ratios were equivalent to Hybritech ratios in all respects. Complexed PSA is only marginally better than total PSA for distinguishing negative from positive biopsy of prostates. It is inferior to free PSA and far less useful than free-to-total or complexed-to-total ratios. Prostate size is a decisive variable in men in whom we avoided the expected 25% false-negative biopsy rate in terms of specificity and hopefully avoided insignificant cancer in terms of sensitivity. In the future the performance of PSA serum markers should be related to a transition zone volume of less than 20, 20 to 60 and greater than 60 gm. when comparing assays to each other.

The significance of post-irradiation prostate biopsy with long-term follow-up

Binety-four patients, Stage A2-C, definitively irradiated for adenocarcinoma of the prostate from 1975 to 1981 underwent digitally directed transperineal needle biopsy of a clinically negative prostate gland at least 18 months post-therapy. Ten of 55 patients (18%) treated with Iodine-125 implantation and 7 of 39 patients (18%) externally irradiated were found to have positive biopsy specimens. Overall, clinical local failure occurred in 53% of patients with positive biopsy results but in only 18% with negative specimens, p = .006. The false negative biopsy rate in patients treated with I-125 was nearly three times that for external beam, 24% versus 9%, perhaps because of the greater possibility of inhomogeneous dose distribution with I-125, allowing for a higher degree of sampling error. Actuarial local failure at 5 years was 44% versus 8% with positive and negative biopsies, respectively, and 75% versus 24% at 10 years ( p = .0001). The distant metastatic rate was twice as high in biopsy-positive as compared to biopsy-negative patients, 71% versus 35%, p = .015. Actuarially, only 19% of patients with a positive biopsy are NED at 10 years as compared to 62% of those with a negative biopsy ( p = .0001). PSA values are supportive in those patients thought to be disease-free. The incidence of positive biopsy and associated local recurrence are in keeping with clinical treatment failure rates as reported in multiple studies to date.

Cyto‐histological correlates in a colposcopic clinic: A 1‐year prospective study

As part of the Quality Assurance Program, all surgical pathology reports of cervical colposcopic biopsies, cone biopsies, and hysterectomy specimens of 772 consecutive patients were correlated with cytology results for a period of 1 yr. The abnormality in cytology or histology ranged from HPV effect to invasive carcinoma. Cytohistological correlation within one grade of severity was obtained in 662 (86%) cases. On formal review of the remaining 110 (14%) cases, sampling error occurred in 75 cytology smears and in 21 colposcopic biopsies. Screening and interpretation error occurred in 10 smears and four biopsies. In this study the sensitivity of cervical cytology in detecting epithelial abnormalities was 90%, with a positive predictive value of 99.7%. The false-negative rate of cytology was 11% and the false-positive rate 0.26%. The majority (90%) of false negatives were due to sampling error; the rest were due to laboratory error. The sensitivity of colposcopic biopsy was 97% with a positive predictive value of 99.4%. The false-negative rate of biopsy was 2.7% and the false-positive rate 0.5%. Endocervical cells were seen in 48% (370) of smears and absent in 52% (402). However, in both instances the detection rate of squamous abnormality was 90%. Also 43% (33) of smears that showed endocervical cells failed to contain the abnormal cells. Endocervical curettage or cone biopsy in 16 of these 33 cases clearly showed a small CIN-III lesion high in the endocervical canal. We believe that the value of endocervical cells as an indicator of adequacy is questionable.(ABSTRACT TRUNCATED AT 250 WORDS)