Needle Biopsy Specimens Research Articles

A Prospective Study on Level of Concordance Between Core Needle Biopsy and Surgical Specimen for Assessing Oestrogen Receptor, Progesterone Receptor, and Her2/Neu Receptor Status in Carcinoma Breast and Its Implications on Treatment Decisions.

A prospective study on the level of concordance between core needle biopsy specimen (CNB) and surgical specimen (SS) assesses the oestrogen receptor (ER), progesterone receptor (PR) and Her2/Neu receptor status in Carcinoma breast and its implications on treatment decisions. Ninety consecutive treatment naive operable breast cancer patients treated between September 2015 and April 2017 were included in our prospective study. All patients underwent core needle biopsy prior to definitive surgery. Immunohistochemistry (IHC) studies for ER, PR, and Her2/Neu receptor assay were done in both the CNB specimen and SS. The concordances between CNB specimen and SS for ER, PR, and Her2/Neu receptor were 92%, 88%, and 78% respectively. In our study, overall discordance for ER, PR, and Her2/Neu status based on IHC tests on CNB specimen and its corresponding SS was 41% (37 out of total 90 patients), which was mostly for Her2/Neu (20 patients). Altogether, there was a change in treatment decision based on IHC test results of CNB specimen for 14 out of 37 discordant tests, translating to 15% of the overall study group. Four patients received adjuvant hormonal therapy, and 10 patients got adjuvant Traztuzumab added to their protocol. There is almost perfect to substantial concordance between CNB specimen and SS of IHC tests for ER and PR status. However, the concordance for Her2/Neu receptor is only moderate. Her2/Neu receptor assay by IHC is more sensitive in CNB specimen than in SS.

Upgrade Rate of Flat Epithelial Atypia Diagnosed at Stereotactic Core Needle Biopsy of Microcalcifications: Is Excisional Biopsy Indicated?

Whether the optimal management of pure flat epithelial atypia (FEA) found on core needle biopsy (CNB) specimens is surgical excision or imaging follow-up remains controversial. This study aimed to determine the upgrade rate to ductal carcinoma in situ (DCIS), invasive carcinoma or a high-risk lesion (atypical ductal hyperplasia, atypical lobular hyperplasia, or lobular carcinoma in situ), and it explored the relationship between a family history of breast cancer and the risk of upgrade. Cases with pure FEA found on stereotactic CNB of microcalcifications between March 2011 to December 2017 were followed by excisional biopsy or periodic imaging. The proportion of cases upgraded to a high-risk lesion and the odds of upgrade as related to a family history of breast cancer were determined with 95% confidence intervals (CIs). We identified 622 cases of pure FEA; 101 (16.2%) underwent surgical excision and 269 (43.2%) had imaging follow-up of ≥ 24 months. There were no upgrades to DCIS or invasive cancer in any of these 370 individuals (0%), and 4.6% (17/370; 95% CI: 2.9%-7.2%) were upgraded to a high-risk lesion. There was a nonstatistically significant trend between family history and upgrade to high-risk lesion (odds ratio 1.72 [95% CI: 0.65%-4.57%]). In our study, the upgrade rate of pure FEA to malignancy was 0%. We suggest that regular imaging follow-up is an appropriate alternative to surgery. Because of potential differences in biopsy techniques and pathologist interpretation of the primary biopsy, individual institutions should audit their own results prior to altering their management of FEA.

Diagnostic concordance between ultrasound-guided core needle biopsy and surgical resection specimens for histological grading of extremity and trunk soft tissue sarcoma.

Determination of accurate histological grade impacts on management for soft tissue sarcomas (STSs). Although ultrasound-guided core needle biopsy (US-CNB) accurately establishes tumour subtype compared with surgical specimens, the concordance for tumour grade is uncertain. The aim of this study was to assess the concordance between US-CNB and surgical resection specimens for tumour grade in trunk and extremity STS. Retrospective review of consecutive patients presenting with extremity/trunk STS. Data collected included patient age, gender, lesion location, US-CNB diagnosis and grade, and surgical histology and grade. The histological diagnosis and tumour grade from US-CNB was compared with surgical resection histology. A total of 118 patients were included, 76 males and 42 females with a mean age of 54years (range 10months-90years old). STS size ranged from 26 to 350mm (mean 89.5mm). All US-CNB procedures were performed with a 14G biopsy needle with a mean number of 5 passes. First US-CNB was diagnostic for STS in all patients, and provided adequate tissue for tumour grading in all but one patient. Histological tumour subtype on US-CNB matched surgical specimens in all cases, with 25 (21.2%) STS being low grade and 93 (78.8%) high grade. The concordance for tumour grade was 96.6%, with no difference between low- and high-grade STSs (p > 0.05). The 4 cases of mismatch were considered low grade on US-CNB, but subsequently high grade on surgical resection. US-CNB of STS can reliably predict histological tumour grade compared with surgical resection specimens, thus allowing confident treatment decisions to be made.

Sclerosing epithelioid fibrosarcoma: cytologic characterization with histologic, immunohistologic, molecular, and clinical correlation of 8 cases

Sclerosing epithelioid fibrosarcoma (SEF) is an uncommon malignant fibroblastic neoplasm. The diagnosis is typically made on core needle biopsy or resection specimens. Cytomorphologic characterization of SEF has been limited to rare case reports in the literature. The goal of this study was to review a series of cases of SEF and to determine the feasibility of cytologic diagnosis of this rare tumor. Eight SEF cases from 2009 to 2019 were identified in a retrospective review of 3 participating institutions. Cytomorphologic and corresponding histologic, immunophenotypic, molecular, and clinical data were examined and described. Patients were of median age 41 years old at diagnosis with a median follow-up of 35.5 months. These tumors, with a median greatest dimension of 13.4 cm, were located in the lower extremities, abdomen, retroperitoneum, head, groin, sacrum, and lung. The tumor cells ranged from small round, medium-sized ovoid/short spindle, to epithelioid/plasmacytoid cells. A sclerotic, fibrous to myxoid stroma was seen. Most samples revealed low-grade cytology. Two cases showed tumor necrosis. Only 3 cases with cell block/positive MUC4 immunostain were diagnostic. Corresponding molecular testing for EWSR1 gene rearrangement and/or EWSR1-CREB3L1 fusion were positive in 5 of 8 cases on biopsy or surgical samples. An additional case was positive for FUS-CREB3L2 fusion. Diagnosis of SEF based solely upon cytologic features remains challenging. Epithelioid or plasmacytoid morphology mimics common malignancies. A supportive clinical history, MUC4 immunohistochemistry, and characteristic molecular result should be used to aid the diagnosis.

Evaluating the Effect of Cryptorchidism on Clinical Stage of Testicular Seminoma.

ObjectiveTo study the effect of cryptorchidism on clinical stage (CS) of testicular seminoma (TS).Patients and MethodsIn the Surveillance Epidemiology and End Results (SEER) database (2006‐2016), people with TS were enrolled in our research. Multivariable logistic regression models were constructed to compare the impact of cryptorchidism on CS.ResultsThis research was based on the registry information of 12,991 TS patients. All patients with a median age of 36 (13–107) years were pathologically diagnosed with orchiectomy or needle biopsy specimens. Patients with CS I, II, and III TS accounted for 70.68% (n = 9182), 8.30% (n = 1078), and 5.75% (n = 747) of all patients, respectively; still there were 15.27% (n = 1984) of patients whose CS could not be identified or was not available. Among all included patients, 43.45% (n = 5644) of them had normal testis, 2.93% (n = 272) had cryptorchidism, and the primary site of 54.46% (n = 7075) of patients’ testis was unavailable. According to our study, patients with cryptorchidism were more likely to suffer advanced CS [OR=1.14, 95% CI (1.01–1.28), p=0.0407]. Furthermore, this effect became more remarkable after adjusting for other factors including age, region, marital status, race, year of diagnosis and laterality [OR=1.23, 95% CI (1.13–1.32), p<0.0001].ConclusionAccording to this study, TS patients with cryptorchidism would be at a higher risk of suffering advanced cancer than patients with normal testis. It demonstrates that surgical correction for cryptorchidism should be timely, and specific management should be conducted on this kind of TS patients.

Can sentinel node biopsy after neoadjuvant systemic chemotherapy (NAC) be safely omitted in selected patient with early breast cancer?

564 Background: There is a recent trend of performing minimum axillary surgery considering the prognostic value and fewer complications for primary breast cancer patients since the results of ACOSOG Z011. Nodal status after NAC is not be useful for postoperative treatment in most of cN0 patients. Therefore, sentinel node biopsy (SNB) may be omitted if ypN0 after NAC can be predicted in cN0 patients. We assessed clinicopathological factors associated with ypN0 after NAC in cN0 primary breast cancer patients. Methods: Two-institutional retrospective cohort study of clinically N0 breast cancer patients before NAC and who underwent breast surgery was conducted, including 419 consecutive patients between 2009 and 2016 in St. Luke's International Hospital and St. Marianna University School of Medicine hospital. Each institutional review board approved this study. In the patients with or without nodal metastasis on SNB after NAC, we compared clinicopathological factors including Estrogen Receptor (ER), Progesterone Receptor (PgR), human epidermal growth factor receptor 2 (HER2), Ki-67 on needle biopsy specimens, and tumor size before and after NAC on MRI findings. Results: Of the 419 patients, 380 patients (90.7%) were ypN0 and 39 patients (9.3%) were ypN+ after NAC. In univariate analysis, clinical complete response of primary tumor on MRI findings (MRI-CR) (p&lt;0.01), ER-negative (p&lt;0.01), PgR-negative (p&lt;0.01), and high-Ki-67 &gt;30% (p&lt;0.01) were significantly associated with ypN0 on SNB after NAC. In multivariate analysis, MRI-CR (HR 5.12, p&lt;0.01) and high-Ki-67 (HR 2.86, p&lt;0.01) were independent predictive factors of ypN0 after NAC.According to breast cancer subtype, only one of 72 ER-negative and HER2-positive had significantly low risk of ypN+ (1.3%) comparing other subtypes (p&lt;0.01). Conclusions: Achieving cCR of primary tumor after NAC and high-Ki67 in cN0 patients, especially in HER2 type breast cancer, might have ypN0. We are conducting prospective study to omit SNB for these populations based on these results,

CCTG HN.10: A phase II single-arm trial of elective volume adjusted de-escalation radiotherapy (EVADER) in patients with low-risk HPV-related oropharyngeal squamous cell carcinoma (NCT03822897).

TPS6592 Background: Treatment for HPV positive(+) oropharyngeal squamous cell carcinoma (OSCC) is highly effective but associated with significant short and long term treatment related morbidity. We hypothesize that decreasing the regions of elective nodal irradiation (ENI) in the neck will lead to less toxicity and better quality of life/functional outcomes while maintaining high disease control rates in patients with favourable prognosis HPV+ OSCC. Methods: HN.10 is a Canadian Cancer Trials Group phase II trial with a primary objective to evaluate the efficacy of primary definitive radiotherapy (RT) or chemoradiotherapy (CRT) utilizing volume reduced ENI as measured by 2-year event-free survival (EFS) in patients with low-risk HPV+ OPSCC. Secondary objectives include to evaluate overall survival, local control, regional control, locoregional control, out-of-field regional control, distant metastasis free survival, early and late toxicities of treatment, subjective swallowing functions, quality of life, utilization of healthcare resources, work productivity, and prognostic biomarkers. An imaging and biospecimen bank will be compiled as part of trial conduct. Key eligibility criteria include: pathologically proven diagnosis of HPV+ OPSCC; HPV association determined locally by either p16 immunohistochemistry or direct detection of HPV DNA sequences (e.g. by PCR or in situ hybridization) performed on a core needle or surgical biopsy specimen of the primary tumour or involved cervical lymph node; clinical stage T1-3 N0-1 M0 (UICC/AJCC 8th Ed.); fit for radiotherapy +/-chemoradiotherapy. Statistical Design: The primary endpoint is 2-year EFS. Assuming 2-year EFS to be 91% (Ha) for low-risk HPV-related OPSCC with standard treatment, and that the experimental treatment will be considered as ineffective if the 2-year EFS is ≤ 85% (H0), with one-sided alpha of 0.1, a sample size of 100 patients will have 80% power to detect a 6% difference of 2-year EFS. With 3 years of accrual and 2 years of follow-up, the total duration of this study will be 5 years. A total of 304.7 person-years of follow-up is needed for the final analysis. The null hypothesis (H0) will be rejected when the observed survival rate is 88.85% or higher (i.e. if there are 18 or fewer EFS events observed). Conduct to Date: Study activation February 20, 2019. Enrollment as of January 29 2020: 23. Clinical trial information: NCT03822897 .

A diagnostic review of carcinomas and sarcomas of the mediastinum: making the diagnosis on fine-needle aspiration and core needle biopsy specimens.

The mediastinum is a complex anatomic region that can pose many diagnostic challenges on fine-needle aspiration (FNA) and core needle biopsy (CNB). With the recent technological advancements in EBUS-TBNA and EUS-guided procedures, FNA/CNB is being increasingly utilized to obtain the initial and, in many cases, the only diagnosis. As a result, it is imperative to have an understanding of the pearls and pitfalls associated with both the more common and rarer malignancies that occur at this site. Although the vast majority of mediastinal malignancies encountered in routine clinical practice are metastatic carcinomas to mediastinal lymph nodes, primary tumors and tumors that directly extend into the mediastinum are also encountered. As always, a multimodal approach with clinical and radiographic correlation, a targeted IHC panel, and molecular testing when indicated are indisposable and necessary tools in the diagnostic workup of mediastinal malignancies. This review focuses on the salient diagnostic features of malignancies of epithelial and mesenchymal origin, excluding tumors of neurogenic, thymic, hematolymphoid, and germ cell origins, which are discussed in separate articles of this issue.

Collection and Handling of Thoracic Small Biopsy and Cytology Specimens for Ancillary Studies: Guideline From the College of American Pathologists in Collaboration With the American College of Chest Physicians, Association for Molecular Pathology, American Society of Cytopathology, American Thoracic Society, Pulmonary Pathology Society, Papanicolaou Society of Cytopathology, Society of Interventional Radiology, and Society of Thoracic Radiology.

The need for appropriate specimen use for ancillary testing has become more commonplace in the practice of pathology. This, coupled with improvements in technology, often provides less invasive methods of testing, but presents new challenges to appropriate specimen collection and handling of these small specimens, including thoracic small biopsy and cytology samples. To develop a clinical practice guideline including recommendations on how to obtain, handle, and process thoracic small biopsy and cytology tissue specimens for diagnostic testing and ancillary studies. The College of American Pathologists convened an expert panel to perform a systematic review of the literature and develop recommendations. Core needle biopsy, touch preparation, fine-needle aspiration, and effusion specimens with thoracic diseases including malignancy, granulomatous process/sarcoidosis, and infection (eg, tuberculosis) were deemed within scope. Ancillary studies included immunohistochemistry and immunocytochemistry, fluorescence in situ hybridization, mutational analysis, flow cytometry, cytogenetics, and microbiologic studies routinely performed in the clinical pathology laboratory. The use of rapid on-site evaluation was also covered. Sixteen guideline statements were developed to assist clinicians and pathologists in collecting and processing thoracic small biopsy and cytology tissue samples. Based on the systematic review and expert panel consensus, thoracic small specimens can be handled and processed to perform downstream testing (eg, molecular markers, immunohistochemical biomarkers), core needle and fine-needle techniques can provide appropriate cytologic and histologic specimens for ancillary studies, and rapid on-site cytologic evaluation remains helpful in appropriate triage, handling, and processing of specimens.

Factors influencing agreement of breast cancer luminal molecular subtype by Ki67 labeling index between core needle biopsy and surgical resection specimens

Reliable determination of Ki67 labeling index (Ki67-LI) on core needle biopsy (CNB) is essential for determining breast cancer molecular subtype for therapy planning. However, studies on agreement between molecular subtype and Ki67-LI between CNB and surgical resection (SR) specimens are conflicting. The present study analyzed the influence of clinicopathological and sampling-associated factors on agreement. Molecular subtype was determined visually by Ki67-LI in 484 pairs of CNB and SR specimens of invasive estrogen receptor (ER)–positive, human epidermal growth factor (HER2)–negative breast cancer. Luminal B disease was defined by Ki67-LI > 20% in SR. Correlation of molecular subtype agreement with age, menopausal status, CNB method, Breast Imaging Reporting and Data System imaging category, time between biopsies, type of surgery, and pathological tumor parameters was analyzed. Recurrence-free survival (RFS) and overall survival (OS) were analyzed using the Kaplan–Meier method. CNB had a sensitivity of 77.95% and a specificity of 80.97% for identifying luminal B tumors in CNB, compared with the final molecular subtype determination after surgery. The correlation of Ki67-LI between CNB and SR was moderate (ROC-AUC 0.8333). Specificity and sensitivity for CNB to correctly define molecular subtype of tumors according to SR were significantly associated with tumor grade, immunohistochemical progesterone receptor (PR) and p53 expression (p < 0.05). Agreement of molecular subtype did not significantly impact RFS and OS (p = 0.22 for both). The identified factors likely mirror intratumoral heterogeneity that might compromise obtaining a representative CNB. Our results challenge the robustness of a single CNB-driven measurement of Ki67-LI to identify luminal B breast cancer of low (G1) or intermediate (G2) grade.

Significance of nuclear factor - kappa beta activation on prostate needle biopsy samples in the evaluation of Gleason score 6 prostatic carcinoma indolence.

BackgroundThe goal of our study was to find out whether the immunohistochemical expression of nuclear factor-kappa beta (NF-κB) p65 in biopsy samples with Gleason score 3 + 3 = 6 (GS 6) can be a negative predictive factor for Prostate cancer (PCa) indolence.Patients and methodsStudy was conducted on a retrospective cohort of 123 PCa patients with initial total PSA ≤ 10 ng/ml, number of needle biopsy specimens ≥ 8, GS 6 on biopsy and T1/T2 estimated clinical stage who underwent laparoscopic radical prostatectomy and whose archived formalin-fixed and paraffin-embedded (FFPE) prostate needle biopsy specimens were used for additional immunohistochemistry staining for detection of NF-κB p65. Both cytoplasmic and nuclear NF-κB p65 expression in biopsy cores with PCa were correlated with postoperative pathological stage, positive surgical margins, GS and biochemical progression of disease.ResultsAfter follow-up of 66 months, biochemical progression (PSA ≥ 0.2 ng/ml) occurred in 6 (5.1%) patients, 3 (50%) with GS 6 and 3 (50%) with GS 7 after radical prostatectomy. Both cytoplasmic and nuclear NF-κB p65 expressions were not significantly associated with pathological stage, positive surgical margin and postoperative GS. Patients with positive cytoplasmic NF-kB reaction had significantly more frequent biochemical progression than those with negative cytoplasmic NF-kB reaction with PSA 0.2 ng/ml as cutoff point (p = 0.015) and a trend towards more biochemical progression with PSA ≥ 0.05 ng/ml as cutoff point (p = 0.068).ConclusionsCytoplasmic expression of NF-κB is associated with more biochemical progression and might be an independent prognostic factor for recurrence-free survival (RFS), but further studies including larger patient cohorts are needed to confirm these initial results.

PD-L1 and PD-L2 expression in the tumor microenvironment including peritumoral tissue in primary central nervous system lymphoma

BackgroundThe prevalence of programmed death-ligand 1 (PD-L1) and PD-L2 expression on tumor cells and tumor-infiltrating immune cells in primary central nervous system lymphoma (PCNSL) remains unclear. In the present study, we analyzed needle biopsy and craniotomy specimens of patients with PCNSL to compare the PD-L1 and PD-L2 levels in the tumor and surrounding (peritumoral) tissue. We also assessed the correlation between biological factors and the prognostic significance of PD-L1 and PD-L2 expression.MethodsWe retrospectively analyzed the cases of 70 patients histologically diagnosed with PCNSL (diffuse large B-cell lymphoma). Immunohistochemistry for CD20, CD68, PD-L1, and PD-L2 was performed. In cases with specimens taken by craniotomy, the percentages of PD-L1- and PD-L2-positive macrophages were evaluated in both tumor and peritumoral tissue. The Kaplan-Meier method with log-rank test and Cox proportional hazard model were used for survival analysis.ResultsThe tumor cells expressed little or no PD-L1 and PD-L2, but macrophages expressed PD-L1 and PD-L2 in most of the patients. The median percentage of PD-L2-positive cells was significantly higher among peritumoral macrophages (32.5%; 95% CI: 0–94.6) than intratumoral macrophages (27.5%; 95% CI: 0–81.1, p = 0.0014). There was a significant correlation between the percentages of PD-L2-positive intratumoral macrophages and PD-L2-positive peritumoral macrophages (p = 0.0429), with very low coefficient correlation (ρ = 0.098535). PD-L1 expression on macrophages was significantly associated with biological factors (intratumoral macrophages: better KPS, p = 0.0008; better MSKCC score, p = 0.0103; peritumoral macrophages: low proportion of LDH elevation, p = 0.0064) and longer OS (for intratumoral macrophages: high PD-L1 = 60 months, 95% CI = 30–132.6; low PD-L1 = 24 months, 95% CI = 11–48; p = 0.032; for peritumoral macrophages: high PD-L1 = 60 months, 95% CI = 30.7–NR; low PD-L1 = 14 months, 95% CI = 3–26). PD-L1 expression on peritumoral macrophages was strongly predictive of a favorable outcome (HR = 0.30, 95% CI = 0.12–0.77, p = 0.0129).ConclusionsMacrophages in intratumoral and peritumoral tissue expressed PD-L1 and PD-L2 at a higher rate than tumor cells. PD-L1 expression, especially on peritumoral macrophages, seems to be an important prognostic factor in PCNSL. Future comprehensive analysis of checkpoint molecules in the tumor microenvironment, including the peritumoral tissue, is warranted.

Ultrasonography Findings of Breast Microcalcifications without Accompanying Mass and Evaluation of Ultrasound-Guided Biopsy Results

Objective: Ultrasonography guided core needle biopsy is a real-time, inexpensive method with higher patient comfort. The aim of this study was to evaluate ultrasonography findings of microcalcifications without accompanying mass and also to investigate the accuracy of ultrasonography guided core needle biopsy results.&#x0D; Materials and Methods: The study included a total of 54 patients, with microcalcifications observed on mammography and no accompanying mass, who underwent ultrasonography guided core needle biopsy and surgical excision. Core needle biopsy specimen x-rays were obtained from 23 patients. In 11 patients, the location of microcalcification was confirmed by mammography following the administration of contrast agent under ultrasonography guidance. Ultrasonography findings of microcalcifications were identified. The results of ultrasonography guided core needle biopsy were compared with the excisional pathology results.&#x0D; Results: The microcalcifications without accompanying mass were presented with punctate echogenous foci, hypoechoic area, small distortion, ductal abnormality or fibrocystic changes on ultrasonography. Hypoechoic area and distortion were seen more in malignant lesions, and fibrocystic changes and ductal abnormalities in benign lesions but the difference was not statistically significant. The agreement between ultrasonography guided core needle biopsy and the excisional pathology results was high (Kappa = 0.781). When a specimen x-ray was obtained or core needle biopsy was performed after confirming the location of the microcalcifications with the use of contrast agent, Kappa values were even higher (0.87 and 1, respectively).&#x0D; Conclusions: Microcalcifications can be seen with targeted ultrasonography imaging and ultrasonography guided core needle biopsy has high accuracy. Taking a specimen x-ray, or biopsy performed after identifying of the location of microcalcifications with a trace amount of contrast agent, can increase the accuracy of ultrasonography guided core needle biopsy.

The "histological replacement growth pattern" represents aggressive invasive behavior in liver metastasis from pancreatic cancer.

BackgroundIn the case of liver metastasis (LM), tumors showing the replacement growth pattern (RGP), in which metastatic cells infiltrate and replace hepatocytes with minimal desmoplastic reaction and inflammatory cell infiltration, associate with a poor prognosis. The heterogeneity, frequency, and prognostic value of the RGP in LM from pancreatic cancer (PCa) are not well known.MethodsIn the circumference of treatment‐naïve resected LMs from patients with PCa, the heterogeneity of the GP was assessed. Next, the clinicopathological features of LMs showing the RGP in needle biopsy specimens were investigated in patients with treatment‐naïve advanced PCa.ResultsThirteen of the 14 (93%) in all resected LMs and 7 of the 9 (78%) in RGP component GP in resected LMs showed homogeneous GP. A RGP was found in 50% of the needle biopsy specimens of LMs obtained from 107 patients. The median overall survival times in the RGP group and non‐RGP group were 3.6 and 10.4 months. Multivariate analysis identified RGP as an independent poor prognostic factor. Median value of CD8 positive percentage in RGP was lower than that in non‐RGP (0.75 vs 1.46, P = .04). Median overall survival times in low CD8 groups tend to be shorter than those in high CD8 group (8.2 vs 4.2 months).ConclusionMost LMs from PCa show a homogeneous GP. The RGP was observed in about a half of the LMs from PCa patients, and was identified as a poor prognostic factor.

Quantification of Liver Iron Overload: Correlation of MRI and Liver Tissue Biopsy in Pediatric Thalassemia Major Patients Undergoing Bone Marrow Transplant.

Determination of the magnitude of body iron stores helps to identify individuals at risk of iron-induced organ damage in Thalassemia patients. The most direct clinical method of measuring liver iron concentration (LIC) is through chemical analysis of needle biopsy specimens. Here we present a noninvasive method for the measurement of LIC in vivo using magnetic resonance imaging (MRI). Twenty-three pediatric Thalassemia major patients undergoing bone marrow transplantation at our centre were studied. All 23 patients had MRI T2* and R2* decay time for evaluation of LIC on a 1.5Tesla MRI system followed by liver tissue biopsy for the assessment of iron concentration using an atomic absorption spectrometry. Simultaneously, serum ferritin levels were measured by enzymatic assay. We have correlated biopsy LIC with liver T2* and serum ferritin values with liver R2*. Of the 23 patients 11 were males, the mean age was 8.3 ± 3.7years. The study results showed a significant correlation between biopsy LIC and liver T2* MRI (r = 0.768; p < 0.001). Also, there was a significant correlation between serum ferritin levels and liver R2* MRI (r = 0.5647; p < 0.01). Two patients had high variance in serum ferritin levels (2100 and 4100mg/g) while their LIC was around 24mg/g, whereas the difference was not seen in T2* MRI. Hence, the liver T2* MRI is a better modality for assessing LIC. Serum ferritin is less reliable than quantitative MRI. The liver T2* MRI is a safe, reliable, feasible and cost-effective method compared to liver tissue biopsy for LIC assessment.

BRCAness as an Important Prognostic Marker in Patients with Triple-Negative Breast Cancer Treated with Neoadjuvant Chemotherapy: A Multicenter Retrospective Study.

Triple-negative breast cancer (TNBC) has several subtypes. The identification of markers associated with recurrence and poor prognosis in patients with TNBC is urgently needed. BRCAness is a set of traits in which BRCA1 dysfunction, arising from gene mutation, methylation, or deletion, results in DNA repair deficiency. In the current study, we evaluated the clinical significance and prognosis of BRCAness in a multicenter retrospective study. Ninety-four patients with TNBC treated with neoadjuvant chemotherapy were enrolled from three university hospitals for this retrospective study. BRCAness was evaluated in 94 core needle biopsy (CNB) specimens prior to neoadjuvant chemotherapy and 49 surgical specimens without pathological complete response (pCR). The samples were assessed using multiplex ligation-dependent probe amplification, and the amplicons were scored. Of the 94 patients, 51 had BRCAness in CNB specimens. There were no significant differences in pCR rates or recurrence between the BRCAness and non-BRCAness groups. Among surgical specimens, the BRCAness group had a significantly shorter recurrence-free survival and overall survival compared with the non-BRCAness group. The BRCAness of surgical specimens was found to be an important marker to predict prognosis in patients with TNBC after neoadjuvant chemotherapy. A clinical trial to assess the clinical impact of carboplatin with BRCAness is planned.

Abstract P4-06-14: Heterogeneity of multigene signatures in breast cancer among multiple specimens taken by core needle biopsy

Abstract Use of multigene predictive signatures pre-chemotherapy in core needle biopsy specimens in low-resource systems in not applied due to multiple reasons. We are seeking a method of cost-effective integration of gene expression analysis into initial breast cancer subtype assessment pre-chemotherapy.The aim of the analysis was to assess the heterogeneity of independent cores taken from primary tumor in the context of prediction of its clinical parameters by gene expression profiling.Material and methods. The study group consisted of 65 women with high-risk breast cancer, before preoperative chemotherapy, median age at the start of therapy 41,2 years (range 29-62 yr). Among the diagnosed breast cancers, 71% were grade 3 (G3), while G1 only in 3% of individuals. The most common breast cancer biological subtypes were triple negative breast cancer (38%), luminal B HER2-negative (defined as Ki67&amp;gt;20% or PR-negative, 24%) and HER2-positive tumors (23%) of tumors were of lobular histology. In core needle biopsies taken before preoperative breast cancer chemotherapy gene expression profiling was carried out by oligonucleotide microarrays (U133A/U133 Plus 2.0), three independent cores were analyzed (192 microarrays). Analysis was carried out by JMP Genomics (SAS Institute, Cary, USA) and R/Bioconductor genefu package.At first step, the overall tumor profile was analysed by Principal Component Analysis. Based on first two principal components, 44 patients (68%) showed highly concordant profile in all three cores, whereas in 21 tumors (32%) larger scatter was observed. We analysed research versions of commercially available multigene predictors, PAM50 are presented in abstract. Prediction was done independently for each core. In 40% of patients all three cores provided identical predictions for all analysed signatures (mainly triple-negative tumors). In 17% of patients we observed minor discordances (in one core 1 or 2 signatures discordant), in 10% discordances in 2 cores. Profound differences were found in 33% of patients (similar to overall profile scatter seen by PCA), mainly in luminal and HER2-positive tumors. Subtypes predicted by genomic testing were - as expected - slightly different from immunohistochemistry prediction. The most often occurring was Basal subtype (87% of TNBC patients, but occurring also in HER2-positive tumors, 20-25% and luminal B tumors, 26.7%). The second molecular subtype was LumB. These tumors constituted 60% of clinically diagnosed luminal B patients, molecular LumB subtype was also frequent among clinically luminal B HER2-positive individuals (30%). Genomic LumA subtype was found in all clinical subgroups, in 10-25% of these patients. Her2 subtype by PAM50 classification was occurring less frequently, in 50% of HER2-nonluminal and 40% luminal B HER2-positive tumors. The concordance of results improved, when classification included both immunohistochemistry results as well as the results of genomic measurements. ER and HER2 showed excellent concordance between three tumor cores and showed bimodal expression, while MKI67 and PGR although concordant showed continuous pattern of expression rather than any visible subgroups. Conclusions. Significant heterogeneity is seen in genomic profile of at least 1/3 of tested breast cancers and shall be taken into account. The error of sampling was lowest in triple negative subtype Citation Format: Michal Jarzab. Heterogeneity of multigene signatures in breast cancer among multiple specimens taken by core needle biopsy [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-06-14.

How Can We Optimize Tools and Techniques for Endoscopic Ultrasound–Guided Liver Biopsy?

How Can We Optimize Tools and Techniques for Endoscopic Ultrasound–Guided Liver Biopsy?

Pathological Association Between Radical Prostatectomy and Needle Biopsy Specimen in Prostate Cancer Patients

Background: Prostate cancer (PCa) is the second most common cancer in men worldwide. The accuracy of Gleason score (GS), as a useful system for histopathological assessment, is important because any fault in the assessment and calculation leads to inappropriate approaches and complications. Multifocality is common in PCa and it is expected that different grading of cancer would be seen in different areas. This is one of the sources of diversity in pathologic reports of transrectal ultrasound guided biopsy (TRUS BX) and radical prostatectomy, which is obtained in 41% to 43% of samples with exact accordance; so, when choosing the treatment plan is based on of the needle biopsy sample, the accuracy of TRUS BX GS is bolded. Objectives: In this study, we compared the pathology reports of initial biopsy and final pathology of the prostate after radical prostatectomy to determine the discrepancy among the Iranian population. Methods: In this retrospective study, 105 of 127 patients that underwent both TRUS Bx and radical prostatectomy in Shohada-e-Tajrish Hospital from August 2009 to October 2017 enrolled in the study. Results: In the current study, 55% of the patients were without change and 36% were upgraded. The rate of abnormal digital rectal examination and the increase of prostate-specific antigene levels have a statistically significant correlation with the upgrading of GS, respectively (P = 0.001 and 0.02). Conclusions: It is generally concluded that the initial biopsy with the final pathology of radical prostatectomy is similar in our investigation.

Immunohistochemical analysis of IDH2 R172 hotspot mutations in breast papillary neoplasms: applications in the diagnosis of tall cell carcinoma with reverse polarity.

Tall cell carcinoma with reverse polarity is a rare subtype of breast carcinoma with solid and papillary growth and nuclear features reminiscent of those of the tall cell variant of papillary thyroid carcinoma. These tumors harbor recurrent IDH2 R172 hotspot mutations or TET2 mutations, co-occurring with mutations in PI3K pathway genes. Diagnosis of tall cell carcinomas with reverse polarity is challenging in view of its rarity and the range of differential diagnosis. We sought to determine the sensitivity and specificity of IDH2 R172 immunohistochemistry for the detection of IDH2 R172 hotspot mutations in this entity. We evaluated 14 tall cell carcinomas with reverse polarity (ten excision and five core needle biopsy specimens), 13 intraductal papillomas, 16 solid papillary carcinomas and five encapsulated papillary carcinomas by Sanger sequencing of the IDH2 R172 hotspot locus and of exons 9 and 20 of PIK3CA, and by immunohistochemistry using monoclonal antibodies (11C8B1) to the IDH2 R172S mutation. The fourteen tall cell carcinomas with reverse polarity studied harbored IDH2 R172 hotspot mutations, which co-occurred with PIK3CA hotspot mutations in 50% of cases. None of the other papillary neoplasms analyzed displayed IDH2 R172 mutations, however PIK3CA hotspot mutations were detected in 54% of intraductal papillomas, 6% of solid papillary carcinomas and 20% of encapsulated papillary carcinomas tested. Immunohistochemical analysis with anti-IDH2 R172S antibodies (11C8B1) detected IDH2 R172 mutated protein in 93% (14/15) of tall cell carcinomas with reverse polarity samples including excision (n=9/10) and core needle biopsy specimens (n=5), whereas the remaining papillary neoplasms (n=34) were negative. Our findings demonstrate that immunohistochemical analysis of IDH2 R172 is highly sensitive and specific for the detection of IDH2 R172 hotspot mutations, and likely suitable as a diagnostic tool in the evaluation of excision and core needle biopsy material of tall cell carcinomas with reverse polarity.