Needle Biopsy Specimens Research Articles

Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update.

Purpose To update key recommendations of the American Society of Clinical Oncology/College of American Pathologists human epidermal growth factor receptor 2 (HER2) testing in breast cancer guideline. Methods Based on the signals approach, an Expert Panel reviewed published literature and research survey results on the observed frequency of less common in situ hybridization (ISH) patterns to update the recommendations. Recommendations Two recommendations addressed via correspondence in 2015 are included. First, immunohistochemistry (IHC) 2+ is defined as invasive breast cancer with weak to moderate complete membrane staining observed in > 10% of tumor cells. Second, if the initial HER2 test result in a core needle biopsy specimen of a primary breast cancer is negative, a new HER2 test may (not "must") be ordered on the excision specimen based on specific clinical criteria. The HER2 testing algorithm for breast cancer is updated to address the recommended work-up for less common clinical scenarios (approximately 5% of cases) observed when using a dual-probe ISH assay. These scenarios are described as ISH group 2 ( HER2/chromosome enumeration probe 17 [CEP17] ratio ≥ 2.0; average HER2 copy number < 4.0 signals per cell), ISH group 3 ( HER2/CEP17 ratio < 2.0; average HER2 copy number ≥ 6.0 signals per cell), and ISH group 4 ( HER2/CEP17 ratio < 2.0; average HER2 copy number ≥ 4.0 and < 6.0 signals per cell). The diagnostic approach includes more rigorous interpretation criteria for ISH and requires concomitant IHC review for dual-probe ISH groups 2 to 4 to arrive at the most accurate HER2 status designation (positive or negative) based on combined interpretation of the ISH and IHC assays. The Expert Panel recommends that laboratories using single-probe ISH assays include concomitant IHC review as part of the interpretation of all single-probe ISH assay results. Find additional information at www.asco.org/breast-cancer-guidelines .

Immunohistochemistry for histone H3G34W and H3K36M is highly specific for giant cell tumor of bone and chondroblastoma, respectively, in FNA and core needle biopsy.

Diagnosing giant cell-rich bone tumors can be challenging on limited biopsies. H3 histone family member 3A (H3F3A) (G34W/V/R/L) mutations are present in the majority of giant cell tumors (GCTs) of bone and H3 histone family member 3B (H3F3B) (K36M) mutations are present in nearly all chondroblastomas, but are absent in histologic mimics. Mutation-specific immunohistochemistry (IHC) is highly specific for GCT and chondroblastoma in surgical excisions. The objective of the current study was to validate H3G34W and H3K36M IHC in the diagnosis of giant cell-rich bone tumors on fine-needle aspiration and core needle biopsy specimens. IHC was performed using monoclonal antibodies against histone H3.3 G34W and K36M in GCTs of bone (26 cases, including 2 malignant cases), GCT of Paget disease (1 case), chondroblastoma (8 cases), aneurysmal bone cyst (7 cases), and osteosarcoma (13 cases) with available fine-needle aspiration and/or core needle biopsy specimens from 2 institutions. H3F3A and H3F3B Sanger sequencing was performed on all 4 H3G34W IHC-negative GCTs. IHC for H3G34W was positive in 22 of 26 GCTs (85%) and negative in all histologic mimics. IHC for H3K36M was positive in all 8 chondroblastomas and negative in all histologic mimics. IHC results were concordant between biopsy and surgical specimens in 152 of 158 samples (96%). Sequencing identified alternate H3F3A G34L and G34V mutations in 1 IHC-negative GCT each, but no mutation was found in the remaining 2 cases. H3G34W and H3K36M IHC is highly specific for GCT and chondroblastoma, respectively, among giant cell-rich bone tumors, and is useful for confirming the diagnosis in limited biopsies. The presence of alternate H3F3A mutations accounts for the H3G34W IHC negativity in a subset of GCT of bone cases. Cancer Cytopathol 2018. © 2018 American Cancer Society.

Assessment of HER2 status in breast cancer biopsies is not affected by accelerated tissue processing.

To establish whether core needle biopsy (CNB) specimens processed with an accelerated processing method with short fixation time can be used to determine accurately the human epidermal growth factor receptor 2 (HER2) status of breast cancer. A consecutive case-series from two high-volume breast clinics was created. We compared routine HER2 immunohistochemistry (IHC) assessment between accelerated processing CNB specimens and routinely processed postoperative excision specimens. Additional amplification-based testing was performed in cases with equivocal results. The formalin fixation time was less than 2 h and between 6 and 72 h, respectively. Fluorescence in-situ hybridisation and multiplex ligation-dependent probe amplification were used for amplification testing. One hundred and forty-four cases were included, 15 of which were HER2-positive on the routinely processed excision specimens. On the CNB specimens, 44 were equivocal on IHC and required an amplification-based test. Correlation between the CNB specimens and the corresponding excision specimens was high for final HER2 status, with an accuracy of 97% and a kappa of 0.85. HER2 status can be determined reliably on CNB specimens with accelerated processing time using standard clinical testing methods. Using this accelerated technology the minimum 6 h of formalin fixation, which current guidelines consider necessary, can be decreased safely. This allows for a complete and expedited histology-based diagnosis of breast lesions in the setting of a one-stop-shop, same-day breast clinic.

Pathology of idiopathic non-cirrhotic portal hypertension.

Idiopathic non-cirrhotic portal hypertension is an under-recognized vascular liver disease of unknown etiology, characterized by clinical signs of portal hypertension in the absence of cirrhosis. By definition, any disorder known to cause portal hypertension in the absence of cirrhosis and any cause of chronic liver disease must be excluded to make a diagnosis of idiopathic non-cirrhotic portal hypertension. However, the diagnosis is often difficult because the disease resembles cirrhosis and there is no gold standard test. Liver biopsy is an essential tool: it is able to exclude cirrhosis and other causes of portal hypertension and it allows the identification of the characteristic lesions. Nonetheless, the histological diagnosis of idiopathic non-cirrhotic portal hypertension is not always straightforward, in particular by needle biopsy samples, because there is no pathognomonic lesion, but rather a variety of vascular changes which are unevenly distributed, very subtle, and not all necessarily identified in a single specimen. Pathologists should be able to recognize several patterns of injury, involving portal/periportal areas as well as parenchymal structures.The histological features of idiopathic non-cirrhotic portal hypertension are described in this review, focusing on their interpretation in needle biopsy specimens.

Assessment of Hormone Receptor Profile in Breast Cancer Using 18F‐Fluro‐Estradiol PET CT: A Pilot Study

Hormone Receptor (HR) status has vital implications in prognosis and therapy of breast cancer. Currently, HR status is assessed by immunohistochemistry (IHC) of core needle biopsy or surgical specimen. In this technique tumor is not studied in entiretyThis technique &amp; has 3–5% false negative rate.AimEvaluate use of 18F‐FES PET‐CT in determining receptor status of breast cancer.MethodsER expression on IHC: Core needle biopsy/excision specimens were fixed in formalin and paraffin embedded sections made &amp; subjected to IHC. Proportion of positive cells was given score of 0 to 5 &amp; intensity of uptake was given a score of 0 to 3. Total score was then calculated by summing up the total. Imaging with FES PET CT performed using standard protocol and images acquired. SUV of lesion, SUV ratio between lesion and background activity &amp; visual interpretation grading were correlated to ER expression on IHC. For SUV ratio, SUV of the breast lesion was compared to the SUV of the mediastinal blood pool in the thoracic aorta. Visual grading of the breast lesion on 18F‐FES PET‐CT CT was done as follows:Grade 1‐ no uptake on 18F‐FES PET‐CT;Grade 2‐uptake of lesion less than mediastinal blood pool; Grade 3‐uptake of lesion similar to mediastinal blood pool.; Grade 4‐Lesion well defined, uptake more than mediastinal blood pool/similar to liver. Correlation between lesion SUV, SUV ratio of lesion and mediastinal blood pool &amp; visual grading score with ER score as on IHC was calculated using the Spearman's correlation coefficient. The value of SUV ratio above which the lesion was considered ER positive was calculated using the receiver operating characteristic curve (ROC curve). P value of &lt; 0.05 was considered significant. Data analysis was done using Stata 11.2.ResultsTwenty four patients were enrolled for the study. Most of the patients were females (F:M= 22:2). All patients had invasive ductal carcinoma (NST) except for a 55 yr old lady who had high grade DCIS and no invasive component was found. IHC done on core needle biopsy specimens was used to determine the receptor status of the breast lumps. 16 patients were HR +ve ( 12 strongly +ve and 4 moderately +ve) and 8 were HR −ve. ROC curve (Fig 1) was plotted for SUV and tumours with SUV of &gt;/= 1.8 on 18F‐FES PET‐CT were categorized as ER+ (AUC=0.8190, sensitivity =73.33% &amp; specificity=71.43%). Comparison of HR status as assessed by FES PETCT and IHC is given in Table I. The sensitivity, specificity, false negative rates of of FES PETCT in evaluating HR status were 87.5%, 100% and 12,5% respectively. Out of the two false negative patients, one patient was on tablet anastrazole (anti estrgoen medication). Correlation between HR status of tumor as assessed by IHC &amp; SUV of tumour, tumour to background ratio and visual grading (Table II) was assessed and it was found that correlation was strongest for visual grading (0.7737) followed by tumour to background ratio (0.6640) &amp; SUV of lesion(0.5305).Conclusions18FES PETCT shows promise in evaluating HR status of breast cancer as it is high sensitive and specific. It scores over the currently used technique of IHC as it assesses the tumor in its entirety. Among the various parameters of assessment of HR expression on FES PETCT, we recommend visual grading as it correlates the best with HR expression on IHC. Limitations of the Study: Small sample size. Larger studies are needed before FES PET CT is recommended to be included in the routine clinical armamentarium for management of breast cancer.Support or Funding InformationnoneThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

MP11-09 METABOLIC SYNDROME INCREASES THE RISK OF UPGRADING EPSTEIN 2015 GLEASON SCORE IN PATIENTS WITH PROSTATE CANCER ON BIOPSY: A RADICAL PROSTATECTOMY MULTICENTER COHORT STUDY

You have accessJournal of UrologyProstate Cancer: Localized: Surgical Therapy II1 Apr 2018MP11-09 METABOLIC SYNDROME INCREASES THE RISK OF UPGRADING EPSTEIN 2015 GLEASON SCORE IN PATIENTS WITH PROSTATE CANCER ON BIOPSY: A RADICAL PROSTATECTOMY MULTICENTER COHORT STUDY Cosimo De Nunzio, Giuseppe Simone, Costantino Leonardo, Riccardo Mastroianni, Collura Devis, Giovanni Muto, Michele Gallucci, Riccardo Lombardo, Carlo De Dominicis, and Andrea Tubaro Cosimo De NunzioCosimo De Nunzio More articles by this author , Giuseppe SimoneGiuseppe Simone More articles by this author , Costantino LeonardoCostantino Leonardo More articles by this author , Riccardo MastroianniRiccardo Mastroianni More articles by this author , Collura DevisCollura Devis More articles by this author , Giovanni MutoGiovanni Muto More articles by this author , Michele GallucciMichele Gallucci More articles by this author , Riccardo LombardoRiccardo Lombardo More articles by this author , Carlo De DominicisCarlo De Dominicis More articles by this author , and Andrea TubaroAndrea Tubaro More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.375AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Aim of our study was to investigate the association of metabolic syndrome (Mets) with the risk of upgrading and down grading in patients with PCA on biopsy using the new Epstein Gleason score classification in a series of men undergoing radical prostatectomy(RP). METHODS Between 2012 and 2016, 400 patients with clinically localized PCa were treated with retropubic radical prostatectomy (RRP) at three tertiary referral centres. Body mass index (BMI) and waist circumference were measured before RRP. Blood samples were collected for PSA, fasting glucose, triglycerides and HDLs. Blood pressure was recorded. All the patients underwent a 12 core trans-rectal ultrasound-guided prostate needle biopsy in the same referral center where the radical prostatectomy was performed. Biopsy specimens as well as radical prostatectomy specimens were graded according to 2015 Epstein Gleason grading system and then compared. Clinically significant upgrading was defined as: Epstein score raising from = 2 to =3 or from 3 to 5. As well clinically significant downgrading was defined as: Epstein score decreasing from =3 to = 2 or from 5 to = 3. The accuracy of the biopsy for patients with and without MetS was determined using the kappa coefficient of agreement: <0.4 poor agreement, 0.4-0.75 good agreement and > 0.75 excellent agreement. MetS was defined according to Adult Treatment Panel III (ATPIII). RESULTS Median age and preoperative PSA levels were 65 years (IQR: 60-70) and 7.4 ng/ml (IQR: 5.5-10.9), respectively. Median BMI was 26.0 kg/m2 (IQR: 24.3-28.0). On pathological evaluation 163/400 (40,8%) had locally advanced disease (=pT3a), 115/400 (28,7%) had high grade disease and 15/400 (3,8%) had nodal involvement. Overall 148/400 (37%) patients presented the MetS. Patients with MetS presented higher upgrading rates (33/148:22.3% vs 25/252:9.9%; p = 0.001) on RRP specimens when compared to patients without MetS while downgrading rates were similar (13/148 : 8.7% vs 18/252: 7.1 %; p=0.566). The kappa-statistics measures of agreement between needle biopsy and radical prostatectomy specimens was worst for patients with MetS when compared to patients without MetS (k= 0.439±0.071 vs k= 0.553±0.071). Patients with MetS also presented a significantly higher rates of pT3 disease (84/148:56.8% vs 79/252:31,3%, p=0.001) and Epstain Gleason score > 2 (61/148:41% vs 54/252, p=0.001), data confirmed on multivariate analysis (OR: 2.818; CI: 1.774-4.476, p=0.001 and OR: 3.577; CI: 2.230-5.737, p=0.001respectively) CONCLUSIONS In this multicenter radical prostatectomy cohort, MetS represents a significant risk factor for advanced disease and high grade disease. Nonetheless patients with MetS carry a higher risk of upgrading on RRP specimens. Further studies with a pathological review and reclassification of the specimens are needed to confirm our data. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e130-e131 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Cosimo De Nunzio More articles by this author Giuseppe Simone More articles by this author Costantino Leonardo More articles by this author Riccardo Mastroianni More articles by this author Collura Devis More articles by this author Giovanni Muto More articles by this author Michele Gallucci More articles by this author Riccardo Lombardo More articles by this author Carlo De Dominicis More articles by this author Andrea Tubaro More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Abstract P3-02-01: Impact of prognoses on the discrepancies in histological grade of breast cancer between core needle biopsy and surgical excision specimen

Abstract Purpose: The high reliability and utility of core needle biopsy (CNB) have been previously described. Histological grade in CNB is one of the main determinants of the need for neoadjuvant systemic therapy. Our aim in this study was to clarify the host and histopathological factors influencing the discrepancies in histological grade (HG) between CNB and surgically excision specimen (SES). Methods: A total of 1342 operable invasive breast carcinoma biopsies were assessed and compared with surgical specimens in our hospital. Patients who required neoadjuvat chemotherapy were excluded. Histological grade (tubule formation, nuclear pleomorphism and mitotic index) was assessed between paired CNB and SET samples. ER and PgR status were determined using immunohistochemistry(IHC). HER2 status was determined using IHC and scored from 0 to 3+. Fluorescence in-situ hybridization analysis was carried out in HER2 2+ cases. The cut off point for ER and PgR positivity was set at 1%. Results: The clinicopathological characteristics of tumors showed in Clinico-pathological characteristics of 1342 patients and tumors by discordance group between CNB and SES for histological grade LL groupHH groupHL groupLLHgroupp valupTT1a31 (94%)0(0%)2(6%)0(0%)0.001 T1b162(92%)4(2%)1(1%)10(6%) T1c421(79%)43(8%)14(3%)52(10%) T2335(68%)63(13%)10(2%)82(17%) T352(68%)8(10%)2(3%)15(19%) T425(71%)4(11%)0(0%)6(17%) pNnegtive668(78%)73(9%)13(2%)101(12%)0.08 positive358(74%)49(10%)16(3%)64(13%) lynegative600(79%)6(4(8%)14(2%)85(11%)0.18 positive426(74%)58(10%)15(3%)80(14%) vnegative799(80%)81(5%)23(2%)98(10%)0.001 positive227(67%)41(12%)6(2%)67(20%) ER/PgRmegative82(33%)83(33%)13(5%)72(29%)0.001 positive944(86%)39(4%)16(1%)93(9%) HER2negative932(80%)86(7%)22(2%)121(10%)0.001 positive94(52%)36(20%)7(4%)44(24%) CNB;core needle biopsy, SES;surgical excision specimen, HH group (high grade in CNB/high grade in SES), LL group (low grade in CNB/low grade in SES), HL group (high grade in CNB/low grade in SES) and LH group (low grade in CNB/high grade in SES) . The concordance rates of HG of luminal type, HER2 type luminal HER2 type and Triple negative type in CNB and SES were 91%, 64%, 73% and 66%, respectively (p&amp;gt;0.001). Factors of discrepancy were T size, vessel invasion and ER/HER2 status for HG. The discrepancy factors were assessed with univariate and multivariate analysis. The underestimate and overestimate rates of HG in CNB compared to SES were7.5% and 1.3% in ER(+)HER2(-) type, 32%, and 3.1% in HER2 type, 22% and 4.3% in ER(+) HER2(+) type and 29% and 5.5% in Triple negative type(TN), respectively. The concordance rates of tubule formation, nuclear pleomorphism and mitotic index in CNB and SES were 81%, 97% and 93% in luminal type, 85%, 66% and 33% in HER2 type, 77%, 87% and 83% in luminal HER2 type and 82%, 67% and 73% in TN type respectively. Conclusions: Using the largest known dataset to date of paired samples from a single institution, we evaluated the accuracy of CNB and the discrepancy factors between CNB and SES in breast cancer patients. We conclude that CNB for histological grade assessment in patients with HER2 positive or TN breast cancer before neoadjuvant treatment should be used with caution. Citation Format: Nakamura R, Yamamoto N, Miyaki T, Teranaka R, Itami M. Impact of prognoses on the discrepancies in histological grade of breast cancer between core needle biopsy and surgical excision specimen [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-02-01.

Abstract P3-05-10: Impact of neoadjuvant systemic therapy on sTIL in breast cancer

Abstract Background Multiple studies have shown a correlation between the presence of stromal tumor infiltrating lymphocytes (sTIL) and breast cancer outcomes. Higher sTIL are associated with higher rates of pCR, DFS, and OS. These findings have been primarily observed in TNBC and in HER2+ rather than in HR+, which overall has lower sTIL. Despite this growing body of prognostic evidence, there is little data comparing sTIL at diagnosis to sTIL after neoadjuvant systemic treatment. Understanding the impact of treatment on sTIL may lead to novel techniques to increase host immune response in the tumor microenvironment. The objective of this study was to correlate sTIL in paired samples before and after standard neoadjuvant systemic therapy, and then to identify the direction and magnitude of change in sTIL along with any associated features. Methods Institutional pathology database was queried for invasive breast carcinoma with “yp” in staging designation. From July 2013 to September 2016, there were 122 cases identified. When cases were excluded due to unavailable biopsy slides, there were 61 cases remaining. Needle biopsy and finalsurgical specimens were evaluated using International TIL Working Group 2014 guidelines and reported as a whole number percentage. In specimens with pCR, where there are no applicable guidelines, sTIL were determined by estimating the lymphoplasmacytic infiltrate in the tumor bed. Additional information gathered from the electronic medical record included patient age, clinical TNM stage, breast cancer subtype (HR+, HER2+, TNBC), neoadjuvant systemic therapy regimen (anthracycline, nonanthracycline, Trastuzumab-containing, endocrine), and response to treatment (pCR, residual invasive disease). A negative binomial generalized linear mixed model was used for analysis. Results Overall the sTIL declined from biopsy to surgery by about 36% (β = -0.448, S.E. = 0.223, pvalue = 0.045). However, there were 19/61 patients who had an increase in sTIL with neoadjuvant systemic therapy. For this group, the mean biopsy sTIL was 9.7% while the mean surgery sTIL was 28.7%, significantly higher than the mean biopsy (p-value &amp;lt; 0.001). This group was not associated with age, stage, breast cancer subtype, or regimen. We examined our results in the 37/61 patients who did not achieve pCR. In all breast cancer subtypes, this group had an increase from biopsy to surgery in sTIL, with no significant difference between treatment regimens. Increasing age was significantly associated with lower sTIL in both biopsy and surgery specimens (p-value = 0.033). For every decade increase in age, sTIL decreased by about 37%. Discussion Overall the sTIL declined from biopsy to surgery. In the group of patients with an increase in sTIL, there was no significant correlation with systemic treatment regimen. There was a nonsignificant trend towards increasing sTIL and residual disease at surgery. We hypothesize that the host immune response declined after tumor eradication in pCR and remained active when residual disease was present. Increasing age was significantly associated with lower sTIL. Further work to identify additional factors associated with sTIL is needed to guide efforts to alter the immune response for improved breast cancer outcomes. Citation Format: Armaghani A, Asirvatham R, Mramba L, Daily K. Impact of neoadjuvant systemic therapy on sTIL in breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-05-10.

Abstract P2-03-02: Macrodissection prior to closed system RT-qPCR is not necessary for estrogen receptor and HER2 concordance with IHC/FISH in breast cancer

Abstract Background: An on-demand, closed system RT-qPCR (the GeneXpert system, Cepheid, Sunnyvale, CA) has the potential to provide biomarker information in low resourced settings. The system consists of an inexpensive, single-use, disposable, macrofluidic cartridge and an instrument that automates RT-qPCR. Here we use it with a research use only cartridge (STRAT4) that measures the mRNA expression levels of ESR1, PGR, ERBB2, and MKi67 using a single 5uM thick FFPE tissue section from an excisional or core biopsy specimen containing invasive carcinoma of the breast. The assay, results are expressed as a delta cycle threshold (dCt) value, defined as the Ct of a control gene (CYFIP1) minus the Ct of the target gene (ESR1, PGR, ERBB2, or MKi67). We determine whether the dCt result for each marker is equivalent using the entire non-macrodissected section (non m-d) to the dCt results obtained following tumor macro-dissection (m-d) to eliminate non-tumor elements from the assay. Methods: We evaluated the impact of m-d versus non m-d using STRAT4 on a cohort of 62 formalin-fixed paraffin-embedded (FFPE) tumor core needle biopsy specimens with a range of HER2 expression determined by clinical immunohistochemistry and fluorescence in situ hybridization (IHC/FISH). Concordance (sensitivity and specificity) of the STRAT4 ESR1 and HER2 mRNA versus ER and HER2 IHC/FISH measurements were also assessed. Results: We observed excellent agreement of the resulting dCt between the paired samples, m-d versus non m-d, for ESR1 (R2=0.92), PGR (R2=0.90), ERBB2 (R2=0.94) and MKi67 (R2=0.90). No significant difference (P value &amp;gt; 0.99) was observed when we compared the dCt between the paired samples m-d versus non m-d. In addition, using the predefined STRAT4 dCt cutoff for ESR and ERBB2 positivity, we found a significant concordance between RT-qPCR and IHC/FISH for ESR-positivity for the paired samples, m-d (P value &amp;lt; 0.001; sensitivity = 0.98; specificity = 1; PPV = 1; NPV = 0.95) versus non m-d (P value &amp;lt; 0.001; sensitivity = 0.98; specificity = 1; PPV = 1; NPV = 0.95) and HER2-positivity for the paired samples, m-d (P value &amp;lt; 0.001; sensitivity = 0.85; specificity = 0.98; PPV = 0.92; NPV = 0.96) versus non m-d (P value &amp;lt; 0.001; sensitivity = 0.71; specificity = 0.98; PPV = 0.90; NPV = 0.92), respectively. Conclusion: These data suggest that mRNA for ESR and ERBB2 is sufficiently low in surrounding tissues that m-d of whole sections is not required for accurate assessment of key breast cancer mRNA markers in a closed system RT-qPCR assay. The simplicity of the assay workflow may be particularly valuable in low resourced settings where routine access to pathology expertise and to high quality IHC/FISH is challenging. Citation Format: Gupta S, Carvajal-Hausdorf DE, Wasserman BE, Ho K, Weidler J, Wong W, Rhees B, Bates M, Rimm DL. Macrodissection prior to closed system RT-qPCR is not necessary for estrogen receptor and HER2 concordance with IHC/FISH in breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-03-02.

Artificial intelligence, physiological genomics, and precision medicine.

Big data are a major driver in the development of precision medicine. Efficient analysis methods are needed to transform big data into clinically-actionable knowledge. To accomplish this, many researchers are turning toward machine learning (ML), an approach of artificial intelligence (AI) that utilizes modern algorithms to give computers the ability to learn. Much of the effort to advance ML for precision medicine has been focused on the development and implementation of algorithms and the generation of ever larger quantities of genomic sequence data and electronic health records. However, relevance and accuracy of the data are as important as quantity of data in the advancement of ML for precision medicine. For common diseases, physiological genomic readouts in disease-applicable tissues may be an effective surrogate to measure the effect of genetic and environmental factors and their interactions that underlie disease development and progression. Disease-applicable tissue may be difficult to obtain, but there are important exceptions such as kidney needle biopsy specimens. As AI continues to advance, new analytical approaches, including those that go beyond data correlation, need to be developed and ethical issues of AI need to be addressed. Physiological genomic readouts in disease-relevant tissues, combined with advanced AI, can be a powerful approach for precision medicine for common diseases.

A rare case of low-grade fibromyxoid sarcoma with ossification which was radiologically detected as apparent calcification and histopathologically proven

Low-grade fibromyxoid sarcoma (LGFMS) is a rare soft-tissue malignant neoplasm with a deceptively benign histological appearance and a potential for late recurrence and metastasis. LGFMS cases with significant ossification are extremely rare. To our knowledge, only three cases of LGFMS with bone formation which is detected as apparent calcification by radiological examinations and proven by histopathology have been reported. Here, we report the fourth such case. A 39-year-old female presented with a 10-year history of a painless tumor in her right buttock. Computed tomography images showed multiple foci of intratumoral calcification. A needle biopsy specimen of the tumor revealed a spindle cell neoplasm with hyalinizing/collagenous stroma and ossification. The tumor cells were immunohistochemically positive for MUC4 and the molecular analysis of the tumor detected FUS-CREB3L2 fusion. Pathological diagnosis of LGFMS was made. Total resection of the tumor with wide margins was performed, and histology of the resected sample showed multiple foci of intratumoral ossification.

The new Epstein gleason score classification significantly reduces upgrading in prostate cancer patients

PurposeTo evaluate the differences between the old and the new Gleason score classification systems in upgrading and downgrading rates. Materials and methodsBetween 2012 and 2015, we identified 9703 patients treated with retropubic radical prostatectomy (RP) in four tertiary centers. Biopsy specimens as well as radical prostatectomy specimens were graded according to both 2005 Gleason and 2014 ISUP five-tier Gleason grading system (five-tier GG system). Upgrading and downgrading rates on radical prostatectomy were first recorded for both classifications and then compared. The accuracy of the biopsy for each histological classification was determined by using the kappa coefficient of agreement and by assessing sensitivity, specificity, positive and negative predictive value. ResultsThe five-tier GG system presented a lower clinically significant upgrading rate (1895/9703: 19,5% vs 2332/9703:24.0%; p = .001) and a similar clinically significant downgrading rate (756/9703: 7,7% vs 779/9703: 8%; p = .267) when compared to the 2005 ISUP classification. When evaluating their accuracy, the new five-tier GG system presented a better specificity (91% vs 83%) and a better negative predictive value (78% vs 60%). The kappa-statistics measures of agreement between needle biopsy and radical prostatectomy specimens were poor and good respectively for the five-tier GG system and for the 2005 Gleason score (k = 0.360 ± 0.007 vs k = 0.426 ± 0.007). ConclusionsThe new Epstein classification significantly reduces upgrading events. The implementation of this new classification could better define prostate cancer aggressiveness with important clinical implications, particularly in prostate cancer management.

Prostate cancer reporting and staging: needle biopsy and radical prostatectomy specimens

Prostatic adenocarcinoma remains the most common cancer affecting men. A substantial majority of patients have the diagnosis made on thin needle biopsies, most often in the absence of a palpable abnormality. Treatment choices ranging from surveillance to radical prostatectomy or radiation therapy are largely driven by the pathologic findings in the biopsy specimen. The first part of this review focuses on important morphologic parameters in needle biopsy specimens that are not covered in the accompanying articles. This includes tumor quantification as well as other parameters such a extraprostatic extension, seminal vesicle invasion, perineural invasion, and lymphovascular invasion. For those men who undergo radical prostatectomy, pathologic stage and other parameters are critical in prognostication and in determining the appropriateness of adjuvant therapy. Staging parameters, including extraprostatic extension, seminal vesicle invasion, and lymph node status are discussed here. Surgical margin status is also an important parameter and definitions and reporting of this feature are detailed. Throughout the article the current reporting guidelines published by the College of American Pathologists and the International Collaboration on Cancer Reporting are highlighted.

Ultrasonographic Echogenicity and Histopathologic Correlation of Thyroid Nodules in Core Needle Biopsy Specimens.

ObjectiveTo determine the histopathologic features associated with ultrasonographic echogenicity of thyroid nodules.Materials and MethodsThis study included 95 nodules of 95 patients (76 women, 19 men; mean age 47.5 ± 12.9 years) with homogeneous echogenicity in which core needle biopsy was performed during a one year period. The nodule echogenicity was categorized into 4 grades (hyperechogenicity, isoechogenicity, mild hypoechogenicity, and marked hypoechogenicity). The biopsy specimens were evaluated by a pathologist regarding the histopathologic features of fibrosis, lymphoid infiltration, microfollicular pattern, uniform follicular pattern, and hypercellularity in nodules. We evaluated the association of each histopathologic feature among 3 categories of nodule echogenicity by multinomial regression analysis.ResultsThe nodule echogenicity was isoechoic in 28 (29.5%), mildly hypoechoic in 37 (38.9%), and markedly hypoechoic in 30 (31.6%), and there was no hyperechoic nodule. There was a trend of increasing frequency of fibrosis (> 30%) as nodule echogenicity decreased (isoechogenicity, 10.7%; mild hypoechogenicity, 32.4%; and marked hypoechogenicity, 80%; p < 0.001). The microfollicular pattern, uniform follicular pattern, and hypercellularity were frequently found in mildly hypoechoic nodules than in isoechoic nodules (p ≤ 0.018). The fibrosis (> 30%) and hypercellularity were independently associated with mild or marked hypoechogenicity as compared to isoechogenicity (fibrosis; p ≤ 0.004 and hypercellularity; p ≤ 0.036), and only fibrosis (> 30%) was independently associated with marked hypoechogenicity as compared to mild hypoechogenicity (p = 0.004).ConclusionThe fibrosis (> 30%) and high cellularity are independently associated with mild or marked hypoechogenicity of nodules. The knowledge of the relationship of echogenicity and histopathology of thyroid nodules could improve management of patients with thyroid nodules.

Tumor-infiltrating lymphocytes affect the efficacy of trastuzumab-based treatment in human epidermal growth factor receptor 2-positive breast cancer.

Immune responses play an important role in interrupting the progression of cancer cells. Tumor-infiltrating lymphocytes (TILs) are basic components of the immune system. In triple negative breast cancer, increased number of TILs is associated with excellent prognosis and response of chemotherapy. Here, we investigated whether TILs affect the efficacy of trastuzumab-based treatment in human epidermal growth factor receptor 2 (HER2)-positive breast cancer. The study included 97 patients with stage I-III HER2-positive breast cancer. All patients were preoperatively treated with an anthracycline-based combination regimen, followed by taxane with trastuzumab from 2009 to 2013. Pathological complete response (pCR) was defined as the disappearance of invasive cancer cells regardless of the presence of in situ components. TILs were evaluated using pre-therapeutic needle biopsy specimens. We assessed the percentage of the breast stroma with TILs over the total intratumoral stroma and classified the specimens in three grades: TILs1+ <30%, TILs2+ 30-50%, and TILs3+ >50%. Overall, 80.4% of the specimens were TILs1+, 15.5% were TILs2+ and 4.1% were TILs3+. The pCR rate was 44.9% (35/78) in the TILs1+ cases, 80.0% (12/15) in the TILs2+ cases and 75.0% (3/4) in the TILs3+ cases. TILs were significantly associated with pCR (P=0.0228). Multivariate analysis using TILs, hormone receptor (HR), nuclear grade (NG) and age indicated that TILs (OR 4.32, 95% CI 1.04-23.33, P=0.0436) and HR (OR 8.76, 95% CI 3.30-25.44, P<0.0001) were independent predictors for pCR. TILs are associated with the efficacy of trastuzumab-based treatment in HER2-positive breast cancer.

Clinicopathologic Features of Benign Neurogenic Tumor of Urinary Bladder.

Benign neurogenic tumor involving the urinary bladder is a very rare and heterogeneous disease group. The clinical and radiological diagnosis may be difficult because of the disease's rarity and the histological similarities of each disease especially in needle biopsy specimens. However, accurate diagnosis is very important because the clinical course of each disease, even within the same diseases, is quite variable. In this study, we investigated 7 benign neurogenic tumors to better understand the rare disease entity in the urinary bladder by analyzing histological and immunohistochemical findings and comparing clinicopathologic features. We collected the cases by searching the medical records database of Seoul National University Hospital from 2000 to 2016. We identified 3 ganglioneuromas, 2 schwannomas, 1 neurofibroma, and 1 granular cell tumor involving the urinary bladder. There were some limitations for the initial clinical and radiological diagnosis and even pathologic diagnosis using needle biopsy specimens. One infant patient was diagnosed radiologically with rhabdomyosarcoma, but the final diagnosis changed to ganglioneuromatosis. The initial needle biopsy diagnosis of 2 ganglioneuroma cases showed neurofibroma. All patients underwent a local resection, and 1 granular cell tumor patient suffered with pain because of a recurrent tumor. One neurofibromatosis patient had a lesion appear 34 months after the bladder operation, so he underwent repeated debulking operations, but he was diagnosed with malignant transformation after 8 years. An understanding of benign neurogenic tumors involving the urinary bladder and the sharing of rare experiences surrounding them are required to provide accurate diagnoses.

Pathologic Diagnosis and Genetic Analysis of a Lung Tumor Needle Biopsy Specimen Obtained Immediately After Radiofrequency Ablation.

To evaluate the possibility of pathologic diagnosis and genetic analysis of percutaneous core-needle biopsy (CNB) lung tumor specimens obtained immediately after radiofrequency ablation (RFA). Patients who underwent CNB of lung tumors immediately after RFA from May 2013 to May 2016 were analyzed. There were 19 patients (8 men and 11 women; median age, 69years; range, 52-88years) and 19 lung tumors measuring 0.5-2.6cm (median, 1.6cm). Thirteen tumors were solid, and 6 were predominantly ground-glass opacity (GGO) on computed tomography. All specimens were pathologically examined using hematoxylin and eosin (H&E) staining and additional immunostaining, as necessary. The specimens were analyzed for EGFR and KRAS genetic mutations. The safety and technical success rate of the procedure and the possibility of pathologic diagnosis and genetic mutation analysis were evaluated. Major and minor complication rates were 11% (2/19) and 53% (10/19), respectively. Tumor cells were successfully obtained in 16 cases (84%, 16/19), and technical success rate was significantly lower for GGO-dominant tumors (50%, 3/6) compared with solid lesions (100%, 13/13, p=0.02). Pathologic diagnosis was possible in 79% (15/19) of cases based on H&E staining alone (n=12) and with additional immunostaining (n=3). Although atypical cells were obtained, pathologic diagnosis could not be achieved in 1 case (5%, 1/19). Both EGFR and KRAS mutations could be analyzed in 74% (14/19) of the specimens. Pathologic diagnosis and genetic analysis could be performed even for lung tumor specimens obtained immediately after RFA.

Prognostic parameter for high risk prostate cancer patients at initial presentation.

High-risk prostate cancer can be defined by a patient's Gleason score (GS), prostate-specific antigen (PSA) level, and clinical T (cT) stage, but a novel marker is needed due to heterogeneity of the disease. In this study, we evaluated whether intraductal carcinoma of the prostate (IDC-P) confirmed by needle biopsy is an adverse prognostic parameter for progression-free survival (PFS) and cancer-specific survival (CSS) in patients with high-risk prostate cancer. We retrospectively evaluated 204 patients with high-risk prostate cancer treated by radical prostatectomy from 1991 to 2005 at Nagoya University and its affiliated hospitals. Data on each patient's PSA level, biopsy GS, cT stage, presence of Gleason pattern 5, presence of IDC-P, percentage of the core involved with cancer, and maximum percentage of the core involved with cancer were analyzed. The median follow-up period was 108 months (range, 11-257 months). Forty-eight patients (24%) showed disease progression. Thirty-four patients (17%) died of the disease during follow-up. The IDC-P component was detected in 74 (36%) needle biopsy samples. The 5-, 10-, and 15-year CSS rates of the IDC-P-negative cases were 3.2%, 9.0%, and 23.7%; the corresponding rates of the IDC-P-positive cases were 23.9%, 33.7%, and 52.7%, respectively (P = 0.0001). In the Fine and Gray's model for PFS, IDC-P, maximum percentage of the core involved with cancer, and cT stage were significantly associated (P = 0.013, P = 0.003, P = 0.007). In the Fine and Gray's model for CSS, only IDC-P was significant (P = 0.027). In a multivariate Cox regression analysis, IDC-P (P = 0.04; hazard ratio [HR], 1.95) and maximum percentage of the core involved with cancer (P = 0.021; HR, 0.43) were significant factors in predicting overall survival (OS). The presence of IDC-P in a needle biopsy was a prognostic factor for PFS, CSS, and OS in patients with high-risk prostate cancer who underwent radical prostatectomy. Multimodal pre-and/or post- surgical therapy may be needed when IDC-P is found in a needle biopsy specimen.

Using TILs to Predict Therapeutic Effect of Chemotherapy (Pertuzumab, Trastuzumab, Docetaxel) on HER2-positive Breast Cancer.

Recently, reports of the clinical implications of tumor-infiltrating lymphocytes (TILs) in breast cancer treatment have increased. We evaluated that chemotherapy with a TPD regimen (trastuzumab, pertuzumab, docetaxel) against HER2-positive breast cancer, using TILs as indicators. The subjects were 24 patients who had received TPD-chemotherapy. A semi-quantitative evaluation of lymphocytes invading the stroma in needle biopsy specimens prior to treatment as TILs was conducted, after which, sensitivity to chemotherapy and patient prognosis were evaluated. Overall response rate was significantly higher in the high-TILs group than in the low-TILs group. Significant extension of the progression-free survival (PFS) and overall survival was found in the high-TILs group compared to the low-TILs group. In addition, high TILs numbers significantly contributed to the extension of PFS. Monitoring antitumor immune response using TILs might be a useful indicator for predicting the curative effects of TPD chemotherapy for HER2-positive breast cancer.

Inverserelationship between Ki67 and survival in early luminal breast cancer: confirmation in a multivariate analysis.

Ki67 is a prognostic marker in early breast cancer, but its real usefulness remains controversial. The standard cut-off values for Ki67 have not been universally accepted and different values may be used depending on the type of biopsy (fine needle biopsy versus surgical specimen biopsy). The objective of this study was to evaluate the prognostic significance of Ki67 and to determine the most accurate prognostic cut-off. 495 tissue samples from patients with luminal tumours who underwent breast surgery between 2005 and 2011 were collected from the Department of Pathology at Hospital de la Santa Creu i Sant Pau, Barcelona. Patients with stage IV, HER2-positive tumours or triple-negative breast carcinoma were excluded from the study. Pathology data including tumour grading and ki67 percentage were obtained retrospectively from clinical records. In all cases, the percentage of ki67 was evaluated in fine needle biopsies. In the multivariate analysis, Ki67 as a continuous variable was associated with poor overall survival (OS) and cancer-specific survival (CSS) (OS p=0.0001, HR 1.037, CI 1.014-1.059; CSS p=0.0001, HR 1.063, CI 1.031-1.096) (Cox regression model). CSS was poor when associated with a KI67 cut-off point >14% (p=0.013, HR 14.85; CI 1.074-120.53) (Cox regression model). Disease-free survival (DFS) was not associated with Ki67 CONCLUSIONS: Prognosis of luminal breast carcinoma can be predicted using Ki67 as a continuous variable and a standard cut-off value of 14%. Information about the specimen type used to determine ki67 should be recorded in the pathological report.