68 results on '"Balassanian R"'
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2. Science, Medicine, and Cytology: An Educational Program of the Diversity, Equity, and Inclusion (DEI) Committee of the American Society of Cytopathology
- Author
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Gimenez, C., primary, Balassanian, R., additional, Banet, N., additional, Barkan, G., additional, DeRobbio, K., additional, Henderson-Jackson, E., additional, Jenkins, E., additional, I, Kilic, additional, Lai, L., additional, Lura, T., additional, Morgenstern, N., additional, Mito, J., additional, Reid, M., additional, Rivera-Colon, G., additional, Stewart, J., additional, and Lowe, A., additional
- Published
- 2024
- Full Text
- View/download PDF
3. Oncogenic activation of the PI3-kinase p110β isoform via the tumor-derived PIK3CβD1067V kinase domain mutation
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Pazarentzos, E, Giannikopoulos, P, Hrustanovic, G, St John, J, Olivas, V R, Gubens, M A, Balassanian, R, Weissman, J, Polkinghorn, W, and Bivona, T G
- Published
- 2016
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4. Intratumor Heterogeneity of the Estrogen Receptor and the Long-term Risk of Fatal Breast Cancer
- Author
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Benz, C.C., Datnow, B., Fornander, T., Hoadley, K.A., Esserman, L.J., Lindstr��m, L.S., Thompson, C.K., Zhang, Y., Yau, C., Lin, F., Hasteh, F., Krings, G., Bishop, J.W., Czene, K., St��l, O., Borowsky, A.D., Balassanian, R., Carpenter, P.M., Van't Veer, L.J., Chen, Y.-Y., and Nordenskj��ld, B.
- Subjects
Sweden ,Time Factors ,Antineoplastic Agents, Hormonal ,Breast Neoplasms ,Articles ,Middle Aged ,Survival Analysis ,Tamoxifen ,Receptors, Estrogen ,Chemotherapy, Adjuvant ,Risk Factors ,Humans ,Female ,Registries ,Neoplasm Grading ,Aged ,Randomized Controlled Trials as Topic ,Retrospective Studies - Abstract
Background: Breast cancer patients with estrogen receptor (ER)���positive disease have a continuous long-term risk for fatal Breast cancer, but the biological factors influencing this risk are unknown. We aimed to determine whether high intratumor heterogeneity of ER predicts an increased long-term risk (25 years) of fatal Breast cancer. Methods: The STO-3 trial enrolled 1780 postmenopausal lymph node���negative Breast cancer patients randomly assigned to receive adjuvant tamoxifen vs not. The fraction of cancer cells for each ER intensity level was scored by Breast cancer pathologists, and intratumor heterogeneity of ER was calculated using Rao���s quadratic entropy and categorized into high and low heterogeneity using a predefined cutoff at the second tertile (67%). Long-term Breast cancer-specific survival analyses by in-tra-tumor heterogeneity of ER were performed using Kaplan-Meier and multivariable Cox proportional hazard modeling adjusting for patient and tumor characteristics. Results: A statistically significant difference in long-term survival by high vs low intratumor heterogeneity of ER was seen for all ER-positive patients (P < .001) and for patients with luminal A subtype tumors (P �� .01). In multivariable analyses, patients with high intratumor heterogeneity of ER had a twofold increased long-term risk as compared with patients with low intratumor heterogeneity (ER-positive: hazard ratio [HR] �� 1.98, 95% confidence interval [CI] �� 1.31 to 3.00; luminal A subtype tumors: HR �� 2.43, 95% CI �� 1.18 to 4.99). Conclusions: Patients with high intratumor heterogeneity of ER had an increased long-term risk of fatal Breast cancer. Interestingly, a similar long-term risk increase was seen in patients with luminal A subtype tumors. Our findings suggest that intratumor heterogeneity of ER is an independent long-term prognosticator with potential to change clinical management, especially for patients with luminal A tumors.
- Published
- 2017
5. Oncogenic activation of the PI3-kinase p110β isoform via the tumor-derived PIK3CβD1067V kinase domain mutation
- Author
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Pazarentzos, E, primary, Giannikopoulos, P, additional, Hrustanovic, G, additional, St John, J, additional, Olivas, V R, additional, Gubens, M A, additional, Balassanian, R, additional, Weissman, J, additional, Polkinghorn, W, additional, and Bivona, T G, additional
- Published
- 2015
- Full Text
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6. Oncogenic activation of the PI3-kinase p110β isoform via the tumor-derived PIK3CβD1067Vkinase domain mutation
- Author
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Pazarentzos, E, Giannikopoulos, P, Hrustanovic, G, St John, J, Olivas, V R, Gubens, M A, Balassanian, R, Weissman, J, Polkinghorn, W, and Bivona, T G
- Abstract
Activation of the phosphoinositide 3-kinase (PI3K) pathway occurs widely in human cancers. Although somatic mutations in the PI3K pathway genes PIK3CAand PTENare known to drive PI3K pathway activation and cancer growth, the significance of somatic mutations in other PI3K pathway genes is less clear. Here, we establish the signaling and oncogenic properties of a recurrent somatic mutation in the PI3K p110β isoform that resides within its kinase domain (PIK3CβD1067V). We initially observed PIK3CβD1067Vby exome sequencing analysis of an EGFR-mutant non-small cell lung cancer (NSCLC) tumor biopsy from a patient with acquired erlotinib resistance. On the basis of this finding, we hypothesized that PIK3CβD1067Vmight function as a novel tumor-promoting genetic alteration, and potentially an oncogene, in certain cancers. Consistent with this hypothesis, analysis of additional tumor exome data sets revealed the presence of PIK3CβD1067Vat low frequency in other patient tumor samples (including renal cell carcinoma, glioblastoma multiforme, head and neck squamous cell carcinoma, melanoma, thyroid carcinoma and endometrial carcinoma). Functional studies revealed that PIK3CβD1067Vpromoted PI3K pathway signaling, enhanced cell growth in vitro, and was sufficient for tumor formation in vivo. Pharmacologic inhibition of PIK3Cβ with TGX-221 (isoform-selective p110β inhibitor) specifically suppressed growth in patient-derived renal-cell carcinoma cells with endogenous PIK3CβD1067Vand in NIH-3T3 and human EGFR-mutant lung adenocarcinoma cells engineered to express this mutant PI3K. In the EGFR-mutant lung adenocarcinoma cells, expression of PIK3CβD1067Valso promoted erlotinib resistance. Our data establish a novel oncogenic form of PI3K, revealing the signaling and oncogenic properties of PIK3CβD1067Vand its potential therapeutic relevance in cancer. Our findings provide new insight into the genetic mechanisms underlying PI3K pathway activation in human tumors and indicate that PIK3CβD1067Vis a rational therapeutic target in certain cancers.
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- 2016
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7. Diagnosis of recurrent breast cancer by ductoscopy.
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Valdes EK, Feldman SM, Balassanian R, Cohen J, and Boolbol SK
- Published
- 2005
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8. Change in Biomarker Profile After Neoadjuvant Chemotherapy is Prognostic and Common Among Patients with HER2+ Breast Cancer.
- Author
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Tchou J, Gottipati S, Goldbach M, Baxter M, Venters S, Balassanian R, Vohra P, Gonzalves D, Ahmad Z, Nayak A, Boughey JC, Mukhtar RA, and Chen YY
- Subjects
- Humans, Female, Middle Aged, Follow-Up Studies, Survival Rate, Prognosis, Receptors, Progesterone metabolism, Adult, Receptors, Estrogen metabolism, Aged, Neoplasm Staging, Chemotherapy, Adjuvant, Triple Negative Breast Neoplasms drug therapy, Triple Negative Breast Neoplasms pathology, Triple Negative Breast Neoplasms metabolism, Carcinoma, Ductal, Breast drug therapy, Carcinoma, Ductal, Breast metabolism, Carcinoma, Ductal, Breast pathology, Receptor, ErbB-2 metabolism, Neoadjuvant Therapy, Biomarkers, Tumor metabolism, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Breast Neoplasms drug therapy, Breast Neoplasms pathology, Breast Neoplasms metabolism, Neoplasm, Residual
- Abstract
Background: Rates of pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) for breast cancer have improved, especially among human epidermal growth factor 2-positive (HER2+) and triple-negative subtypes. The frequency and significance of biomarker profile change in residual disease are unclear. This study aimed to determine the rate of biomarker profile changes after NAC and the impact on clinical outcomes in a contemporary cohort., Methods: Upon institutional review board approval, the study identified 634 consecutive patients treated with NAC between 2010 and 2022 at two academic institutions. The study cohort was focused on patients with residual disease who underwent biomarker profile retesting. Biomarker profile change for each subtype was compared across groups using Fisher-Irwin tests. Cox Proportional Hazards Model and Kaplan-Meier plots were performed to evaluate the association of changed versus unchanged biomarker profile with event-free survival., Results: Biomarker retesting was performed for 259 (61.4 %) of 422 patients with residual disease. Biomarker profile change occurred in 18.1 % overall and was significantly higher among those with pre-NAC HER2+ disease (32.7 %, 17/52) than among those with HER2-disease (14.5 %, 30/207) (p = 0.004). Conversion of pre-NAC biomarker profiles of HR+HER2- and HR+HER2+ to triple-negative breast cancer (TNBC) post-NAC may be associated with worse event-free survival, hazard ratios of 2.23 (95 % confidence interval [CI], 0.90-5.53; p = 0.08), trending toward significance, and 36.7 (95 % CI, 2.2-610.8; p = 0.01), respectively., Conclusions: The results from one of the largest contemporary cohorts demonstrated that biomarker profile change in patients with residual disease after NAC was common. Furthermore, specific biomarker profile change in residual disease may have prognostic value. These findings strengthen the rationale for routine re-testing of biomarkers in residual disease after NAC., (© 2024. The Author(s).)
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- 2024
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9. Utility and performance of cell blocks in cerebrospinal fluid cytology: Experience at two teaching hospitals.
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Yoon H, Chen CV, Krishnan V, Grochowski J, Iezza G, Vohra P, Balassanian R, and Greenland NY
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- Humans, Retrospective Studies, Female, Male, Middle Aged, Adult, Aged, Cerebrospinal Fluid cytology, Aged, 80 and over, Young Adult, Adolescent, Cytodiagnosis methods, Hospitals, Teaching
- Abstract
Background: Cytology cell blocks (CBs) are not routinely made for cerebrospinal fluid (CSF) specimens. The goal of this study was to identify when CSF CB preparation improves diagnostic performance., Materials and Methods: Under institutional review board approval, a retrospective review of CSF cytology cases was conducted at a tertiary university-based hospital and an affiliated county hospital. Patient history, CSF volume, final diagnosis, use of stains, and whether the CB was contributory was determined from the cytopathology report. CSF nucleated cell count data was obtained from the medical record., Results: A total of 69 CSF specimens with CBs from January 2006 to March 2023 were identified from 61 patients. The median CSF volume was 8 mL (interquartile range, 4-13 mL; range, 1-800 mL), with immunohistochemical stains performed on 29 (42%) cases. Per cytology report, CB was contributory in 23 cases (33%), not contributory in 34 cases (49%), and not discussed in 12 cases (17%). The median volume was 8 mL for cases in which CB was contributory, not contributory, or not discussed. There was no difference in average nucleated cell counts between cases in which CB was contributory versus not contributory (73.9 vs. 40.0, p = .175)., Conclusions: CBs for CSF samples were contributory in a subset (33%) of cases. The authors were unable to identify any specific pre-analytic factors, including specimen volume and average nucleated cell counts, for cases in which CB was contributory. Further evaluation is needed to identify if there are scenarios in which CSF CBs should be routinely prepared., (© 2024 The Authors. Cancer Cytopathology published by Wiley Periodicals LLC on behalf of American Cancer Society.)
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- 2024
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10. Datopotamab-deruxtecan in early-stage breast cancer: the sequential multiple assignment randomized I-SPY2.2 phase 2 trial.
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Khoury K, Meisel JL, Yau C, Rugo HS, Nanda R, Davidian M, Tsiatis B, Chien AJ, Wallace AM, Arora M, Rozenblit M, Hershman DL, Zimmer A, Clark AS, Beckwith H, Elias AD, Stringer-Reasor E, Boughey JC, Nangia C, Vaklavas C, Omene C, Albain KS, Kalinsky KM, Isaacs C, Tseng J, Roussos Torres ET, Thomas B, Thomas A, Sanford A, Balassanian R, Ewing C, Yeung K, Sauder C, Sanft T, Pusztai L, Trivedi MS, Outhaythip A, Li W, Onishi N, Asare AL, Beineke P, Norwood P, Brown-Swigart L, Hirst GL, Matthews JB, Moore B, Fraser Symmans W, Price E, Beedle C, Perlmutter J, Pohlmann P, Shatsky RA, DeMichele A, Yee D, van 't Veer LJ, Hylton NM, and Esserman LJ
- Abstract
Among the goals of patient-centric care are the advancement of effective personalized treatment, while minimizing toxicity. The phase 2 I-SPY2.2 trial uses a neoadjuvant sequential therapy approach in breast cancer to further these goals, testing promising new agents while optimizing individual outcomes. Here we tested datopotamab-deruxtecan (Dato-DXd) in the I-SPY2.2 trial for patients with high-risk stage 2/3 breast cancer. I-SPY2.2 uses a sequential multiple assignment randomization trial design that includes three sequential blocks of biologically targeted neoadjuvant treatment: the experimental agent(s) (block A), a taxane-based regimen tailored to the tumor subtype (block B) and doxorubicin-cyclophosphamide (block C). Patients are randomized into arms consisting of different investigational block A treatments. Algorithms based on magnetic resonance imaging and core biopsy guide treatment redirection after each block, including the option of early surgical resection in patients predicted to have a high likelihood of pathological complete response, the primary endpoint. There are two primary efficacy analyses: after block A and across all blocks for the six prespecified breast cancer subtypes (defined by clinical hormone receptor/human epidermal growth factor receptor 2 (HER2) status and/or the response-predictive subtypes). We report results of 103 patients treated with Dato-DXd. While Dato-DXd did not meet the prespecified threshold for success (graduation) after block A in any subtype, the treatment strategy across all blocks graduated in the hormone receptor-negative HER2
- Immune- DNA repair deficiency- subtype with an estimated pathological complete response rate of 41%. No new toxicities were observed, with stomatitis and ocular events occurring at low grades. Dato-DXd was particularly active in the hormone receptor-negative/HER2- Immune- DNA repair deficiency- signature, warranting further investigation, and was safe in other subtypes in patients who followed the treatment strategy. ClinicalTrials.gov registration: NCT01042379 ., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)- Published
- 2024
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11. Fine needle aspiration biopsy in low- and middle-income countries.
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Khorsandi N, Balassanian R, and Vohra P
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- Biopsy, Fine-Needle methods, Humans, Neoplasms pathology, Neoplasms diagnosis, Developing Countries
- Abstract
Fine needle aspiration biopsy (FNAB) in low- and middle-income countries (LMIC), can provide minimally invasive, cost-effective tissue diagnosis with rapid assessment and specimen triage, which is advantageous in these resource-limited settings. Nevertheless, challenges such as equipment shortages, reagents, and lack of trained personnel exist. This article discusses the effectiveness of FNAB for diagnosis of malignant and inflammatory conditions across various organs, such as lymph nodes, breast, soft tissue, and thyroid and advocates for increased training opportunities and collaboration with academic centers to enhance diagnostic accuracy and access to pathology services., (© 2024 Wiley Periodicals LLC.)
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- 2024
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12. Cytopathology in the era of social media.
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Baskota S, Shaker N, Balassanian R, and Vohra P
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- Humans, Cytology, Social Media
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In today's medical landscape, social media (SoMe) platforms have expanded their reach beyond mere communication and entertainment, making a significant impact in the pathology field, including cytopathology. In recent years, SoMe platforms have become increasingly adopted by cytopathologists, facilitating continued education, professional networking, enhancing patient engagement, and entertainment. This adoption has influenced the professional growth of cytopathologists, and at its best, has led to the establishment of a robust professional online presence and ultimately contributed to leadership positions, fellowship opportunities, and academic promotions. Moreover, the integration of SoMe into the academic field has shown a profound impact on the visibility of academic journals and has provided a platform for lower-impact factor journals to expand their reach, ultimately increasing article citation rates and positively contributing to journal impact factor growth. SoMe platforms created a modern avenue for conference networking that has revolutionized knowledge dissemination and enhanced real-time engagement. The advantages of SoMe have extended to a global scale, positively enhancing professional expertise sharing, facilitating effective communication and teleconsultation worldwide, and reaching developing countries. Drawing insights from the recent medical literature and the practical insight from the experts' personal experience, this article provides a comprehensive review of how SoMe and cytopathology intersect to create new opportunities, facilitating informed discussions, global collaboration, and advancements in the field of cytopathology. This article also delves into the challenges surrounding SoMe platform navigation and addresses ethical and regulatory concerns, providing guidelines on what to post and what not to post on SoMe platforms., (© 2024 Wiley Periodicals LLC.)
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- 2024
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13. Demographic and clinical characteristics of patients with metastatic breast cancer and leptomeningeal disease: a single center retrospective cohort study.
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Huppert LA, Fisch S, Tsopurashvili E, Somepalle SS, Salans M, Vasudevan HN, Jo Chien A, Majure M, Rugo HS, Balassanian R, Boreta L, and Melisko ME
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- Humans, Female, Middle Aged, Retrospective Studies, Aged, Adult, Aged, 80 and over, Meningeal Carcinomatosis secondary, Meningeal Carcinomatosis therapy, Meningeal Carcinomatosis mortality, Receptor, ErbB-2 metabolism, Prognosis, Breast Neoplasms pathology, Breast Neoplasms therapy, Breast Neoplasms mortality, Meningeal Neoplasms secondary, Meningeal Neoplasms therapy, Meningeal Neoplasms mortality
- Abstract
Purpose: Leptomeningeal disease (LMD) is a devastating complication of metastatic breast cancer (MBC). It is critical to better understand the risk factors, natural history, and treatment outcomes, including patients in a modern cohort., Methods: In this single center retrospective cohort study, we identified patients with MBC and LMD who received care from 2000 to 2024 and abstracted key clinical, treatment, and survival data., Results: We identified 111 patients with MBC and LMD, including patients with the following subtypes: HR+/HER2- (n = 53, 47.7%), HER2+ (n = 30, 27.0%), and triple negative breast cancer (TNBC; n = 28, 25.2%). Median time from the diagnosis of MBC to LMD was 16.4 months (range 0-101.3 months). After the diagnosis of LMD, most patients received systemic therapy (n = 66, 59.5%) and/or central nervous system (CNS)-directed therapy (n = 94, 84.7%) including intrathecal therapy (n = 42, 37.8%) and/or CNS-directed radiation therapy (n = 70, 63.1%). In all patients, median overall survival (OS) from the diagnosis of LMD to death was 4.1 months (range 0.1-78.1 months) and varied by subtype, with HR+/HER2- or HER2+ MBC patients living longer than those with TNBC (4.2 and 6.8 months respectively vs. 2.0 months, p < 0.01, HR 2.15, 95% CI 1.36-3.39). Patients who received CNS-directed therapy lived longer than those who did not (4.2 vs. 1.3, p = 0.02 HR 0.54, 0.32-0.91). Patients diagnosed with LMD from 2015 to 2024 lived longer than those diagnosed from 2000 to 2014 (6.4 vs. 2.9 months, p = 0.04, HR 0.67, 95% CI 0.46-0.99). On multivariable analysis, having TNBC was associated with shorter OS from time of LMD to death (p = 0.004, HR 2.03, 95% CI 1.25-3.30)., Conclusion: This is one of the largest case series of patients with MBC and LMD. Patients diagnosed with LMD from 2015 to 2024 lived longer than those diagnosed from 2000 to 2014, although median OS was short overall. Patients with TNBC and LMD had particularly short OS. Novel therapeutic strategies for LMD remain an area of unmet clinical need., (© 2024. The Author(s).)
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- 2024
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14. Education and diversity in cytopathology: Past, present, and future.
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Fitzhugh VA, Reynolds JP, Flanagan M, and Balassanian R
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- Humans, History, 21st Century, History, 20th Century, Pathology, United States, Cytology, Cytodiagnosis methods
- Abstract
Diversity, equity, and inclusion is a powerful goal which many of us strive toward in medicine, both in patient care and administrative leadership. As the world evolves, the practice of medicine must evolve with it. We are cognizant of the importance of the history of our medical specialties. If we do not acknowledge all parts of our history, we are doomed to repeat it. This special issue is unique and unlike anything that has previously been published in Diagnostic Cytopathology. This issue looks at some of the history of cytopathology. This historical review is followed by some of the present state of cytopathology. There are insights into global cytopathology. The final portion of this issue examines the critical need for cytotechnology schools in the United States. All of these areas are critical to the past, present, and future of cytopathology., (© 2024 Wiley Periodicals LLC.)
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- 2024
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15. Unleash your potential: Inside interventional pathology.
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Villar-Zarra K, Balassanian R, and Vielh P
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Interventional pathology has emerged as a pivotal force in modern healthcare, heralding a paradigm shift from traditional diagnostic approaches to patient-centered care. This innovative field bridges the gap between pathology and cytopathology, empowering pathologists to streamline diagnoses and reduce waiting times for patients. Collaborative mentorship and knowledge sharing ensure a lasting legacy of diagnostic excellence for future generations. Interventional pathology stands as a symbol of innovation and patient empowerment, offering a unified approach to diagnostics and improved care in the era of personalized medicine. This narrative chronicles the evolution of interventional pathologists from behind-the-scenes diagnostic specialists to frontline innovators. This is the story of the rise of the interventional pathologist: a testament to innovation, dedication, and an unwavering commitment to patient well-being., (© 2024 John Wiley & Sons Ltd.)
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- 2024
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16. Science, Medicine, and Cytology: an educational program of the Diversity, Equity, and Inclusion Committee of the American Society of Cytopathology.
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Gimenez C, Balassanian R, Banet N, Barkan G, DeRobbio K, Henderson-Jackson E, Jenkins E, Kilic A, Lai L, Lura T, Morgenstern N, Mito J, Reid MD, Rivera-Colon G, Stewart J 3rd, and Lowe AC
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- Humans, Female, Male, Curriculum, United States, Pathology education, Minority Groups education, Cultural Diversity, Pathologists education, Adult, Cytology, Societies, Medical
- Abstract
Introduction: As our field of pathology continues to grow, our trainee numbers are on the decline. To combat this trend, the ASC Diversity, Equity, and Inclusion Committee established the Science, Medicine, and Cytology SumMer Certificate program to improve exposure to pathology/cytopathology with a focus on diversity, equity, and inclusion. Herein, we report our findings of the first 2 years of the program., Materials and Methods: An online course was developed targeting students who are underrepresented in medicine at the high school and college level. It consisted of several didactic sessions, presenting the common procedures involving cytopathologists and cytologists. Interviews with cytopathologists were also included. Participants were surveyed for demographic information and provided course evaluations., Results: In the first year of the program (2021), 34 participants completed the program, which increased to 103 in 2022. In both years there was a diversity in participant demographic backgrounds; however, only a minority of participants self-identified as being underrepresented in medicine. A vast majority (>85%) of participants in both years were high school or college students. In 2021, 100% of participants stated that the program format was effective and 94% thought the content was appropriate for their level of education; in 2022 the results were similar. In 2021, 66% considered health care as a potential career; this value increased in 2022 to 83%. In 2021 and 2022, 31% and 38%, respectively, considered cytology as a career., Conclusions: Evaluations were excellent, generating interest in cytopathology. Barriers in reaching underrepresented minorities exist and additional work is needed. Expansion to a wider audience may increase outreach., (Copyright © 2024 American Society of Cytopathology. All rights reserved.)
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- 2024
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17. Wilms Tumor: An Unexpected Diagnosis in Adult Patients.
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Chan GJ, Stohr BA, Osunkoya AO, Croom NA, Cho SJ, Balassanian R, Charu V, Bean GR, and Chan E
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- Adult, Female, Humans, Biomarkers, Tumor genetics, Biomarkers, Tumor analysis, Immunohistochemistry, Mutation, Retrospective Studies, WT1 Proteins genetics, WT1 Proteins metabolism, Cohort Studies, Kidney Neoplasms diagnosis, Kidney Neoplasms genetics, Kidney Neoplasms pathology, Wilms Tumor diagnosis, Wilms Tumor genetics, Wilms Tumor pathology
- Abstract
Context.—: Wilms tumor (WT) in adult patients is rare and has historically been a diagnostic and therapeutic conundrum, with limited data available in the literature., Objective.—: To provide detailed diagnostic features, molecular profiling, and patient outcomes in a multi-institutional cohort of adult WT patients., Design.—: We identified and retrospectively examined 4 adult WT cases., Results.—: Two patients presented with metastatic disease, and diagnoses were made on fine-needle aspiration of their renal masses. The aspirates included malignant primitive-appearing epithelioid cells forming tubular rosettes and necrosis, and cell blocks demonstrated triphasic histology. In the remaining 2 cases, patients presented with localized disease and received a diagnosis on resection, with both patients demonstrating an epithelial-predominant morphology. Tumor cells in all cases were patchy variable positive for PAX8 and WT1 immunohistochemistry. Next-generation sequencing identified alterations previously reported in pediatric WT in 3 of 4 cases, including mutations in ASXL1 (2 of 4), WT1 (1 of 4), and the TERT promoter (1 of 4), as well as 1q gains (1 of 4); 1 case showed no alterations. Three patients were treated with pediatric chemotherapy protocols; during follow-up (range, 26-60 months), 1 patient died of disease., Conclusions.—: WT is an unexpected and difficult entity to diagnose in adults and should be considered when faced with a primitive-appearing renal or metastatic tumor. Molecular testing may help exclude other possibilities but may not be sensitive or specific because of the relatively large number of driver mutations reported in WT., Competing Interests: The authors have no relevant financial interest in the products or companies described in this article., (© 2024 College of American Pathologists.)
- Published
- 2024
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18. One procedure-one report: the Re-Imagine Cytopathology Task Force position paper on small tissue biopsy triage in anatomic pathology.
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Ly A, Balassanian R, Alperstein S, Donnelly A, McGrath C, Sohani AR, Stelow EB, Thrall MJ, Zhang ML, and Pitman MB
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- Humans, Biopsy, Large-Core Needle, Pathologists, United States, Biopsy, Triage
- Abstract
Introduction: Endoscopic biopsy procedures increasingly generate multiple tissue samples from multiple sites, and frequently retrieve concurrent cytologic specimens and small core needle biopsies. There is currently lack of consensus in subspecialized practices as to whether cytopathologists or surgical pathologists should review such samples, and whether the pathology findings should be reported together or separately., Materials and Methods: In December 2021, the American Society of Cytopathology convened the Re-Imagine Cytopathology Task Force to examine various workflows that would facilitate unified pathology reporting of concurrently obtained biopsies and improve clinical care., Results and Conclusions: This position paper summarizes the key points and highlights the advantages, challenges, and resources available to support the implementation of such workflows that result in "one procedure-one report"., (Copyright © 2023 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2023
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19. Utility and performance of cell blocks in urine cytology: Experience at three teaching hospitals.
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Greenland NY, Khorsandi N, Peng Y, Balassanian R, Tabatabai ZL, Tiffany Shing TW, and Vohra P
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- Humans, Cytodiagnosis methods, Hospitals, Teaching, Urine cytology, Carcinoma, Transitional Cell diagnosis, Carcinoma, Transitional Cell pathology, Urinary Bladder Neoplasms diagnosis, Urinary Bladder Neoplasms pathology
- Abstract
Background: The use of cell block (CB) preparation is underused in urine cytology (UC) and varies among hospitals. In addition to confirming a diagnosis, CBs can be useful in cases of metastatic disease, diagnoses requiring immunohistochemical (IHC) staining, and for ancillary studies. The role of this study is to examine the performance of CBs for UC at three affiliated teaching hospitals., Materials and Methods: A retrospective review of UC cases with a CB was conducted at a county hospital, Veterans Affairs hospital, and tertiary university-based hospital. For each specimen, patient demographics, specimen type, volume, original diagnosis, and IHC stains were recorded. Each case was reviewed for diagnosis based on ThinPrep alone, diagnosis based on ThinPrep and CB, utility of CB for diagnosis, and CB cellularity., Results: A total of 250 UC specimens with CB from 186 patients was identified. Bladder washes were the most common (72.1%). IHC stains were performed on 17.2% of cases. On blinded review, CB preparation was deemed useful in 61.2% of cases, with the highest rate for suspicious for high-grade urothelial carcinoma (SHGUC) cases (87.0%). The diagnosis based on ThinPrep review changed with incorporation of CB in 13.2% of cases, with the highest rate for SHGUC cases (43.5%)., Conclusions: The results demonstrate that use of CB in UC confirms the final diagnosis in more than one-half of cases and changes the diagnosis in a subset of cases. Use of CB was most helpful in the SHGUC category. Further evaluation of the types of cases in which CB are prepared is warranted., (© 2023 American Cancer Society.)
- Published
- 2023
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20. Small volume biopsy diagnostic yield at initial diagnosis versus recurrence/transformation of follicular lymphoma: A retrospective Cyto-Heme Interinstitutional Collaborative study.
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Fitzpatrick MJ, Sundaram V, Ly A, Abramson JS, Balassanian R, Cheung MC, Cook SL, Falchi L, Frank AK, Gupta S, Hasserjian RP, Lin O, Long SR, Menke JR, Mou E, Reed DR, Ruiz-Cordero R, Volaric AK, Wang L, Wen KW, Xie Y, Zadeh SL, and Gratzinger D
- Subjects
- Humans, Retrospective Studies, Biopsy, Fine-Needle, Biopsy, Large-Core Needle, Clinical Decision-Making, Lymphoma, Follicular diagnosis, Lymphoma, Follicular pathology
- Abstract
Background: Few studies have evaluated diagnostic yield of small volume biopsies (SVB) for the diagnosis and management of follicular lymphoma (FL)., Methods: The authors performed a multi-institutional retrospective analysis of SVBs including fine-needle aspiration (FNA) and needle core biopsy (NCB) for initial FL diagnosis and suspected recurrence or transformation of FL. A total of 676 workups beginning with SVB were assessed for the mean number of biopsies per workup, the proportion of workups requiring multiple biopsies, and the proportion with a complete diagnosis including grade, on initial biopsy., Results: Compared to workups performed for question transformation/recurrence, those done for initial FL diagnosis were significantly more likely to require multiple biopsies (p < .01), had a higher mean number of biopsies per workup (1.7 vs. 1.1, absolute standardized difference = 1.1), and a lower complete diagnosis rate at initial biopsy (39% vs. 56%). At initial FL diagnosis, NCB +/- FNA was associated with fewer biopsies per workup compared to FNA +/- CB (1.2 vs. 1.9), fewer workups requiring multiple biopsies (23% vs. 83%), and a higher complete diagnosis rate (71% vs. 18%). In contrast, during assessment for transformation/recurrence, NCB and FNA showed a similar mean number of biopsies per workup (1.2 vs. 1.2) and few workups required multiple biopsies (6% vs. 19%)., Conclusions: SVB at initial FL diagnosis often required additional biopsies to establish a complete diagnosis. In contrast, when assessing for transformed/recurrent FL, additional biopsies were generally not obtained regardless of SVB type, suggesting that in these clinical settings SVB may be sufficient for clinical decision-making., (© 2022 The Authors. Cancer Cytopathology published by Wiley Periodicals LLC on behalf of American Cancer Society.)
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- 2023
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21. Interventional cytology benefits patients undergoing thyroid FNA.
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Vohra P, Khanafshar E, and Balassanian R
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- Humans, Cytodiagnosis, Retrospective Studies, Thyroid Neoplasms diagnosis, Thyroid Neoplasms surgery, Thyroid Neoplasms pathology, Thyroid Nodule diagnosis, Thyroid Nodule pathology
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- 2023
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22. Telecytology versus in-room cytopathologist for EUS-guided FNA or fine-needle biopsy sampling of solid pancreatic lesions.
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Kouanda A, Mclean R, Faggen A, Demissie E, Balassanian R, Kamal F, Avila P, Arain M, Dai SC, and Munroe C
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- Humans, Endoscopic Ultrasound-Guided Fine Needle Aspiration methods, Cohort Studies, Pancreas pathology, Pancreatic Neoplasms diagnosis, Pancreatic Neoplasms pathology, COVID-19
- Abstract
Background and Aims: Rapid on-site-evaluation (ROSE) with an in-room cytopathologist (ROSE-P) has been shown to improve the diagnostic yield of specimens obtained from patients undergoing EUS-guided FNA or fine-needle biopsy sampling (EUS-FNAB) of pancreatic lesions. Recently, there has been an increased interest and use of ROSE using telecytology (ROSE-T) to optimize clinical workflows and to address social distancing mandates created during the coronavirus disease 2019 pandemic. The purpose of this study was to compare diagnostic outcomes of ROSE-P and ROSE-T., Methods: A single-center cohort study of patients who underwent EUS-FNAB of solid pancreatic lesions with ROSE was conducted. The primary outcome was overall diagnostic yield of cancer. All patients who underwent EUS-FNAB were entered into a prospectively maintained database. Statistical analyses were performed using descriptive statistics and univariate analysis., Results: There were 165 patients in each arm. There was no difference in diagnostic yield between ROSE-P and ROSE-T (96.4% vs 94.5%, P = .428). ROSE-T was associated with an increased use of 22-gauge needles (P = .006) and more needle passes (P < .001). No significant differences were found in age, gender, lesion size, needle type, procedure times, or adverse events between the 2 groups (P < .05 for all). More pancreatic tail lesions were sampled in the ROSE-P group (P < .001)., Conclusions: ROSE-T was not associated with any difference in final histologic diagnosis for EUS-FNAB of solid pancreatic masses. This has important implications for optimizing clinical workflows., (Copyright © 2023 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)
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- 2023
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23. Diagnostic Discrepancies in Small-volume Biopsy for the Initial Diagnosis, Recurrence, and Transformation of Follicular Lymphoma: A Multi-Institutional Collaborative Study.
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Volaric AK, Lin O, Balassanian R, Cook S, Falchi L, Fitzpatrick MJ, Frank AK, Gupta S, Hasserjian RP, Long S, Ly A, Menke JR, Mou E, Natkunam Y, Reed DR, Ruiz-Cordero R, Wang L, Wen KW, Xie Y, Zadeh SL, and Gratzinger D
- Subjects
- Humans, Biopsy, Fine-Needle methods, Biopsy, Large-Core Needle, Flow Cytometry, Retrospective Studies, Lymphoma, Follicular diagnosis
- Abstract
Small-volume biopsies (SVBs) including fine-needle aspiration (FNA), cell block, and needle core biopsies (NCB) are increasingly utilized to diagnose and guide the clinical management of lymphoma. We established a multi-institutional interdisciplinary collaboration of cytopathologists, hematopathologists, and oncologists focused on the role of SVB in the management of patients with follicular lymphoma (FL). To assess the performance characteristics of SVB in this setting, we evaluated all consecutive SVBs performed for clinical indications of initial diagnosis, recurrence, or transformation of FL over a 5-year period and focused on the 182 that had at least one subsequent biopsy within 3 months as part of the same clinical work-up. The most common outcome of a subsequent biopsy as part of the same clinical work-up was a more specific diagnosis usually assigning the pathologic grade (111/182, 61%), followed by a complete agreement with the SVB (24/182, 13%), and change from nondiagnostic on initial biopsy to diagnostic on subsequent biopsy (21/182, 12%). A minority resulted in a diagnostic change from benign to lymphoma (17/182, 9%), a change in FL grade (5/182, 3%), or change in the lymphoma diagnostic category (4/182, 2%). There were no cases where an initial diagnosis of lymphoma was overturned. The distribution of discrepancies was similar across initial SVB types (FNA, FNA + cell block, NCB with or without FNA). Tissue limitations were noted in a minority of cases (53/182, 29%) and were enriched among initially nondiagnostic biopsies (16/21, 76%). Flow cytometry immunophenotyping was performed in the majority of cases both at the first and last biopsy (147/182, 81%). SVB can be a powerful method to detect FL in various clinical indications, with discrepant cases mostly resulting from a refinement in the initial diagnosis., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2023
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24. Association of Residual Ductal Carcinoma In Situ With Breast Cancer Recurrence in the Neoadjuvant I-SPY2 Trial.
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Osdoit M, Yau C, Symmans WF, Boughey JC, Ewing CA, Balassanian R, Chen YY, Krings G, Wallace AM, Zare S, Fadare O, Lancaster R, Wei S, Godellas CV, Tang P, Tuttle TM, Klein M, Sahoo S, Hieken TJ, Carter JM, Chen B, Ahrendt G, Tchou J, Feldman M, Tousimis E, Zeck J, Jaskowiak N, Sattar H, Naik AM, Lee MC, Rosa M, Khazai L, Rendi MH, Lang JE, Lu J, Tawfik O, Asare SM, Esserman LJ, and Mukhtar RA
- Subjects
- Adult, Female, Humans, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Neoadjuvant Therapy, Neoplasm Recurrence, Local epidemiology, Neoplasm Recurrence, Local drug therapy, Neoplasm, Residual drug therapy, Receptor, ErbB-2, Retrospective Studies, Young Adult, Middle Aged, Aged, Breast Neoplasms drug therapy, Breast Neoplasms surgery, Carcinoma, Ductal, Breast drug therapy, Carcinoma, Ductal, Breast surgery, Carcinoma, Intraductal, Noninfiltrating surgery, Carcinoma, Intraductal, Noninfiltrating drug therapy
- Abstract
Importance: Pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) in breast cancer strongly correlates with overall survival and has become the standard end point in neoadjuvant trials. However, there is controversy regarding whether the definition of pCR should exclude or permit the presence of residual ductal carcinoma in situ (DCIS)., Objective: To examine the association of residual DCIS in surgical specimens after neoadjuvant chemotherapy for breast cancer with survival end points to inform standards for the assessment of pathologic complete response., Design, Setting, and Participants: The study team analyzed the association of residual DCIS after NAC with 3-year event-free survival (EFS), distant recurrence-free survival (DRFS), and local-regional recurrence (LRR) in the I-SPY2 trial, an adaptive neoadjuvant platform trial for patients with breast cancer at high risk of recurrence. This is a retrospective analysis of clinical specimens and data from the ongoing I-SPY2 adaptive platform trial of novel therapeutics on a background of standard of care for early breast cancer. I-SPY2 participants are adult women diagnosed with stage II/III breast cancer at high risk of recurrence., Interventions: Participants were randomized to receive taxane and anthracycline-based neoadjuvant therapy with or without 1 of 10 investigational agents, followed by definitive surgery., Main Outcomes and Measures: The presence of DCIS and EFS, DRFS, and LRR., Results: The study team identified 933 I-SPY2 participants (aged 24 to 77 years) with complete pathology and follow-up data. Median follow-up time was 3.9 years; 337 participants (36%) had no residual invasive disease (residual cancer burden 0, or pCR). Of the 337 participants with pCR, 70 (21%) had residual DCIS, which varied significantly by tumor-receptor subtype; residual DCIS was present in 8.5% of triple negative tumors, 15.6% of hormone-receptor positive tumors, and 36.6% of ERBB2-positive tumors. Among those participants with pCR, there was no significant difference in EFS, DRFS, or LRR based on presence or absence of residual DCIS., Conclusions and Relevance: The analysis supports the definition of pCR as the absence of invasive disease after NAC regardless of the presence or absence of DCIS., Trial Registration: ClinicalTrials.gov Identifier NCT01042379.
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- 2022
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25. Limitations and opportunities for tumor infiltrating lymphocytes in breast FNA.
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Balassanian R and Vohra P
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- Biopsy, Needle, Female, Humans, Breast Neoplasms diagnosis, Lymphocytes, Tumor-Infiltrating
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- 2022
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26. Standardizing Pathologic Evaluation of Breast Carcinoma After Neoadjuvant Chemotherapy.
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Sahoo S, Krings G, Chen YY, Carter JM, Chen B, Guo H, Hibshoosh H, Reisenbichler E, Fan F, Wei S, Khazai L, Balassanian R, Klein ME, Shad S, Venters SJ, Borowsky AD, Symmans WF, and Ocal IT
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- Humans, Female, Neoplasm, Residual pathology, Breast pathology, Lymph Nodes pathology, Chemotherapy, Adjuvant, Neoplasm Staging, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Neoadjuvant Therapy methods, Breast Neoplasms drug therapy, Breast Neoplasms pathology
- Abstract
Context.—: Neoadjuvant systemic therapy refers to the use of systemic agent(s) for malignancy prior to surgical treatment and has recently emerged as an option for most breast cancer patients eligible for adjuvant systemic therapy. Consequently, treated breast carcinomas have become routine specimens in pathology practices. A standard protocol has not yet been universally adopted for the evaluation and reporting of these specimens. The American Joint Committee on Cancer staging system recognizes the challenges in staging breast carcinomas after neoadjuvant treatment and provides important data points but does not currently provide detailed guidance in estimating the residual tumor burden in the breast and lymph nodes. The Residual Cancer Burden system is the only Web-based system that quantifies treatment response as a continuous variable using residual tumor burden in the breast and the lymph nodes., Objective.—: To provide clarifications and guidance for evaluation and reporting of postneoadjuvant breast specimens, discuss issues with the current staging and reporting systems, and provide specific suggestions for future modifications to the American Joint Committee on Cancer system and the Residual Cancer Burden calculator., Data Sources.—: English-language literature on the subject and the data from the I-SPY 2, a multicenter, adaptive randomization phase 2 neoadjuvant platform trial for early-stage, high-risk breast cancer patients., Conclusions.—: This article highlights challenges in the pathologic evaluation and reporting of treated breast carcinomas and provides recommendations and clarifications for pathologists and clinicians. It also provides specific recommendations for staging and discusses future directions.
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- 2022
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27. Global Cytopathology-Hematopathology Practice Trends.
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Zadeh SL, Balassanian R, Cheung MC, Falchi L, Hasserjian R, Lin O, Long SR, Ly A, Menke JR, Mou E, Natkunam Y, Ruiz-Cordero R, Volaric AK, Wang L, Wen KW, and Gratzinger D
- Subjects
- Biopsy, Fine-Needle methods, Biopsy, Large-Core Needle, Cross-Sectional Studies, Humans, Immunophenotyping, Pathologists
- Abstract
Objectives: Small-volume biopsy-fine-needle aspiration biopsy (FNAB) with or without core biopsy-is in increasing use in diagnosis and management of lymphoma patients. Our objective was to survey the current practice in small-volume biopsy diagnosis of lymphoma, focusing on the interaction among hematopathologists and cytopathologists and the integration of FNAB, core biopsy, and flow cytometry studies at sign-out., Methods: This study used a cross-sectional survey design employing the RedCap database distributed via nine pathology professional society email listservs. The survey consisted of 25 multiple-choice questions and several free text fields. In total, 128 pathologists participated., Results: Most respondents indicated that FNAB specimens in which lymphoma is a diagnostic consideration (FNAB-L) are seen daily or weekly (68/116; 58.6%). However, most institutions have separate hematopathology and cytopathology services (72/116; 62.1%) with inconsistent communication. When communication occurred, respondents were frequently inclined to reconsider their original diagnoses. Barriers identified included lack of communication, inadequate access to diagnostic studies, no formal subspecialty training, and various opinions regarding FNAB in diagnosing lymphoma., Conclusions: This survey showed that FNAB-L specimens are common, with a lack of uniformity in how complementary fine-needle aspiration and core biopsy specimens or flow immunophenotyping results are shared across hematopathology and cytopathology services., (© American Society for Clinical Pathology, 2021. All rights reserved.For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2022
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28. Utility and Outcomes of Preoperative Screening Breast MRI for Planned Bilateral Prophylactic Mastectomy in High-Risk Patients.
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Taliaferro AS, Price ER, Hayward JH, Wong JM, Balassanian R, Fay JS, Freimanis RI, Joe BN, and Lee AY
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- Breast diagnostic imaging, Breast surgery, Databases, Factual, Female, Humans, Mass Screening, Middle Aged, Retrospective Studies, Risk, Treatment Outcome, Breast Neoplasms diagnostic imaging, Breast Neoplasms surgery, Magnetic Resonance Imaging methods, Preoperative Care methods, Prophylactic Mastectomy methods
- Abstract
BACKGROUND. There is a paucity of data and consensus guidelines on the utility of preoperative MRI for planned bilateral prophylactic mastectomy. OBJECTIVE. The purpose of this study was to evaluate the utility of breast MRI performed in high-risk patients for the indication of planned bilateral prophylactic mastectomy, with attention given to the diagnostic performance for breast cancer detection. A secondary aim was to assess the potential impact of breast MRI findings on the decision to perform sentinel lymph node biopsy at the time of prophylactic mastectomy. METHODS. A retrospective database review identified MRI examinations performed at an academic medical center from August 2003 to January 2020 for the indication of planned bilateral prophylactic mastectomy. Patient demographics, imaging findings, operative details, and pathology were recorded. BI-RADS category 1 and 2 assessments were considered negative examinations, and BI-RADS category 3, 4, and 5 assessments were considered positive examinations. Descriptive statistics and performance metrics were calculated. RESULTS. The final cohort included 53 patients (mean age, 45 years). Most (35/53; 66.0%) studies were baseline examinations. Of the 53 patients, 31 (58.5%) had negative MRI examinations and 22 (41.5%) had positive MRI examinations. MRI detected two malignancies (one invasive lobular carcinoma and one high-grade ductal carcinoma in situ), both of which were assessed as BI-RADS category 4. The patient with invasive lobular cancer underwent sentinel lymph node biopsy at the time of mastectomy, which showed metastasis. Breast MRI had sensitivity of 100.0% and specificity of 60.8% for overall breast cancer detection and sensitivity of 100.0% and specificity of 59.6% for invasive cancer detection. CONCLUSION. Preoperative MRI for planned bilateral prophylactic mastectomy detected all cancers, indicating a potential role for MRI in impacting surgical decision making. CLINICAL IMPACT. Given the high NPV for cancer, our results suggest that lymph node biopsy may be safely avoided in patients with a negative MRI examination. This is clinically relevant because sentinel nodes cannot be identified after mastectomy.
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- 2022
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29. Corrigendum to: Global Cytopathology-Hematopathology Practice Trends.
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Zadeh SL, Balassanian R, Cheung MC, Falchi L, Hasserjian R, Lin O, Long SR, Ly A, Menke JR, Mou E, Natkunam Y, Ruiz-Cordero R, Volaric AK, Wang L, Wen KW, and Gratzinger D
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- 2022
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30. Impact of initial biopsy type on the time to final diagnostic biopsy in patients with follicular lymphoma and suspected histologic transformation.
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Mou E, Falchi L, Sundaram V, Abramson JS, Balassanian R, Beygi S, Fitzpatrick MJ, Frank AK, Gupta S, Lin O, Reed JR, Long SR, Ly A, Menke JR, Reed DR, Ruiz-Cordero R, Volaric AK, Xie Y, Wang L, Wen KW, Zadeh SL, Natkunam Y, Cheung MC, and Gratzinger D
- Subjects
- Biopsy, Fine-Needle methods, Biopsy, Large-Core Needle methods, Humans, Positron Emission Tomography Computed Tomography, Retrospective Studies, Lymphoma, Follicular diagnosis
- Abstract
Diagnosis of histologic transformation (HT) of follicular lymphoma (FL) requires tissue biopsy. While surgical biopsy represents the gold standard, less invasive procedures such as fine-needle aspiration biopsy (FNAB) and core needle biopsy (CNB) are frequently performed. In this retrospective multi-institutional study including 269 patients with FL and suspected HT, the median time from initial clinical suspicion to final diagnostic biopsy was similar whether the workup began with FNAB, CNB, or surgical biopsy (4, 9, and 6 days, respectively; p =.27), despite more subsequent biopsies performed following initial FNAB. Periprocedural complications were uniformly minimal. Biopsy-proven HT was more common in the initial surgery group and in workups including positron emission tomography/computed tomography (PET/CT). Our findings, derived from US academic centers with specialized procedural and pathology expertise, suggest that FNAB, CNB, and surgical biopsy are all viable initial diagnostic procedures that can inform clinical decision-making in select FL patients with suspected HT.
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- 2021
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31. Assessment of Residual Cancer Burden and Event-Free Survival in Neoadjuvant Treatment for High-risk Breast Cancer: An Analysis of Data From the I-SPY2 Randomized Clinical Trial.
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Symmans WF, Yau C, Chen YY, Balassanian R, Klein ME, Pusztai L, Nanda R, Parker BA, Datnow B, Krings G, Wei S, Feldman MD, Duan X, Chen B, Sattar H, Khazai L, Zeck JC, Sams S, Mhawech-Fauceglia P, Rendi M, Sahoo S, Ocal IT, Fan F, LeBeau LG, Vinh T, Troxell ML, Chien AJ, Wallace AM, Forero-Torres A, Ellis E, Albain KS, Murthy RK, Boughey JC, Liu MC, Haley BB, Elias AD, Clark AS, Kemmer K, Isaacs C, Lang JE, Han HS, Edmiston K, Viscusi RK, Northfelt DW, Khan QJ, Leyland-Jones B, Venters SJ, Shad S, Matthews JB, Asare SM, Buxton M, Asare AL, Rugo HS, Schwab RB, Helsten T, Hylton NM, van 't Veer L, Perlmutter J, DeMichele AM, Yee D, Berry DA, and Esserman LJ
- Subjects
- Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Female, Humans, Middle Aged, Neoplasm, Residual, Prognosis, Progression-Free Survival, Receptor, ErbB-2 analysis, Breast Neoplasms pathology, Neoadjuvant Therapy methods
- Abstract
Importance: Residual cancer burden (RCB) distributions may improve the interpretation of efficacy in neoadjuvant breast cancer trials., Objective: To compare RCB distributions between randomized control and investigational treatments within subtypes of breast cancer and explore the relationship with survival., Design, Setting, and Participants: The I-SPY2 is a multicenter, platform adaptive, randomized clinical trial in the US that compares, by subtype, investigational agents in combination with chemotherapy vs chemotherapy alone in adult women with stage 2/3 breast cancer at high risk of early recurrence. Investigational treatments graduated in a prespecified subtype if there was 85% or greater predicted probability of higher rate of pathologic complete response (pCR) in a confirmatory, 300-patient, 1:1 randomized, neoadjuvant trial in that subtype. Evaluation of a secondary end point was reported from the 10 investigational agents tested in the I-SPY2 trial from March 200 through 2016, and analyzed as of September 9, 2020. The analysis plan included modeling of RCB within subtypes defined by hormone receptor (HR) and ERBB2 status and compared control treatments with investigational treatments that graduated and those that did not graduate., Interventions: Neoadjuvant paclitaxel plus/minus 1 of several investigational agents for 12 weeks, then 12 weeks of cyclophosphamide/doxorubicin chemotherapy followed by surgery., Main Outcomes and Measures: Residual cancer burden (pathological measure of residual disease) and event-free survival (EFS)., Results: A total of 938 women (mean [SD] age, 49 [11] years; 66 [7%] Asian, 103 [11%] Black, and 750 [80%] White individuals) from the first 10 investigational agents were included, with a median follow-up of 52 months (IQR, 29 months). Event-free survival worsened significantly per unit of RCB in every subtype of breast cancer (HR-positive/ERBB2-negative: hazard ratio [HZR], 1.75; 95% CI, 1.45-2.16; HR-positive/ERBB2-positive: HZR, 1.55; 95% CI, 1.18-2.05; HR-negative/ERBB2-positive: HZR, 2.39; 95% CI, 1.64-3.49; HR-negative/ERBB2-negative: HZR, 1.99; 95% CI, 1.71-2.31). Prognostic information from RCB was similar from treatments that graduated (HZR, 2.00; 95% CI, 1.57-2.55; 254 [27%]), did not graduate (HZR, 1.87; 95% CI, 1.61-2.17; 486 [52%]), or were control (HZR, 1.79; 95% CI, 1.42-2.26; 198 [21%]). Investigational treatments significantly lowered RCB in HR-negative/ERBB2-negative (graduated and nongraduated treatments) and ERBB2-positive subtypes (graduated treatments), with improved EFS (HZR, 0.61; 95% CI, 0.41-0.93) in the exploratory analysis., Conclusions and Relevance: In this randomized clinical trial, the prognostic significance of RCB was consistent regardless of subtype and treatment. Effective neoadjuvant treatments shifted the distribution of RCB in addition to increasing pCR rate and appeared to improve EFS. Using a standardized quantitative method to measure response advances the interpretation of efficacy., Trial Registration: ClinicalTrials.gov Identifier: NCT01042379.
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- 2021
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32. Evaluation of diagnostic ultrasound use in a breast cancer detection strategy in Northern Peru.
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Aklilu S, Bain C, Bansil P, de Sanjose S, Dunstan JA, Castillo V, Tsu V, Contreras I, Balassanian R, Hayes Constant TK, and Scheel JR
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- Adult, Female, Humans, Observer Variation, Peru, Point-of-Care Testing, Reproducibility of Results, Retrospective Studies, Breast Neoplasms diagnosis, Ultrasonography, Mammary
- Abstract
To evaluate the diagnostic impact of point-of-care breast ultrasound by trained primary care physicians (PCPs) as part of a breast cancer detection program using clinical breast exam in an underserved region of Peru. Medical records and breast ultrasound images of symptomatic women presenting to the Breast Cancer Detection Model (BCDM) in Trujillo, Peru were collected from 2017-2018. Performance was measured against final outcomes derived from regional cancer center medical records, fine needle aspiration results, patient follow-up (sensitivity, specificity, positive, and negative predictive values), and by percent agreement with the retrospective, blinded interpretation of images by a fellowship-trained breast radiologist, and a Peruvian breast surgeon. The diagnostic impact of ultrasound, compared to clinical breast exam (CBE), was calculated for actual practice and for potential impact of two alternative reporting systems. Of the 171 women presenting for breast ultrasound, 23 had breast cancer (13.5%). Breast ultrasound used as a triage test (current practice) detected all cancer cases (including four cancers missed on confirmatory CBE). PCPs showed strong agreement with radiologist and surgeon readings regarding the final management of masses (85.4% and 80.4%, respectively). While the triage system yielded a similar number of biopsies as CBE alone, using the condensed and full BI-RADS systems would have reduced biopsies by 60% while identifying 87% of cancers immediately and deferring 13% to six-month follow-up. Point-of-care ultrasound performed by trained PCPs improves diagnostic accuracy for managing symptomatic women over CBE alone and enhances access. Greater use of BI-RADS to guide management would reduce the diagnostic burden substantially., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2021
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33. Early onset, multiple, bilateral fibroadenomas of the breast: a case report.
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Im CJ, Miller A, Balassanian R, and Mukhtar RA
- Subjects
- Adolescent, Breast, Female, Genetic Testing, Humans, Breast Diseases, Breast Neoplasms diagnostic imaging, Breast Neoplasms genetics, Fibroadenoma diagnostic imaging, Fibroadenoma genetics
- Abstract
Background: While fibroadenomas are common in the general population, affecting 10-20% of women, they are rarely early-onset, multiple, and bilateral., Case Presentation: An 18-year-old woman presented with a 6 year history of multiple, bilateral breast masses without family history of breast disease. Magnetic resonance imaging (MRI, Fig. 1) of the breasts showed innumerable, bilateral breast masses ranging in size from 0.5 to 4 cm. Two needle biopsies showed fibroadenoma. Although the patient's family history did not meet National Comprehensive Cancer Network (NCCN) guidelines for genetic testing, it was performed due to the rarity of her presentation. Genetic testing identified a pathogenic mutation in the phosphatase and tensin homolog (PTEN) gene., Conclusions: A germline mutation in PTEN is associated with an increased risk of breast cancer and often occurs as part of Cowden Syndrome. This case highlights the importance of genetic testing in patients with unusual presentations of early-onset, bilateral, and multiple (greater than four) fibroadenomas.
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- 2021
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34. Cutaneous T-Cell Lymphoma PDX Drug Screening Platform Identifies Cooperation between Inhibitions of PI3Kα/δ and HDAC.
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Wu CH, Yang CY, Wang L, Gao HX, Rakhshandehroo T, Afghani S, Pincus L, Balassanian R, Rubenstein J, Gill R, Bandyopadhyay S, McCormick F, Moasser M, and Ai WZ
- Subjects
- Aminopyridines pharmacology, Aminopyridines therapeutic use, Animals, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Cell Line, Tumor, Circulating Tumor DNA blood, Class I Phosphatidylinositol 3-Kinases antagonists & inhibitors, Class I Phosphatidylinositol 3-Kinases genetics, Class I Phosphatidylinositol 3-Kinases metabolism, Drug Synergism, Female, Gene Knockdown Techniques, High-Throughput Screening Assays, Histone Deacetylase Inhibitors therapeutic use, Histone Deacetylases metabolism, Humans, Lymphoma, T-Cell, Cutaneous blood, Lymphoma, T-Cell, Cutaneous diagnosis, Lymphoma, T-Cell, Cutaneous pathology, Mice, Morpholines pharmacology, Morpholines therapeutic use, Protein Kinase Inhibitors therapeutic use, Skin pathology, Skin Neoplasms blood, Skin Neoplasms diagnosis, Skin Neoplasms pathology, Tumor Burden drug effects, Xenograft Model Antitumor Assays, Antineoplastic Combined Chemotherapy Protocols pharmacology, Histone Deacetylase Inhibitors pharmacology, Lymphoma, T-Cell, Cutaneous drug therapy, Protein Kinase Inhibitors pharmacology, Skin Neoplasms drug therapy
- Abstract
Cutaneous T-cell lymphoma is a form of non-Hodgkin lymphoma that manifests initially in the skin and disseminates systemically as the disease progresses. Mycosis fungoides and Sézary syndrome are the most common subtypes of cutaneous T-cell lymphoma. Advanced mycosis fungoides and Sézary syndrome are life threatening with few treatment options. We searched for new agents by high-throughput screening of selected targeted compounds and identified high-value targets, including phosphatidylinositol 3-kinase (PI3K) and cyclin-dependent kinases. To validate these hits from the screen, we developed patient-derived xenograft mouse models that recapitulated the cardinal features of mycosis fungoides and Sézary syndrome and maintained histologic and molecular characteristics of their clinical counterparts. Importantly, we established a blood-based biomarker assay using tumor cell-free DNA to measure systemic tumor burden longitudinally in living mice during drug therapy. A PI3K inhibitor, BKM120, was tested in our patient-derived xenograft model leading to disease attenuation and prolonged survival. Isoform-specific small interfering RNA knockdowns and isoform-selective PI3K inhibitors identified PI3K-δ as required for tumor proliferation. Additional studies showed a synergistic combination of PI3K-α/δ inhibitors with histone deacetylase inhibitors. The strong preclinical efficacy of this potent combination against multiple patient-derived xenograft models makes it an excellent candidate for further clinical development., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
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35. Results from the 2019 American Society of Cytopathology survey on rapid onsite evaluation (ROSE)-part 2: subjective views among the cytopathology community.
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Sauter JL, Chen Y, Alex D, Balassanian R, Cuda J, Flanagan MB, Griffith CC, Illei P, Johnson DN, McGrath CM, Randolph ML, Reynolds JP, Spiczka AJ, van Zante A, and VanderLaan PA
- Subjects
- Cytodiagnosis economics, Humans, Insurance, Health, Reimbursement, Laboratories, Hospital, Patient Care economics, United States, Cytodiagnosis methods, Health Knowledge, Attitudes, Practice, Pathologists psychology, Patient Care methods, Societies, Medical, Surveys and Questionnaires
- Abstract
Introduction: This study aims to improve understanding of the cytopathology community's perspective regarding the value of rapid onsite evaluation (ROSE) in clinical practice., Materials and Methods: The American Society of Cytopathology membership was surveyed in 2019 to obtain subjective data on the cytopathology community's perceptions regarding ROSE. Comments were categorized by major themes and attitudes and analyzed by respondent's role in laboratory, practice size, and practice setting (Fisher's exact and χ
2 tests)., Results: A total of 541 responses were received from 255 cytopathologists/pathologists, 261 cytotechnologists, 19 trainees, and 6 others (as previously reported). Reasons for which cytopathology personnel provide this service aligned with their perceptions of why clinicians request ROSE. A minority of respondents, disproportionally from high volume centers, felt ROSE is unnecessary. Overall attitude regarding ROSE was generally positive. There were no significant differences in attitude regarding ROSE according to role in laboratory or practice size, but respondents from academic centers provided a significantly higher percentage of positive comments than those in private or community practice. Although survey respondents generally felt that ROSE is valuable to patient care, they also highlighted several challenges, including staffing, time commitment, and inadequate reimbursement. Implementation of telecytology was felt to potentially alleviate some of these challenges., Conclusions: Survey results show that the cytology community views ROSE favorably, practices vary considerably, and there is a perceived need for improved reimbursement. Data from this study may be used to identify areas that warrant additional research to clarify the clinical value of ROSE., (Copyright © 2020 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)- Published
- 2020
- Full Text
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36. Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer Is Associated with Indigenous American Ancestry in Latin American Women.
- Author
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Marker KM, Zavala VA, Vidaurre T, Lott PC, Vásquez JN, Casavilca-Zambrano S, Calderón M, Abugattas JE, Gómez HL, Fuentes HA, Picoaga RL, Cotrina JM, Neciosup SP, Castañeda CA, Morante Z, Valencia F, Torres J, Echeverry M, Bohórquez ME, Polanco-Echeverry G, Estrada-Florez AP, Serrano-Gómez SJ, Carmona-Valencia JA, Alvarado-Cabrero I, Sanabria-Salas MC, Velez A, Donado J, Song S, Cherry D, Tamayo LI, Huntsman S, Hu D, Ruiz-Cordero R, Balassanian R, Ziv E, Zabaleta J, Carvajal-Carmona L, and Fejerman L
- Subjects
- Adult, Aged, Asian People ethnology, Asian People statistics & numerical data, Black People ethnology, Black People statistics & numerical data, Breast Neoplasms genetics, Colombia ethnology, Female, Humans, Indians, North American, Indians, South American, Latin America ethnology, Linear Models, Logistic Models, Mexico ethnology, Middle Aged, Peru ethnology, Receptor, ErbB-2 genetics, Receptors, Estrogen blood, Receptors, Progesterone blood, United States, White People ethnology, White People statistics & numerical data, Young Adult, Black or African American, Breast Neoplasms chemistry, Breast Neoplasms ethnology, Hispanic or Latino genetics, Receptor, ErbB-2 analysis
- Abstract
Women of Latin American origin in the United States are more likely to be diagnosed with advanced breast cancer and have a higher risk of mortality than non-Hispanic White women. Studies in U.S. Latinas and Latin American women have reported a high incidence of HER2 positive (+) tumors; however, the factors contributing to this observation are unknown. Genome-wide genotype data for 1,312 patients from the Peruvian Genetics and Genomics of Breast Cancer Study (PEGEN-BC) were used to estimate genetic ancestry. We tested the association between HER2 status and genetic ancestry using logistic and multinomial logistic regression models. Findings were replicated in 616 samples from Mexico and Colombia. Average Indigenous American (IA) ancestry differed by subtype. In multivariate models, the odds of having an HER2
+ tumor increased by a factor of 1.20 with every 10% increase in IA ancestry proportion (95% CI, 1.07-1.35; P = 0.001). The association between HER2 status and IA ancestry was independently replicated in samples from Mexico and Colombia. Results suggest that the high prevalence of HER2+ tumors in Latinas could be due in part to the presence of population-specific genetic variant(s) affecting HER2 expression in breast cancer. SIGNIFICANCE: The positive association between Indigenous American genetic ancestry and HER2+ breast cancer suggests that the high incidence of HER2+ subtypes in Latinas might be due to population and subtype-specific genetic risk variants., (©2020 American Association for Cancer Research.)- Published
- 2020
- Full Text
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37. Stop using expired plasma for cell blocks.
- Author
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Balassanian R, Ng DL, and van Zante A
- Subjects
- Humans, DNA Contamination, Thrombin
- Published
- 2019
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- View/download PDF
38. Granulomatous inflammation diagnosed by fine-needle aspiration biopsy.
- Author
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Ng DL and Balassanian R
- Subjects
- Adenocarcinoma pathology, Adolescent, Adult, Aged, Aged, 80 and over, Biopsy, Fine-Needle, Child, Child, Preschool, Female, Granuloma microbiology, Humans, Infant, Inflammation microbiology, Male, Middle Aged, Young Adult, Granuloma pathology, Inflammation pathology
- Abstract
Introduction: Fine-needle aspiration biopsy (FNAB) is a minimally invasive biopsy technique and an important tool for diagnosing infectious diseases. Rapid onsite evaluation allows for triage for ancillary testing, including microbiologic cultures. We aimed to determine the etiology of granulomatous inflammation diagnosed by FNAB by correlating with culture results and clinical history., Materials and Methods: A 16-year retrospective review of cases diagnosed as "granulomatous inflammation" or "granuloma" was performed at the Departments of Pathology at the Zuckerberg San Francisco General Hospital and Trauma Center and University of California, San Francisco., Results: A total of 339 FNABs diagnosed as granulomatous inflammation were identified. Necrotizing granulomatous inflammation was present in 117 of 339 cases (34.5%) and non-necrotizing granulomatous inflammation was present in 222 of 339 cases (65.5%). A pathogen was detected in 100 of 339 (29.5%) FNABs by either cytomorphology, special stains, or culture, or a combination of more than one test. Of the 100 pathogen-positive cases, necrotizing granulomatous inflammation was seen in 50 of 100 (50%) and non-necrotizing granulomatous inflammation was identified in 50 of 100 (50%) cases. Culture results were available in 239 cases and positive in 70 (29%). Positive culture results included 40 of 239 (17%) cases with Mycobacterium tuberculosis complex, 15 of 239 (6.3%) with atypical mycobacterial species, 6 of 239 (3%) with Coccidioides immitis, 2 of 239 (<1%) with Histoplasma capsulatum, and 2 of 239 with Talaromyces marneffei (<1%)., Conclusions: Granulomatous inflammation is a nonspecific finding and suggests a broad range of disease processes, ranging from infection to malignancy. FNAB is an excellent minimally invasive technique that allows for ancillary testing critical for definitive diagnosis., (Copyright © 2019 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2019
- Full Text
- View/download PDF
39. Results from the 2019 American Society of Cytopathology survey on rapid on-site evaluation-Part 1: objective practice patterns.
- Author
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VanderLaan PA, Chen Y, Alex D, Balassanian R, Cuda J, Hoda RS, Illei PB, McGrath CM, Randolph ML, Reynolds JP, Spiczka AJ, VandeHaar MA, van Zante A, and Sauter JL
- Subjects
- Humans, Cytodiagnosis methods, Practice Patterns, Physicians', Societies, Scientific, Surveys and Questionnaires
- Abstract
Introduction: Rapid on-site evaluation (ROSE) is a service provided by cytologists that helps ensure specimen adequacy and appropriate triage for ancillary testing. However, data on the current usage patterns across different practice settings have been lacking., Materials and Methods: To obtain an accurate and timely assessment of the current state of practice of ROSE, a 14-question online survey was constructed by the Clinical Practice Committee of the American Society for Cytopathology. The survey was available to the membership of the American Society for Cytopathology for a 3-week period in early 2019., Results: A total of 541 responses were received, including from 255 cytopathologists/pathologists, 261 cytotechnologists, 19 cytology resident/fellow trainees, and 6 others. ROSE was offered as a clinical service by 95.4% of the respondents, with telecytology for ROSE used in 21.9% of the practices. Endobronchial ultrasound-guided transbronchial needle aspiration was the procedure most frequently reported to use ROSE (mean, 59.1%; median, 70%). Cytotechnologists were involved in ROSE in most practices. The number of daily ROSE procedures correlated with the annual nongynecologic cytology volumes. Approximately 70% of ROSE procedures were reported to require >30 minutes, on average, for the cytologist., Conclusions: The results from our survey of cytologists have shown that the reported practice patterns for the usage of ROSE vary considerably. The presented data can help inform future guideline recommendations and the implementation of ROSE in different clinical settings., (Copyright © 2019 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2019
- Full Text
- View/download PDF
40. Tuberculosis mastitis presenting as bilateral breast masses.
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Qiao Y, Hayward JH, Balassanian R, Ray KM, Joe BN, and Lee AY
- Subjects
- Breast Neoplasms pathology, Diagnosis, Differential, Female, Granulomatous Mastitis diagnosis, Granulomatous Mastitis pathology, Humans, Mastitis pathology, Middle Aged, Skin pathology, Tuberculosis pathology, Breast pathology, Mastitis diagnosis, Tuberculosis diagnosis
- Abstract
Tuberculosis mastitis can be a challenging diagnosis, often presenting with clinical and imaging findings that are suspicious for malignancy. We present a case of a 49-year-old female with a breast mass initially diagnosed as idiopathic granulomatous mastitis. Failure to respond to standard treatments, development of new breast masses, and discovery of a concurrent ulcerating thigh rash with similar histologic findings as the breast masses prompted further investigation, which ultimately lead to the diagnosis of tuberculosis mastitis. There was rapid resolution of both breast and skin symptoms after initiation of empiric drug therapy., (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Published
- 2018
- Full Text
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41. Efficacy of an Intensive, Ultrasound-Guided Fine-Needle Aspiration Biopsy Training Workshop in Tanzania.
- Author
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Ng DL, Vuhahula E, Zhang L, Waterhouse EG, White KL, Mushi BP, Nyeriga MS, Philipo GS, Mmbaga EJ, Sheth S, Van Loon K, Lee AY, and Balassanian R
- Subjects
- Female, Humans, Male, Tanzania, Biopsy, Fine-Needle methods, Image-Guided Biopsy methods, Simulation Training methods, Ultrasonography methods
- Abstract
Background: Fine-needle aspiration biopsy (FNAB) is a minimally invasive, cost-effective diagnostic tool that can be used in low-resource settings. However, adequacy and accuracy of FNAB is highly dependent on the skills of the operator and requires specialized training. Poor technique can preclude definitive diagnoses because of insufficient quality or quantity of FNAB samples. We evaluated the efficacy of an intensive training experience in Tanzania on improving ultrasound-guided FNAB techniques., Methods: A 2-day workshop offered didactic lectures, demonstrations, and hands-on practicum on fundamentals of ultrasound imaging and FNAB technique. A prospective interventional study design was used with pre- and postintervention surveys and assessments to measure the effect of the workshop on specific skills related to slide smearing and ultrasound-guidance among participants., Results: Twenty-six pathologists and radiologists, including trainees in each specialty, participated in the workshop. Pre- and postworkshop assessments demonstrated that most participants improved significantly in nearly all technical skills for slide smearing and ultrasound-guided FNAB. After the workshop, most participants demonstrated substantial improvements in ability to prepare the ultrasound equipment, measure the lesion in three dimensions by ultrasound, target lesions in one pass using both parallel and perpendicular approaches, and prepare high-quality aspirate smears., Conclusion: An in-country 2-day workshop in Tanzania was efficacious in transferring basic skills in FNAB smear preparation and ultrasound-guided FNAB, resulting in skills enhancement among participating pathologists and radiologists. Although mastery of skills was not the goal of this short workshop, participants demonstrated proficiency in most technical elements after workshop completion, and the workshop generated interest among select participants to pursue additional intensive training in cytopathology.
- Published
- 2018
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42. Improved diagnostic precision of urine cytology by implementation of The Paris System and the use of cell blocks.
- Author
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Chan E, Balassanian R, Tabatabai ZL, Lou H, and Vohra P
- Subjects
- Adult, Aged, Aged, 80 and over, Biopsy, Fine-Needle, Female, Follow-Up Studies, Humans, Male, Middle Aged, Prognosis, Retrospective Studies, Young Adult, Cytodiagnosis standards, Specimen Handling, Urinary Tract pathology, Urine cytology, Urologic Neoplasms diagnosis, Urologic Neoplasms urine
- Abstract
Background: The Paris System for Reporting Urinary Cytology (TPS) published in 2016 provides a standardized approach to evaluating urine cytology. In the authors' practice, a TPS-like approach was adopted in 2012 using similarly defined cytologic criteria and correlating cystoscopic findings, and they also began incorporating the use of cell block (CB) material. The objective of the current study was to assess whether this TPS-like approach with the use of CB, as well as direct implementation of TPS, improved the diagnostic value of urine cytology., Methods: In total, 188 consecutive urine cytology specimens from 2010 through 2016 that had concurrent or subsequent histologic specimens available were retrospectively analyzed for diagnostic correlation. Urine cytology performance was compared between the periods 2010 to 2012 (pre-TPS-like), 2013 to 2016 (TPS-like), and after TPS reclassification, including blind review by a cytopathologist. The contribution of available CB material to final diagnoses also was assessed., Results: Both the TPS-like approach and TPS reclassification resulted in significantly lowering the rate of atypical urothelial cells (AUC) diagnosis from 48%, to 21%, to 9% (from pre-TPS, to TPS-like, to after TPS reclassification, respectively; P < 0.01) while increasing the positive predictive value of an AUC diagnosis for high-grade urothelial carcinoma from 21%, to 43%, to 83%, respectively. The use of CBs contributed to a definitive final diagnosis in 24 of 36 cases (66.7%)., Conclusions: In support of the new TPS recommendations, the application of stringent "TPS-like" and TPS criteria improves the value of an AUC diagnosis for clinicians and patients by lowering the AUC rate and increasing the positive predictive value of AUC for high-grade urothelial carcinoma. CBs can be used to help resolve problematic cases for more definitive diagnostic categorization., (© 2018 American Cancer Society.)
- Published
- 2018
- Full Text
- View/download PDF
43. Intratumor Heterogeneity of the Estrogen Receptor and the Long-term Risk of Fatal Breast Cancer.
- Author
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Lindström LS, Yau C, Czene K, Thompson CK, Hoadley KA, Van't Veer LJ, Balassanian R, Bishop JW, Carpenter PM, Chen YY, Datnow B, Hasteh F, Krings G, Lin F, Zhang Y, Nordenskjöld B, Stål O, Benz CC, Fornander T, Borowsky AD, and Esserman LJ
- Subjects
- Aged, Antineoplastic Agents, Hormonal therapeutic use, Breast Neoplasms drug therapy, Breast Neoplasms pathology, Chemotherapy, Adjuvant, Female, Humans, Middle Aged, Neoplasm Grading, Randomized Controlled Trials as Topic, Receptors, Estrogen analysis, Registries, Retrospective Studies, Risk Factors, Survival Analysis, Sweden epidemiology, Tamoxifen therapeutic use, Time Factors, Breast Neoplasms metabolism, Breast Neoplasms mortality, Receptors, Estrogen metabolism
- Abstract
Background: Breast cancer patients with estrogen receptor (ER)-positive disease have a continuous long-term risk for fatal breast cancer, but the biological factors influencing this risk are unknown. We aimed to determine whether high intratumor heterogeneity of ER predicts an increased long-term risk (25 years) of fatal breast cancer., Methods: The STO-3 trial enrolled 1780 postmenopausal lymph node-negative breast cancer patients randomly assigned to receive adjuvant tamoxifen vs not. The fraction of cancer cells for each ER intensity level was scored by breast cancer pathologists, and intratumor heterogeneity of ER was calculated using Rao's quadratic entropy and categorized into high and low heterogeneity using a predefined cutoff at the second tertile (67%). Long-term breast cancer-specific survival analyses by intra-tumor heterogeneity of ER were performed using Kaplan-Meier and multivariable Cox proportional hazard modeling adjusting for patient and tumor characteristics., Results: A statistically significant difference in long-term survival by high vs low intratumor heterogeneity of ER was seen for all ER-positive patients (P < .001) and for patients with luminal A subtype tumors (P = .01). In multivariable analyses, patients with high intratumor heterogeneity of ER had a twofold increased long-term risk as compared with patients with low intratumor heterogeneity (ER-positive: hazard ratio [HR] = 1.98, 95% confidence interval [CI] = 1.31 to 3.00; luminal A subtype tumors: HR = 2.43, 95% CI = 1.18 to 4.99)., Conclusions: Patients with high intratumor heterogeneity of ER had an increased long-term risk of fatal breast cancer. Interestingly, a similar long-term risk increase was seen in patients with luminal A subtype tumors. Our findings suggest that intratumor heterogeneity of ER is an independent long-term prognosticator with potential to change clinical management, especially for patients with luminal A tumors.
- Published
- 2018
- Full Text
- View/download PDF
44. Breast Cancer, Version 4.2017, NCCN Clinical Practice Guidelines in Oncology.
- Author
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Gradishar WJ, Anderson BO, Balassanian R, Blair SL, Burstein HJ, Cyr A, Elias AD, Farrar WB, Forero A, Giordano SH, Goetz MP, Goldstein LJ, Isakoff SJ, Lyons J, Marcom PK, Mayer IA, McCormick B, Moran MS, O'Regan RM, Patel SA, Pierce LJ, Reed EC, Salerno KE, Schwartzberg LS, Sitapati A, Smith KL, Smith ML, Soliman H, Somlo G, Telli ML, Ward JH, Kumar R, and Shead DA
- Subjects
- Breast Neoplasms etiology, Carcinoma, Ductal, Breast diagnosis, Carcinoma, Ductal, Breast etiology, Carcinoma, Ductal, Breast therapy, Carcinoma, Intraductal, Noninfiltrating diagnosis, Carcinoma, Intraductal, Noninfiltrating etiology, Carcinoma, Intraductal, Noninfiltrating therapy, Combined Modality Therapy, Disease Management, Female, Humans, Retreatment, Treatment Outcome, Watchful Waiting, Breast Neoplasms diagnosis, Breast Neoplasms therapy
- Abstract
Ductal carcinoma in situ (DCIS) of the breast represents a heterogeneous group of neoplastic lesions in the breast ducts. The goal for management of DCIS is to prevent the development of invasive breast cancer. This manuscript focuses on the NCCN Guidelines Panel recommendations for the workup, primary treatment, risk reduction strategies, and surveillance specific to DCIS., (Copyright © 2018 by the National Comprehensive Cancer Network.)
- Published
- 2018
- Full Text
- View/download PDF
45. Radiologic-Pathologic Correlation for Benign Results After MRI-Guided Breast Biopsy.
- Author
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Maglione KD, Lee AY, Ray KM, Joe BN, and Balassanian R
- Subjects
- Diagnosis, Differential, Female, Humans, Sensitivity and Specificity, Breast Diseases diagnostic imaging, Breast Diseases pathology, Image-Guided Biopsy, Magnetic Resonance Imaging, Interventional
- Abstract
Objective: The majority of MRI-guided breast biopsies yield benign pathology. The purpose of this article is to provide a comprehensive overview of benign pathologic entities commonly encountered at MRI-guided breast biopsy., Conclusion: Proper radiologic-pathologic correlation is an integral component of MRI-guided breast biopsy. Familiarity with the spectrum of MRI findings and key histopathologic features of common benign entities will enhance the radiologist's confidence in determining concordance and lead to improved patient management recommendations.
- Published
- 2017
- Full Text
- View/download PDF
46. NCCN Guidelines Insights: Breast Cancer, Version 1.2017.
- Author
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Gradishar WJ, Anderson BO, Balassanian R, Blair SL, Burstein HJ, Cyr A, Elias AD, Farrar WB, Forero A, Giordano SH, Goetz MP, Goldstein LJ, Isakoff SJ, Lyons J, Marcom PK, Mayer IA, McCormick B, Moran MS, O'Regan RM, Patel SA, Pierce LJ, Reed EC, Salerno KE, Schwartzberg LS, Sitapati A, Smith KL, Smith ML, Soliman H, Somlo G, Telli M, Ward JH, Shead DA, and Kumar R
- Subjects
- Axilla, Combined Modality Therapy methods, Disease Management, Female, Humans, Neoplasm Staging, Sentinel Lymph Node Biopsy, Breast Neoplasms diagnosis, Breast Neoplasms therapy
- Abstract
These NCCN Guidelines Insights highlight the important updates/changes to the surgical axillary staging, radiation therapy, and systemic therapy recommendations for hormone receptor-positive disease in the 1.2017 version of the NCCN Guidelines for Breast Cancer. This report summarizes these updates and discusses the rationale behind them. Updates on new drug approvals, not available at press time, can be found in the most recent version of these guidelines at NCCN.org., (Copyright © 2017 by the National Comprehensive Cancer Network.)
- Published
- 2017
- Full Text
- View/download PDF
47. Clinical Experience With Mammary Ductoscopy.
- Author
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Valdes EK, Boolbol SK, Cohen JM, Balassanian R, and Feldman SM
- Subjects
- Breast Neoplasms surgery, Carcinoma, Ductal, Breast surgery, Carcinoma, Intraductal, Noninfiltrating surgery, Female, Humans, Margins of Excision, Mastectomy, Segmental, Neoplasm, Residual, Patient Selection, Prospective Studies, Risk Factors, Breast Neoplasms diagnostic imaging, Carcinoma, Ductal, Breast diagnostic imaging, Carcinoma, Intraductal, Noninfiltrating diagnostic imaging, Endoscopy, Mammary Glands, Human diagnostic imaging, Nipple Discharge diagnostic imaging
- Abstract
Background: Most breast cancers begin in the ductal epithelium with normal cells and progress to atypia and finally to carcinoma. Mammary ductoscopy enables one to directly visualize and sample the ductal epithelium and, therefore, identify early changes cytologically. This article describes our initial experience with mammary ductoscopy at Beth Israel Medical Center., Methods: A prospective review of all patients who underwent ductoscopy at Beth Israel Medical Center from November 2001 to February 2004 was performed. The indications for ductoscopy were a persistent nipple discharge, high-risk status, or intraoperative margin assessment in patients undergoing lumpectomy., Results: Seventy-four patients underwent ductoscopic evaluation of 88 ducts. Of the 32 patients who underwent office ductoscopy, 15 were high risk, and 17 had spontaneous nipple discharge. Spontaneous nipple discharge was the indication for ductoscopy in 40 of 42 intraoperative procedures. The remaining two patients underwent ductoscopy for margin assessment during breast conservation, and final pathologic analysis revealed negative margins. Thirty-eight of the 40 patients who had spontaneous nipple discharge had abnormal findings during ductoscopy and therefore underwent ductoscopically guided duct excision. Carcinoma was the final diagnosis in 5 (8.8%) of the 57 patients who were scoped for nipple discharge., Conclusions: Mammary ductoscopy is a potentially useful tool in the evaluation of patients with spontaneous nipple discharge. This is a well-tolerated office procedure with minimal risks and complications. Mammary ductoscopy may have a role in the assessment of high-risk women. Further research is necessary to confirm these potential applications.
- Published
- 2016
- Full Text
- View/download PDF
48. A superior method for cell block preparation for fine-needle aspiration biopsies.
- Author
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Balassanian R, Wool GD, Ono JC, Olejnik-Nave J, Mah MM, Sweeney BJ, Liberman H, Ljung BM, and Pitman MB
- Subjects
- Biopsy, Fine-Needle, Histocytological Preparation Techniques standards, Humans, Cytodiagnosis methods, Histocytological Preparation Techniques methods, Neoplasms diagnosis
- Abstract
Background: Cell block (CB) techniques for fine-needle aspiration biopsies (FNABs) vary. A direct comparison of CB techniques with statistical validation was performed to identify the best method., Methods: Three CB techniques were compared: 1) FNAB rinsed in saline and clotted with plasma and thrombin (SPT); 2) FNAB rinsed in formalin and clotted with HistoGel (HG); and 3) FNAB rinsed in formalin, centrifuged, and the pellet captured in a collodion bag (ColB). FNAB was performed on 35 random surgical specimens for smears and each CB technique. A randomized blinded review of hematoxylin and eosin-stained CB slides was performed and each case was scored on a scale of 1 to 3 for cellularity, preservation, and architecture and the overall best CB was identified. Significance was determined by the Mann-Whitney U test for nonparametric ordinal data., Results: The mean cellularity score was 1.71 for SPT (standard deviation [SD], 0.89), 1.68 for HG (SD, 0.67), and 3.0 for ColB (SD, 0). The mean preservation score was 1.31 for SPT (SD, 0.58), 1.54 for HG (SD, 0.70), and 2.91 for ColB (SD, 0.37). The mean architecture score was 1.45 for SPT (SD, 0.70), 1.43 for HG (SD, 0.60), and 2.71 for ColB (SD, 0.57). There was no statistical significance noted between SPT or HG when compared for each category. ColB was found to be superior to both SPT and HG when compared for each category (P<.05). The overall best CB was obtained with ColB in 33 of 35 cases (94%), with SPT proving superior in 1 of 35 cases (3%) and HG superior in 1 of 35 cases (3%)., Conclusions: ColB appears to be a superior technique for CB, yielding greater cellularity, preservation, and architecture in the majority of cases. Cancer Cytopathol 2016;124:508-18. © 2016 American Cancer Society., (© 2016 American Cancer Society.)
- Published
- 2016
- Full Text
- View/download PDF
49. Fine-Needle Aspiration Biopsy of Palpable Breast Masses: Patterns of Clinical Use and Patient Experience.
- Author
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Ly A, Ono JC, Hughes KS, Pitman MB, and Balassanian R
- Subjects
- Adult, Aged, Aged, 80 and over, Breast Neoplasms pathology, Female, Humans, Male, Middle Aged, Young Adult, Biopsy, Fine-Needle methods, Breast Neoplasms diagnosis
- Abstract
Background: Timeliness is an important and recognized measure of health care quality. Multiple health organizations worldwide have published timeliness targets for breast cancer care. We performed the first comparison of patient wait times and utilization patterns for palpable breast mass diagnosis and treatment with regard to biopsy method., Patients and Methods: Palpable breast masses in women biopsied via a fine-needle aspiration (FNA) or core biopsy at 2 affiliated academic medical centers in 2009 were analyzed if subsequently treated with excision or neoadjuvant therapy. Patient demographics, mass size and radiologic features, pathology diagnoses, and wait times to diagnosis and treatment were recorded., Results: Patients diagnosed by FNA biopsy received their biopsy diagnosis more than 8 days sooner than those diagnosed by core biopsy. Most FNA biopsies occurred the same day the patient clinically presented. Time to treatment did not differ significantly between groups. Both biopsy methods demonstrated comparable diagnostic accuracy. Breast masses diagnosed by FNA biopsy had Breast Imaging Reporting and Data System (BI-RADS) scores ranging from 1 through 5, whereas nearly all core biopsy cases had a BI-RADS score of 4 or greater. All patient groups were demographically comparable and presented with similar breast mass sizes., Conclusions: Wait times for breast biopsies were significantly shorter for patients diagnosed by FNA compared with core biopsy. FNA biopsy was often used to evaluate breast masses of low clinical suspicion. In light of health care goals for practice improvement and cost containment, breast FNA biopsy may be an underused resource., (Copyright © 2016 by the National Comprehensive Cancer Network.)
- Published
- 2016
- Full Text
- View/download PDF
50. Invasive Breast Cancer Version 1.2016, NCCN Clinical Practice Guidelines in Oncology.
- Author
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Gradishar WJ, Anderson BO, Balassanian R, Blair SL, Burstein HJ, Cyr A, Elias AD, Farrar WB, Forero A, Giordano SH, Goetz M, Goldstein LJ, Hudis CA, Isakoff SJ, Marcom PK, Mayer IA, McCormick B, Moran M, Patel SA, Pierce LJ, Reed EC, Salerno KE, Schwartzberg LS, Smith KL, Smith ML, Soliman H, Somlo G, Telli M, Ward JH, Shead DA, and Kumar R
- Subjects
- Chemotherapy, Adjuvant adverse effects, Combined Modality Therapy, Female, Fertility drug effects, Fertility Preservation, Humans, Mammaplasty methods, Mastectomy methods, Neoplasm Invasiveness, Neoplasm Staging, Radiotherapy, Adjuvant adverse effects, United States, Breast Neoplasms pathology, Breast Neoplasms therapy
- Abstract
Breast cancer is the most common malignancy in women in the United States and is second only to lung cancer as a cause of cancer death. The overall management of breast cancer includes the treatment of local disease with surgery, radiation therapy, or both, and the treatment of systemic disease with cytotoxic chemotherapy, endocrine therapy, biologic therapy, or combinations of these. This article outlines the NCCN Guidelines specific to breast cancer that is locoregional (restricted to one region of the body), and discusses the management of clinical stage I, II, and IIIA (T3N1M0) tumors. For NCCN Guidelines on systemic adjuvant therapy after locoregional management of clinical stage I, II and IIIA (T3N1M0) and for management for other clinical stages of breast cancer, see the complete version of these guidelines at NCCN.org., (Copyright © 2016 by the National Comprehensive Cancer Network.)
- Published
- 2016
- Full Text
- View/download PDF
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