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Context: The Modified Masood Scoring Index (MMSI) categorizes breast fine needle aspirates into four categories non-proliferative breast diseases (PBD), PBD without atypia, PBD with atypia and carcinoma in situ/carcinoma. The International Academy of Cytology Yokohama System classifies the aspirates into five categories - inadequate, benign, atypical, suspicious, and malignant. Very few studies have been conducted so far to compare the diagnostic accuracy of this system., Aims: The objectives of the study were to classify breast fine needle aspirates according to the MMSI and IAC Yokohama and assess their risk of malignancy (ROM) and performance parameters., Materials and Methods: All breast FNAs received from June 2020 to May 2023 were classified according to the MMSI and IAC Yokohama. Using histopathological diagnosis as the gold standard, ROM and performance parameters were calculated., Results: Out of the 559 breast fine needle aspirates, the histopathological correlation was available for 337 cases. The ROM for non-PBD, PBD without atypia, PBD with atypia and carcinoma in situ/carcinoma categories were 0%, 1.2%, 9.1% and 93%, respectively. The ROM for each of the categories of Yokohama system was 16.6%, 1.1%, 4.3%, 86.2% and 97.6%, respectively. The values for the sensitivity, specificity, PPV, NPV and diagnostic accuracy were slightly higher for IAC Yokohama (97.3%, 97.2%, 94.7%, 98.6% and 97.2%, respectively) than the MMSI (96.4%, 96.2%, 93%, 98.1% and 96.3%, respectively). Furthermore, another shortfall of MMSI is the inability to compare the Inadequate category of the Yokohama system., Conclusion: Overall Yokohama system proved to be a better system for categorizing breast lesions on FNAB as the scoring system provides more objective categorization and minimizes false positive and false negative cases., (© 2024 John Wiley & Sons Ltd.)

Aim: Carcinogenesis is associated with multiple mutations that lead to chromosomal instability (CIN). Our aim was to study the role of markers of CIN on breast cytology and correlate with histopathological diagnosis., Materials and Methods: A retrospective observational study was conducted over a year on 100 breast cytology cases. Leishman-stained smears were examined for the number of micronuclei (MN), chromatin bridge (CB), and multipolar mitosis (MPM). MNs were counted manually in 1,000 cells under oil immersion (1000×). The frequency of CB and MPM was also noted. The malignant cases were graded as low (grades 1 and 2) and high (grade 3)., Results: The mean age of the patients was 43.47 ± 15.81 years. The mean MN score for fibroadenoma cases was 4.54 (±1.5) and for malignant cases was 29.32 (±8.15). The receiver-operator curve (ROC) curve analysis confirmed >9 MN score as 100% specific and 100% sensitive for malignancy (area under the curve [AUC] =1). A significant comparison was noted between the mean MN of benign and malignant cases (P < 0.000001). The mean MN score for low-grade cases was 26.64 (±5.85) and for high-grade cases was 33.68 (±5.85) with a significant difference observed on comparing the population mean MN with a grade of malignancy (P-value = 0.01886). The difference between the frequencies of CB in low and high-grade cases was also found to be significant (P-value = 0.04135)., Conclusion: The presence and scoring of markers of CIN (MN, CB, and MPM) on breast cytology have potential significance in the diagnosis of breast lesions., (Copyright © 2023 Copyright: © 2023 Journal of Cancer Research and Therapeutics.)

Objective: The Visiopharm artificial intelligence (AI) algorithm for oestrogen receptor (ER) immunohistochemistry (IHC) in whole slide images (WSIs) has been successfully validated in surgical pathology. This study aimed to assess its efficacy in cytology specimens., Methods: The study cohort comprised 105 consecutive cytology specimens with metastatic breast carcinoma. ER IHC WSIs were seamlessly integrated into the Visiopharm platform from the Image Management System (IMS) during our routine digital workflow, and an AI algorithm was employed for analysis. ER AI scores were compared with pathologists' manual consensus scores. Optimization steps were implemented and evaluated to reduce discordance., Results: The overall concordance between pathologists' scores and AI scores was excellent (99/105, 94.3%). Six cases exhibited discordant results, including two false-negative (FN) cases due to abundant histiocytes incorrectly counted as negatively stained tumour cells by AI, two FN cases owing to weak staining, and two false-positive (FP) cases where pigmented macrophages were erroneously counted as positively stained tumour cells by AI. The Pearson correlation coefficient of ER-positive percentages between pathologists' and AI scores was 0.8483. Optimization steps, such as lowering the cut-off threshold and additional training using higher input magnification, significantly improved accuracy., Conclusions: The automated ER AI algorithm demonstrated excellent concordance with pathologists' assessments and accurately differentiated ER-positive from ER-negative metastatic breast carcinoma cytology cases. However, precision in identifying tumour cells in cytology specimens requires further enhancement., (© 2024 John Wiley & Sons Ltd.)

Objectives: Cytology reports of metaplastic breast carcinoma (MBC) are rare and limited to short series and simple case reports. To adapt cytology diagnostic criteria to the most recent fifth edition of the World Health Organization Classification of Breast Tumours from 2019, we have reviewed our series from the files of the Institut Curie., Methods: A cohort of 66 female patients investigated by cytology with corresponding histologic diagnosis of MBC was identified. Eight cytologic characteristics were analyzed: cellularity, adenocarcinoma cells, squamous cells, spindle cells, giant cells, cytonuclear atypia, necrosis, and osseous/chondroid matrix and compared with histology., Results: Cytologic diagnoses were malignant in 58 (88%) cases (of which 29 cases were typed cytologically as MBC), suspicious in 6 (9%) cases, and nondiagnostic in 2 (3%) cases. None of the cytologic examinations was a benign diagnosis. Low-grade adenosquamous carcinoma and fibromatosis-like metaplastic carcinoma exhibited a low degree of cellular atypia. Fibromatosis-like metaplastic carcinoma and spindle cell carcinoma (SpCC) presented spindle cells, while SpCC also demonstrated varying degrees of atypia, the presence of giant cells, and necrosis. Squamous cell carcinoma was characterized by the presence of squamous cells, and metaplastic carcinoma with osseous/chondroid differentiation displayed an osseous/chondroid matrix., Conclusions: Fine-needle aspiration holds considerable potential as a valid, independent, and complementary approach to histologic examination of MBC., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Per the College of American Pathologist's National Breast Fine Needle Aspiration Biopsy (FNAB) Practice Survey, ∼40% of laboratories use liquid-based cytology (LBC) for breast FNAB. The reproducibility of the International Academy of Cytology Yokohama System (YS) for reporting breast FNAB on LBC was explored., Design: Breast FNAB specimens submitted as LBC only (all ThinPrep) between January 2017 and January 2021 were retrieved. Cases without histopathologic follow-up were excluded. Clinical and radiologic information was collected. One cytologist and six cytopathologists rendered diagnoses per YS. All reviewers were blinded to the original diagnosis and histopathologic follow-up. The risk of malignancy was calculated. Concordance rates were calculated by a weighted Cohen Kappa score (κ)., Results: Review of 110 cases demonstrated substantial to near-perfect agreement between each reviewer (κ = 0.73-0.91) and follow-up histopathology (κ = 0.66-0.85). The agreement was lowest in the inadequate (κ = 0.05) and atypical (κ = 0.04) categories. The lack of concordance in the atypical category was common in cases with low cellularity or incomplete structural features. The risk of malignancy for inadequate, benign, atypical, suspicious for malignancy, and malignant categories were 12.5% (2/16), 3% (2/65), 67%, (8/12) 100% (1/1), and 100% (16/16)., Conclusion: Interobserver agreement is excellent using the five YS categories in LBC. Lack of cellularity and incomplete architectural features were barriers to perfect agreement. Established pitfalls in the interpretation of LBC were cause for atypical diagnoses. Continuous training and education are recommended to avoid misdiagnosis because of the nonconventional cytomorphologic features of LBC and to improve inadequate and atypical rates within YS., (© 2024 American Cancer Society.)

Background: Sentinel lymph node (SLN) is the first lymph node to drain the lymph from a particular region involved by cancer. The commonly performed intraoperative methods for SLN evaluation are touch imprint cytology (TIC) and frozen section (FS). The present study aimed to determine the sensitivity, specificity and accuracy of TIC and FS with histopathological diagnosis as gold standard., Materials and Methods: The nodes were bissected along their long axis and wet surface was imprinted on to clean glass slides followed by toluidine blue and rapid Papanicolaou staining. Subsequently the lymph node slices were cut at three levels using the cryostat machine and stained with Hematoxylin and eosin stain. The cytological and FS findings were compared and the specificity, sensitivity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of TIC and FS was evaluated taking histopathological diagnosis as gold standard. In addition, pooled sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy for touch imprint cytology and frozen section were assessed for the studies included in the meta-analysis., Results: The specificity, sensitivity, diagnostic accuracy, positive predictive value and negative predictive value of touch imprint cytology were 100%, 88.2%, 90%, 100% and 60% respectively. The specificity, sensitivity, diagnostic accuracy, PPV and NPV of frozen section were 100%, 94.1%, 95%, 100% and 75% respectively. The sensitivity of TIC and FS for detection of micrometastasis was 60% and 80% respectively. The pooled sensitivity and specificity for touch imprint cytology were 85.24% (95% CI, 83.46%-86.90%), and 98.99% (95% CI, 98.69%-99.23%) respectively. The pooled sensitivity and specificity for frozen section examination were 90.45% (95% CI, 85.15%-94.34%), and 100% (95% CI, 99.24%-100%) respectively., Conclusion: Even though the sensitivity of FS was better than imprint cytology in detection of micrometastasis, TIC is a rapid inexpensive technique which can be utilized in remote areas in absence of cryostat machine. The sensitivity of the two techniques with respect to detection of macrometastasis was comparable. This meta-analysis highlights the accuracy of the touch imprint cytology and frozen section examination in the intra-operative detection of malignancy in breast cancer.

Fine-needle aspiration cytology (FNAC) is a versatile diagnostic procedure uniquely suited for tissue biopsy of breast carcinomas and axillary metastases and/or recurrences. With the expanding treatment options and accompanying theragnostic tests, it is crucial to recognize the developments on ancillary testing and digital cytopathology techniques related to aspiration cytology of metastatic breast carcinoma. In this review, we aim to summarize and update the evidence of immunocytochemistry, for the detection of carcinoma cells (epithelial markers), confirmation of breast primary (breast-specific markers), assessment of surrogate immunostains (hormone receptors, ki-67 proliferative index and HER2) and theragnostic biomarkers, with discussion on potential diagnostic pitfalls, followed by the application of molecular tests, and digital cytopathologic techniques for assessing metastatic breast carcinoma in cytology., (© 2023 John Wiley & Sons Ltd.)

Introduction: Cancer genome analysis using next-generation sequencing requires adequate and high-quality DNA samples. Genomic analyses were conventionally performed using formalin-fixed paraffin-embedded sections rather than cytology samples such as cell block or smear specimens. Specimens collected from liquid-based cytology (LBC) have the potential to be sources of high-quality DNA suitable for genetic analysis even after long-term storage., Methods: We collected breast tumor/lesion fractions from 92 residual LBC specimens using fine-needle aspiration (FNA) biopsy, including breast carcinoma (1 invasive carcinoma and 4 ductal carcinomas in situ), papillomatous lesion (5 intraductal papillomas), and fibroepithelial lesion (19 phyllodes tumors and 53 fibroadenomas) samples, and others (1 ductal adenoma, 1 hamartoma, 1 fibrocystic disease, and 7 unknown). DNA was extracted from all samples and subjected to DNA integrity number (DIN) score analysis., Results: Average DIN score collected from 92 LBC specimens was significantly higher score. In addition, high-quality DNA with high DIN values (7.39 ± 0.80) was successfully extracted more than 12 months after storage of residual LBC specimens., Conclusion: Residual LBC specimens collected from FNA of the breast were verified to carry high-quality DNA and could serve as an alternate source for genetic analysis., (© 2024 S. Karger AG, Basel.)

Background: Fine-needle aspiration cytology (FNAC) is a cornerstone technique for the initial assessment of breast lesions, offering a rapid and minimally invasive option for cytological evaluation. While FNACs can forego the need for core needle biopsies (CNBs), variations in technique, subjective interpretation, and intrinsic limitations present diagnostic challenges. The International Academy of Cytology (IAC) established the Yokohama system and is developing the WHO Reporting System for Breast Cytopathology jointly with IARC, to standardize diagnostic criteria, aiming to enhance diagnostic precision and consistency. Due to the preference for CNBs, expertise in breast FNAC is low in the developed world., Summary: This review assesses common pitfalls in breast cytopathology. These common and uncommon entities may easily lead to false-negative or false-positive diagnoses, due to morphological overlap or misleading clinical and radiological contexts. For instance, pauci-cellular lesions, such as lobular carcinomas, often lead to false-negative diagnoses, whereas complex sclerosing lesions, fibroadenomas, and papillary lesions may show concerning features, resulting in a false positive. The same is true for some benign inflammatory pathologies, such as steatonecrosis, and uncommon lesions, such as collagenous spherulosis. Ductal carcinoma in situ can lead to both false-negative and false-positive diagnoses, and high-grade lesions are impossible to tell apart from invasive carcinomas. These are discussed in detail. Procedural and preanalytical conditions, and the role of ancillary testing, are also briefly addressed., Key Messages: Breast FNAB is a powerful diagnostic technique, fast and minimally invasive. Even in contexts which lack expertise, this technique can be successfully adopted with a cautious approach and as long as pitfalls are kept in mind, benefiting patients and healthcare systems., (© 2024 S. Karger AG, Basel.)

Introduction: In fine-needle aspiration of the breast (FNAB), the "atypical" category encompasses both benign and malignant lesions, particularly papillary proliferative lesions, as per the latest WHO classification. We aimed to reduce atypical cases and improve diagnostic accuracy by investigating the utility of cell block (CB) analysis., Methods: FNAB CB samples (2018-2022) were reviewed using smear only or CBs. CB-based diagnosis was performed with 2D morphological analysis and immunocytochemistry using ER, CK5/6, p63, SMA, and CD56. Samples were reclassified as "benign," "atypical," "suspicious of malignancy," "malignant," or "insufficient/inadequate." Atypical cases were reexamined. Diagnoses were validated histologically., Results: On examining the FNAB samples (n = 149; 32 atypical), 2D CB sectioning achieved a clearer definition of myoepithelial cells and fibrovascular cores than Papanicolaou staining. Immunocytochemistry was evaluated for 36 cases: estrogen receptor (ER)- and CK5/6+ tumors were reclassified as benign; ER+ and CK5/6- tumors as malignant; p63- tumors as invasive; papillary malignant tumors with a smooth muscle actin (SMA)+ fibrovascular core and p63- myoepithelial cells as encapsulated papillary carcinoma; and CD56+ carcinomas as neuroendocrine carcinoma. Diagnostic rates were as follows: benign (44% FNAB, 51% CB), atypical (21% FNAB, 3% CB), suspicious of malignancy and malignant (28% FNAB, 40% CB), and insufficient/inadequate (7% FNAB, 6% CB). CB achieved &gt;85% sensitivity, specificity, and positive and negative predictive values., Conclusion: CBs represent 3D FNA cell morphology using 2D sections, enabling adaption of pathology criteria to the cytological material. Immunocytochemical staining of CBs can predict low nuclear grade papillary tumors and reduce atypical case frequency, improving diagnostic accuracy., (© 2023 S. Karger AG, Basel.)

Background: Stratification of breast lesions for appropriate management is achieved through an integration of clinical examination, imaging, and fine needle aspiration biopsy (FNAB). The current study aimed to evaluate the combined effectiveness of the widely used Breast Imaging-Reporting and Data System (BI-RADS) with the recently proposed International Academy of Cytology (IAC) Yokohama System for Reporting Breast Fine Needle Aspiration Biopsy Cytopathology., Methods: A retrospective analysis was done on all breast FNABs from 2016 through 2020. The cases were categorised according to the IAC Yokohama System. Histopathological correlation of the BI-RADS and IAC Yokohama System was performed. The rate of malignancy (ROM) for each category of the BI-RADS and IAC Yokohama System was calculated., Results: The ROM values for categories I to V were 38%, 0.6%, 21.9%, 100%, and 97%, respectively. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of FNAB with category III assumed as malignant were 98.9%, 85%, 76.1%, 99.3%, and 89.5%, respectively. With category III assumed as benign, these indices were 90.8%, 98.9%, 97.5%, 95.7%, and 96.2%, respectively. The sensitivity, specificity, PPV, NPV and accuracy of BI-RADS were 91.5%, 81.9%, 72%, 95%, and 85.1%, respectively., Conclusions: FNAB is still an indispensable test in the evaluation of breast lesions. The utilisation of the IAC Yokohama reporting system for breast cytology in conjunction with ACR BI-RADS aids in better stratification of lesions., (© 2021 John Wiley & Sons Ltd.)

Fine-needle aspiration biopsies (FNABs) of the breast are minimally invasive procedures enabling the diagnosis of suspicious breast lesions. Unfortunately, they are often perceived as inferior to core-needle biopsies, namely because they are supposedly unable to differentiate between high-grade ductal carcinoma in situ and invasive carcinoma or provide material for ancillary testing. Several studies have shown, however, that FNAB samples, when handled properly, are indeed capable of providing sufficient and adequate material for ancillary testing, namely immunocytochemistry (ICC). We reviewed the published literature regarding the use of ICC for both diagnostic and theranostic uses in the different types of cytological samples obtained from FNABs of the breast, including smears, liquid-based cytology samples, and cellblocks. We found that p63 and 34βE12 show promise in aiding in the differential diagnosis between in situ and invasive lesions and that most other diagnostic markers may be used as in tissue. Regarding theranostic ICC markers, results vary between publications, but with care, these can successfully be performed in cytological samples. Air-dried smears should be avoided, and cellblocks are overall more versatile than cytology slides, enabling the evaluation of not only hormonal receptors and HER2 by ICC, but also of Ki-67. Particular attention should be paid to fixation and antigen retrieval procedures in all cases. We recommend that laboratories without experience perform short validation runs before adopting these techniques into clinical practice., (© 2022 S. Karger AG, Basel.)

Background: Classification of breast lesions into different cytological groups can accurately be done using the International Academy of Cytology (IAC) Yokohama System for reporting breast cytopathology. Fine needle aspiration biopsy (FNAB) of breast lesions has been considered to be the primary investigation in detecting breast cancers, especially in low-cost settings. The main objective of this study was to prospectively re-confirm the diagnostic accuracy of breast FNAB using the IAC Yokohama system. Additionally, separate secondary subgroup analysis was done to confirm the accuracy of breast FNAB excluding lymph-node positive and lymphadenopathy positive tumors., Material and Methods: A prospective study was done on patients undergoing biopsy of breast lesions between September 01, 2019 and November 30, 2020 (519 biopsies on 487 unique patients). Of these 519 histopathology biopsies, 505 had corresponding FNAB report of the same site. The FNAB was reported using the IAC Yokohama system and the most suitable category was allotted in every case. The rates of malignancy for each category and the accuracy of breast FNAB in diagnosing malignancy were calculated., Results: Of the total 487 patients, 120 cases were benign on histology, while 367 were malignant. The rates of malignancy in benign, atypical, suspicious and malignant categories were 5%, 25%, 71%, and 99.7%, respectively. The diagnostic accuracy of atypical, suspicious and malignant categories was calculated as 90.1%, 95.2%, and 93.3%, respectively., Conclusion: The high diagnostic accuracy for each BIRADS category suggest excellent accuracy for Breast FNAB using the IAC Yokohama system., (© 2021 Wiley Periodicals LLC.)

Phyllodes tumor (PT) accounts for less than 1% of all primary tumors of the breast and 2% to 3% of all fibroepithelial lesions. We report a case of heterologous liposarcomatous elements in a malignant PT of the breast on Fine needle aspiration cytology (FNAC) and later confirmed by histopathological examination. A 58-years-old woman presented with a huge breast mass for which FNAC was done. Cytology showed features of malignant PT with a good representation of heterologous liposarcomatous areas. The cytological findings were in concordance with the histologic features. Malignant PT and its various heterologous elements of stroma can be diagnosed on FNA cytology when performed optimally. They can be vital for the preoperative assessment of patients suspected with malignancy to formulate the surgical plan accordingly., (© 2020 Wiley Periodicals LLC.)

Background: The International Academy of Cytology (IAC) Yokohama reporting system was recently proposed to serve as a standardized diagnostic platform for the cytological interpretation of breast fine needle aspiration biopsy (FNAB). Five cytological categories were suggested, linked to a certain risk of malignancy (ROM). The aim of this study was to assess the potency of this newly proposed reporting guideline, with a review of literatures., Methods: This is a retrospective study over 8-year duration in which all the breast FNABs performed in our institution were recategorized in accordance to the IAC Yokohama reporting system. Kappa coefficient was used to evaluate the agreement between the proposed cytological category and corresponding histological diagnosis, with the level of significance set at 5%. Cyto-histopathological correlation and its diagnostic performance were also assessed., Results: A total of 1136 breast FNABs were analyzed, including 31 repeat FNABs. Of these, 521 (47.1%) cases had matched histopathological results. Respective ROM for each category was: "insufficient" 13.6%, "benign" 0.4%, "atypical" 25.0%, "suspicious" 85.7%, and "malignant" 100%. There was substantial agreement (κ=0.757) between cytology and histopathological results. Our data revealed a high-diagnostic specificity, sensitivity, positive and negative predictive value of 99.3% (95% CI: 97.6%-99.9%), 94.2% (95% CI: 87.9%-97.9%), 98.0% (95% CI: 92.5%-99.5%), 98.0% (95% CI: 96.1%-99.1%) respectively when both the "suspicious" and "malignant" cases were considered as positive tests, with area under the curve of 0.993., Conclusions: The IAC Yokohama system is a reliable, evidence-based, and standardized reporting system that helps to facilitate communication among cytopathologists, radiologists, and surgeons toward individualized patient management., (© 2021 Wiley Periodicals LLC.)

We report a case of a 55-year-old woman with left breast cosmetic augmentation performed 5 years earlier, showing at ultrasound a left small amount of peri-implant effusion suspicious for an anaplastic large cell lymphoma localization. The final diagnosis was obtained by cytology using a small amount of fluid (6 ml). Subsequently, hybrid 18F-FDG PET/MRI was used for pre-operative staging and follow-up. An appropriate management of BIA-ALCL could be obtained even in cases of a small amount of peri-implant effusion, using a comprehensive approach of clinical and imaging evaluation, including PET/MRI as useful and innovative staging imaging technique.

Background: The International Academy of Cytology (IAC) Yokohama system is a recently proposed system for reporting breast cytology by fine needle aspiration biopsies (FNAB). Multiple studies are needed to confirm the risk of malignancy (ROM) of the various reporting categories of this system. The present article studies the accuracy of the IAC Yokohama system in our center., Methods: Over a period of 1 year (September 2018-August 2019), all cases of breast masses assessed by FNAB and histological correlation were studied retrospectively. Sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) and overall accuracy of the IAC Yokohama system for diagnosing malignancy were assessed. The rates of malignancy (ROM) of each diagnostic category were also estimated., Results: Three hundred and twenty-one FNABs had cyto-histological correlation. The percent sensitivity (with 95% Confidence Intervals) when the atypical, suspicious of malignancy and the malignant categories were regarded as positive for malignancy were 98.2% [95.5%, 99.5%], 96.0% [92.5%, 98.2%], and 86.7% [81.5%, 90.8%] respectively. The percent specificity (with 95% Confidence intervals) for the same categories in the same order were 59.5% [47.4%, 70.7%], 91.9% [83.2%, 97.0%], and 100% [95.1%, 100%] respectively. The area under curve (AUC) for diagnosing malignancy was 0.981[0.963, 0.993]. The ROM for the benign, atypical, suspicious of malignancy and malignant category were 8.3% [2.3%, 20.0%], 17.2% [5.8%, 35.8%], 77.8% [57.7%, 91.4%], and 100% [98.1%, 100%] respectively., Conclusion: The IAC Yokohama system is suitable for accurately reporting breast lesions on FNAB., (© 2020 Wiley Periodicals LLC.)

Background: Human epidermal growth factor receptor 2-in situ hybridization (HER2-ISH) is widely approved for diagnostic, prognostic biomarker testing of formalin-fixed paraffin-embedded tissue blocks. However, cytologic ISH analysis has a potential advantage in tumor samples such as pleural effusion and ascites that are difficult to obtain the histological specimens. Our aim was to evaluate the clinical reliability of a novel rapid cytologic HER2 fluorescence ISH protocol (rapid-CytoFISH)., Materials and Methods: Using a new device, we applied a high-voltage/frequency, noncontact alternating current electric field to tissue imprints and needle rinses, which mixed the probe within microdroplets as the voltage was switched on and off (AC mixing). Cytologic samples (n = 143) were collected from patients with immunohistochemically identified HER2 breast cancers. The specimens were then tested using standard dual-color ISH using formalin-fixed paraffin-embedded tissue (FFPE-tissue DISH) for HER2-targeted therapies, CytoFISH, and rapid-CytoFISH (completed within 4 h)., Results: All 143 collected cytologic specimens (50 imprinted cytology specimens from resected tumors and 93 liquid-based cytology specimens from needle rinses) were suitable for FISH analysis. The HER2/chromosome enumeration probe (CEP) 17 ratios did not significantly differ between FFPE-tissue DISH and either CytoFISH protocol. Based on HER2 scoring criteria, we found 95.1% agreement between FFPE-tissue DISH and CytoFISH (Cohen's kappa coefficient = 0.771 and 95% confidence interval (CI): 0.614-0.927)., Conclusion: CytoFISH could potentially serve as a clinical tool for prompt determination of HER2 status in breast cancer cytology. Rapid-CytoFISH with AC mixing will enable cancer diagnoses and HER2 status to be determined on the same day a patient comes to a clinic or hospital., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Although fine needle aspiration cytology (FNAC) is highly accurate for detecting breast malignancies, concerns remain among cytopathologists about false-positive and false-negative diagnoses. Cell block (CB) preparations have been advocated by some cytopathologists as one of the methods to improve and consolidate the diagnostic accuracy of FNAC. The aim of this study was to determine the diagnostic utility of CB in FNAC of palpable breast lesions among female patients., Methods: Following FNA, CBs were prepared using 10% neutral-buffered formalin from the residual breast aspirates of 100 consecutive female patients attending the FNAC clinic. The slides of the conventional smears, CB and excisional biopsies were examined, and results were analysed using the SPSS., Results: Of the 100 patients that had FNAC, 44 (44%) had excisional biopsy performed. An additional 13% diagnostic yield for malignancy was obtained with the use of CB preparations. CB reduced equivocal diagnoses by 25%, corresponding with 90.9% improvement on definitive diagnoses., Conclusion: In our setting, the addition of CB to smear remarkably improved the diagnostic utility of breast FNAC by minimising atypical and suspicious for malignancy diagnostic categories., (© 2020 Wiley Periodicals LLC.)

Background: Pathological nipple discharge (PND) is a relatively common symptom of breast cancer affecting the nipple. Mammary ductscopy (MD) allows direct visualization of the ductal lumen and collection of a cytological specimen using duct-washing cytology (DWC). Herein, we clarified the diagnostic efficacy of DWC for the detection of breast cancers with PND, compared with fine-needle aspiration cytology (FNAC)., Methods: We retrospectively examined 48 patients with PND who underwent DWC by MD (ductosccopy group; histologically determined by intraductal biopsy [IDB] or surgical specimen). The results of sensitivity and specificity of DWC were compared with that of FNAC (conventional group; histologically determined by core needle biopsy). Clinicopathological factors were compared between the ductoscopy and the conventional groups., Results: Of eight histologically malignant cases in the ductoscopy group, one case was cytologically judged as malignant and three as indeterminate. Sensitivity and specificity of DWC were 50.0% and 82.5%, respectively. Malignant cases were mostly solid papillary carcinomas (SPCs), and benign cases were intraductal papillomas (IDPs). In the conventional group, sensitivity and specificity of FNAC were 88.0% and 38.2%, respectively, and malignant cases were mainly invasive carcinomas of no special type. Tumors in the ductocsopy group had more favorable prognostic features than those in the conventional group., Conclusion: DWC has limited diagnostic value due to the high incidence of SPC, whose cytological features are indistinguishable from IDP. As DWC alone may be unreliable, comprehensive examination with IDB and MD findings is recommended., (© 2020 Wiley Periodicals LLC.)

Breast ductal cytologic atypia is an important risk factor for sporadic breast cancer. Characterization of the associated normal breast tissue is needed to develop additional methods of risk assessment and new targets for breast cancer prevention. We conducted a prospective clinical trial evaluating women at normal-risk or at high-risk for sporadic breast cancer. Breast ductal cells were collected and studied cytologically and by gene expression profiling, and breast ductal architectural changes were studied by breast ductal endoscopy (BDE) and breast MRI. One hundred and forty subjects were studied, 70 at high risk (RR, 2.0-4.6) and 70 at normal risk. Cytologic atypia was present in 22.9% of high-risk and 25.7% of normal-risk subjects. Ductal endoscopy was performed in 89 subjects and revealed benign intraductal abnormalities, primarily intraductal fibrous webbing suggesting chronic inflammation, in 40.4% of high-risk and 5.4% of normal-risk subjects, respectively ( P 2 = 0.0002). Two high-risk subjects with atypia and no normal-risk subjects with atypia developed invasive breast cancer. Gene expression profiling of ductal cells showed comparable gene expression profiles without enriched expression of previously defined oncogenic signatures in subjects with cellular atypia compared with those without atypia, and in high-risk subjects compared with normal-risk subjects (FDR > 0.5). Cytologic ductal atypia in normal-risk subjects does not appear to be of clinical significance. Atypia in women at high risk may be associated with benign and malignant breast ductal abnormalities; these characteristics of high-risk ductal cells may not be reflected in gene expression profiles., (©2020 American Association for Cancer Research.)

Context.—: Mitotic count is an important histologic criterion for grading and prognostication in phyllodes tumors (PTs). Counting mitoses is a routine practice for pathologists evaluating neoplasms, but different microscopes, variable field selection, and areas have led to possible misclassification., Objective.—: To determine whether 10 high-power fields (HPFs) or whole slide mitotic counts correlated better with PT clinicopathologic parameters using digital pathology (DP). We also aimed to find out whether this study might serve as a basis for an artificial intelligence (AI) protocol to count mitosis., Design.—: Representative slides were chosen from 93 cases of PTs diagnosed between 2014 and 2015. The slides were scanned and viewed with DP. Mitotic counting was conducted on the whole slide image, before choosing 10 HPFs and demarcating the tumor area in DP. Values of mitoses per millimeter squared were used to compare results between 10 HPFs and the whole slide. Correlations with clinicopathologic parameters were conducted., Results.—: Both whole slide counting of mitoses and 10 HPFs had similar statistically significant correlation coefficients with grade, stromal atypia, and stromal hypercellularity. Neither whole slide mitotic counts nor mitoses per 10 HPFs showed statistically significant correlations with patient age and tumor size., Conclusions.—: Accurate mitosis counting in breast PTs is important for grading. Exploring machine learning on digital whole slides may influence approaches to training, testing, and validation of a future AI algorithm., (© 2020 College of American Pathologists.)

Aims: Tumour genotype and phenotype are related and can predict outcome. In this study, we hypothesised that the visual assessment of breast cancer (BC) morphological features can provide valuable insight into underlying molecular profiles., Methods and Results: The Cancer Genome Atlas (TCGA) BC cohort was used (n = 743) and morphological features, including Nottingham grade and its components and nucleolar prominence, were assessed utilising whole-slide images (WSIs). Two independent scores were assigned, and discordant cases were utilised to represent cases with intermediate morphological features. Differentially expressed genes (DEGs) were identified for each feature, compared among concordant/discordant cases and tested for specific pathways. Concordant grading was observed in 467 of 743 (63%) of cases. Among concordant case groups, eight common DEGs (UGT8, DDC, RGR, RLBP1, SPRR1B, CXorf49B, PSAPL1 and SPRR2G) were associated with overall tumour grade and its components. These genes are related mainly to cellular proliferation, differentiation and metabolism. The number of DEGs in cases with discordant grading was larger than those identified in concordant cases. The largest number of DEGs was observed in discordant grade 1:3 cases (n = 1185). DEGs were identified for each discordant component. Some DEGs were uniquely associated with well-defined specific morphological features, whereas expression/co-expression of other genes was identified across multiple features and underlined intermediate morphological features., Conclusion: Morphological features are probably related to distinct underlying molecular profiles that drive both morphology and behaviour. This study provides further evidence to support the use of image-based analysis of WSIs, including artificial intelligence algorithms, to predict tumour molecular profiles and outcome., (© 2020 The Authors. Histopathology published by John Wiley & Sons Ltd.)

Solid basaloid adenoid cystic carcinoma (SB-AdCC) is a subtype of breast AdCC which shows more aggressive clinical behavior than other subtypes. Fine-needle aspiration (FNA) cytology is a useful diagnostic tool for breast malignancies. However, most of the diagnostic cytological characteristics of AdCC are not present in SB-AdCC and cytomorphological studies of this subtype are limited. Here, we evaluated the utility of FNA in the diagnosis of SB-AdCC of the breast. A search of the pathology archives of our institutions for FNA specimens of histologically confirmed SB-AdCC between 2012 and 2019 identified four patients with SB-AdCC of the breast. All patients were female and the average age was 60 years. Cytologically, one case was classified as malignant, two as indeterminate, and one as unsatisfactory. Smears had low to moderate cellularity. All smears showed ribbon-like material surrounding the clusters and a vertical nuclear arrangement toward the peripheral rim. Hyaline globules appeared only in one case. Cells in all cases showed an oval, angular, and spindle shape hyperchromatic nuclei with mild to severe atypia, and also dispersed naked nuclei similar to the cells of the clusters were detected in one case. In histological sections, these cytological findings were compatible with the histological findings and divergent histological differentiation was detected. Diagnosing of few cellular smears of SB-AdCC is difficult whereas the features of peripheral rim of the clusters, naked nuclei, and the divergent differentiation may be important for diagnosing SB-AdCC of the breast., (© 2020 Wiley Periodicals, Inc.)

Mucinous breast cancer is a slow-growing neoplasm, which has fewer lymph node metastases and favorable prognosis compared with invasive breast cancer no special type. The hematogenous spread of breast mucinous carcinoma is very rare. Though breast cancer involving thyroid has been reported before, there is still no report about thyroid metastatic breast mucinous carcinoma in the literature. Recently by performing thyroid fine-needle aspiration, a 58-year-old woman who had breast cancer 13 years ago was diagnosed as thyroid metastatic mucinous breast carcinoma, cellular variant with neuroendocrine differentiation. For this patient, the thyroid was the only involved site without widespread metastatic diseases, so thyroidectomy and the right cervical lymph nodes dissection were performed to make better survival. As a result, the patient had not shown any signs of recurrence 9 months after the thyroid surgery., (© 2020 Wiley Periodicals, Inc.)

Background/aim: Peritoneal fluid (PF) cytology is critical for distinguishing high-grade serous carcinoma (HGSC) from metastatic disease in patients with breast carcinoma who present with peritoneal carcinomatosis (PC)., Case Report: A 50-year-old woman underwent surgery and adjuvant therapy for pT1N0 grade 2/2 luminal A breast carcinoma. Sixteen months postoperatively, palliative chemotherapy was administered following a pleural biopsy and diagnosis of metastatic carcinoma. The patient developed PC despite chemotherapy. PF cytology specimens suggested metastatic carcinoma. However, we observed a papillary cellular arrangement during the review of cytology slides. HGSC was confirmed by immunocytochemistry showing positive paired box 8 (PAX8) and Wilms' tumor 1 (WT1) expression and negative GATA-binding protein 3 expression., Conclusion: In patients with breast carcinoma history, an awareness of characteristic cytomorphology of HGSC, including a papillary pattern with positive PAX8 and WT1 immunoreactivity, is essential to prevent the misdiagnosis of such cases and in ensuring accurate treatment and management., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Recent years have seen a considerable shift to a more conservative management of the axilla in patients with positive axillary sentinel lymph nodes. The aim of this study was to determine whether some breast cancer patients with a preoperative ultrasound-guided needle aspiration biopsy proven positive node could potentially be spared an axillary lymph node dissection according to the ACOSOG Z0011 trial criteria., Patients and Methods: A retrospective review was performed involving 623 breast cancer patients who underwent axillary lymph node dissection after either ultrasound-guided needle aspiration biopsy proven positive node or sentinel lymph node biopsy., Results: Patients with fine needle aspiration biopsy-proven positive node had worse prognosis and a higher nodal burden (6.7 vs 1.9 nodes, p<0.001), compared to those with positive sentinel lymph nodes., Conclusion: Patients with an ultrasound guided needle aspiration biopsy proven positive node are more likely to have tumor with more aggressive pathological characteristics and a higher nodal burden than those with a positive sentinel lymph node biopsy., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Introduction: Telecytology is the practice of cytology at a distance. The images captured by a camera are sent to the cytopathologist at a different location who views the images and reaches a diagnosis. Recently, smartphone-assisted telepathology has been evaluated for different subspecialities of pathology including cytology for second opinion., Materials and Methods: For the purpose of the study, a total of 151 cases of fine needle aspiration and 10 cases of urine cytology reported by a single pathologist were retrieved from the records. The images of all the cases were captured by a trained pathologist using the primary camera of a smartphone from the ocular of a binocular microscope. The images were sent by WhatsApp to the same pathologist who had made the conventional microscopy diagnosis. The images were viewed on the smartphone screen by the pathologist who replied with the diagnosis after analysing all the images with or without digital zoom., Results: A total of 154 cases out of 161 were correctly diagnosed on smartphone-assisted telepathology (overall intraobserver concordance of 95.6%). For head and neck swellings, the concordance was 65/70 (92.9%), for breast lesions, it was 23/24 (95.8%), and for miscellaneous swellings, it was 57/57 (100%). For urine cytology, the concordance rate was 9/10 (90%)., Conclusion: Though the results of this study are encouraging, further improvement in the smartphone camera resolution and internet connectivity would enhance the utility of smartphone-assisted telecytopathology., (© 2020 S. Karger AG, Basel.)

Introduction: Since the late 1970s, sentinel lymph node biopsy (SLNB) has been used for several solid malignancies to identify lymph node metastases. This procedure is associated with less surgical morbidity than complete lymphadenectomy. Recent evidence suggests that axillary lymphadenectomy is not required for breast sentinel nodes with micrometastases (≤2 mm). Current clinical management of sentinel nodes indicates that only macrometastases (>2 mm) should be detected intraoperatively. In Japan, an intraoperative histopathological frozen section (FS) method is used to identify lymph node metastases, but this method takes more than 30 min and requires complex techniques and expensive equipment. Touch imprint cytology (TIC) is an easier, less expensive, and faster method, but its sensitivity has been shown to be low., Objective: The purpose of this study was to determine if TIC is more useful than FS in identifying macrometastases in sentinel lymph nodes in preoperative node-negative breast cancer operations., Methods: A prospective review of 49 consecutive patients with node-negative breast cancer treated with SLNB and intraoperative TIC and FS between November 2017 and June 2019 was performed. TIC samples were stained using Papanicolaou and Diff-Quick stains. Results were compared with routine postoperative paraffin sections., Results: With TIC, the Papanicolaou stain took a mean of 12 min, and the Diff-Quick stain took a mean of 10 min. Results of both TIC stain methods were the same. In contrast, the FS method took a mean of 80 min (including the transfer of specimens to a different hospital with the necessary equipment). TIC confirmed macrometastases in 5 cases. All macrometastases were diagnosed equally by the 2 techniques. Both the sensitivity and specificity of TIC were 100% for detection of macrometastases., Conclusion: TIC of SLNB for breast cancer is an easy and useful method for the detection of macrometastases of breast sentinel nodes., (© 2020 S. Karger AG, Basel.)

Background: A number of guidelines have been developed to improve standardization of the terminology and criteria for cytologic specimens obtained from the thyroid, pancreas, lung, and salivary glands. A major goal of these guidelines is to improve reproducibility and understanding of the reporting of diagnostic results among cytopathologists and between cytopathologists and clinicians. The International Academy of Cytology Yokohama System for Reporting Breast Fine-Needle Aspiration Biopsy Cytopathology (IAC YSRB) is the most recent of these guidelines. The value of this system is, in part, dependent upon interobserver reproducibility., Design: Ninety consecutive fine-needle aspiration biopsies (FNAB) of the breast, performed over a 6-year period, were independently evaluated by 4 board-certified pathologists blinded to the original diagnoses. The 5 diagnostic categories used were those of the IAC YSRB according to published criteria for these categories. Observed agreement and chance corrected agreement (Fliess κ) were calculated. Differences in κ values were evaluated using the T statistic of Gwent. Statistical calculations were performed using STATA v16.0 (STATA Corp., College Station, TX, USA)., Results: Overall agreement between observers was good. Observed unweighted agreement was 69% and weighted agreement was 91%. The majority of diagnoses were concordant (68.6%)., Conclusions: Interobserver agreement of 4 cytopathologists was good using the 5 categories of the IAC YRSB (69%). Agreement was greater among pathologists with more years of experience. The IAC YSRB system appears to provide greater agreement among viewers than guidelines for cytologic specimens obtained from some other body sites (salivary gland and lung). Most discrepancies were only by a single category, with only 22/113 (19%) differing by more than one category., (© 2020 S. Karger AG, Basel.)

Fine needle aspiration cytology has long been an accepted diagnostic modality in combination with physical examination and mammography to investigate breast lesions. In the present era, more proficient methods such as stereotactic mammographically guided breast biopsy is the preferred choice, however, in low resource setting, FNAC still remains the most cost effective and sampling modality to diagnose breast cancer. With the intention to evaluate the efficacy and limitations of FNAC in evaluation of breast lesions in low resource setting, we employed the Masood's cytological staging system to stratify the breast lesions and correlate them with histopathology wherever possible. All breast lesions aspirates were analyzed and classified according to the Masood's cytological scoring system and correlated with histopathological findings wherever adequate material was available. A total of 776 patients were studied of which 23 aspirates were unsatisfactory, 120 aspirates were categorized as inflammatory breast disease. Six hundred and thirty-three cases were classified according to Masood's cytological system. Nonproliferative breast diseases (Group I) encompassed maximum cases with 55% followed by carcinoma in situ and invasive cancers (Group IV) with 39% and proliferative breast disease without atypia (Group II) and with atypia (Group III) which had equal number of cases constituting 2.4% each. Cyto-histopathological correlation done in 102 cases revealed 100% concordance in group IV and 75% concordance in group III while it could not be performed in Group I and II as no histopathological specimen was available in those patients. Masood Cytological grading for breast aspirates is a reliable and an easily reproducible system which can be used to formulate appropriate treatment protocols in cases presenting with breast lesions., (© 2019 Wiley Periodicals, Inc.)

Nipple discharge (ND) either in the presence or in the absence of underlying mass is a very uncommon presentation in males and its bloody nature is still rarer. ND cytology in males has not been reported much in the literature. Spontaneous and expressed ND, however, can be very useful in establishing the diagnosis. Two males with bloody ND, one, without any palpable mass and another with underlying mass, were evaluated on ND cytology. The presence of loose papillaroid clusters and cell sheets with mild atypia was seen in ND smears itself in case 1. The discharge was more copious in case 2, but the ND smears were paucicellular. The presence of tall columnar cells in ND smears as well as in the FNA from underlying mass with clear features of malignancy was helpful in reaching the diagnosis of papillary carcinoma in case 2. Histopathology in case 1 was a spectrum of ADH to DCIS, whereas in case 2, was tubulopapillary carcinoma. Following two cases highlight the importance of the cytological evaluation of ND smears., (© 2018 Wiley Periodicals, Inc.)

Neuroendocrine tumors (NET) and carcinomas (NEC) of the breast are rare diseases, but NEC has attracted attention in both cytopathology and surgical pathology because of its specific management and prognosis. Fine-needle aspiration biopsy (FNAB) cytology can make the diagnosis in many cases particularly with high-grade NEC, with definitive diagnosis based on histopathology and immunohistochemistry. This review describes the characteristics of the disease based on the WHO classification 2012 and recent literature and -includes discussion related to the International Academy of Cytology Yokohama System of Reporting Breast FNAB -cytology., (© 2019 S. Karger AG, Basel.)

Utilization of fine-needle aspiration biopsy (FNAB) cytology for the diagnosis of diseases of the breast has been met with both excitement and uncertainty during the last couple of decades. Presently, FNAB for the diagnosis of primary and metastatic breast lesions is on the rise again. This is probably due to its fast turnaround time, cost efficiency, and minimal invasiveness, characteristics of this sampling modality which are particularly crucial for patients requiring frequent repeat biopsy in the setting of metastatic lesions. In this article, we will briefly review the main modern applications of FNAB of the breast when coupled with contemporary ancillary techniques. Such contemporary ancillary techniques range from classic immunocytochemistry (ICC) to the most modern molecular techniques, particularly next-generation sequencing. Coupled with contemporary ICC and molecular methods, FNAB of the breast can be used for several applications. The applications reviewed in this article include the primary diagnosis of a breast lesion, the identification of the breast as a primary source of a metastatic lesion, the evaluation of breast prognostic/predictive markers, and the tracking of tumor evolution. In our opinion, FNAB of the breast is an ideal sampling method, sharing many of the advantages of truly liquid and of tissue biopsies. Ultimately, we aim at demystifying the complexity of many of the challenges traditionally associated with the application of ancillary techniques to FNAB of the breast and provide insights into some of the most cutting-edge and clinically useful application scenarios., (© 2019 S. Karger AG, Basel.)

Objective: As fine needle aspiration cytology (FNAC) is the primary tool for evaluation of breast lesions, it is essential to segregate lesions with low and high risk of malignancy. To address this, Masood proposed a cytological scoring system for categorization, Masood's Scoring Index (MSI), which was modified later (Modified Masood's Scoring Index [MMSI]). This study analyses the effectiveness of MMSI over MSI and assesses the concordance between cytological scoring and histopathology., Study Design: All breast FNACs over a period of 2 years were categorized based on MSI and MMSI by 2 reviewers independently. The agreement rate along with specificity, sensitivity, positive predictive value, negative predictive value and diagnostic accuracy were calculated. Correlation and concordance analyses between cytological and histopathological categories were conducted., Results and Discussion: Out of 415 cases of breast FNACs, histopathology was available for 310 for which MSI and MMSI were evaluated. The sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy were 95, 100, 100, 97.6 and 98.3%, respectively. The difference between the concordance rate of MSI and of MMSI for various cytological categories was found to be statistically significant., Conclusion: MMSI has a better concordance with histopathological diagnosis than MSI. MMSI can serve as a uniform standardized scoring system for breast cytology for better categorization of proliferative breast diseases., (© 2019 S. Karger AG, Basel.)

Aims: The diagnosis of breast cancer (BC) is based on clinical examination in combination with imaging, and confirmed by pathological assessment of core needle biopsy or fine-needle aspiration biopsy (FNAB). The biological profile of the lesion is needed to define the prognosis and establish therapy. Given the importance of an early and minimally invasive diagnosis, we aimed to verify whether the biological features detected in FNAB-derived cytological material reflect the biological characteristics of surgical samples., Methods and Results: We used immunohistochemistry and fluorescence in-situ hybridisation to study a panel of conventional biomarkers [oestrogen receptor (ER), progesterone receptor (PgR), Ki67, and human epidermal growth factor receptor 2 (HER2)] in FNAB-derived cytological samples included in cell blocks of 93 BC patients, and compared the results with those obtained from histological evaluation of the same parameters in surgical samples. Median immunopositive values of ER, PgR and Ki67 were similar in cell blocks and surgical samples. The concordance rates of ER and PgR between FNAB-derived cell blocks and histological samples were 98% and 84%, respectively. The concordance rates of Ki67 and HER2 between the two sample types were 90% and 96%, respectively. Tumour subtype classification for triple-negative and HER2-positive BCs in FNAB-derived cell blocks was always concordant with the subtype determined in surgical material., Conclusions: We demonstrated that biological marker determination in FNAB-derived cell blocks is feasible, and provides useful information and comparable results to those obtained with histological evaluation. Given the low cost of the procedure and its minimal impact on patients, we believe that cytological samples could be used as an alternative to tissue samples for early BC biomarker evaluation., (© 2018 John Wiley & Sons Ltd.)

Background: For breast cancer patients, a false-negative rate lower than 10% can be achieved if targeted axillary dissection (TAD) is performed, which includes the excision of both biopsy-proven positive lymph nodes (BxLNs) and sentinel lymph nodes (SLNs). However, little evidence exists on the accuracy of intraoperative touch imprint cytology (ITPC) applied in TAD after neoadjuvant chemotherapy (NAC) for breast cancer patients with initial axillary metastasis. This study aimed to investigate the accuracy of ITPC in TAD after NAC., Methods: Breast cancer patients with biopsy-confirmed nodal metastasis were prospectively enrolled in the study. After completion of NAC, all patients underwent TAD followed by axillary lymph node dissection (ALND). Then ITPC was performed to evaluate BxLNs and SLNs. The accuracy of TAD and ITPC was calculated in comparison with hematoxylin and eosin (H&E) staining of ALNs. The results of ITPC during 6 months at our center in the adjuvant setting were used for comparison ., Results: Overall, the false-negative rate of TAD was 10.8%. In a test with 92 patients, ITPC had an accuracy of 92.4%, a sensitivity of 87.9%, and a specificity of 94.9%. In the non-NAC group, ITPC showed similar accuracy (91.2%) and specificity (97.9%) but significantly lower sensitivity (68.9%; P = 0.03)., Conclusions: The use of ITPC was feasible for TAD among breast cancer patients with biopsy-confirmed axillary metastasis who were treated with NAC. All the misses in the ITPC involved patients with micrometastases or isolated tumor cells. Use of ITPC can help decrease the number of second operations for patients with residual disease in ALNs after NAC.

Axillary lymph node status is an independent prognostic indicator in breast cancer. Intraoperative identification of metastatic carcinoma in sentinel lymph nodes may allow for concurrent axillary lymph node dissection at the time of primary tumor excision. A retrospective review of patients undergoing primary breast cancer excision with sentinel lymph node sampling was performed. Sensitivity and specificity of imprint cytology (touch prep) with and without the incorporation of gross evaluation was determined using permanent section results as the gold standard. Five hundred sixteen lymph nodes were analyzed by imprint cytology in 213 patients, and 203 lymph nodes were analyzed in 74 patients incorporating gross examination. Sensitivity and specificity for the detection of macrometastases by touch prep alone were 60% and 99% respectively with 4 patients undergoing same-day axillary dissection for only micrometastatic disease. False negative causes included lack of transfer of malignant cells in 8 cases and misinterpretation of tumor cells in 6 cases. Incorporating gross examination in the modified protocol resulted in reduced sensitivity of 38%, but achieved the desired 100% specificity and positive predictive value. Imprint cytology alone did not reliably distinguish between micro- and macrometastatic disease. Gross assessment combined with imprint cytology allows for improved assessment of volume of axillary disease, but is an insensitive technique., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: The differential diagnosis of fibroadenoma (FA) and ductal carcinoma in situ (DCIS) has been problematic in fine needle aspiration biopsy (FNAC) because it has been difficult to differentiate between the "large epithelial clusters" associated with FA and those associated with DCIS. The purpose of this study was to prospectively validate the usefulness of immunocytochemical staining using cocktail antibody targeting p63/CK14 in the differential diagnosis of FA and DCIS., Materials and Methods: Twenty patients diagnosed as having an uncertain malignant potential (indeterminate) for breast cancer on the basis of a FNAC finding were selected randomly: ten patients with FA and ten with DCIS. The cover glass on a specimen stained with the Papanicolaou stain on a glass slide was peeled off, and the specimen was restained by immunocytochemical staining of cocktail antibody targeting p63 and CK14., Results: Six of the twenty patients were CK14-immunopositive: FA, 6; DCIS, 0. The remaining patients were CK14-immunonegative: FA, 4; DCIS, 10. The number of CK14-immunopositive DCIS patients was significantly different from that of FA patients (P=.0054). Eight out of the twenty patients were p63-immunopositive: FA, 8; DCIS, 0. The remaining patients were p63-immunonegative: FA, 2; DCIS, 10. The number of p63-immunopositive DCIS patients was significantly different from that of FA patients (P=.0004)., Conclusions: Immunocytochemical staining using cocktail antibody targeting p63/CK14 was useful for the differential diagnosis of FA and DCIS in FNAC of the breast., (© 2017 John Wiley & Sons Ltd.)

Background: Due to its heterogeneity, metaplastic breast carcinoma (MBC) poses diagnostic dilemmas, leading to delayed treatment, thereby aggravating the prognosis. Over the years, there has been controversy regarding the role of fine-needle aspiration (FNA) cytology in timely diagnosis., Case Report: A 54-year-old woman presented with a palpable mass in the upper outer quadrant of her right breast with corresponding mammographic findings and FNA was performed. The smears revealed small- and medium-sized cohesive clusters of malignant cells with atypical nuclei. Sporadically, there was a pleomorphic population of notably large mononuclear cells, with disturbance of nuclear/cytoplasmic ratio, and binucleated or multinucleated malignant cells. The presence of chondromyxoid substance with focally embedded cells in a magenta-colored substrate was predominant in the background. These features, along with the corresponding mammographic findings, allowed for high preoperative suspicion of MBC. Surgical resection followed immediately without neoadjuvant chemotherapy; the pathology report led to the definite diagnosis of MBC., Discussion: MBC is a rare clinical entity with unfavorable prognosis, thus early diagnosis is imperative regarding its management. The effectiveness of FNA in the diagnostic algorithm has been questioned, with data from literature being rather contradictory. FNA seems to provide valuable information, which should always be interpreted in correlation with the clinical and mammographic findings., Conclusion: High preoperative suspicion of MBC with the combination of mammography and FNA cytology necessitated the surgical excision of the lesion as the principal treatment approach. Although the role of FNA in the diagnosis of MBC is debatable, its combination with clinical presentation and corresponding mammographic findings may prevent the administration of neoadjuvant chemotherapy in patients with ambiguous indications, given the poor response rate of this cancer subtype., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Introduction: Intraoperative touch imprint cytology (TIC) of the sentinel lymph node(s) (SLN(s)) in the treatment of breast cancer has significantly reduced the number of axillary block dissections (ABD) required during second surgeries. Based on recent studies, ABD was not considered necessary if the presence of tumor cells/micrometastasis was confirmed in the SLN(s) or in the case of macrometastases in a patient group meeting the inclusion criteria for the ACOSOG Z0011 study. Our aim was to determine the sensitivity and usefulness of TIC with regard to these results., Methods: TICs of the SLN(s) were examined in 1168 patients operated on for breast cancer. The method was also analyzed retrospectively based on the guidelines for the Z0011 study. During TIC, new samples were cut every 250 μm; impression smears were evaluated after being stained with hematoxylin eosin., Results: TIC confirmed metastasis in 202 cases (202/1168, 17.29%). Metastasis was confirmed in SLN(s) in 149 additional cases during a final histological examination. The sensitivity of TIC was found to be 57.18%, and its specificity was 99.63%. An analysis was then performed except for cases that met the inclusion criteria for the Z0011 study and with metastasis smaller than 2 mm (micrometastasis/isolated tumor cells) considered to be positive during intraoperative cytology. The sensitivity of the method decreased to 34.23%, while its specificity was still high at 99.76%., Conclusions: Based on the new guidelines for ABD, imprint cytology cannot be considered a beneficial and cost-effective intervention in the surgical treatment of early breast cancer., (Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

The postoperative follow-up strategies for breast carcinoma (BC) utilize different procedures; the aim of this study was to investigate the role of fine-needle cytology (FNC) in the follow-up of BC patients. Two hundred sixty-six FNC samples from 190 BC patients have been reviewed. The target anatomical sites were 190 breast including 155 ipsilateral and 145 contralateral breast lesions and 76 extra-mammary nodules. Extra-mammary lesions included lymph nodes, thyroidal nodules, soft tissue lesions, (subcutaneous and sub-scars), salivary glands and deep located masses. Diagnostic distribution of the breast lesions was as follows: 51 positive, 15 indeterminate/suspicious, 119 negative and 5 inadequate. Positive cases included 43 ipsilateral and 8 contralateral BC, 9 BC in different quadrants from those of onset of the first BC. Sensitivity, specificity and accuracy have been 90, 91 and 90&, respectively. FNC, in a correct setting, is a reliable and effective method for the follow-up management of BC patients.

Objective: The Breast Marker Cocktail from Biocare Medical comprises five antibodies recognising p63, and cytokeratins (CKs) 7, 18, 5 and 14. Immunohistochemistry using this cocktail is useful for diagnosing proliferative intraductal breast lesions. However, cytology using the cocktail has not been reported., Methods: We report 139 cases of mammary samples collected by fine needle aspiration (FNA) for which histological diagnoses were available. After cell transfer, immunocytochemistry was performed using the cocktail, and clusters of cells were classified. A cluster with no or limited CK5/14 expression (<20% of cells) was classified as a monotonous cluster. One with more than 20% of cells showing CK5/14 expression was defined as a mosaic cluster. When at least one p63-positive cell was present, we defined it as a cluster with p63. We also evaluated background p63-positive myoepithelial cell densities., Results: The diagnostic sensitivity and specificity for carcinomas were 97.8% (89/91) and 91.7% (11/12), respectively, using the criterion of two or more monotonous clusters lacking p63. Two false-negative cases were triple-negative cancers; one false-positive was an apocrine papilloma. The numbers of monotonous clusters with p63 differed significantly between benign lesions, ductal carcinoma in situ (DCIS)/lobular carcinoma in situ (LCIS) and invasive carcinomas (P < 0.001). The background myoepithelial cell density was significantly higher in fibroepithelial tumours than in other lesions (P < 0.001)., Conclusions: Immunocytochemistry using this antibody cocktail showed good sensitivity and specificity for diagnosing breast cancers. Thus, this method is useful for mammary cytology using FNA., (© 2016 John Wiley & Sons Ltd.)

Background: The discordance of the hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) expressions between primary cancer and metastatic lesions is an important issue when selecting the optimal treatments for patients with metastatic breast cancer. A rebiopsy for the metastatic cancer is recommended before selecting the treatment; however, it is not easy to take a tissue sample for all metastatic lesions. Fine needle aspiration cytology (FNA) for regional lymph nodes and aspiration for pleural effusions or ascites are less invasive procedures to obtain the necessary samples to examine the HR/HER2 expression. These cytologic materials are able to be stained as a tissue sample using the cell block method., Patients: We examined the HR/HER2 expression of 20 patients with breast cancer (8 with synchronous metastases and 12 with metachronous metastases) using the cell block method. Among 8 patients with synchronous metastases, 7 patients with axillary lymph node (LN) metastasis were examined by fine needle aspiration (FNA), and one patient with pleural metastases was analyzed for the aspirated fluid. While in 12 patients with metachronous metastases, 7 patients were examined for their pleural effusion, 3 patients were examined for regional lymph node metastases, and 1 patient were examined for aspirated ascites. We compared the HR/HER expression between primary cancer and metastatic lesion in 17 patients (5 cases of 8 synchronous metastases, and all of 12 metachronous metastases)., Results: Discordance of HR was seen in 4 of 17 patients (24 %). Three cases with axillary LN metastasis (2 cases with synchronous metastases and one with metachronous metastasis) showed negative change of ER. Negative change of HER2 expression was seen in one patient with ascites caused by peritoneal dissemination., Conclusions: Cytology materials are easily obtained by FNA for LN metastases and aspiration for malignant effusions and analyzed for HR/HER2 expression using cell block method. We should take advantage of cell block analysis to determine the discordance of the HR/HER2 expression to select the optimal treatment for metastatic breast cancer.

Objective: The purpose of this study was to evaluate the utility of core needle biopsy as a diagnostic tool for palpable breast lumps in developing countries as compared to fine needle aspiration cytology., Material and Method: All patients attending the surgery outpatient department with palpable breast lumps were subjected to fine needle aspiration cytology and core needle biopsy by the same operator in a single session. Fine needle aspiration cytology was performed by the standard technique. Core needle biopsy was done freehand using a 14G manual core biopsy needle. Reporting categories of the two techniques were taken from the standard National Health Service Breast Screening Programme criteria and were compared with the final histopathology results., Results: A total of 107 patients underwent fine needle aspiration cytology and core needle biopsy simultaneously. Histopathology was available for 85 cases. Statistical analysis of fine needle aspiration cytology and core needle biopsy showed no significant difference between the diagnoses offered by core needle biopsy and histopathology while there was a significant difference between fine needle aspiration cytology and histopathology diagnoses., Conclusion: Core needle biopsy detected more breast carcinomas as compared to fine needle aspiration cytology with a sensitivity 95.83% as opposed to 64.58%. Though both the techniques were equally specific (100%), Core needle biopsy was able to correctly categorize borderline / inadequate lesions into definitely benign and malignant categories. We suggest that core needle biopsy should be preferred over fine needle aspiration cytology for the diagnosis of palpable breast lumps with fine needle aspiration cytology being reserved for definitely benign lesions.

Background: Fine-needle aspiration (FNA) is well-established as an accurate technique for the diagnosis of palpable breast masses. While the differential diagnosis of such lesions usually focuses on benign or malignant mammary proliferations, a subset of breast neoplasms arises from skin and soft tissue. Skin adnexal neoplasms such as hidradenoma can pose a particular pitfall on breast FNA cytology (FNAC) as epithelial proliferations that are not of ductal or lobular origin., Case: A 59-year-old female presented with a superficial breast mass. FNAC revealed a hypercellular lesion with marked nuclear atypia that was highly suspicious for carcinoma. However, at partial mastectomy, the histological features of the tumor were consistent with atypical hidradenoma. Negativity for estrogen receptor (ER) and progesterone receptor (PR) confirmed the diagnosis. Eighteen years later, the patient remains free of recurrence or metastasis., Conclusions: This report offers the first description of findings of atypical hidradenoma on FNAC. In the breast, its high cellularity and nuclear atypia can mimic a primary mammary carcinoma on FNAC. Although breast and skin adnexal tumors show a immunohistochemical overlap, negative ER and PR stains in a low-grade tumor can suggest a nonmammary lesion. Skin adnexal neoplasms should be considered in the differential diagnosis of superficial breast tumors., (© 2016 S. Karger AG, Basel.)

Background: Specific cytological criteria for the luminal phenotype of breast carcinoma, despite it being the most common and having a better prognosis as well as targeted therapies under study, remain to be established. Using fine-needle aspiration cytology (FNAC), we aimed to identify the luminal phenotype through the evaluation of cytological criteria recognized in routine practice., Methods: We correlated 169 FNACs of breast carcinomas with their tissue specimens, classified into phenotypes by immunohistochemistry (applying tissue microarray technology) as luminal A, luminal B, HER2 overexpression, and triple negative. All FNAC samples were blindly reviewed according to cellularity, cell cohesion, necrosis, nucleoli, and nuclear atypia. Fisher's exact test was used to test associations between the cytological criteria and phenotypes., Results: The following phenotypes were obtained - luminal A: 107 (63.3%), luminal B: 39 (23.1%), HER2 overexpression: 8 (4.7%), and triple negative: 15 (8.9%). The luminal phenotype showed mild/moderate cellularity (40.4%) (OR = 7.12, 95% CI: 1.61-31.52), inconspicuous, present nucleoli (55.5%) (OR = 8.31, 95% CI: 2.36-29.19), and mild/moderate nuclear atypia (44.5%) (OR = 8.42, 95% CI: 1.90-37.25)., Conclusion: The criteria that might indicate the luminal phenotype of breast carcinoma in FNAC were mild/moderate cellularity, inconspicuous, present, and nonprominent nucleoli, and mild/moderate nuclear atypia., (© 2016 S. Karger AG, Basel.)