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AIMS: Due to its rarity and non-specific clinical and pathological features, low-grade adenosquamous carcinoma (LGASC) of the breast continues to pose diagnostic challenges. Unlike other triple-negative breast carcinomas, LGASC tends to have an indolent clinical behaviour. It is essential to recognise this lesion for accurate diagnosis and appropriate management. METHODS AND RESULTS: Twenty-five cases of LGASC were identified in our archives and collaborating institutes. Cases of LGASC with dominant coexisting other type carcinomas were excluded. We studied the clinical presentation, morphological features, patterns of the commonly used immunohistochemical stains and follow-up. In our cohort, LGASC was commonly located at the outer aspect of the breast and associated with intraductal papilloma. The morphology of LGASC is characterised by infiltrating small glands and nests with variable squamous differentiation. We also found cuffing desmoplastic (fibrolamellar) stromal change in 75% of patients and peripheral lymphocytic aggregates in 87.5% of patients. P63 and smooth muscle myosin (SMM) were the most common myoepithelial markers used to assist in diagnosis. P63 often stained peripheral tumour cells surrounding invasive glands (circumferential staining in 80% of the cases), mimicking myoepithelial cells. It also stained the small nests with squamous differentiation. However, SMM was negative in 63% of the cases. The vast majority of our cases were triple-negative; only a few had focal and weak expressions of ER and PR. One patient who did not have excision developed lymph node metastasis. Most patients underwent excision or mastectomy with negative margins as surgical treatment; there were no recurrences or metastases in these patients with clinical follow-ups up to 108 months. CONCLUSIONS: LGASC has some unique, although not entirely specific, morphological features and immunohistochemical staining patterns. Fibrolamellar stromal change, peripheral lymphocytic aggregates and variable staining of p63 and SMM are valuable features to facilitate the diagnosis.
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Neoplasias da Mama , Carcinoma Adenoescamoso , Carcinoma de Células Escamosas , Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Carcinoma Adenoescamoso/diagnóstico , Carcinoma Adenoescamoso/patologia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Mastectomia , Mama/patologia , Neoplasias de Mama Triplo Negativas/patologia , Carcinoma de Células Escamosas/patologia , Biomarcadores Tumorais/análiseRESUMO
This article reviewed the identification of breast cancer in the distant metastatic setting through traditional immunohistochemical markers, such as mammaglobin and GATA3, compared with the novel immunohistochemical stain, Trichorhinophalangeal syndrome-1 (TRPS1). We review previous studies evaluating TRPS1 staining, which were conducted using cytology specimens, as well as our recently conducted study evaluating this stain using surgical tissue samples, both from primary and distant metastatic invasive breast carcinoma. In summary, although no immunohistochemical stain is 100% specific or sensitive, in the metastatic setting where tissue available for ancillary studies is limited, TRPS1 was a reliable and even a standalone marker for breast origin, particularly in cases of triple-negative breast cancer.
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Adenomyoepitheliomas (AMEs) of the breast are uncommon and span the morphologic spectrum of benign, atypical, in situ, and invasive forms. In exceptionally rare cases, these tumors metastasize to regional lymph nodes or distant sites. In the era of genomic characterization, data is limited regarding AMEs. The aim of this study was to provide insight into the molecular underpinnings of a spectrum of AMEs. Seven cases of AMEs of the breast (benign-1, atypical-2, in situ-1, invasive-3) were identified in our files. The seven samples were interrogated using the Oncomine Comprehensive Assay v3 (ThermoFisher). Two atypical AMEs and the malignant in situ AME harbored the same gain-of-function PIK3CA mutation. The malignant in situ AME also showed EGFR amplification, not described previously. Both a benign AME and a malignant invasive AME shared the same gain-of-function AKT1 variant. The benign AME also showed a GNAS mutation. Moreover, the same gain-of-function HRAS mutation was present in an atypical AME and a malignant invasive AME. We also identified co-occurring HRAS and PIK3CA mutations in an ER-positive atypical AME, which has not been previously described. No fusion drivers were detected. We describe the molecular characteristics of the spectrum of AME tumors of the breast, which harbor alterations in the PI3K/AKT pathway. Our findings are clinically relevant with respect to the current options of targeted therapy in the rare instances where malignant AME tumors of the breast progress.
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Adenomioepitelioma/genética , Neoplasias da Mama/genética , Classe I de Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Adenomioepitelioma/metabolismo , Adenomioepitelioma/patologia , Adulto , Idoso , Mama/metabolismo , Mama/patologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Classe I de Fosfatidilinositol 3-Quinases/metabolismo , Feminino , Humanos , Pessoa de Meia-Idade , Mutação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores de Estrogênio/genética , Receptores de Estrogênio/metabolismoRESUMO
INTRODUCTION: Flat urothelial lesions fall into one of four diagnostic categories including urothelial carcinoma in-situ (CIS). There is morphologic overlap between the categories leading to immunohistochemistry (IHC) utilization in difficult cases. The purpose of this study was to examine the frequency, variation and utility of IHC use in bladder biopsy specimens over a 17â¯year period. METHODS: A search of "CD44", "p53", and "CK20" keywords was conducted from the pathology files (1/1/2003 to 12/31/2017) on bladder biopsy specimens at our institution. Atypical (AUS), dysplastic (UD) and CIS rates were calculated. RESULTS: A total of 4597 cases were identified. IHC was performed on 345 specimens (7.5%, 345/4597). For cases without IHC (H&E only), the AUS rate was 4.8% (206/4252), UD rate was 9.4% (399/4252), and the CIS rate was 8.4% (359/4252). For IHC cases, the AUS rate was 5.2% (18/345), the UD rate was 8.1% (28/345), and the CIS rate was 11.3% (39/345). There was no statistical difference between the H&E only or IHC rates (pâ¯>â¯0.05). The absolute number IHC orders per year increased until 2011 (60 cases) but drastically declined over the last five years (5 total cases in 2017). The CIS rates have remained relatively constant. CONCLUSION: We found the AUS, UD and CIS rates were similar regardless of IHC use. Our institution was an early adopter of IHC and it quickly fell out of favor. We agree with the ISUP in that IHC has limited clinical utility for flat urothelial lesions and morphology remains the gold standard.
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Biomarcadores Tumorais/análise , Carcinoma in Situ/diagnóstico , Carcinoma de Células de Transição/diagnóstico , Imuno-Histoquímica/estatística & dados numéricos , Neoplasias da Bexiga Urinária/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Myofibroblastic, fibroblastic and/or myoid lesions are rare in the breast but comprise the majority of mammary mesenchymal spindle cell lesions. Whereas most have similar features to their counterparts at extramammary sites, pseudoangiomatous stromal hyperplasia is considered a breast-specific myofibroblastic proliferation on the same spectrum as myofibroblastoma. Other lesions with myofibroblastic/fibroblastic differentiation include fibromatosis and nodular fasciitis, as well as more aggressive tumors such as the rarely reported myofibrosarcoma, inflammatory myofibroblastic tumor and fibrosarcoma. Lesions with myoid differentiation include benign leiomyoma, myoid hamartoma and leiomyomatous myofibroblastoma, but primary leiomyosarcoma and rhabdomyosarcoma may also rarely arise in the breast. Furthermore, fibroepithelial lesions and metaplastic carcinomas can demonstrate myoid metaplasia. Diagnosis can be challenging, particularly on core biopsy, but benign lesions with or without recurrence potential must be distinguished from more aggressive tumors, especially metaplastic carcinoma and phyllodes tumors. This article will review lesions with myofibroblastic, fibroblastic and myoid differentiation in the breast, with special emphasis on differential diagnosis.
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Neoplasias da Mama/patologia , Fibroblastos/patologia , Fibroma/patologia , Miofibroblastos/patologia , Neoplasias de Tecido Muscular/patologia , Biomarcadores Tumorais/análise , Biópsia , Neoplasias da Mama/química , Diferenciação Celular , Diagnóstico Diferencial , Feminino , Fibroblastos/química , Fibroma/química , Humanos , Imuno-Histoquímica , Miofibroblastos/química , Neoplasias de Tecido Muscular/química , Valor Preditivo dos Testes , Prognóstico , Sarcoma/química , Sarcoma/patologiaRESUMO
Breast cancer is the most common cancer in females, affecting one in every eight women and accounting for the majority of cancer-related deaths in women worldwide. Germline mutations in the BRCA1 and BRCA2 genes are significant risk factors for specific subtypes of breast cancer. BRCA1 mutations are associated with basal-like breast cancers, whereas BRCA2 mutations are associated with luminal-like disease. Defects in mammary epithelial cell differentiation have been previously recognized in germline BRCA1/2 mutation carriers even before cancer incidence. However, the underlying mechanism is largely unknown. Here, we employ spatial transcriptomics to investigate defects in mammary epithelial cell differentiation accompanied by distinct microenvironmental alterations in preneoplastic breast tissues from BRCA1/2 mutation carriers and normal breast tissues from noncarrier controls. We uncovered spatially defined receptor-ligand interactions in these tissues for the investigation of autocrine and paracrine signaling. We discovered that ß1-integrin-mediated autocrine signaling in BRCA2-deficient mammary epithelial cells may differ from BRCA1-deficient mammary epithelial cells. In addition, we found that the epithelial-to-stromal paracrine signaling in the breast tissues of BRCA1/2 mutation carriers is greater than in control tissues. More integrin-ligand pairs were differentially correlated in BRCA1/2-mutant breast tissues than noncarrier breast tissues with more integrin receptor-expressing stromal cells. IMPLICATIONS: These results suggest alterations in the communication between mammary epithelial cells and the microenvironment in BRCA1 and BRCA2 mutation carriers, laying the foundation for designing innovative breast cancer chemo-prevention strategies for high-risk patients.
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Proteína BRCA1 , Neoplasias da Mama , Humanos , Feminino , Proteína BRCA1/genética , Proteína BRCA2/genética , Ligantes , Mutação , Genes BRCA1 , Neoplasias da Mama/genética , Neoplasias da Mama/prevenção & controle , Mutação em Linhagem Germinativa , Perfilação da Expressão Gênica , Integrinas , Predisposição Genética para Doença , Microambiente Tumoral/genéticaRESUMO
Background. Classification of phyllodes tumors is challenging due unclear diagnostic criteria, recently addressed by consensus review criteria. Herein, we reviewed all malignant phyllodes tumor resections and reclassified them based on the consensus guidelines, correlating with outcome. We hypothesize that application of criteria would result in a significant proportion being "down-graded" to either borderline or benign phyllodes tumor. Methods. Primary resections of malignant phyllodes tumor were reviewed by four AP board-certified, breast fellowship-trained pathologists. Morphologic variables delineated in consensus guidelines (ie stromal cellularity, cellular atypia, tumor border, presence of heterologous elements, presence of stromal overgrowth) were evaluated. Following review, cases were reclassified as benign, borderline, or malignant. Results. Upon reclassification, 20% (5/20) cases were "down-graded" to borderline phyllodes tumor while 80% (15/20) remained malignant phyllodes tumor. Two morphologic features were statistically significant including broadly infiltrating tumor border in 80% (12/15) of malignant phyllodes tumors compared to none in borderline phyllodes tumor (0/5) (p = 0.004) and stromal overgrowth in 67% (10/15) of malignant phyllodes tumor compared to none in borderline phyllodes tumors (0/5) (p = 0.03). Upon review of the pathology reports, 30% (6/20) contained all 5 histomorphologic variables delineated in the consensus review criteria. Malignant phyllodes tumor resulted in five cases with recurrence (33.3%, 5/15) and three cases with metastases (20.0%, 3/15) and borderline phyllodes tumor resulted in one case with recurrence (20.0%, 1/5) and no metastases (0/5). Conclusion. The consensus guidelines for phyllodes tumor are useful for subclassification. We hypothesize that standardize reporting of the histomorphologic variables may lead to better consensus.
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Neoplasias da Mama , Tumor Filoide , Humanos , Feminino , Tumor Filoide/diagnóstico , Tumor Filoide/cirurgia , Tumor Filoide/patologia , Células Estromais/patologia , Mama/patologia , Patologistas , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/cirurgia , Neoplasias da Mama/patologia , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/patologiaRESUMO
Breast cancer is the most common cancer in females, affecting one in every eight women and accounting for the majority of cancer-related deaths in women worldwide. Germline mutations in the BRCA1 and BRCA2 genes are significant risk factors for specific subtypes of breast cancer. BRCA1 mutations are associated with basal-like breast cancers, whereas BRCA2 mutations are associated with luminal-like disease. There are currently few chemoprevention strategies available for BRCA1/2 mutation carriers, and irreversible prophylactic mastectomy is the primary option. Designing chemo-preventive strategies requires an in-depth understanding of the physiological processes underlying tumor initiation. Here, we employ spatial transcriptomics to investigate defects in mammary epithelial cell differentiation accompanied by distinct microenvironmental alterations in preneoplastic breast tissues from BRCA1/2 mutation carriers and normal breast tissues from non-carrier controls. We uncovered spatially defined receptor-ligand interactions in these tissues for the investigation of autocrine and paracrine signaling. We discovered that ß1-integrin-mediated autocrine signaling in BRCA2-deficient mammary epithelial cells differs from BRCA1-deficient mammary epithelial cells. In addition, we found that the epithelial-to-stromal paracrine signaling in the breast tissues of BRCA1/2 mutation carriers is greater than in control tissues. More integrin-ligand pairs were differentially correlated in BRCA1/2-mutant breast tissues than non-carrier breast tissues with more integrin receptor-expressing stromal cells. These results reveal alterations in the communication between mammary epithelial cells and the microenvironment in BRCA1 and BRCA2 mutation carriers, laying the foundation for designing innovative breast cancer chemo-prevention strategies for high-risk patients.
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Nipple adenoma (NA) is a rare, benign proliferation of the nipple ducts. It may be clinically mistaken for Paget disease or squamous cell carcinoma; thus, microscopic evaluation is paramount. A large case series of NA has not been undertaken since the 1980s. Therefore, we undertook this study to evaluate the clinicopathologic characteristics of NA, emphasizing differential diagnoses and follow-up data. We retrieved 50 cases from our in-house archives or consultation files between 2003 and 2022. Available slides were reviewed, and clinical data and follow-up information were obtained. Cases must have exhibited a dense ductal proliferation in the breast tissue with proximity to the nipple epidermis. All patients were women; median age was 56 years. In all, 68% of patients were symptomatic; 53% demonstrated a skin growth. Overall, 67% were excised completely, either primarily (33%) or via re-excision after biopsy (33%). Four histologic patterns were noted: adenosis (dense proliferation of small-to-medium ducts); large duct (medium-to-large caliber ducts); papillary-like (frond-like architecture with branching, slit-like lumens); and pseudoinfiltrative (ducts squished and distorted by dense stromal fibrosis). Follow-up in 44 patients (88%) with a median time of 66 months showed no evidence of recurrence. NA demonstrates a wide spectrum of histopathologic variation. Subtyping of this entity is unlikely to be clinically relevant. Differentiation from invasive carcinoma or other histologic mimics (syringocystadenoma papilliferum, syringomatous adenoma) may be difficult. Simple excision is curative, and recurrence is rare. A definitive link to invasive carcinoma has not been established.
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Adenocarcinoma , Adenoma , Neoplasias da Mama , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Neoplasias da Mama/patologia , Adenoma/patologia , Mamilos/patologia , Mamilos/cirurgia , Adenocarcinoma/patologiaRESUMO
Introduction: Solitary fibrous tumor (SFT) is a fibroblastic tumor with malignant potential that is underpinned by a recurrent inv12(q13q13)-derived NAB2::STAT6 fusion. Breast and axilla are uncommon locations for this entity. Methods: Records of two academic institutions were electronically searched for breast and axillary SFTs. Clinical and pathologic data were reviewed. Literature review for breast or axillary SFTs was performed. Present study and previously reported tumors were stratified using five SFT risk models: original and modified Demicco metastatic risk, Salas local recurrence risk, Salas metastatic risk, and Thompson local recurrence risk. Results: Five patients with breast or axillary SFT were identified. Median age was 49 years, and median follow-up (available for four patients) was 82 months. Three patients showed no evidence of disease, and one developed recurrence. Literature review identified 58 patients with breast or axillary SFT. Median age was 54 years, and median follow-up (available for 35 patients) was 24 months. Thirty-one patients showed no evidence of disease, three developed recurrence, and one developed metastasis. Original and modified Demicco models and Thompson model showed the highest sensitivity; original and modified Demicco models and Salas metastatic risk model demonstrated the highest specificity. Kaplan-Meier models were used to assess recurrence-free probability (RFP). Original and modified Demicco models predicted RFP when stratified by "low risk" and "moderate/intermediate and high risk" tumor, though sample size was small. Conclusions: While many SFTs of breast and axilla remain indolent, a subset may develop recurrence and rarely metastasize. The modified Demicco risk model demonstrated optimal performance characteristics.
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Many crystals and crystal-like structures may be encountered in cytopathology practice and can represent both beautiful novelties and diagnostic aids. The authors present an organ-specific review of the published literature on crystals combined with personal experiences. The purpose is not only to serve as a reference guide by highlighting the clinical and morphologic features of crystals, crystalloids, and crystal-like structures but also to review their significance and to offer reporting strategies in cases that bear management implications.
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Neoplasias das Glândulas Salivares , Soluções Cristaloides , Humanos , Incidência , Estudos Retrospectivos , Neoplasias das Glândulas Salivares/patologiaRESUMO
CONTEXT.: The American Society of Clinical Oncology/College of American Pathologists updated the human epidermal growth factor receptor 2 (HER2) breast carcinoma testing guideline in 2018 to address issues from uncommon HER2 fluorescence in situ hybridization (FISH) results. Based on the 2013 American Society of Clinical Oncology/College of American Pathologists guideline, cases wherein the HER2/chromosome 17 centromere (CEP17) ratio of 2.0 or more with an average HER2 copy number of less than 4.0 were considered in situ hybridization (ISH) positive. Under the 2018 guideline, such cases are classified as ISH Group 2 and are no longer considered eligible for anti-HER2 therapy when the corresponding HER2 immunohistochemistry result is 0, 1+, or 2+. OBJECTIVE.: To assess the clinical, pathologic, and treatment aspects of patients with ISH Group 2 results. DESIGN.: We retrospectively reviewed HER2 FISH results at our center between January 2012 and December 2014 and identified and characterized cases with ISH Group 2 results. RESULTS.: Thirty-nine cases with ISH Group 2 results from 39 patients were reviewed. Twenty of 39 (51%) patients received anti-HER2 therapy. Patients treated with HER2-targeted therapy were less likely to have hormone receptor-positive tumors, compared with patients without anti-HER2 treatment, though not significantly (P = .30). The only significant difference between the 2 patient groups was receipt of cytotoxic chemotherapy treatment (P < .001). Overall, clinical outcome was similar between the 2 groups (P > .99). CONCLUSIONS.: This retrospective study with median follow-up of at least 6 years shows patients with ISH Group 2 tumors had similar clinical outcomes, irrespective of HER2-targeted therapy. Further analysis in the prospective setting would provide valuable data that would potentially inform clinical decision making.
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Neoplasias da Mama , Variações do Número de Cópias de DNA , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/patologia , Centrômero/genética , Cromossomos Humanos Par 17/genética , Feminino , Humanos , Hibridização in Situ Fluorescente/métodos , Oncologia , Patologistas , Estudos Prospectivos , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Estudos RetrospectivosRESUMO
BACKGROUND: The Paris System for Reporting Urinary Cytology (TPS) uses hyperchromasia as major diagnostic criterion for high-grade urothelial carcinoma (HGUC). The purpose of the study was to evaluate cases that were diagnosed as HGUC by TPS and determine whether there are different chromatin distribution patterns (ie, subsets). METHODS: Digital image annotations were performed on microscopic images of HGUC urine specimens with surgical biopsy/resection follow-up. Median gray values were generated for each cell. Neutrophils (polymorphonuclear leukocyte [PMN]) were also enumerated in each case to serve as an internal control. A HGUC/PMN ratio was generated for each case, and the cases were distributed. RESULTS: Sixty-nine HGUC cases yielded 2660 cells, including 2078 HGUC (30.1 cells/case) and 582 PMNs (8.4 cells/case). The average median gray value of an HGUC was 50.6 and of a PMN was 36.8 (P < .0001). Eight of 69 cases (11.6%) contained nuclei that, on average, were darker than or as dark as a PMN (extremely dark, ie, "India ink"). Fifty-one of 69 cases (74.0%) contained nuclei that, on average, were slightly brighter than a PMN (hyperchromatic). Ten of 69 cases (14.5%) contained nuclei that, on average, were much brighter than a PMN (hypochromatic). Within a single case, all cases showed heterogeneity with the hypochromatic cases showing the most dramatic effect. CONCLUSIONS: Digital image analysis reveals that there are large variations in chromasia between cases including a subset of cases with hypochromasia and another with extremely dark or "India ink" nuclei. There was much heterogeneity of chromasia seen within a single sample.
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Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Neoplasias Urológicas , Carcinoma de Células de Transição/diagnóstico , Carcinoma de Células de Transição/patologia , Citodiagnóstico/métodos , Feminino , Humanos , Masculino , Neoplasias da Bexiga Urinária/patologia , Urina , Neoplasias Urológicas/urina , Urotélio/patologiaRESUMO
INTRODUCTION: Telecytology offers a suitable solution to the cost and time efficiency questions on rapid onsite evaluation (ROSE). An increasing number of institutions are adopting new telecytology systems to meet the increasing ROSE requests, although there is no agreement on the details of how a telecytology validation study needs to be conducted. We propose a standardized approach for telecytology validation studies that could be done in a variety of practices. MATERIALS AND METHODS: Consecutive cases from 6 months prior were chosen to reflect a case mix comparable to real life. A fellow assessed the slides at the ROSE site while 6 cytopathology faculty convened in a conference room with a television screen, and noted the adequacy, diagnostic category, and specific diagnoses. All participants were blinded to the original adequacy assessment and final diagnoses. For each case, evaluation time and the slides counts were noted. RESULTS: Fine-needle aspiration specimens from 52 patients were included in the study. Of these, 13 cases were used in the first "test" session. The adequacy concordance rates ranged between 92.3% and 100%, with an overall concordance rate of 94.8%. The diagnostic category concordance rates ranged between 90.3% and 95.5%, with an overall concordance rate of 91.9%. The specific diagnosis concordance rates ranged between 84.6% and 92.9%, with an overall concordance rate of 88.1%. CONCLUSIONS: Validation of telecytology requires a standardized approach just like any other new technology. In this study, we propose an efficient and accurate method for cytopathology departments of various case volumes to conduct telecytology validation studies.
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Biópsia por Agulha Fina , Biópsia por Agulha Fina/métodos , HumanosRESUMO
We report a case of a 49-year-old female diagnosed with extranodal multifocal Rosai-Dorfman disease (RDD) of the breast using mammography and ultrasound. RDD is a rare non-Langerhans cell benign proliferative disorder of histiocytes that usually involves the lymph nodes, but may involve extranodal sites. We review the clinical presentation as well as imaging features of this rare disease on multiple modalities and the importance of recognizing the diagnosis in order to direct treatment.
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Neoplasias da Mama , Histiocitose Sinusal , Mama/diagnóstico por imagem , Neoplasias da Mama/diagnóstico por imagem , Diagnóstico Diferencial , Feminino , Histiócitos , Histiocitose Sinusal/diagnóstico por imagem , Humanos , Pessoa de Meia-IdadeRESUMO
INTRODUCTION: The Paris System for Reporting Urinary Cytology (TPS) was first published in 2016 to standardize reporting and placed a specific emphasis on high-grade urothelial carcinoma (HGUC). The urinary tract is anatomically divided into the upper tract (UT) and the lower tract (LT). A major morphologic criterion in TPS for HGUC defines the nuclear-to-cytoplasmic (N/C) ratio as ≥ 0.7. In this study, we evaluated N/C ratios of HGUC arising from UT and LT urine specimens, to ascertain differences due to location. MATERIALS AND METHODS: Digital annotations of whole slide scanned images were performed and enumerated. RESULTS: The cohort consisted of 59 ThinPrep specimens from 52 patients. The majority of the tumors were located in LT (39 of 59, 66.1%). A total of 590 cells were analyzed (10 cells per case). In UT, the average N/C was 0.58 and LT the average was 0.54 (P < 0.001). The average nuclear area for UT was 126.3 and for LT was 158.2 µm2 (P = 0.01). The average cytoplasmic area for UT was 219.1 µm2 and for LT was 296.2 µm2 (P < 0.001). The average cellular circumference for UT was 59.4 µm and for LT was 66.1 µm (P < 0.001). CONCLUSIONS: We found that UT HGUCs have higher N/C ratios, smaller cell circumference, smaller nuclei, and less cytoplasm compared with LT. When UT was divided into renal pelvis and ureter, no statistical difference was identified.
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Carcinoma/patologia , Detecção Precoce de Câncer , Urina/citologia , Neoplasias Urológicas/patologia , Urotélio/patologia , Idoso , Idoso de 80 Anos ou mais , Carcinoma/urina , Feminino , Humanos , Masculino , Microscopia , Pessoa de Meia-Idade , Gradação de Tumores , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Urinálise , Neoplasias Urológicas/urinaRESUMO
INTRODUCTION: The Paris System for Reporting Urinary Cytology (TPS) was developed for standardization purposes and it placed an emphasis on screening for high-grade urothelial carcinoma (HGUC). Since then, it has shown to reduce atypia rates and better correlate with surgical specimens. The aim of this study was to calculate the negative predictive value (NPV) of urinary cytology for detecting HGUC using TPS and compare these data to our recently published pre-TPS cohort. As a screening test, it is imperative that TPS has a high NPV. MATERIAL AND METHODS: A search of our institution's pathology database for the term "negative for HGUC" from January 1, 2016, to December 31, 2017, was conducted. A true negative was defined as a patient with at least 1 subsequent negative urine cytology/surgical biopsy specimen or the patient being clinically negative for 6 months. NPV rates were calculated based on the data obtained. RESULTS: The cohort consisted of 2960 urine cytology specimens from 1894 patients. A total of 99 false negatives were identified, generating a NPV of 96.7% (2861/2960). This NPV is identical to our previously published pre-TPS cohort (years 2012-2013; NPV: 96.7%). The clinical indication most effected NPV, with a history of urothelial carcinoma with a NPV of 93.9% followed by hematuria at 98.9%. The atypia rate in years 2012-2013 was 8.2% and in 2016-2017 it was 5.7% (P < 0.001). CONCLUSIONS: We demonstrate that TPS did not alter the NPV for detecting HGUC compared to our pre-TPS cohort. We believe that TPS is an effective reporting system for screening HGUC in urinary cytology.
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Carcinoma/patologia , Detecção Precoce de Câncer , Urina/citologia , Neoplasias Urológicas/patologia , Urotélio/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma/urina , Bases de Dados Factuais , Reações Falso-Negativas , Feminino , Humanos , Masculino , Microscopia , Pessoa de Meia-Idade , Gradação de Tumores , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos , Urinálise , Neoplasias Urológicas/urina , Adulto JovemRESUMO
BACKGROUND: Urine cytology is an important screening tool in the diagnosis of high-grade urothelial carcinoma. Diagnosis in urine samples follows criteria outlined by The Paris System for Reporting Urinary Cytology (TPS). However, cytologic characteristics of the recently described urothelial carcinoma in situ with plasmacytoid features (P-CIS) have not been described, and it is unknown whether they conform to TPS criteria for high-grade urothelial carcinoma. This study was aimed at better characterizing possibly unique cytologic features of P-CIS. METHODS: The authors collected urine cytology specimens from patients with subsequent bladder biopsy-proven P-CIS. Specimens were re-reviewed according to the TPS criteria. The proposed cytologic features of P-CIS (eccentric, enlarged, and hyperchromatic nuclei) were evaluated; this included the reproducibility of 3 cytopathologists for the proposed cytologic features. RESULTS: Seventy-four urine specimens from 18 patients with P-CIS-diagnosed bladder biopsies were identified. The TPS diagnoses of the 74 urine cytology specimens were as follows: negative for high-grade urothelial carcinoma (n = 26), atypical urothelial cells (n = 26), suspicious for high-grade urothelial carcinoma (n = 12), and high-grade urothelial carcinoma (n = 10). Only 7 urine specimens met the proposed cytologic criteria for P-CIS, and they had TPS diagnoses of negative for high-grade urothelial carcinoma (n = 1), atypical urothelial cells (n = 3), and high-grade urothelial carcinoma (n = 3). The κ interobserver agreement ranged from poor to fair. CONCLUSION: The features of P-CIS on urine cytology are subtle and infrequently reproducible and often do not meet the TPS criteria for diagnosis as high-grade urothelial carcinoma. In specimens that do not meet TPS criteria for high-grade urothelial carcinoma, P-CIS cytology in isolation would be best classified as atypical urothelial cells.
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Carcinoma in Situ , Neoplasias Urológicas , Biópsia , Carcinoma in Situ/diagnóstico , Carcinoma de Células de Transição/diagnóstico , Carcinoma de Células de Transição/patologia , Citodiagnóstico , Humanos , Reprodutibilidade dos Testes , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/patologia , Neoplasias Urológicas/diagnóstico , Neoplasias Urológicas/patologiaRESUMO
Urothelial carcinomas of the upper urinary tract (UUT) are uncommon. Cytological examination of voided urine or washings from the UUT has been part of the standard workup for upper tract urothelial carcinoma (UTUC); however, its value remains controversial. The lack of uniform terminology and specific diagnostic criteria could also have contributed to the inferior performance of urinary cytology for detecting UTUC. The Paris System for Reporting Urinary Cytology (TPS) has provided a standardized reporting system for urinary cytology specimens with clearly defined cytomorphologic diagnostic criteria and found acceptance on an international level after its implementation in 2016. Recent studies have shown that TPS has led to improved diagnostic performance of urinary cytology; however, most of these studies had focused on the evaluation of lower urinary tract cytology specimens. Only a limited number of new research studies have analyzed the effect of TPS when applied to UUT cytology specimens. In the present report, we have summarized the current understanding and utility of UTUC, including its molecular biology, and reviewed the current literature.