A review of the directly sampled endometrial cytology on LBC samples: Classification, microscopic criteria and beyond.

The Yokohama System for Reporting Endometrial Cytology (TYS) has been proposed by an expert meeting under the auspices of the International Academy of Cytology (IAC) in May 2016 at the IAC in Yokohama. Since its introduction, the TYS has been receiving worldwide acceptance, and this review aims to assess its global impact. The adoption of endometrial cytology as a diagnostic procedure has been hampered in the past by difficulties arising in interpreting the cellular findings due to a number of factors (such as excess blood, cellular overlapping and the complex physiology of endometrium). Recently, the use of liquid-based cytology (LBC), with its ability to remove blood and mucus and to distribute cells uniformly in a thin layer on the slide, has provided an opportunity to re-evaluate the role of endometrial cytology. LBC is a useful tool in the cytologic diagnosis and follow-up of endometrial abnormalities, which remains complementary to the emerging molecular diagnostic cytopathology. The study of LBC from endometrial cytology could be challenging since it is affected by numerous look-alikes and diagnostic pitfalls. This review discusses these various entities and takes into consideration the ancillary techniques that may be useful in the diagnostic procedure. In conclusion, our review of the published data suggests that the TYS is a valid classification scheme that has been widely accepted by cytopathologists globally, is highly reproducible and makes a valuable contribution to clinical therapeutic management. At present, molecular cytopathology is a rapidly evolving field of modern cytopathology, which underlines the effective interplay between genomics and cytology. This review aims to provide a comprehensive review of the drawbacks of endometrial cytopathology, particularly in terms of endometrial cancer diagnosis and molecular testing.

Design and Progress of Child Health Assessments at Community Support Centers in the Birth and Three-Generation Cohort Study of the Tohoku Medical Megabank Project.

The Tohoku Medical Megabank Project (TMM) has been conducting a birth and three-generation cohort study (the BirThree Cohort Study). We recruited 73,529 pregnant women and their family members for this cohort study, which included 23,143 newborns and 9,459 of their siblings. We designed and are in the process of conducting three-step health assessments for each newborn at approximately ages of 5, 10 and 16. These health assessments are administered at seven community support centers. Trained genome medical research coordinators conduct physical examinations of and collect biological specimens from each participant. The Sendai Children's Health Square has been established as the headquarters for these child health assessments and is utilized to accumulate knowledge that can facilitate the proper practice of child health assessments. We designed all the relevant health assessments facilities to allow parents and their children to participate in the health assessments concomitantly. Our centers serve as places where child participants and their parents can feel at ease as a result of the implementation of safety measures and child hospitality measures. The TMM BirThree Cohort Study is in the process of conducting strategically detailed health assessments and genome analysis, which can facilitate studies concerning the gene-environment interactions relevant to noncommunicable diseases. Through these operations, our study allows for a significant depth of data to be collected in terms of the number of biospecimens under study and the comprehensiveness of both basic and clinical data alongside relevant family information.

A study on preserving endometrial glandular architecture during preparation using BD SurePath™ liquid-based cytology reagents: Cellular fixation with preservative fluid requires at least 18 h.

INTRODUCTION: This study aimed to determine the causes of disruption of the three-dimensional architecture of endometrial glands prepared using BD SurePath™ liquid-based cytology (SP-LBC) reagents. One sample preparation method for endometrial cytology is presented in which this three-dimensional architecture can be retained. METHODS: SP-LBC specimens were prepared by the following three methods: (1) using the BD PrepMateTM (PrepMate) System after cellular fixation for 1-6 h (method A); (2) without using the PrepMate System after cellular fixation for 1-6 h (method B); and (3) using the PrepMate System after cellular fixation for at least 18 h (method C). Size and numbers of endometrial cell clusters and numbers of solitary scattered cells were then evaluated. RESULTS: Significantly higher numbers of cell clusters with a major axis of 200 µm or more were yielded by method C (71.3 ± 57.2) than methods A (9.3 ± 5.9, P < 0.001) or B (44.3 ± 28.8, P < 0.05). Method B yielded significantly higher numbers of cell clusters than method A (P < 0.001). Method A (132.2 ± 107.7, p < 0.001) yielded significantly higher numbers of solitary scattered cells than methods B (29.1 ± 14.8) and C (35.7 ± 23.3). No significant difference in solitary cell numbers was found between methods B and C. CONCLUSIONS: Retention of endometrial glandular architecture is rendered possible by allowing sample fixation times of 18 h or more when preparing specimens using the PrepMate System.

The expression pattern of CD10 and CD31 identifies fine fibrovascular stroma of grade 1-endometrial endometrioid carcinomas in cytology.

INTRODUCTION: The objective of this study was to assess the diagnostic utility of CD10 in the differential diagnosis of grade 1-endometrial endometrioid carcinoma (G1-EEC) and the metaplastic changes associated with the endometrial glandular and stromal breakdown (EGBD) on liquid-based cytological (LBC) samples. METHODS: (1) The type and distribution of CD10-positive cells in EGBD and G1-EEC patients were evaluated. (2) Based on the results from (1), histological and cytological specimens were double-immunostained with CD31 and CD10 to confirm whether CD10-positive tubular-canalicular material found in (1) was represented by fine threads of endometrial-type fibrovascular stroma. (3) Based on the results from (2), additional immunostaining of histological specimens was performed for CD146 and αSMA as markers of perivascular cells. RESULTS: (1) CD10 positive cells showed two main patterns of expression: cytoplasmic immunoreactivity in the form of dense brown granules in EGBD and tubular-canalicular branching patterns in G1-EEC. (2) The tubular-canalicular material observed in cytological specimens of G1-EEC samples co-expressed CD10 and CD31, and was interpreted as representing fine threads of endometrial fibrovascular stroma in the corresponding histological samples. Conversely, metaplastic changes in EGBD cases, only a few CD31-positive signals were found inside the condensed stromal clusters with CD10-positive. (3) Cells surrounding the CD31-positive vascular endothelial cells expressed CD146 and αSMA; moreover, some of the thin CD10-positive fibrous stromal strands also co-expressed αSMA. CONCLUSIONS: CD10 is a very useful immunomarker for distinguishing between G1-EEC and the metaplastic changes of EGBD in LBC samples.

Nuclear morphometry as an adjunct to cytopathologic examination of endometrial brushings on LBC samples: A prospective approach to combined evaluation in endometrial neoplasms and look alikes.

OBJECTIVE: In this study, we aimed to retrospectively investigate and confirm whether atypical nuclear findings in endometrial cytology are useful when assessed by image morphometry in liquid-based cytology (LBC) and compared with microscopic evaluation. METHODS: In total, 53 cases were selected for this study, including 11 presenting proliferative endometrium, 12 with surface papillary syncytial change with endometrial glandular and stromal breakdown (EGBD-SPSC), 10 endometrioid carcinoma grade 1 (G1-EEC), 10 EEC grade 3 (G3-EEC), and 10 endometrial serous carcinomas (ESC). Nuclear image morphometry for nuclear geometric features (area, grey value, aspect ratio, internuclear distance, nucleolar diameter) was performed using ImageJ computer software. For assessing nucleoli, 3861 nuclei were measured, and for nuclear findings, except for nucleoli, 4036 nuclei were measured in total. RESULTS: (a) Compared with G1-EEC, G3-EEC and ESC presented a marked increase in all six parameters (nuclear enlargement, anisonucleosis, nuclear shade, nuclear shape, irregularity of nuclear arrangement, and nucleolar size). (b) EGBD-SPSC presented a marked increase in two parameters (nuclear shade, nuclear shape) when compared with G1/G3-EEC and ESC. (c) Compared with EGBD-SPSC, EEC and ESC demonstrated a marked increase in nucleolar size (≥2.0 µm). (d) ESC presented a marked increase in nucleolar size (≥3.0 µm) when compared with G3-EEC. CONCLUSIONS: Here we confirmed that atypical nuclear findings evaluated by image morphometry are as useful as microscopic evaluations in endometrial cytology. We believe that the objective evaluation of nucleolar size could contribute to an accurate diagnosis of endometrial-LBC samples.

Insulin-like growth factor-II mRNA-binding protein 3 immunocytochemical expression in direct endometrial brushings: Possible diagnostic help in endometrial cytology.

INTRODUCTION: This study evaluated the immunocytochemical (ICC) expression of IMP3 in direct endometrial brushings processed as liquid-based cytology (LBC) samples of endometrioid adenocarcinoma (EAC), serous carcinoma (ESC) and surface papillary syncytial change (SPSC) with endometrial glandular and stromal breakdown (EGBD) to exploit its possible differential diagnostic aid. METHODS: In total, 333 samples of LBC samples were obtained from selected outpatients in parallel with Pipelle endometrial sampling. They consisted of 97 EAC (83 grade 1: EAC-1, 14 EAC-3), 35 ESC and 201 benign endometrial samples (51 proliferative, 42 secretory, 38 atrophic, 70 SPSC with EGBD). ICC expression of insulin-like growth factor-II mRNA-binding protein 3 (IMP3) was manually performed on Papanicolaou-stained LBC samples. RESULTS: The ESC samples showed positive staining cells in 100%, EAC-3 in 28.5%, and EAC-1 in 2.4% cases. All the benign endometrium samples were negative. Only ESC cases showed strong immunoreactivity (≥3+) in more than 50% of tumour cells with an average frequency of 80%. CONCLUSIONS: IMP3 is a helpful immunomarker to distinguish ESC from EAC and SPSC in endometrial cytology.

Evaluation of cellular adequacy in endometrial liquid-based cytology.

OBJECTIVE: This study evaluated cellular adequacy in endometrial liquid-based cytology (LBC) specimens. METHODS: In total, 1267 cases were obtained and the rate of unsatisfactory specimen and diagnostic accuracy for malignancy were assessed. If ≥10 cellular clusters composed of ≤30 endometrial cells were found per specimen, then the sample was provisionally considered adequate. RESULTS: The unsatisfactory rate (with fewer than 10 clusters) was 15.4%. Diagnostic accuracy in specimens with ≥10 clusters was significantly higher (90.5% vs 36.4%) than that in specimens with fewer than10 clusters. Moreover, the unsatisfactory rate in patients aged ≥60 years was significantly higher (33.8% vs 13.2%) than that in patients younger than 60 years. Although the unsatisfactory rate was decreased, significant differences were not found between cases with fewer than five clusters (22.6%) and fewer than 10 clusters (33.8%) in patients aged ≥60 years. Diagnostic accuracy in cases with five or more clusters was significantly higher (90.3% vs 0%) than that in cases with fewer than five clusters. CONCLUSIONS: We propose that ≥10 clusters with ≥30 endometrial cells per cluster could be used as a specimen adequacy criterion for endometrial LBC. If ≥10 clusters cannot be found in patients aged ≥60 years, then the use of the alternative criterion of five or more clusters may yield satisfactory specimen adequacy.

Guidelines for the cytopathologic diagnosis of epithelioid and mixed-type malignant mesothelioma. Complementary statement from the International Mesothelioma Interest Group, also endorsed by the International Academy of Cytology and the Papanicolaou Society of Cytopathology.

OBJECTIVE: To provide practical guidelines for the cytopathologic diagnosis of malignant mesothelioma. DATA SOURCES: Cytopathologists with an interest in the field involved in the International Mesothelioma Interest Group (IMIG) and the International Academy of Cytology (IAC) contributed to this update. Reference material includes peer-reviewed publications and textbooks. RATIONALE: This article is the result of discussions during and after the IMIG 2012 conference in Boston, followed by thorough discussions during the 2013 IAC meeting in Paris. Additional contributions have been obtained from cytopathologists and scientists who could not attend these meetings, with final discussions and input during the IMIG 2014 conference in Cape Town.

Efficacy of CytoLyt® hemolytic action on ThinPrep® LBC using cultured osteosarcoma cell line LM8.

OBJECTIVE: The removal of blood components is necessary to improve the quality of the liquid-based cytology (LBC) preparations. In ThinPrep® (TP) samples a cell suspension in a methanol-based fixative undergoes a vacuum filtration method, whereas in SurePath™ (SP) samples a cell suspension in an ethanol-based fixative is processed through a density gradient centrifugation system prior to gravity deposition of the specimen onto a glass slide. We compared the cyto-architectural features for the cytologic diagnosis of endometrial adenocarcinoma using parallel TP and SP preparations in a previous publication. STUDY DESIGN: We performed our study on LM8 cells (a cultured osteosarcoma cell line). LM8 cells at a concentration of 1.25 × 10(3) cell/cm(2) were seeded on a 35-mm plate in culture medium, which contained 10% fetal bovine serum (FBS), 100 units/ml penicillin, and 100 µ/ml streptomycin in Dulbecco's modified Eagle's medium (DMEM), and aliquots of the cell suspension obtained in this way were compared after the addition of a hemolytic agent, i.e. Cytolyt® (CyL). LBC preparations were then obtained on cell suspensions treated with CyL after different time intervals of hemolysis. RESULTS: Treatment with CyL did not alter the cellularity of the preparation, but reduction of the nuclear area and a tendency towards nuclear chromatin condensation with a subsequent higher brightness were found. Because CyL is a 25% methanol-buffered solution, its alcoholic concentration is low; it was our impression that, while its fixative effect was weak, its hemolytic effect was high. Water influx or efflux through the cell membrane is controlled by osmotic pressure changes induced by the buffer solution in the CyL solution. While CyL was not shown to alter the cell shape, nuclear shrinkage was thought to be probably due to the increasing cell dehydration caused by longer exposure intervals to methanol. CONCLUSION: This study has allowed us to make significant observations on the hemolytic properties of CyL, and on its combined effects with PreservCyt on the cytomorphology of cells suspensions.

Evaluation of endometrial cytology prepared with the Becton Dickinson SurePath™ method: a pilot study by the Osaki Study Group.

OBJECTIVE: To evaluate the sensitivity and specificity of the BD SurePath™ liquid-based Papanicolaou test for assessing the cytology of intrauterine endometrial samples according to newly devised cytological diagnostic criteria and a novel descriptive reporting format. MATERIALS AND METHODS: One hundred and twenty-two endometrial samples were analyzed. All samples were obtained directly from the intrauterine cavity using the Uterobrush or Honest Super Brush. The samples used for the histological examination and cytological tests were collected simultaneously. Our study group devised new cytological diagnostic criteria for examining endometrial samples: the Osaki Study Group method. In this study, histological diagnosis was considered to be the gold standard for cytological diagnosis. A novel descriptive reporting format was also used. RESULTS: Satisfactory cytological specimens were obtained in all cases. The sensitivity and specificity of the SurePath endometrial cytological examination method were 96.4 and 100%, respectively. CONCLUSION: These results indicate that the SurePath method is acceptable for clinical use. Since the SurePath method seems to be easier and allows greater preparation standardization than the conventional method, coupling it with our newly devised cytological diagnostic criteria and descriptive reporting format might represent a reliable diagnostic method for assessing endometrial specimens.

Assessment of the localization of chondroitin sulfate in various types of endometrial carcinoma.

INTRODUCTION: This study aimed to assess the localization of chondroitin sulfate (CS), a primary extracellular matrix component, in the stromal region of endometrial carcinoma (EC). METHODS: Immunostaining was performed on 26 endometrial endometrioid carcinoma (EEC) samples of different grades and 10 endometrial serous carcinoma (ESC) samples to evaluate CS localization. This was further confirmed by Alcian Blue (AB) staining as well. RESULTS: In the G1-EEC samples, CS showed reactivity with fibrovascular stroma, supporting closely packed glandular crowding and papillary structures. As the grade increased, the original interstitial structure was re-established, and the localization of CS in the perigulandular region decreased. In the ESC samples, the thick fibrous strands supporting the papillary architecture showed reactivity with CS; however, the delicate stromal region branching into the narrow region showed poor reactivity. The AB staining results showed similar characteristics to the immunostaining ones. CONCLUSIONS: The characteristic localization of CS in various EC types was elucidated. The present study provides new information on endometrial stromal assessment.

Staining Pattern of Alcian Blue in Endometrial Cytology: Utility in Distinguishing Grade 1-Endometrial Endometrioid Carcinoma from Endometrial Glandular Stromal Breakdown.

Background and Objective: In endometrial cytology, differentiating endometrial glandular stromal breakdown (EGBD) from endometrial endometrioid carcinoma (G1-EEC) is often difficult. In this study, we provided a new focus on chondroitin sulfate (CS), a major substrate component of the endometrial stroma, and assessed the diagnostic utility of Alcian Blue (AB) staining in the differential diagnosis in liquid-based cytological (LBC) samples. Materials and Methods: LBC specimens from 19 patients with a proliferative endometrium, 36 with EGBD, and 30 with G1-EEC who underwent endometrial cytology were stained with AB (pH 1.0), and their reactivity was observed. In addition, immunocytochemical staining of CS and CD31 was performed for five cases each to evaluate their interrelationship with blood vessels. Results: Regarding the 30 G1-EEC cases, at least one of the three representative staining patterns was observed by AB staining: dot-like, microtubular, and finely branched linear patterns. Moreover, the inner portion of the tubular material observed by AB staining expressed CD31. Conversely, in the 36 EGBD cases, only five metaplastic clusters with irregular protrusions and condensed stromal clusters (CSCs) showed a dot-like positive pattern, and background CSCs did not show reactivity to AB staining in any of the cases. Furthermore, the vascular structure expressing CD31 in cell clusters was also unclear. Conclusions: We demonstrated that AB staining shows different staining patterns in G1-EEC and EGBD, reflecting their different tissue structures. Our data provide new insights into endometrial cell diagnosis changes and demonstrate that AB staining is a potential new diagnostic aid tool for the differentiation of G1-EEC from EGBD.

The role of liquid-based preparation in the evaluation of endometrial cytology.

OBJECTIVE: Liquid-based preparation (LBP) of the endometrial lesions is an important diagnostic tool for a variety of endometrial abnormalities because of its simplicity and high quali-quantitative diagnostic yield. We aimed to investigate the LBP method for endometrial cytology to evaluate both benign and abnormal endometrial lesions. STUDY DESIGN: LBP is a semiautomated methodology that has recently become widely available and has gained popularity as a method of collecting and processing both gynecologic and nongynecologic cellular specimens. RESULTS: Some peculiar endometrial cytoarchitectural features were described using LBPs. These were advantageous to screen as compared to conventional slides due to a smaller screening area and an excellent quality of cell preparations. CONCLUSIONS: LBP is a useful tool in the cellular diagnosis and follow-up of endometrial abnormalities, which remains complementary to the emerging molecular diagnostic cytopathology. The study of LBPs from endometrial cytology could be challenging since it is affected by numerous look-alikes and diagnostic pitfalls. This review discusses these various entities and takes into consideration the ancillary techniques that may be useful in the diagnostic procedure.

Tohoku Medical Megabank Brain Magnetic Resonance Imaging Study: Rationale, Design, and Background.

The Tohoku Medical Megabank Brain Magnetic Resonance Imaging Study (TMM Brain MRI Study) was established to collect multimodal information through neuroimaging and neuropsychological assessments to evaluate the cognitive function and mental health of residents who experienced the Great East Japan Earthquake (GEJE) and associated tsunami. The study also aimed to promote advances in personalized healthcare and medicine related to mental health and cognitive function among the general population. We recruited participants for the first (baseline) survey starting in July 2014, enrolling individuals who were participating in either the TMM Community-Based Cohort Study (TMM CommCohort Study) or the TMM Birth and Three-Generation Cohort Study (TMM BirThree Cohort Study). We collected multiple magnetic resonance imaging (MRI) sequences, including 3D T1-weighted sequences, magnetic resonance angiography (MRA), diffusion tensor imaging (DTI), pseudo-continuous arterial spin labeling (pCASL), and three-dimensional fluid-attenuated inversion recovery (FLAIR) sequences. To assess neuropsychological status, we used both questionnaire- and interview-based rating scales. The former assessments included the Tri-axial Coping Scale, Impact of Event Scale in Japanese, Profile of Mood States, and 15-item Depression, Anxiety, and Stress Scale, whereas the latter assessments included the Mini-Mental State Examination, Japanese version. A total of 12,164 individuals were recruited for the first (baseline) survey, including those unable to complete all assessments. In parallel, we returned the MRI results to the participants and subsequently shared the MRI data through the TMM Biobank. At present, the second (first follow-up) survey of the study started in October 2019 is underway. In this study, we established a large and comprehensive database that included robust neuroimaging data as well as psychological and cognitive assessment data. In combination with genomic and omics data already contained in the TMM Biobank database, these data could provide new insights into the relationships of pathological processes with neuropsychological disorders, including age-related cognitive impairment.

Cytologic and immunophenotypic features of CD34+ stem cells in body cavity fluids.

OBJECTIVES: The possibility of leakage of CD34+ bone marrow stem cells from the peripheral blood into the coelomic cavity and the capability of coelomic fluid factors to induce their non-hematogenous differentiation were examined by immunocytochemistry (ICC). STUDY DESIGN: Body cavity fluid smears from 12 and 18 patients with and without cancer, respectively, were processed for double immunoperoxidase or double fluorescent ICC methods using antibodies against CD34, CD14, CD16, CD68, AE1/AE3, epidermal growth factor receptor (EGFR), D2-40, and CA125. RESULTS: Heavily irritated exudative fluid from 6 patients with or without cancer contained a few small round cells positive for CD34. Some of them co-expressed myeloid or monocytic markers such as CD14, CD68 or CD16. Some of the CD34+ cells also co-expressed AE1/AE3 or EGFR. In addition, D2-40 and CA125 were also demonstrated though the expression of the latter was quite sporadic. CONCLUSION: These findings support the concept that CD34+ stem cells can be released into irritated body cavity fluid and the possibility of subsequent differentiation to a non-hematogenous lineage under the influence of local humoral factors, in agreement with our previous in vitro experiments. The possibility of such a phenomenon should be kept in mind when body cavity fluid specimens are analyzed by ICC for diagnostic purposes.

Cytologic diagnosis of central neurocytoma in intraoperative squash preparations: a report of 2 cases.

BACKGROUND: Central neurocytoma is a rare central nervous system tumor typically found in the lateral ventricles and at the spectrum pellucidum. Two patients with central neurocytoma underwent intraoperative frozen section diagnoses, and the cytologic evaluations are described. CASES: Case 1 was a 21-year-old female who complained about reduced visual acuity. Magnetic resonance imaging (MRI) showed enhancement of a ventricular tumor. Over 80% of the tumor was removed, but after 14 months' follow-up, the disease progressed and regrowth occurred. The patient had a second tumor resection with gamma knife surgery. Case 2 was a 30-year-old female who presented with headaches. An MRI showed an enhancement of a ventricular tumor, and complete tumor removal was achieved. Cellular samples of both cases typically revealed ill-defined cytoplarm, oval nuclei with finely granular chromatin and micronucleoli. A fibrillose matrix in the background was noted. A typical appearance of perinuclear halo was also recognized. In both cases histopathologic examination was consistent with a central neurocytoma. Immunohistochemistry of both tumors was synaptophysin(+), NSE (+), NeuN(+), GFAP(-), but MIB-1 labeling index was 3.4% in case 1 and 1.1% in case 2. CONCLUSION: These are 2 illustrative cases in which the authors report cytologic evaluation of central neurocytomna in intraoperative preparations. These tumors possess distinct cellular features that help with the intraoperative distinction from other intraventricular tumors. Moreover, it should be emphasized that immunostains for neural markers are essential for distinguishing them from other clear cell tumors of the brain, especially oligodendroglioma and clear cell ependymomal neoplasm. A combination of imaging, cytomorphology and immunohistochemical features of central neurocytoma can help to differentiate this condition from other intraventricular tumors. It is thought that careful scrutiny of intraoperative preparations allows one to make a distinction.

Cytopathological evaluation of potential malignancy of duodenal gastrinoma using aspiration smears from two patients' resected tumors (NET G1, NET G2): A case report.

Sporadic gastrin-producing neuroendocrine tumors (NETs) of the duodenum present with either Zollinger-Ellison syndrome or unspecific syndromes. Ki-67 scoring in cytopathology is an alternative approach for establishing the gastrinoma grade. Although the majority of NETs, including gastrinomas, occur in the duodenum, most research regarding the Ki-67 index is focused on tumors of pancreatic origin. To the best of our knowledge, there is no study on the Ki-67 index for cytological analysis of duodenal gastrinoma. The current report presents two cases of a 56-year-old man and a 66-year-old woman with NET G1 and G2 gastrinoma, respectively, arising in the duodenal bulb. The present report focused on the differences in nuclear pleomorphism and Ki-67 index between these two cases.

A Diagnostic Approach to Endometrial Cytology by Means of Liquid-Based Preparations.

The adoption of endometrial cytology as a diagnostic procedure has been hampered in the past by difficulties arising in interpreting the cellular findings due to a number of factors (such as excess blood, cellular overlapping, and the complex physiology of endometrium). Recently, the use of liquid-based cytology (LBC), with its ability to remove blood and mucus and to distribute cells uniformly in a thin layer on the slide, has provided an opportunity to reevaluate the role of endometrial cytology. LBC samples are easier to screen compared to conventional ones, due to a smaller screening area and an excellent quality of cell preparations. LBC by using peculiar cytoarchitectural features is a useful tool in the cellular diagnosis and follow-up of abnormalities, which, however, remains complementary to histopathology and to the emerging molecular diagnostic cytopathology. This review discusses these various entities and takes into consideration the ancillary techniques that may be useful in the diagnostic procedure. Herein, we also summarize the process and rationale by which updates were made to the standardized terminology in 2018 and outline the contents of the new Bethesda-style classification (the Yokohama system) for the endometrial cytology.

Imprint cytology of primary cardiac sarcomas: a report of 3 cases.

Primary cardiac sarcomas are rare instances and only occasionally documented in the cytologic literature. Usually, the diagnosis of these rare lesions can be made at echocardiography, aspiration biopsy cytology, cardiac biopsy, and open cardiac surgery (intraoperative diagnosis). In this study, cytologic configurations and immunohistochemistry for 3 primary cardiac sarcomas (rhabdomyosarcoma, angiosarcoma, and malignant fibrous histiocytoma) were revealed. In rhabdomyosarcoma (right ventricle), the tumor cells exhibited an anisocytotic spindle-shaped nuclei with hyperchromasia and an obscure cytoplasmic margin. Vimentin and myosin were positive throughout the cytoplasm for the tumor cells. In angiosarcoma (right atrium), small clusters of anisocytotic spindle-shaped tumor cells appeared as vascular-like structures and hemosiderin-laden macrophages in many erythrocyte-rich backgrounds. Nuclei showed round to oval shape with hyperchromasia and prominent large nucleoli. Cytoplasm was obscure and elongated. Factor VIII related antigen and CD34 were strongly positive throughout the cytoplasm for the tumor cells. In malignant fibrous histiocytoma (right ventricle), the tumor cells exhibited oval to spindle-shaped and elongated nuclei and coarse granular chromatins with hyperchromasia. The nuclear margin was thin. A few small round nucleoli appeared. Elongated obscure and foamy cytoplasm was stained pale blue. Vimentin and alpha(1)-antitrypsin were positive throughout the cytoplasm for the tumor cells. This study elucidated the cellular characteristics and immunohistochemistry for cardiac sarcomas using imprint smears as an aid to cytopathologic diagnosis.

Expression of immunoreactivity and genetic mutation in eosinophilic and ciliated metaplastic changes of endometrial glandular and stromal breakdown: cytodiagnostic implications.

Various metaplastic changes may be present in endometrium, in which also cellular atypias may often be observed. Particularly, eosinophilic and ciliated changes (ECCs) occur in both nonneoplastic and neoplastic endometrium. This may cause confusion in the cytodiagnosis. This study was enterprised to investigate the possible help of immunocytochemical and cytogenetic study in the diagnostic and biologic assessment of ECC cells. In immunocytochemistry for p53 protein, Ki-67, and cyclin A, the material consists of 40 cases of cytologic smears examined by direct sampling of the endometrial cavity comprising 30 cases of ECC in endometrial glandular and stromal breakdown (EGBD) and 10 cases of well-differentiated adenocarcinoma (G1). After cytodiagnosis, immunostaining for p53 protein, Ki-67, and cyclin A was performed on multiple wet-fixed slides from each single case to evaluate the immunoreactivity, intensity of nuclear staining, and nuclear labeling index (N-LI). The intensity of nuclear staining was scored as negative (0), weak (1), moderate (2), or strong (3), and the N-LI was scored as less than 10% (0), from 10% to 25% (1), from 26% to 50% (2), or more than 50% (3), and the final score was calculated by adding both partial scores. A statistical significance test was performed by using Mann-Whitney U test, and the result was judged as significant when the P value was less than .05. For genetic mutation analysis of p53, the material comprised 6 cases of EGBD in which a high score was measured with immunocytochemistry for p53 protein, and the presence of ECC was confirmed on the hematoxylin and eosin. The ECC cells on paraffin-embedded specimens were captured using laser capture microdissection technology. Mutations in p53 gene (exons 5-8) were examined using DNA sequencing analysis. In immunocytochemistry for p53 protein, Ki-67, and cyclin A, the proportions of immunoreactive cells for p53 were statistically higher in ECC compared with those of G1 (P < .05). The proportions of the immunoreactive cells for Ki-67 and cyclin A were statistically higher in G1 compared with those of ECC (P < .05). (2) In genetic mutation analysis of p53, DNA sequencing of p53 in 6 cases revealed no mutations. The percentage of immunoreactive cells for p53 protein were higher in ECC than in G1, but the mutation point was not confirmed in genetic mutation analysis. The differential expression of these biologic parameters in ECC cells could be considered of possible relevance to the cytopathologic diagnosis in the future.