Cytopathologic differential diagnosis of low‐grade urothelial carcinoma and reactive urothelial proliferation in bladder washings: a logistic regression analysis

Conventional cytomorphologic assessment is the first step to establish an accurate diagnosis in urinary cytology. In cytologic preparations, the separation of low‐grade urothelial carcinoma (LGUC) from reactive urothelial proliferation (RUP) can be exceedingly difficult. The bladder washing cytologies of 32 LGUC and 29 RUP were reviewed. The cytologic slides were examined for the presence or absence of the 28 cytologic features. The cytologic criteria showing statistical significance in LGUC were increased numbers of monotonous single (non‐umbrella) cells, three‐dimensional cellular papillary clusters without fibrovascular cores, irregular bordered clusters, atypical single cells, irregular nuclear overlap, cytoplasmic homogeneity, increased N/C ratio, pleomorphism, nuclear border irregularity, nuclear eccentricity, elongated nuclei, and hyperchromasia (p ? 0.05), and the cytologic criteria showing statistical significance in RUP were inflammatory background, mixture of small and large urothelial cells, loose monolayer aggregates, and vacuolated cytoplasm (p ? 0.05). When these variables were subjected to a stepwise logistic regression analysis, four features were selected to distinguish LGUC from RUP: increased numbers of monotonous single (non‐umbrella) cells, increased nuclear cytoplasmic ratio, hyperchromasia, and presence of small and large urothelial cells (p = 0.0001). By this logistic model of the 32 cases with proven LGUC, the stepwise logistic regression analysis correctly predicted 31 (96.9%) patients with this diagnosis, and of the 29 patients with RUP, the logistic model correctly predicted 26 (89.7%) patients as having this disease. There are several cytologic features to separate LGUC from RUP. Stepwise logistic regression analysis is a valuable tool for determining the most useful cytologic criteria to distinguish these entities.     

Cytopathologic differential diagnosis of malignant mesothelioma, adenocarcinoma and reactive mesothelial cells: A logistic regression analysis

Distinguishing malignant mesothelioma, adenocarcinoma and reactive mesothelial proliferation in both cytologic and surgical pathologic specimens is often a diagnostic challenge. Conventional cytomorphologic assessment is an important step in the differential diagnosis of these entities.The pleural effusion cytologies from 40 cases of malignant mesothelioma, 40 cases of adenocarcinoma and 30 cases of reactive mesothelial proliferation diagnosed between 1997 and 2007 were reviewed. Twenty-seven cytologic features which are regarded as useful in the differential diagnosis of mesothelioma, adenocarcinoma and benign mesothelial proliferation were assessed. These cytologic features were subjected to a stepwise logistic regression analysis. Three features were selected to distinguish malignant mesothelioma from adenocarcinoma: giant atypical mesothelial cell (P = 0.0001), nuclear pleomorphism (P = 0.0001) and acinar structures (P = 0.0001), the latter two being characteristics of adenocarcinoma. The variables selected to differentiate malignant mesothelioma from reactive mesothelial cells were: cell ball formation (P = 0.0001), cell in cell engulfment (P = 0.0001) and monolayer cell groups (P = 0.0001), the latter being a feature of benign mesothelial proliferation. When these selected variables were subjected to a stepwise logistic regression analysis, the logistic model correctly predicted 90% of cases of benign mesothelial proliferation versus 97.5% of malignant mesothelioma and 92.5% of malignant mesothelioma versus 92.5% of adenocarcinoma.Conventional cytomorphologic assessment is the first step to establish an accurate diagnosis in pleural effusions. Several cytologic features have predictive value to separate malignant mesothelioma from adenocarcinoma and reactive mesothelial proliferation.     

Cytomorphologic features of metastatic urothelial carcinoma in serous effusions

Metastatic urothelial carcinoma (UC) to serous effusion (SE) is extremely rare and its cytomorphological features have only been described in case reports. In this study, we searched the pathology database at University of Michigan for SEs due to metastatic UC in the last 20 years. A total of 25 cases from 20 patients with clinically and pathologically confirmed metastatic UC in SEs were retrieved. The specimens consisted of 15 pleural, 8 peritoneal, and 2 pericardial effusions. Smears were reviewed and evaluated for the following features: cellularity, single cells, cell clusters or short cords, cell wrapping, “windows” between the cells, two‐tone cytoplasm, cytoplasmic vacuoles, signet ring cells, nuclear to cytoplasmic (N/C) ratio, nuclear hyperchromasia, irregular nuclear membrane, nuclear centricity, double or multiple nuclei, nucleoli, anaplastic cells and mitosis. Our results showed that UC manifested in SEs predominantly as a single cell population with or without clusters or short cords, and frequently exhibited the “cell wrapping” of two or more cells. Individual UC cell in SEs exhibited nuclear enlargement with increased N/C ratio, irregular nuclear membranes, hyperchromatic coarse chromatin and frequently prominent nucleoli. Double or multinucleated cells, cells with vacuolated cytoplasm or signet ring appearance were also frequently present. Our results demonstrated that while certain features could suggest the diagnosis of UC, the cytomorphological features are not specific and often overlap with those of reactive mesothelium, mesothelioma, metastatic adenocarcinoma, or squamous cell carcinoma in SEs. Accurate diagnosis of UC rests on the combination of clinical history, cytomorphologic features and appropriate immunohistochemical panel. Diagn. Cytopathol. 2013. © 2012 Wiley Periodicals, Inc.     

Fine‐needle aspiration of gray zone lesions of the breast: Fibroadenoma versus ductal carcinoma

While breast lesions have characteristic cytological features, some lesions, particularly adenocarcinoma and fibroadenoma, may present with overlapping features causing erroneous diagnoses. The current study aimed to define significant cytomorphologic features predictive of fibroadenoma and adenocarcinoma, respectively. Further, we intended to evaluate the predictive characteristics for differentiation between gray zone lesions and to identify root causes contributing to misdiagnoses. First, direct smears prepared from 14 histology‐confirmed fibroadenomas and 14 adenocarcinomas were reviewed and characteristics of commonly encountered morphologic features were assessed. We then retrospectively and blindly reviewed nine cytohistologic discrepant cases using the significant characteristic as a guideline, in order to assess whether these discrepant cases could be correctly categorized. Morphologic characteristics predictive of fibroadenoma included moderate cellularity, large, folded cellular sheets/aggregates, staghorn projections, smooth and round borders, monolayers, honeycomb arrangement, smaller nuclear size, and background bipolar cells. Predictive characteristics of adenocarcinoma included high cellularity, loose cohesive sheets/aggregates, pointed projections, irregular borders, larger nuclear size, irregular nuclear membrane, prominent nucleoli, and single atypical epithelial cells. Retrospective, blind review correctly re‐classified seven out of nine cytohistologic discrepant cases, including five false negative cases and two false positive cases. Root causes contributing to the misdiagnoses were large branching sheets of carcinoma mimicking folded sheets of fibroadenoma; fibroblasts mimicking myoepithelial cells; apocrine cells mimicking carcinoma cells; and not recognizing the loose myxoid matrix presenting as soap bubbles in fibroadenoma. In conclusion, this study identified significant characteristics that can assist in achieving accurate diagnosis in a subpopulation of breast aspirates that present with overlapping features. Diagn. Cytopathol. 2013;41:806–811. © 2012 Wiley Periodicals, Inc.     

Atypia in fine-needle aspiration cytology of the breast: a histologic follow-up study of 301 cases

A gray area of uncertainty exists in fine-needle aspiration (FNA) cytology of the breast in which common criteria to distinguish benign from malignant lesions overlap. Aims of this study were to define this area and to evaluate statistically cytomorphologic criteria in a semiquantitative analysis. In a test set of specimens from well-differentiated carcinomas and benign proliferative lesions, signs of malignancy were cell dissociation, arrangement in small clusters, nuclei greater than 16 microns, anisonucleosis, irregular nuclear borders, nucleoli, and necrosis. Features in favor of benignancy were large monolayers, nuclei less than 16 microns without variation in size, smooth nuclear borders, and bipolar nuclei in the monolayers. Originally the term "atypia" had been applied to 956 (12%) of all FNAs of the breast performed at our institute from 1974 to 1985. Using these criteria in a review of all 301 cases in which histologic follow-up and cellular smears were available, much better results were obtained than originally; specificity increased from 80% to 95%, and sensitivity increased from 60% to 90%. The number of overdiagnoses decreased from 24 to seven, and underdiagnoses decreased from 57 to nine. In this selected series, the area of uncertainty was restricted to 16% of the cases; the number of these cases that proved to be malignant and benign was equal. In such cases of indistinct cytomorphologic criteria, a surgical biopsy is indicated for histologic studies.     

Cytopathology of malignant mesothelioma: a stepwise logistic regression analysis.

Twenty-four cytologic features, previously reported to be useful in the distinction of malignant mesothelioma, adenocarcinoma, and benign mesothelial proliferation in serous effusions were assessed. Forty-four cases of malignant mesotheliomas, 46 cases of metastatic adenocarcinomas, and 30 cases of benign mesothelial proliferations were examined for these parameters. When these cytologic features were subjected to a stepwise logistic regression analysis, five features were selected to distinguish malignant mesothelioma from adenocarcinoma. These were true papillary aggregates, multinucleation with atypia, cell-to-cell apposition, acinus-like structures, and balloon-like vacuolation, the latter two features being characteristic of adenocarcinoma. The four variables selected to distinguish malignant mesothelioma from benign mesothelial proliferations were nuclear pleomorphism, macronucleoli, cell-in-cell engulfment, and monolayer cell groups, the latter being a feature of benign proliferations. Using these selected variables, the logistic model correctly predicted 95.4% of cases of malignant mesothelioma versus 100% of adenocarcinoma and 100% of malignant mesotheliomas versus 90% of benign mesothelial proliferations. The results of regression analysis suggest that many of the previously described cytologic features are not important diagnostic discriminators.     

Cytological features of lung adenocarcinoma with micropapillary pattern in the pleural or pericardial effusion: analysis of 5 cases

Micropapillary pattern is a distinct histopathological pattern, and usually shows a high frequency of lymphatic invasion and lymph node metastases. This pattern is also reported in lung adenocarcinoma, however, only one cytological report of lung adenocarcinoma with micropapillary pattern has been reported. In this study, we analyzed the cytological features of this type of carcinoma in the pleural or pericardial effusion. This study was comprised of 5 consecutive cases of lung adenocarcinoma with micropapillary pattern, in which the tumor cells were present in the pleural or pericardial effusion and whose diagnoses were histopathologically confirmed. The characteristic cytological findings in the pleural or pericardial effusion were as follows: i) tightly cohesive small nests of tumor cells showing papillary structure without fibrovascular core, ii) these nests were comprised of approximately 5-20 tumor cells, iii) cauliflower-like and acinar-like structures were also observed, iv) intracytoplasmic vacuoles were observed in 40% of the cases, and v) the neoplastic cells had large round to oval nuclei containing coarse chromatin and occasional conspicuous nucleoli. It has been reported that the presence of micropapillary structure and intracytoplasmic vacuolation are also characteristic cytological features of micropapillary carcinoma of the urinary bladder, therefore, they are thought to be common cytological features of carcinomas with micropapillary pattern. Consequently, detection of these features can lead to a cytodiagnosis of lung adenocarcinoma with micropapillary pattern in the pleural or pericardial effusion. Recognition of these features is important because this type of tumor shows an aggressive clinical course.     

Low-grade urothelial carcinoma: reappraisal of the cytologic criteria on ThinPrep

The diagnostic criteria for low-grade urothelial lesions that have been described in the past were based on urinary specimens prepared by the cytospin method. Recognizing the recent popularity of the ThinPrep methodology and the cytologic alterations it introduces to the cellular features, we sought to evaluate the reproducibility of these criteria in ThinPrep urinary samples. One hundred twenty-six ThinPrep urinary specimens with a tissue diagnosis of low-grade urothelial carcinoma (LGUC) and 45 negative controls were evaluated. Three pathologists blindly reviewed the slides separately and the consensus on each feature was used in the study. Logistic regression analysis was used to determine which criteria in combination were most predictive of low-grade urothelial carcinoma. All specimens were evaluated for the following 18 features: nucleus/cytoplasm ratio, irregular nuclear border, cytoplasm homogeneity, cell clusters, high cellularity, prominent nucleoli, granular nuclear chromatin, hyperchromasia, acute inflammation, vesicular chromatin, nuclear molding, nuclear eccentricity, elongated nuclei, necrosis, anisonucleosis, irregular bordered fragments, absent cytoplasmic collar, and peripheral palisading. High nucleus-to-cytoplasm ratio, irregular nuclear borders, and homogeneous cytoplasm (combination sensitivity of 59% and specificity of 100%) were the best predictive features for LGUC. Minor predictive criteria were eccentric nuclei and nuclear molding. ThinPrep provides well preserved, cleaner specimens without significantly altering the morphology. The three key criteria applied in cytospin specimens to diagnose LGUC were reproducible in ThinPrep specimens.     

Atypical granular cell tumor of the thyroid: cytomorphologic features on fine needle aspiration

Granular cell tumors are uncommon soft tissue neoplasms of nerve sheath origin, which are predominately benign and are characterized by abundant granular cytoplasm, uniform nuclei, and indistinct cell borders. Features of malignancy include spindle cell morphology, necrosis, prominent nucleoli, increased nuclear to cytoplasmic ratio, nuclear pleomorphism, and increased mitotic rate. Granular cell tumors are most common in the soft tissues of the head and neck, but have only been rarely described in the thyroid gland. Here we report a case of an atypical granular cell tumor of the thyroid seen on fine needle aspiration, which displayed focal atypical cells with spindle cell morphology, increased nuclear to cytoplasmic ratio, and prominent nucleoli. The differential diagnosis of such findings is also presented.     

Pancreatic adenocarcinoma: regression analysis to identify improved cytologic criteria

The incidence of pancreatic adenocarcinoma is increasing and it is usually unresectable at the time of diagnosis. Consequently, fine-needle aspiration biopsy (FNAB) is being used more frequently for diagnosis. The reported sensitivity of diagnosing pancreatic adenocarcinoma by FNAB has varied between 50% and 100%. In an attempt to increase the diagnostic sensitivity, we retrospectively reviewed a series of pancreatic FNABs. Fifteen cytologic criteria were evaluated in 78 patients who had pancreatic FNABs. Of these patients, 49 had primary adenocarcinomas and 29 had benign, non-neoplastic lesions. Using a stepwise logistic regression analysis we identified three key cytologic criteria for this diagnosis. Our study identified anisonucleosis (P = 0.001), large nuclei (P = .007), and nuclear molding (P = .03) as the significant cytologic features for diagnosing pancreatic adenocarcinoma. In combination, these three criteria had a sensitivity of 98% and a specificity of 100%.     

The value of ThinPrep and cytospin preparation in pleural effusion cytological diagnosis of mesothelioma and adenocarcinoma

The diagnosis of malignant mesothelioma requires an integration of the clinical presentation, radiological studies, and immunohistochemical stain of histological sections. Cytological diagnosis on pleural effusions of mesothelioma and pulmonary adenocarcinoma is highly desirable but debatable. A spectrum of cytological features has been found to be associated more commonly with malignant mesothelioma (e.g., peripheral cytoplasmic skirt, bubbly cytoplasm, cyanophilic cytoplasm, and scalloped border of cell balls) vs. adenocarcinoma (e.g., two-cell population, inspissated cytoplasmic material, cytoplasmic vacuole, angulated and indented nuclei, and smooth border of cell balls) to only name a few. The current study is designed to assess whether the introduction of a liquid-based technology such as ThinPrep (TP) can provide additional diagnostic value in addition to the conventional cytospin Diff-Quik (DQ) preparations. Pleural effusion specimens were prepared with split samples for DQ-stained cytospin and Papanicolaou-stained liquid-based TP. Fifteen pleural effusion samples with immunohistologically confirmed malignant mesothelioma and 13 pleural effusion samples of immunohistologically confirmed pulmonary adenocarcinomas were retrieved from our files. Both DQ cytospin- and Papanicolaou-stained TP slides were evaluated for the known cytological features associated with malignant mesothelioma (25 cytological features) and adenocarcinoma (22 cytological features) without knowledge of the original cytological and histological diagnoses. The McNemar test was used to compare these two cytological preparations for both malignant mesothelioma and pulmonary adenocarcinoma. In the malignant mesothelioma group, 4 of 25 cytological features evaluated, bubbly cytoplasm (P = 0.002), vacuolated cytoplasm (P = 0.005), cell-in-cell arrangement (P = 0.007) and irregular nuclear contour (P = 0.083), were seen more frequently in the DQ cytospin preparation, as opposed to only one feature, nuclear size enlargement (P = 0.008), more readily seen using TP. In the pulmonary adenocarcinoma group, only 1 of 22 cytological features evaluated, presence of angulated or indented nuclei (P = 0.025), was seen more frequently in DQ as opposed to two features, presence of two- cell population (P = 0.04) and presence of micropapillary structures (P = 0.1), were seen more readily in TP. All other cytological features evaluated distinguishing mesotheliomas (20 features) and pleural adenocarcinomas (19 features) were seen equally readily in both types of specimen preparation techniques. This study suggests that the liquid-based TP preparation of pleural effusions does not appear to provide additional diagnostic value when compared with the DQ cytospin preparation in the cytological distinction between mesothelioma and adenocarcinoma in pleural effusions. Most cytological features evaluated, 20 of 25 (mesothelioma) and 19 of 22 (adenocarcinoma), can be seen in both preparation techniques.     

Cytomorphological criteria,subclassifications of endocervical glandular cell abnormalities,and histopathological outcome: A frequency study

The objective of this study was to evaluate the frequency and the significance of cytomorphological criteria defined in studies as being predictive of neoplasia in cervical smears of women with a cytological diagnosis of atypical glandular cells (AGC) or adenocarcinoma in situ (AIS). Women (n = 103) with cytological findings suggestive of AGC or AIS, whose diagnoses were later established by histopathology, were included in the study. The criteria analyzed and classified as present or absent in cervical smears previously classified as AGC‐NOS (not otherwise specified), AGC‐FN (favor neoplasia), or AIS were as follows: irregular nuclear membranes; scanty cytoplasm; dyskeratotic cells; increased nuclear/cytoplasmic ratio; nucleoli; overlapping; papillary clusters, feathering; loss of polarity; nuclear enlargement; coarsely granular chromatin; and pseudostratified strips. Histopathology resulted in neoplastic diagnoses in 55 cases (53.3%) and nonneoplastic diagnoses in 48 cases (46.6%). Coarsely granular chromatin was observed in 62.5% of cases with a diagnosis of neoplasia. Feathering was present in 80% of cases of histopathological AIS. Loss of polarity and coarsely granular chromatin were significantly associated with neoplastic diagnosis considering all subcategories of glandular abnormalities diagnosis. In AGC‐SOE subclassification, coarsely granular chromatin was significantly associated with neoplastic diagnosis. The presence of nucleoli was significantly associated with neoplastic diagnosis in cervical smears qualified as AGC‐FN and AIS. Nuclear enlargement, increased nuclear/cytoplasmic ratio, coarsely granular chromatin and overlapping cells were found in all the subclassifications of glandular cell abnormalities irrespective of the histopathological results. Chromatin aspects, polarity, and presence of nucleoli can predict neoplasia. Diagn. Cytopathol. 2010;38:806‐810. © 2010 Wiley‐Liss, Inc.     

Use of the ThinPrep method in bile duct brushings: analysis of morphologic parameters associated with malignancy and determination of interobserver reliability

Recent work suggests the ThinPrep method can improve diagnostic sensitivity and accuracy in bile duct brushings. However, the proportion of atypical and suspicious diagnoses remains high. The aim of this study was to identify the most useful morphologic features in ThinPrep bile duct cytology and evaluate interobserver reliability. We evaluated 100 bile duct brushings prepared by ThinPrep, all with either histology or long term clinical follow-up (55 malignant, 45 benign). Morphologic features were evaluated by four experienced cytopathologists blind to clinical information and follow-up diagnoses. These features included cellularity, blood or diathesis, mitoses, inflammation, three-dimensional groups, discohesive atypical cells, macronucleoli, well-defined cytoplasmic borders, and nuclear features of malignancy (nuclear membrance irregularity, chromatin clumping). The data were analyzed by intraclass correlation (ICC) and stepwise multiple logistic regression. Reviewers showed unanimous agreement in 29% of cases, one degree of disagreement in 58% of cases, and full disagreement in 13% of cases. Of benign cases, 38% were thought to be diagnostic of malignancy by at least one of the four reviewers. Sensitivity for the morphologic parameters varied from 18 to 67%; the highest sensitivity was for discohesive atypical cells, well-defined cytoplasmic borders, nuclear features of malignancy, and cellularity (67, 62, 51 and 46%, respectively). Specificity of parameters varied from 16 to 100%; the highest specificity was for mitoses, three-dimensional groups, nuclear features of malignancy, and macronucleoli (100, 98, 93, and 93%, respectively). Interobserver reliability (ICC) was very good for specimen cellularity (0.72) and nuclear features of malignancy (0.60). In logistic regression analysis, only nuclear features of malignancy and increasing patient age separated benign from malignant. On ThinPrep bile duct brushings, nuclear features of malignancy are most useful in distinguishing benign from malignant, and interobserver reliability for this parameter is very good. Discohesive atypical cells show moderate sensitivity and specificity, while three dimensional clusters and macronucleoli are specific but not sensitive for malignancy, and are not significant in multivariate logistic regression models. The relatively high proportion of benign cases thought to be diagnostic of malignancy by at least one reviewer argues for a consensus approach to this diagnosis.     

Malignant pleural effusion from papillary thyroid carcinoma diagnosed by pleural effusion cytology: A case report

Papillary thyroid carcinoma (PTC) is by far the most common thyroid malignancy (over 85%) of all the thyroid cancers. It has excellent prognosis and 10‐year survival rate in most of the cases (95%). Most of the tumors are indolent and do not recur or metastasize after removal. However, widespread metastases to lung, skeleton, central nervous system and, occasionally, other organs may be observed. In rare instances, this disease may metastasize to the pleura and manifest as a malignant pleural effusion (MPE) and portend poor prognosis. This article reports the cytomorphologic and immunocytochemical findings of a female patient with a symptomatic pleural effusion resulting from PTC metastatic to the pleura. Pleural fluid cytology revealed abundant papillary clusters with relatively nuclear pleomorphism, intranuclear cytoplasmic inclusions and nuclear grooves, small and distinct nucleoli as well as small discrete vacuoles. Psammoma bodies were not seen. Immunocytochemical staining was positive for TGB, EMA, Ber‐EP4, CK19, and negative for TTF‐1. Metastasis of PTC to pleural fluid is extremely rare and diagnosing the disease by cytology is challenging and requires medical expertise as well as knowledge of clinical context and immunocytochemical staining. Additionally, a cytologic diagnosis of MPE due to PTC provides important treatment information and plays an important role in prognosis.     

应用细针吸取细胞技术诊断乳腺导管病变的细胞学指标

目的 探讨采用细针吸取细胞学(FNAC)诊断乳腺导管病变的有效和联合的指标,以建立有效的乳腺导管病变FNAC诊断模式.方法 收集澳门镜湖医院6年内400例有随访结果的乳腺FNAC病例作回顾性分析.按组织学诊断结果分为导管上皮非增生性病变(104例)和增生性病变(163例)及癌(133例)三组,对涂片进行60个细胞学指标分析,再根据各指标的程度或量采用半定量分级评估.以组织学诊断结果为金标准对病变分类,研究各指标对诊断导管病变的意义.采用Logistic多重回归模型和分类树模型进行统计学分析.结果 (1)400例良、恶性病变组,上皮细胞团中掺杂肌上皮细胞(P<0.05)、上皮细胞排列成大的细胞团(P<0.05)、上皮细胞排列成小的细胞团(P<0.05)、细胞质内空泡(P<0.05)和细胞套细胞(P<0.1)为有统计学意义的鉴别诊断指标.最重要的鉴别指标为上皮细胞团中有无掺杂有肌上皮细胞.良性病变的诊断指标为上皮细胞团中掺杂有肌上皮细胞,联合大量的上皮细胞排列成大的细胞团,94.4%为良性病变,中等至大量的上皮细胞排列成小的细胞团,倾向为增生性病变;癌的诊断指标为上皮细胞团中无掺杂肌上皮细胞,上皮细胞排列成小的细胞团,细胞质内空泡和细胞套细胞.上皮细胞团中无掺杂肌上皮细胞时,癌占81.3%.(2)267例非增生性和增生性良性导管上皮病变组,上皮细胞团中见不规则的细胞间腔隙(P=0.001)、上皮细胞团成松散排列(P<0.05)和细胞核深染(P<0.1)为诊断增生的有意义指标.两结构指标在涂片中出现的量越多,越提示为增生.单一上皮细胞团中见不规则的细胞间腔隙,增生性病变占70.1%;当中等至大量时增生占82.7%,若同时伴上皮细胞团成松散排列,诊断增生的阳性预测价值为87.5%.(3)伴不典型细胞学改变的35例中,组织学诊断26例增生,多为导管上皮增生性纤维腺瘤,极少数为不典型增生或癌.结论 在乳腺病变FNAC诊断中,结构指标较细胞指标更重要,联合指标和对其量的评估可更有效地鉴别良恶性病变、非增生性和增生性良性病变;对伴不典型细胞学改变的病例应避免误诊为癌,均应组织活检.     

Myelomatous pleural effusion in a patient with plasmablastic myeloma: A case report

Myelomatous pleural effusion is an unusual clinical condition associated with poor outcomes. We report a case with myelomatous pleural effusion upon the presentation of the disease. The patient had multiple risk factors for inferior prognosis of multiple myeloma, including old age, immunoglobulin D (IgD) isotype, high lactate dehydrogenase, C‐reactive protein, β2‐microglogulin levels, and a high myeloma cell burden in the bone marrow. The myeloma cells in both bone marrow and pleural effusion had characteristic features of plasmablasts, including gigantic size, large and eccentrically placed nuclei, fine cytoplasm, and prominent nucleoli. Immunophenotypical analysis showed the plasmablastic cells in the pleural effusion were positive for surface CD38, cytoplasmic immunoglobulin, both κ and λ light chains but negative for surface CD19 or CD79a. Our experience suggests that the diagnosis of myelomatous pleural effusion should be made with clinical alertness and careful cytological examination, preferably supplemented by immunophenotypical analysis. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.     

Cytology of metastatic renal medullary carcinoma in pleural effusion: A study of two cases

Renal medullary carcinoma (RMC) is a rare and aggressive malignant epithelial neoplasm of the kidney. It almost exclusively affects children and young adults with a sickle cell trait or sickle cell disease. The majority of RMC patients present with widely disseminated disease at the time of diagnosis. Herein, we report two cases of young African‐American patients with history of sickle cell trait, hematuria and renal mass, who present with malignant right pleural effusions. The cytology of pleural effusion reveals predominantly clusters and individual tumor cells. The tumor cells show high nuclear to cytoplasmic (NC) ratios and large nuclei with nuclear pleomorphism, nuclear grooves, and prominent single or multiple nucleoli. The cytoplasm is dense with a vacuolated and two‐tone appearance. Surgical specimens of renal mass and lymph node show features of RMC. Metastatic RMC to the serous cavity is rare and may present a diagnostic dilemma since it may mimic a poorly differentiated adenocarcinoma or other high‐grade malignant neoplasms. RMC should be considered in the differential diagnosis in young patients with a renal mass, particularly in those with history of sickle cell trait or sickle cell disease. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.     

Metastatic epithelioid hemangioendothelioma in a pleural effusion: Diagnosis by cytology

Epithelioid hemangioendothelioma (EH) is a vascular neoplasm of uncertain malignant potential. We report a 22-yr-old female with a primary malignant EH of the iliac bone with adjacent soft tissue involvement which, during its metastatic course, presented as a pleural effusion. The effusion was cellular with tumor cells present both singly and in clusters. Distinguishing cytologic features included cytoplasmic vacuolization consistent with primitive intracytoplasmic lumen formation, variability in cell size, biphasic cytoplasmic staining with Diff-Quik stain, multinucleation, cell in cell engulfment, and multiple prominent nucleoli. Differential diagnosis based on morphology included malignant mesothelioma and adenocarcinoma. Immunocytochemical stains on the neoplastic cells were positive for Ulex Europaeus, Factor VIII-related antigen, and CD34, reflecting vascular differentiation and confirming the diagnosis of metastatic EH to the pleural cavity. Diagn Cytopathol 1994;11:64–67. © 1994 Wiley-Liss, Inc.

1 This article is US government work and, as such, is in the public domain in the United States of America

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Cytologic criteria of hyperplastic lesions in endometrial samples obtained by the endocyte sampler

The present investigation attempted to identify useful parameters for the cytologic diagnosis of endometrial hyperplasias in samples obtained with the Endopap endometrial sampler. A clinical and morphological classification dividing hyperplasia into benign simple hyperplasia (BSH); benign complex hyperplasia (BCH); and endometrial intraepithelial neoplasia (EIN) has been suggested by Meisels, et al. based on five valuable cytologic criteria. To these we added six of our own and applied them to 1.172 cases, 432 of which had a previous histologic diagnosis of normal proliferative endometrium (NPE); 462 were BSH, 210 were BCH, and 14 fit the EIN pattern. The cytologic criteria evaluated were overlapping cells, enlarged nuclei, aniso karyosis, granularity of chromatin, stromal cells, branching glandular structures, and moruloid or papillary-like cellular aggregates, dilated glandular borders in cellular sheets, nuclear clearing, clumped chromatin, and enlarged eosinophilic cytoplasm. Our results are consistent with the following findings: (1) there is no useful parameter for cytologic differentiation between NPE and BSH; (2) BCH is characterized by cellular aggregates, dilated glandular borders in cellular sheets, and branching glandular structures; (3) EIN is characterized by nuclear clearing, clumped chromatin, and anisokaryosis; and (4) enlargement of nucleoli and eosinophilic cytoplasm alone is not sufficient for the diagnosis of EIN.     

Quantitation of the prostatic intra-epithelial neoplasia. Analysis of the nucleolar size, number and location.

Correlation has previously been demonstrated between qualitative and quantitative architectural and cytological features of the prostatic intra-epithelial neoplasia. In the present study, a standard Zeiss microscope and a horizontal eyepiece micrometer were used in an attempt to quantitatively define the size, number and location of nucleoli in relation to the degree of prostatic intra-epithelial neoplasia and associated benign prostatic hyperplasia and adenocarcinoma. In total, 20 prostatectomies, where features of benign prostatic hyperplasia (20 cases), prostatic intra-epithelial neoplasia of grade 1 (10 cases) and grade 2 (10 cases), and adenocarcinoma (20 cases) were present, were studied. The quantitative analysis showed that, going from benign prostatic hyperplasia to prostatic intra-epithelial neoplasia of grade 1 and 2, and to adenocarcinoma, the values of the size-related nucleolar features, are progressively greater; when considering the frequency-related nucleolar features, the percentage of nucleolated nuclei increased sharply. This was associated with the decrease in the proportion of mononucleolated nuclei and increase in nuclei with two and three nucleoli. When considering the location-related nucleolar features, the degree of shift of the nucleoli to the periphery of the nucleus increased. Among all the quantitative features, the most evident changes in the nucleolar size were expressed by the nucleolar hypertrophy index after including in the calculation only those nucleoli with a diameter larger than 3 arbitrary units, whereas the percentage of nucleolated nuclei and the proportion of nuclei with two and three nucleoli best represented the modifications to the frequency.(ABSTRACT TRUNCATED AT 250 WORDS)