Fine-needle aspiration cytology of benign and malignant adenomyoepithelioma: report of two cases.

Cytological features of a malignant spindle-cell variant and a benign tubular variant of adenomyoepithelioma were examined to improve diagnosis of this tumor. Fine-needle aspiration cytology, of both a malignant and a benign case, characterized cellular and cohesive cell clusters composed of epithelial and myoepithelial cells. The smears of the malignant case were rich in spindle-shaped myoepithelial cells, admixed with a few epithelial cells. In about a fourth of the clusters, atypical cells with enlarged hyperchromatic nuclei and prominent nucleoli comprised more than 20% of cells. The smears of the benign case were composed of tubular epithelial cells surrounding one to several layers of myoepithelial cells with clear cytoplasm. Mild atypia was occasionally noticed. A review of the literature showed that a cytological diagnosis of malignancy is not warranted, if nuclear atypia is not generally severe. Focal severe atypia is not definitively indicative of benignity or malignancy.     

Fine-needle aspiration of neurilemoma (schwannoma). A clinicocytopathologic study of 116 patients

The preoperative fine-needle aspiration cytology (FNAC) diagnoses in 116 surgically excised neurilemomas were reviewed and compared with the corresponding histopathologic diagnoses made on surgical specimens and with clinical data. In addition, the utility of adjunctive techniques was analyzed and other spindle-cell lesions in the differential diagnoses were discussed. An unequivocal, benign diagnosis was rendered by FNAC in 80 cases, 67 of which were correctly labelled as neurilemoma in a review of the original cytology reports. There were 6 false-positive malignant diagnoses while 23 smears were considered insufficient and 7 inconclusive as to whether benign or malignant. On reevaluation, the diagnostic smears in most cases contained spindle cells with wavy nuclei embedded in a fibrillar, occasionally collagenous, and/or myxoid matrix and Antoni A/Antoni B tissue fragments. A moderate to abundant admixture of round to oval cells was also frequent. Nuclear palisading was seen in 41 smears with distinctive Verocay bodies in 10. Markedly pleomorphic nuclei were seen in smears from 8 ancient and 6 conventional neurilemomas, and slight to moderate nuclear pleomorphism was observed in 38 additional cases. Thus most neurilemomas have distinct cytomorphologic features that allow correct diagnosis. The major problem in FNAC of neurilemoma is to obtain sufficient material. Furthermore aspirates showing predominantly Antoni A features, nuclear pleomorphism, and/or myxoid changes can easily be confused with other types of benign or malignant soft-tissue tumors.     

Cytomorphology and B72.3 labeling of benign and malignant ductal epithelium in pancreatic lesions compared to gastrointestinal epithelium

Endoscopic ultrasound-guided pancreatic fine-needle aspiration biopsy very frequently produces gastrointestinal epithelial contamination (GIC). We studied the cytomorphology and B72.3 immunoreactivity of lesional epithelium of benign and malignant ductal lesions of the pancreas and compared the findings to our previously established template of GIC. Air-dried smears, fixed smears, and ThinPrep (TP) specimens were obtained using a cytobrush, directly from benign and malignant ductal lesions of 18 Whipple specimens, to ensure purity of the epithelium studied. Smear background, cell architecture, and cellular features were analyzed. Immunocytochemical staining with B72.3 was performed in 14 cases. Epithelium of ductal carcinoma was distinguished from benign ductal epithelium in chronic pancreatitis and GIC primarily by crowded architecture and atypical cellular features, including high nuclear-to-cytoplasmic ratio, irregular nuclei, nucleoli, and vacuolated cytoplasm. Benign ductal and GIC epithelium were only distinguished by architecture (goblet cells and brush borders), but not consistently, especially gastric epithelium that lacked these features. B72.3 shows promise in the differentiation between GIC and benign and malignant ductal epithelium, with no staining supporting benign ductal cells, fine punctate perinuclear staining correlating with GIC, and strong cytoplasmic staining supporting malignancy.     

Cytological detection of epithelial dysplasia in the oral mucosa using Feulgen-DNA-image cytometry

Cytological scrape material of the oral mucosa from 114 patients with epithelial dysplasia and with oral cancer was stained with the Feulgen-reaction and investigated with an image analyzer. The size and the integrated optical density of cell nuclei, and four chromatin texture features were measured. All tumor slides contained cell nuclei with DNA greater than 5c, 16% of the slides had cell nuclei with DNA greater than 8c. A total of 14.5% of the tumor patients showed significantly increased DNA values in nuclei distant from the tumor. Two smears with severe epithelial dysplasia showed nuclei with DNA greater than 5c both in the tumor material and far from the tumor. Texture analysis allowed discrimination between benign, dysplastic and malignant smears. No correlation was found between DNA content and tumor staging. Image cytometry was a reliable method for detecting tumor cells. Epithelial dysplasia in areas distant from the tumor is probably due to "field canceration" of the epithelium.     

Using classification and regression trees,liquid‐based cytology and nuclear morphometry for the discrimination of endometrial lesions

‘The objective of this study is to investigate the potential of classification and regression trees (CARTs) in discriminating benign from malignant endometrial nuclei and lesions. The study was performed on 222 histologically confirmed liquid based cytological smears, specifically: 117 benign cases, 62 malignant cases and 43 hyperplasias with or without atypia. About 100 nuclei were measured from each case using an image analysis system; in total, we collected 22783 nuclei. The nuclei from 50% of the cases (the training set) were used to construct a CART model that was used for knowledge extraction. The nuclei from the remaining 50% of cases (test set) were used to evaluate the stability and performance of the CART on unknown data. Based on the results of the CART for nuclei classification, we propose two classification methods to discriminate benign from malignant cases. The CART model had an overall accuracy for the classification of endometrial nuclei equal to 85%, specificity 90.68%, and sensitivity 72.05%. Both methods for case classification had similar performance: overall accuracy in the range 94–95%, specificity 95%, and sensitivity 91–94%. The results of the proposed system outperform the standard cytological diagnosis of endometrial lesions. This study highlights interesting diagnostic features of endometrial nuclear morphology and provides a new classification approach for endometrial nuclei and cases. The proposed method can be a useful tool for the everyday practice of the cytological laboratory. Diagn. Cytopathol. 2014;42:582–591. © 2013 Wiley Periodicals, Inc.     

Nucleolar organizer regions distribution in fine needle aspiration cytological smears from breast lesions

Fine needle aspiration (FNA) cytology is now an integral part of the pre-operative investigation of breast lesions and the therapeutic protocol is today often planned on the basis of cytodiagnosis. However, from time to time the cytological picture may be equivocal or inconclusive. In recent years, nucleolar organizer region (NOR) scores have been explored for potential value in the diagnosis of malignancy as the scores in malignant nuclei are seen to be higher than in benign or reactive nuclei. With a view to applying NOR scoring in the evaluation of cytologically equivocal cases, we adopted the argyrophil technique for staining NOR s (AgNOR) in FNA cytological smears of 56 breast lesions, comprising 31 benign and 25 malignant lesions. Histological correlation was possible in 26 of these cases (17 malignant and 9 benign) and AgNOR scoring was done on paraffin sections of these as well. There was a significant difference between mean AgNOR scores in benign and malignant lesions in the cytological smears (P < 0.001). The AgNOR scores ranged from 2.5 to 5.0 per cell in benign lesions and 5.8 to 17.2 per cell in malignant lesions. None of the cases fell into the gray zone of overlap. One malignant lesion that was cytologically equivocal showed a mean AgNOR score of 6.08. The AgNOR scores on histological sections also showed a statistically significant difference (P < 0.001) between benign and malignant lesions with mean scores ranging from 1.34 to 2.58 dots per cell in benign lesions and scores of 2.42 to 5.28 dots per cell in malignant lesions. However, the scores overlapped in four cases and therefore it was considered unsuitable for routine diagnostic work. From this preliminary study, we conclude that an FNA AgNOR score of 5.0 and less strongly favours a benign lesion whereas a score above 5.0 would be in favour of a malignant lesion. A larger study would be needed to verify our impression that AgNOR scoring can be useful in cytologically equivocal cases.     

Aspiration biopsy of mammary lesions with abundant extracellular mucinous material. Review of 43 cases with surgical follow-up

We reviewed 43 fine-needle aspiration biopsy (FNAB) smears with abundant extracellular mucinous material to determine whether accurate classification of mucinous lesions is achievable on FNAB: 26 had carcinoma (pure colloid carcinoma [CCA], 23; mixed CCA/invasive ductal carcinoma [IDC], 3); 17 had benign lesions on follow-up (benign MLL, 6; fibrocystic change [FCC], 6; myxoid fibroadenoma [MFA], 5). All carcinomas were identified correctly as malignant on FNAB. The initial cytologic diagnoses in benign cases were benign in 8, atypical in 8, and "suspicious" for carcinoma in 1. CCAs were moderate to markedly cellular with mild to moderate atypia and lacked oval bare nuclei. Marked nuclear atypia was confined predominantly to cases with mixed CCA/IDC. A distinct feature of CCA was thin-walled capillaries. FCCs and benign MLLs had overlapping cytologic features and showed variable cellularity and no or mild atypia. MFAs were markedly cellular with dyscohesion and variable atypia; stromal fragments and oval bare nuclei were present in every case. Mucinous lesions can be divided into 2 categories by FNAB: those that are adenocarcinomas and those that are not. CCAs have distinctive features that allow a definitive diagnosis on FNAB. Unnecessary surgery can be avoided in MFA by careful evaluation of smear characteristics. Cytologic features of FCC and MLL overlap. Owing to the documented association of MLL with carcinoma, we recommend that lesions that cannot be classified definitively as adenocarcinoma or MFA be considered for conservative excision, even in the absence of atypia.     

ThinPrep vs. conventional smear cytologic preparations in analyzing fine-needle aspiration specimens from palpable breast masses.

Limited data exist concerning the cellular features of the ThinPrep (Cytyc Corp., Boxborough, MA) technique in the analysis of breast fine-needle aspiration specimens. Therefore, we analyzed a series of 75 surgically excised palpable breast masses and compared ThinPrep and conventional smear fine-needle aspiration preparations. Each mass was aspirated twice. The first sample was used for two alcohol-fixed conventional smears, and the second sample was rinsed into CytoLyt (Cytyc Corp., Boxborough, MA) solution for processing into a ThinPrep slide. The paired slides were separated and independently analyzed for adequacy, overall cellularity, single epithelial cells (absent, rare, moderate, or numerous), epithelial architecture (sheets or three-dimensional clusters), myoepithelial cells and stripped bipolar nuclei (present or absent), and nuclear detail (poor, satisfactory, or excellent). Each sample was classified as negative, negative consistent with fibroadenoma, atypical favoring benign, atypical favoring malignant, or positive for malignant cells. The 75 breast masses included 32 carcinomas and 43 benign lesions. Four conventional smears and one ThinPrep were unsatisfactory. Significantly, more conventional smears were limited by drying artifact (9 vs. 0). ThinPrep aspirates of carcinomas had better nuclear detail (P = 0.03) and greater cellularity (P = 0.05). ThinPrep aspirates of benign masses had greater epithelial cellularity (P = 0.007) and better nuclear detail (P < 0.001), and more specimens had myoepithelial cells (P = 0.007). The ThinPrep interpretation classified 29 of 32 carcinomas (91%) as positive and three as atypical favoring malignant (sensitivity = 100%). The conventional smear interpretation classified 28 of 31 carcinomas (90%) as positive and three as atypical favoring malignant (sensitivity = 100%). The ThinPrep interpretation classified 42 benign lesions as negative (23 cases), negative consistent with fibroadenoma (8 cases), atypical favoring benign (10 cases), and atypical favoring malignant (1 case) (specificity = 74%). The conventional smear interpretation classified 40 benign lesions as negative (25 cases), negative consistent with fibroadenoma (12 cases), and atypical favoring benign (3 cases) (specificity = 93%). ThinPrep was less specific, but the difference was not statistically significant (P = 0.065). In summary, ThinPrep aspirates had greater cellularity and better nuclear detail than conventional smears, and were just as sensitive in identifying the carcinomas. The difference in specificity between the two techniques was not statistically significant (P = 0.065). Diagn. Cytopathol. 1999;21:137-141.     

Aspiration biopsy of the breast tumors. Analysis of diagnostically difficult cases.

In this paper the authors described those of the breast fine needle aspirates which were difficult for interpretation e.g. clear-cut differentiation between benign and malignant character of the lesion could not be made. There were 40 such cases (1.96%) out of 2332 breast tumors biopsied between 1987-1989. In the cases that proved to be malignant on histology the authors described cytological features which speak in favour of malignancy. In the group of smears which proved to be benign on histology the authors described the features that imitate atypia and should not be misdiagnosed as malignant. The described criteria may be of some help in cytological diagnosis of breast masses.     

Morphological characteristics and distribution patterns of epithelial cells in the cytological diagnosis of gastric cancer.

The morphological features of epithelial cells in gastric biopsy touch smears from 296 cases (248 benign, 48 malignant) were retrospectively reviewed. By subjective criteria no single purely morphological characteristic could be identified that was consistently capable of separating benign from malignant specimens. The value of cell distribution patterns in diagnosis was therefore objectively analysed in the 231 adequate specimens (190 benign, 41 malignant). A score of over 20% for single epithelial cells was found to have a sensitivity of 95.1% and specificity of 99.5% in the diagnosis of carcinoma. Quantitative analysis of cell distribution pattern is a simple test, which does not require special equipment, yet can be helpful in the interpretation of gastric cytology.     

Nucleolar organizer regions in FNAC smears of breast lesions.

The argyrophil technique for staining proteins associated with nucleolar organizing regions was applied to the fine-needle aspiration cytology smears of 45 cases of breast disease. These included 14 malignant and 31 benign lesions. A correlation with histology sections was done in 12 cases. There was a significant difference between AgNOR count of benign and malignant breast disease with one case out of 45 falling in the "gray" zone of overlap. Infiltrating lobular carcinoma was found to have the lowest NOR counts among the malignant lesions. The smear staining was superior to that on sections, the positive features being lack of background staining and better dispersion of NORs in the nucleoli.     

Ductal adenoma of the breast: The cytological features of six cases

Ductal adenoma of the breast may simulate malignancy by both clinical, histological, and cytological examination. Fine-needle aspirations from breast lesions are now daily routine and preoperative recognition of this benign lesion is desirable. This study describes the cytologic features of six additional cases of ductal adenoma. The smears from all the lesions were highly cellular with epithelial cells in sheets. Numerous large fragments of purple stroma in tight connection with epithelial cells often making finger-like hyaline structures or globules between cells were seen. Naked oval nuclei in the background were observed in all cases indicating benignancy. We find the cytologic picture in fine-needle aspirations from ductal adenomas sufficiently characteristic for preoperative diagnosis. The differential diagnoses toward other benign and malignant conditions are discussed. © 1994 Wiley-Liss, 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.     

Routine DNA cytometry of benign and malignant pleural effusions by means of the remote quantitation server Euroquant: a prospective study

AIM: To analyse the practicability and potential assistance of static DNA cytometry performed by means of the remote quantitation server Euroquant and the internet in routine diagnostic analysis of pleural effusions, and to outline the role of DNA cytometry on pleural effusions in distinguishing between benign and malignant (and herein primary versus metastatic) effusions. MATERIALS AND METHODS: Cytological smears of 294 pleural effusions were stained with the Feulgen method. The DNA content of a minimum of 300 randomly chosen analysis nuclei and 30 reference nuclei (lymphocytes) was measured by internet connection to the remote quantitation server Euroquant. Cytometric features were derived from the histograms, and the time needed for case evaluation, the reliability of staining and measurement procedures, and the contribution to the final diagnosis were evaluated. RESULTS: Only 120 of 294 pleural effusions could be measured. The total measurement time for each specimen was 60 minutes. The guidelines of the consensus report on DNA measurements were fulfilled. Seventy eight malignant (18 mesotheliomas, 60 metastatic tumours) and 42 benign effusions were measured. Seven of 78 malignant effusions were euploid and none of 42 benign effusions were aneuploid. The sensitivity and specificity were 91% and 100%, respectively, for distinguishing benign from malignant effusions, and 95% and 100%, respectively, for discriminating between benign and malignant effusions caused by metastatic malignant tumours. CONCLUSIONS: Static DNA cytometry using the remote quantitation server Euroquant can be performed reliably in the routine diagnosis of pleural effusions; however, only 40% of effusions meet the technical requirements for static DNA cytometry. Within the measurable cases, static DNA cytometry made an important contribution to the confirmation/exclusion of malignancy.     

Benign and malignant neoplasms of myoepithelial cells: Cytologic findings

We report two myoepithelial cell neoplasms; a salivary gland tumor was malignant and a breast neoplasm was benign. Both were studied histologically, immunohistochemically, cytologically, and ultrastructurally. The malignant myoepithelioma recurred twice and metastasized to one regional lymph node. This tumor was infiltrative with areas of necrosis and hemorrhage. It was composed of malignant-appearing spindle and plasmacytoid cells. Both types of cells were immunoreactive to muscle specific actin, S-100 protein, cytokeratin, vimentin, and neuron-specific enolase. Ultrastructurally, features of myoepithelial cells were seen. Fine-needle aspirate smears showed spindle and plasmacytoid cells, numerous mitoses, and malignant-appearing nuclei. Spindle-cell adenomyoepithelioma of the breast, a small well-circumscribed firm nodule, featured multiple lobules of spindle cells associated with clear-cell glands at the tabular periphery. Histologically and cytologically, the lesion was cellular but appeared benign. The differential diagnosis of myoepithelial neoplasms is discussed.     

Immunohistochemical localization of prekeratin filaments in benign and malignant cells in effusions. Comparison with intermediate filament distribution by electron microscopy.

An immunoperoxidase technique employing antibody to prekeratin was used to study distribution and pattern of staining of prekeratin filaments in cytological smears obtained from 42 specimens of pleural and peritoneal effusions (27 benign, 15 malignant). The smears were either air-dried or ethanol-fixed. Both benign and malignant mesothelial cells showed distinctive peripheral or perinuclear staining patterns which differed from the characteristic arborizing pattern in adenocarcinoma cells. The ultrastructure of these 2 cell types studied in 27 body fluids (12 benign, 15 malignant) and in 13 malignant tumors (3 mesotheliomas, 10 adenocarcinomas) showed a distinctive localizaton of intermediate filaments which corresponded to and could explain the pattern of staining obtained using the immunoperoxidase technique. The immunohistochemical and ultrastructural findings appeared characteristic for benign and malignant mesothelial cells as well as for adenocarcinoma cells, and could be used as markers to differentiate mesothelial tumors and reactive mesothelial cells from adenocarcinomas.     

Papillary tissue fragments in cervicovaginal (Pap) smears: cytomorphologic characteristics and clinicopathologic significance

Papillary epithelial fragments (PEFs) are a rarely described architectural feature in cervicovaginal (Pap) smears. Morphologically, PEFs often consist of small, finely branching glandular tissue fragments with varying cytomorphology. This study identified 21 Pap smears (1978-2009) containing PEFs to determine the clinicopathologic significance of such findings. Patients ranged in age from 36 to 81 years (mean, 54 years). The Pap smear diagnoses consisted of 48% overt malignant neoplasms, 24% atypical fragments, and 28% benign entities. The papillary fragments featured a range of cytomorphologies consisting of benign features, mild to marked atypia, and overt malignancy. PEFs were more commonly found (57%) in specimens from patients with significant pathologic outcomes. Hence, the presence of PEFs in a Pap smear should raise concern for a neoplastic process. In smears displaying atypical to malignant cytomorphologic features recommendations for further clinical work-up and/or tissue studies should be made.     

Fine-needle aspiration cytology of hepatic leiomyosarcoma

Hepatic leiomyosarcoma is a rare malignancy to involve the liver, occurring as a primary liver sarcoma in patients without an underlying medical disorder, as a metastatic malignancy, and with increasing incidence, as a primary tumor in AIDS patients. A series of hepatic leiomyosarcomas diagnosed by FNA biopsy, including the first reported case in an adult AIDS patient, were reviewed with respect to cytomorphologic features. The series consisted of five men and two women ranging from 24 to 72 years of age. One case was a primary hepatic lesion in a 24-yr-old man with AIDS and six were metastatic from a number of sites (stomach, small bowel, retroperitoneum, vena cava, and seminal vesicle). Two cytologic patterns were identified. Aspirates of spindle-cell leiomyosarcomas (six cases) generally produced hypocellular smears composed primarily of small irregular clusters of cells with blunt-ended, uniform, overlapping nuclei. The differential diagnosis included benign reactive processes and other benign and malignant spindle-cell neoplasms. The aspirate of an epithelioid leiomyosarcoma (one case) revealed a second pattern characterized by highly cellular smears with many single polygonal cells having eccentric, malignant nuclei and a characteristic clear quality to the cytoplasm in Papanicolaou-stained material. This epithelial appearance generated a differential diagnosis that included hepatocellular carcinoma, metastatic carcinoma, and melanoma. Careful integration of clinical information, cytomorphologic features, and ancillary studies will allow specific FNA diagnosis of hepatic leiomyosarcoma in most cases. Diagn Cytopathol 1994;11:321–327. © 1994 wiley-Liss, Inc.     

Cytology of the prostate

A series of prostates has been studied cytologically by making smears directly from surgically excised glands. The cytological findings in these smears are described. Benign conditions of the prostate can be readily diagnosed by this means but it is not a satisfactory method for finding latent carcinomas. In addition, the cells in the smears obtained from the excised glands were compared with the cells found in smears obtained by prostatic massage from a series of patients attending with prostatic disorders. It was found that direct smears from prostatectomy specimens give a useful indication of the types of benign cells which may be found in smears obtained by massage. They provide help in the differentiation of malignant from benign epithelium in the massage specimens although they give little indication of the appearances of the malignant cells themselves.     

Fibroadenomas with atypia: causes of under- and overdiagnosis by aspiration biopsy.

Fibroadenoma (FA) is a common benign breast lesion frequently sampled by fine-needle aspiration biopsy (FNAB). Although the cytologic diagnosis is straightforward in most cases, cellular discohesion and atypia in FAs may lead to falsely atypical or positive FNAB diagnoses. Conversely, some adenocarcinomas mimic a fibroadenomatous pattern on FNAB, resulting in a false-negative diagnosis. We reviewed the cytologic and histologic findings in 25 cases with a preoperative FNAB diagnosis of FA, wherein excision was recommended based on atypia. Our aim was to analyze the spectrum of changes causing under- or overdiagnosis in such cases. The smears were assessed for cellularity, cellular discohesion, presence of dissociated intact cells and nucleoli, nuclear pleomorphism, oval bare nuclei, and stromal fragments. The histologic findings were correlated with FNAB features. At excision, 88% of FAs classified as atypical on FNAB were benign (FA with ductal hyperplasia and lactational change, myxoid FA, and other fibroepithelial lesions). Differentiating myxoid FA from colloid carcinoma was difficult due to the abundance of extracellular mucin in which the dissociated epithelial cells were floating. Two (8%) cases were carcinomas on excision; the reasons for underdiagnosis in one case reflected sampling, and in the other, interpretative error. There was one (4%) benign phyllodes tumor which lacked stromal fragments and single stromal cells on FNAB smears. The lesion was called atypical, based on the epithelial discohesion on the smears. We conclude that the majority of FAs with atypia on FNAB are benign lesions. Considering the grave consequences of a false-positive cytologic diagnosis, we recommend a conservative approach in interpreting FNAB smears which overall display a fibroadenomatous pattern.