Carcinoma In Fine-needle Aspirates Research Articles

English

BACKGROUND Breast cancer is increasing in developing countries and the management options are wide; therefore, providing the surgeon with accurate prognostic information on which mode of therapy will be chosen becomes important. Fine needle aspiration cytology (FNAC) is a routinely used initial investigation of choice for rapid diagnosis of breast cancer. Apart from diagnosis of cancer, it also has the ability to predict the grade on smears which will add its diagnostic value without any additional morbidity or expense for the patients. Among various cytological grading systems, Robinson grading is most commonly used for breast carcinoma in fine needle aspirates. The purpose of this study is to evaluate the correlation between Robinson’s cytological grading and Bloom Richardson’s histological grading. METHODS This is a 3 - year retrospective analytical study. 40 cases of infiltrating duct carcinoma (IDC) of breast diagnosed on cytology were included in the study. Cytological grading was done using Robinson’s grading and corresponding histopathology slides were taken, and histological grading using Bloom Richardson’s system was done. Finally, correlation between cytological and histological grading was done using statistical package for social sciences (SPSS) software. RESULTS Age of the patients varied between 32 and 70 yrs. Cytologically, 32.5 % cases were grade I, 40 % were grade II and 27.5 % cases were grade III respectively. Histologically 22.5 %, 47.5 % and 30 % cases were grade I, grade II, and grade III, respectively. Concordance rate between grade I tumours in cytology and histology was 53.84 %, for grade II tumours it was 75 %, and for grade III tumours it was 63.63 %. The absolute concordance rate was 65 %. CONCLUSIONS Robinson’s cytological grading (RCG) of breast carcinoma correlates well with Bloom - Richardson’s histological grading system and could be a helpful parameter in selecting a neoadjuvant treatment for the breast cancer patients on fine needle aspiration cytology alone. KEYWORDS Breast Carcinoma, Robinson’s Cytological Grading, Bloom Richardson’s Histological Grading

Validation of molecular biomarkers for preoperative diagnostics of human papillary thyroid carcinoma in fine needle aspirates.

Despite substantial efforts, reliable preoperative diagnostic for human thyroid malignancies in case of cytologically indeterminate nodules is still missing, resulting in high number of unnecessary thyroidectomies. In an attempt to increase precision of existing preoperative diagnostics, we aimed at validating the panel of molecular biomarkers predictive for papillary thyroid carcinoma (PTC) in preoperative fine needle aspirate (FNA) samples. In this prospective study conducted in preoperative thyroid FNA from 44 thyroid nodules, expression levels of 11 molecular biomarkers previously validated on the postoperative samples of PTCs were measured by Cell-to-CT and QuantiGene Plex methods and correlated with final diagnosis. The QuantiGene Plex resulted in reliable gene expression measurements for FNA and core-needle biopsy (CNB) samples, however this method was less sensitive than pre-amplification based Cell-to-CT. Measurements conducted on the same samples by the two methods significantly correlated for most of the genes. Expression levels of TIMP1, c-MET and ARNTL were upregulated in PTC nodules as compared to benign counterparts, supporting previous post-operative studies. Strong correlation was observed between these biomarker alterations in the same samples. Within the sub-group of 15 indeterminate nodules (Bethesda II-V), TIMP1 had 100% specificity and 83% sensitivity for PTC cases. Assessment of TIMP1, c-MET and core-clock gene ARNTL expression levels by QuantiGene Plex assay in FNA samples holds promise as an ancillary method to the cytological preoperative diagnostics.

Branchial cleft cyst presenting as metastatic squamous carcinoma in fine needle aspirates: report of three cases

Bas ve boynun metastatik skuamoz karsinomunun bir alt kumesi boyunda kistik kitlelerle ortaya cikmaktadir. Siklikla yassi epitel hucreli karsinomun bu kistik metastazlarini brankiyal yarik kist gibi iyi huylu kistik boyun lezyonlarindan ayirt etmek cok zor olabilmektedir. Iyi huylu kistik lezyonlarin ic yuzeyini kaplayan yassi epitel hucreler onemli hucre atipisi gosterebilerek yassi epitel hucreli karsinomdan kaygilanilmasina neden olurlar. Kisitli sayida numune alinan ince igne biyopsilerini degerlendirirken boynun iyi ve kotu huylu kistik skuamoz lezyonlari arasinda ayrim yapmak daha cok zorlasmaktadir. Burada brankiyal yarik kistleri olan uc hasta sunulmaktadir. Hepsine baslangicta metastatik yassi epitel hucreli karsinom tanisi konmustu. Gereksiz radikal boyun diseksiyonu gibi cerrahi prosedurlerin uygulanmasina yol acabilen metastatik yassi epitel hucreli karsinom eksizyonu ihtimalinden kacinmak icin deneyimli bir sitolog tarafindan ince igne aspirasyon sitolojisinin yorumlanmasinin onemi vurgulanmaktadir.

Subclassification of pulmonary non-small cell lung carcinoma in fine needle aspirates using a limited immunohistochemistry panel

Background:Newer treatment modalities require subtyping of non-small cell lung carcinomas (NSCLC). Morphological differentiation is often difficult and various immunohistochemical (IHC) panels have been used to maximize the proportion of accurately subtyped NSCLC.Aim:The aim of this study was to subtype NSCLC on fine needle aspirates (FNA) using a minimal antibody panel.Materials and Methods:Cell blocks from 23 FNA samples with a morphological diagnosis of NSCLC were taken. IHC was evaluated (blinded to clinical data) for thyroid transcription factor-1 (TTF-1), cytokeratin (CK)7, CK20, and tumor protein p63.Results:TTF-1 was positive in 14 and negative in 9 cases. The p63 was positive in two cases each of TTF-1 positive and negative tumors. CK7 was positive in 12 of the 14 TTF-1 positive tumors and 4 of the TTF-1 negative tumors. CK20 was negative in all. All the 14 TTF-1 positive tumors were primary lung tumors, 12 being NSCLC and 2 being squamous cell carcinoma. Five of nine TTF-1 negative tumors were metastatic tumors from endometrium, kidney, and head and neck region (two), and one was an unknown primary. Four of the nine TTF-1 negative tumors were morphologically NSCLC and were clinically considered to be primary lung tumors. Three of these tumors stained positive for CK7 but negative for CK20 and p63, and one case was negative for the immunomarkers.Conclusion:Use of limited IHC panel helps categorize primary versus secondary tumors to the lung. The p63 is a useful marker for detecting squamous cell carcinoma. In countries where antibodies are not readily available, using a limited IHC panel of TTF-1, p63, and CK7 can help further type NSCLC lung tumors.

Diagnostic Accuracy of Follicular Variant of Papillary Thyroid Carcinoma in Fine-Needle Aspirates Processed by Ultrafast Papanicolaou Stain: Histologic Follow-up of 125 Cases

Diagnostic Accuracy of Follicular Variant of Papillary Thyroid Carcinoma in Fine-Needle Aspirates Processed by Ultrafast Papanicolaou Stain: Histologic Follow-up of 125 Cases

Biomarkers in Diagnosis of Pancreatic Carcinoma in Fine-Needle Aspirates: ATranslational Research Application

This study was undertaken to determine whether recently identified proteins could be translated to clinical practice as markers to distinguish pancreatic adenocarcinoma from chronic pancreatitis on fine-needle aspirate (FNA) samples. Resected pancreatic tissue sections (n = 40) and FNA samples (n = 65) were stained for clusterin-β, MUC4, survivin, and mesothelin. For each biomarker, the staining patterns in adenocarcinoma and in reactive ductal epithelium were evaluated and compared. Clusterin-β stained reactive ductal epithelium significantly more frequently than pancreatic adenocarcinoma (P < .001). In comparison, MUC4 and mesothelin were expressed more frequently in pancreatic adenocarcinoma on tissue sections. Positive staining for MUC4 (91% vs 0%; P < .001) and mesothelin (62% vs 0%; P = .01) and absence of staining for clusterin-β (90% vs 7%; P < .001) were noted significantly more frequently in adenocarcinoma cells than in reactive cells in FNA samples. Clusterin-β and MUC4 can help distinguish reactive ductal epithelial cells from the cells of pancreatic adenocarcinoma in FNA samples.

Biomarkers in Diagnosis of Pancreatic Carcinoma in Fine-Needle Aspirates

This study was undertaken to determine whether recently identified proteins could be translated to clinical practice as markers to distinguish pancreatic adenocarcinoma from chronic pancreatitis on fine-needle aspirate (FNA) samples. Resected pancreatic tissue sections (n = 40) and FNA samples (n = 65) were stained for clusterin-beta, MUC4, survivin, and mesothelin. For each biomarker, the staining patterns in adenocarcinoma and in reactive ductal epithelium were evaluated and compared. Clusterin-beta stained reactive ductal epithelium significantly more frequently than pancreatic adenocarcinoma (P < .001). In comparison, MUC4 and mesothelin were expressed more frequently in pancreatic adenocarcinoma on tissue sections. Positive staining for MUC4 (91% vs 0%; P < .001) and mesothelin (62% vs 0%; P = .01) and absence of staining for clusterin-beta (90% vs 7%; P < .001) were noted significantly more frequently in adenocarcinoma cells than in reactive cells in FNA samples. Clusterin-beta and MUC4 can help distinguish reactive ductal epithelial cells from the cells of pancreatic adenocarcinoma in FNA samples.

Diagnostic accuracy of follicular variant of papillary thyroid carcinoma in fine-needle aspirates processed by ultrafast Papanicolaou stain

Detection of follicular variant (FV) of papillary carcinoma (PC) of the thyroid is considered difficult in cytology. Various ancillary studies have been used to increase the sensitivity in the detection of FVPC in fine-needle aspiration (FNA). We previously reported that the clear nuclei of PC became conspicuous in Ultrafast Papanicolaou (UFP)-stained smears. This study reports our experience on using this UFP-induced artifact in the detection of FVPC. Over an 11-year period, 5637 ultrasound-guided thyroid FNAs were performed. All samples were smeared and air-dried. Diff-Quik stain was used to assess the colloid and UFP stain was used to study the nuclei. Histologic follow-up was available from 125 cases. Of the 107 aspirates with diffuse "grape-like" watery clear nuclei, histologic follow-up showed 94 PCs, 8 follicular adenomas containing atypical nuclei, and 5 nonneoplastic lesions. Of the 18 aspirates with focal clear nuclei, histologic follow-up showed 6 PCs, 8 follicular adenomas, and 4 nonneoplastic nodules. As reported previously, histologic follow-up of 147 FNAs contained follicles with normal nuclei showed 107 true follicular neoplasms, 32 hyperplastic nodules, and 8 FVPC. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy in the detection of PC were 93.6%, 94.9%, 93.6%, 94.9%, and 94.3%, respectively, when follicular adenomas containing atypical nuclei were counted as encapsulated FVPC; and 92.6%, 85.6%, 80%, 94.9%, and 88.3%, respectively, when follicular adenomas containing atypical nuclei were counted as benign. UFP stain is one of the options to increase the sensitivity of detection of FVPC in preoperative FNA, and to triage microfollicular nodules into those that require surgery no matter how small, and those which can be followed when small.

Fine-Needle Aspirates of Hepatocellular Carcinoma That Are Misclassified as Adenocarcinoma: Correlating Cytologic Features and Performance in the College of American Pathologists Nongynecologic Cytology Program

The cytologic features of hepatocellular carcinoma in fine-needle aspirates are well described. While some cases are easily distinguished from adenocarcinoma, poorly differentiated tumors can be difficult to differentiate. We reviewed the cytologic findings for 9 aspirates from cases of hepatocellular carcinoma that were frequently misclassified as adenocarcinoma and compared them with another 10 cases of hepatocellular carcinoma that were rarely misclassified. To compare the cytologic features of cases of hepatocellular carcinoma in fine-needle aspirates that were both rarely and frequently misclassified as adenocarcinoma. We reviewed a total of 762 interpretations from 19 different cases of hepatocellular carcinoma in liver fine-needle aspiration specimens in the College of American Pathologists Nongynecologic Cytology Program and correlated the cytologic features with performance in the program. Overall, cases that were frequently misclassified as adenocarcinoma were misclassified 39% of the time (range, 18%-70%), while cases that were rarely misclassified were classified as adenocarcinoma 2% of the time (range, 0%-8%). The difference was statistically significant (P < .001). On review, 4 cytologic patterns were found. The most common pattern for cases that were rarely misclassified was prominent trabeculae of cells and endothelial cells wrapping the trabeculae (6/10 cases vs 2/9 cases that were frequently misclassified). The most common pattern among cases that were frequently misclassified was clusters of cells with granular cytoplasm and associated stripped nuclei (5/9 cases vs 2/10 cases that were rarely misclassified). However, the distribution of neither pattern was significantly different (P = .16 for both). One case with large atypical granular cells, as seen in the fibrolamellar variant, was rarely misclassified. The remaining 3 cases (2 frequently misclassified, 1 rarely misclassified) had a nonspecific a pattern of cells with granular cytoplasm without obvious trabeculae or stripped nuclei. Correctly classifying hepatocellular carcinoma by cytology alone remains a significant challenge. While some patterns are more common in cases that performed well and other patterns are more common in cases that performed poorly, there was no significant difference in the distribution of these patterns. These results suggest that people should support their interpretations of aspirations with either immunologic evidence, biopsy evidence, or review by an experienced cytopathologist. Continued educational efforts in this area may be of value.

Fine-Needle Aspirates of Adenocarcinoma/Metastatic Carcinoma That Resemble Hepatocellular Carcinoma: Correlating Cytologic Features and Performance in the College of American Pathologists Nongynecologic Cytology Program

The cytologic features of adenocarcinoma/ metastatic carcinoma in liver fine-needle aspirates are well described. We review the cytologic findings from 16 aspirates of adenocarcinoma/metastatic carcinoma that were frequently misclassified as hepatocellular carcinomas and compare them with 17 cases that were rarely misclassified. To compare the cytologic features of adenocarcinoma/metastatic carcinoma in fine-needle aspiration specimens of the liver that were frequently misclassified as hepatocellular carcinoma with those of aspirates that were rarely misclassified. We reviewed a total of 1712 interpretations from 33 different cases of adenocarcinoma/metastatic carcinoma tumor in liver fine-needle aspiration specimens in the College of American Pathologists Nongynecologic Cytology Program and correlated the cytologic features with performance in the program. Overall, cases that were frequently misclassified as hepatocellular carcinoma were misclassified on average 26% of the time (range, 13%-54%), while infrequently misclassified cases were interpreted as hepatocellular carcinoma on average 0.7% of the time (range, 0%-3%). The difference was statistically significant (P < .001). On review, cases that were frequently misclassified most often had moderate amounts of granular cytoplasm (16/16 cases) and round nuclei with even chromatin (13/16 cases). Trabeculae (3/16 cases), bare nuclei (2/16 cases), and endothelial wrapping (1/16 cases) were also occasionally present. In contrast, cases that were rarely misclassified were more likely to have areas with cells showing scant cytoplasm that were crowded and overlapped or molded (13/17 cases) and contained dark hyperchromatic chromatin (13/17 cases) compared to cases that were frequently misclassified (P < .001 and P = .002, respectively). Trabeculae (2/17) and bare nuclei (2/17 cases) were also rarely present. Cases of adenocarcinoma/metastatic carcinoma with moderate amounts of granular cytoplasm and round nuclei with even chromatin are frequently misclassified as hepatocellular carcinoma. Recognition of this problem, attention to cytologic criteria, and frequent use of immunohistochemical studies and core biopsy may help avoid this pitfall.

The importance of intracytoplasmic DPAS positivity in fine needle aspirates of breast lesions

Aims—For many years the presence of strong intracytoplasmic periodic acid Schiff (PAS) positive, diastase resistant (DPAS) staining within atypical cells has been used in this laboratory as a marker for...

Cytodiagnosis of hepatocellular carcinoma in fine-needle aspirates of the liver: its differentiation from reactive hepatocytes and metastatic adenocarcinoma.

Fine-needle aspiration (FNA) cytology is a useful tool for diagnosis of primary malignancies and metastatic lesions of the liver. However, well-differentiated hepatocellular carcinoma (HCC) may resemble benign/reactive hepatocytes, and less differentiated HCC may simulate poorly differentiated adenocarcinoma, leading to difficulties in interpretation of aspirates from liver. To determine the subtle cytomorphological features which can differentiate these lesions, ultrasound-guided FNA smears from 86 cases of liver malignancy were subjected to detailed cytologic assessment. These included 20 cases of HCC, 38 cases of metastatic adenocarcinoma, and 28 cases of benign/reactive hepatocytes. The important features for separating HCC or well-differentiated HCC from benign/reactive hepatocytes were excessive cellularity, trabecular pattern vs. thin cords of hepatocytes, nuclear pleomorphism, atypical stripped nuclei, and macronucleoli (P < 0.001 to < 0.0001). The most significant features for differentiating HCC from metastatic adenocarcinoma were trabecular growth pattern, hepatocytic cells vs. columnar/cuboidal cells, eosinophilic granular cytoplasm, lipid vacuoles, bile pigments, and atypical stripped nuclei (P < 0.001 to < 0.0001). The cytomorphological features which may distinguish poorly differentiated HCC from poorly differentiated adenocarcinoma were polygonal (hepatocytic) cells, eosinophilic granular cytoplasm and lipid vacuoles in HCC, and columnar/cuboidal cells and acinar/glandular formation in adenocarcinoma (P < 0.05 to < 0.001). Diagn. Cytopathol. 1999;21:370-377.

Cytologic aspect of fibrolamellar hepatocellular carcinoma in fine-needle aspirates.

This is a review of the cytologic and clinicopathological findings seen in a series of six fibrolamellar hepatocellular carcinomas (FL-HCC) studied by means of fine-needle aspiration (FNA). A comparison of several cellular measurements (cell, nuclear and nucleolar sizes, and N/C ratios) of FL-HCC, ordinary hepatocellular carcinoma (O-HCC), and normal hepatocytes was also carried out in order to find out if these figures could be of help in the cytologic diagnosis. Aspirates were made up of a rather monotonous population of large discohesive cells resembling the morphology of the oncocytes seen in thyroid aspirates; trabecular arrangement of tumor cells was not observed. Cytoplasmic pale bodies and hyaline cytoplasmic bodies were seen in variable quantities. Microbiopsies displaying the fibrolamellar pattern were observed in four cases. FL-HCC individual tumor cells were larger than individual O-HCC tumor cells (P < 0.001), as were nuclear (P < 0.007) and nucleolar sizes (P < 0.001), but N/C ratio of O-HCC was higher than the N/C ratio of FL-HCC (P < 0.005). Based on the findings, a single cell aspirated from an FL-HCC is three times the size of a normal hepatocyte and 1.60 times the size of a single cell aspirated from a well-differentiated O-HCC. The cytologic findings of FL-HCC are very characteristic and permit a correct diagnosis of this liver malignancy, provided the cytopathologist is aware of the clinical, demographic, CT-image, biochemical, and pathological features of this neoplasm. Diagn. Cytopathol. 21:180-187, 1999.

Cercariform cells for helping distinguish transitional cell carcinoma from non-small cell lung carcinoma in fine needle aspirates.

To determine if cercariform cells, a recently described finding in transitional cell carcinomas (TCC), can aid in distinguishing fine needle aspirates (FNA) of TCC from non-small cell lung carcinoma (NSCLC). We compared the incidence of cercariform cells in FNAs of 14 cases of TCC with 22 cases of NSCLC. Cercariform cells were identified in 8/14 (57%) cases of TCC as compared with 3/22 (14%) cases of NSCLC. Cercariform cells were often present and abundant (> 10 per case) in cases of TCC without squamous differentiation (8/9) but were not present in TCCs with extensive squamous differentiation (0/5). In NSCLCs, cercariform cells were rare (< 10 per case), and the cytoplasmic borders were sometimes not as well defined. The number of cercariform cells was significantly higher in FNAs of TCC without squamous differentiation than in FNAs of NSCLCs (P < .001). The presence of numerous cercariform cells in an FNA favors TCC over NSCLC.

Cytomorphologic and DNA Cytometric Features of Hepatocellular Carcinoma in Fine Needle Aspirates

To classify hepatocellular carcinoma according to DNA ploidy patterns and to evaluate distinct cytomorphologic features of hepatocellular carcinoma that correlate with DNA ploidy patterns. Fine needle aspiration smears of 36 histologically proven hepatocellular carcinomas were performed for DNA measurement by image analysis after Feulgen restaining of the specimens. Nuclear features-prominent nucleoli, nuclear cleavage, nuclear area and nuclear/cytoplasmic ratio-were correlated with the DNA ploidy patterns. Of the 36 cases, 14 were either diploid (n = 7) or polyploid (n = 7), 19 tumors had a single aneuploid stemline, 2 cases had multiple stemlines, and 1 case had no discernible stemline. A preponderance of prominent nucleoli was seen in 7/7 diploid tumors (2c), 6/7 polyploid tumors (4c, 8c) and 6/8 aneuploid tumors (> 4c). Conspicuous nuclear cleavage in a high number of tumor cells was present substantially in tumors with large nuclear areas (4c, > 4c). Most hepatocellular carcinoma studied had a distinct stemline so that the tumors could be designated DNA diploid, polyploid or aneuploid. The prevalence of prominent nucleoli and nuclear cleavage was a distinguishing cytologic feature that could predict DNA ploidy patterns. No special association of the nuclear/cytoplasmic ratio with any of the ploidy groups was noted.

Cytologic features of ductal and lobular carcinoma in fine needle aspirates of the breast.

To define cytologic criteria that reliably distinguish lobular (LC) and ductal (DC) carcinoma and classical LC from its variants-alveolar, solid and mixed infiltrative patterns. Fine needle aspiration (FNA) specimens from 29 cases each of histologically proven LC and DC were reviewed without knowledge of their histologic diagnoses. Malignant cells were seen and evaluated in 23 cases each of DC and LC (13 classic and 10 variant) for cellularity; cell size, pleomorphism and arrangement (group size, Indian filing, single cells); nuclear features (molding, nucleoli, intranuclear inclusions); and cytoplasmic features (vacuoles, signet-ring cells, granules). Features associated with LC included low cellularity (DC: 26%, LC: 70%), low pleomorphism (DC: 26%, LC: 61%), vacuoles (DC: 22%, LC: 61%), small nucleoli (DC: 43%, LC: 78%), and signet-ring cells (DC: 4%, LC: 48%). Features associated with DC included granular cytoplasm (DC: 39%, LC: 0%), high cellularity (DC: 57%, LC: 13%), high pleomorphism (DC: 48%, LC: 0%), medium to large nucleoli (DC: 35%, LC: 0%) and large sheets of cells (DC: 48%, LC: 17%). The range of cell size was larger in DC (1-20 times the size of RBCs) than in LC (1-8 times). Few cytologic differences were seen between the classic and variant patterns of LC. Variant patterns were slightly more likely to have intranuclear inclusions than classic LC; that was the only statistically significant difference seen. Most features studied were seen in at least a few examples of both DC and LC and in both classic and variant patterns of LC. However, some features were more characteristic of one entity than others.

Anaplastic thyroid carcinoma in fine needle aspirates.

To analyze the diagnostic problems with fine needle aspiration biopsy in anaplastic thyroid carcinoma (ATC) and to describe the cytomorphologic characteristics in 113 cases. A retrospective analysis of 113 fine needle aspirates and 67 surgical specimens from 113 patients with ATC admitted to the Institute of Oncology, Ljubljana, in 1972-1992. In a series of 113 fine needle aspirates of ATC, 3 (2.7%) were inadequate, 3 (2.7%) suboptimal and 107 (94.7%) diagnostic of malignancy. On reexamination, 96/107 (89.7%) were diagnosed as ATC, 6 (5.6%) as differentiated thyroid carcinoma, and 5 (4.6%) as a malignant tumor not otherwise specified. As to the predominant cell population, fine needle aspirates showed three different cell patterns: (1) pleomorphic cell (43 cases), (2) round cell (33 cases), and (3) spindle cell pattern (7 cases). In the present retrospective analysis we identified three main reasons for inadequate or nonrepresentative fine needle aspiration biopsy sampling: (1) tumor regressive changes (necrosis, hemorrhage, leukocytic infiltration), (2) extensive tumor fibrosis, and (3) distinct differentiated and anaplastic patterns in the same tumor. The major diagnostic problem with fine needle aspiration biopsy (FNAB) of ATC is related to sample quality. Cytomorphologic features of ATC are highly specific and easy to recognize. Due to the simple technique and high diagnostic accuracy, FNAB is the method of choice in patients with ATC.