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.     

P53 mutations analysis in benign and malignant breast lesions: using needle rinses from fine-needle aspirations

The fine-needle aspiration (FNA) technique is a widely used method for diagnostic assessment of breast diseases. In the current study we investigated the feasibility of sampling material for genetic studies from the same FNA samples as would be used for breast cytology. After making smears for cytological examination, the needle was rinsed into phosphate-buffered saline (PBS) solution. The material gained was sufficient for a polymerase chain reaction (PCR)-based study. As the FNA samples reflect a broad range of breast diseases, it is possible to study genetic changes at various stages of the neoplastic process. We looked for mutations in the p53 tumor suppressor gene in 198 FNA needle rinses, 42 from carcinomas and 156 from cytologically benign lesions. In the malignant samples, 22% carried mutations in the p53 gene. We also looked for p53 mutations in matching tissue sections from tumors and found the FNA needle rinses to represent the tumor well. In addition, three mutations in cytologically benign lesions were found, but none of these 3 patients were diagnosed with malignant tumors in the time frame of the study. The clinical significance of p53 mutations in benign breast tissue remains to be determined.     

Ultrasound-guided fine-needle aspiration biopsy remains a valid approach in the evaluation of nonpalpable breast lesions

The use of ultrasound-guided fine-needle aspiration (FNA) biopsy for nonpalpable breast lesions varies considerably. This retrospective study stresses the role of breast FNA in evaluating sonographically suspicious nonpalpable breast masses using a probabilistic reporting system. One hundred and eight consecutive ultrasound-guided FNA biopsies diagnosed as positive (32), suspicious (8), atypical (11), benign (55), and unsatisfactory (2) were analyzed and correlated with 61 subsequent surgical specimens. All positive cytologies showed carcinoma on histology; suspicious cases were followed by 5 carcinomas, 2 fibroadenomas, and 1 papillary lesion. Follow-up of atypical cases included 4 carcinomas, 3 fibroadenomas, and 2 papillary lesions, while all 10 biopsies following benign cytology showed fibrocystic changes. Two cases with suspicious sonographic findings but unsatisfactory cytology had lobular carcinoma. The remainder of the benign and atypical cases were followed clinically and radiographically for at least 10 months and had no evidence of carcinoma. Positive predictive values were positive, 100%; suspicious, 63%; atypical, 36%; benign, 0%. Most (40/43; 93%) carcinomas were invasive. In conclusion, ultrasound-guided FNA for nonpalpable breast lesions is highly accurate, and probabilistic reporting helps direct patient management.     

Comparison of ThinPrep and conventional preparations in pancreatic fine-needle aspiration biopsy

Use of ThinPrep preparation for fine-needle aspiration biopsy (FNA) is gaining popularity. However, there may be a difference in the morphology and the operating characteristics between ThinPrep and conventional methods. The objective of this study was to compare the accuracy of the two methods and to address the pitfalls of ThinPrep preparation in pancreatic FNA. A computer search identified 67 pancreatic FNAs with both conventional smears and ThinPrep preparation during a 19-mo period. These cases, obtained under endoscopic ultrasound-guidance, consisted of 47 malignant neoplasms (44 ductal carcinomas, two mucinous neoplasms, and one islet cell tumor) and 20 benign lesions. Direct smears were prepared first and the remaining material was then put into PreservCyt Solution for ThinPrep slides. All slides were reviewed and the cytologic diagnoses were correlated with histologic and clinical follow-up. Five conventional and 16 ThinPrep specimens were unsatisfactory due to insufficient cellularity. These cases were excluded from the analysis. Among the 62 cases evaluated by conventional preparation, 77% (34) were diagnosed as positive and 14% (seven) atypical/suspicious by conventional smears. For the 51 ThinPrep specimens, 58% (22) were interpreted as positive and 31% (12) atypical/suspicious. The sensitivity, specificity, and accuracy of diagnosing a malignancy were 77%, 100%, and 84% for conventional smears and 58%, 100%, and 67% for ThinPrep preparation, respectively. There were no false positives with either method. However, three benign lesions were interpreted as atypical/suspicious with ThinPrep preparation because of the presence of single atypical cells with distinct nucleoli. One of the two mucinous neoplasms was incorrectly diagnosed with ThinPrep preparation because of lack of mucin. The diagnostic accuracy of pancreatic FNA using ThinPrep is inferior to that of conventional smears. This may be partly due to the use of split sample technique resulting in scant cellularity in ThinPrep preparation and partly due to the differences in morphology between the two preparations. Therefore, the current morphologic criteria may need modification for ThinPrep preparation in pancreatic FNA.     

Neutrophil phagocytosis by tumor cells--a cytological study

Cell cannibalism is defined as the ability of a cell to phagocytose another cell. Malignant tumor cells may develop phagocytic property and demonstrate phagocytosis of own cells or cells of other series like neutrophils and lymphocytes. We report 11 cases in which the tumor cells showed evidence of neutrophil phagocytosis/emperipolesis on FNAC smears. Cases of malignancies diagnosed on FNA over a period of 1 year were retrieved, and smears were examined for neutrophil phagocytosis by tumor cells. These cases were classified according to type and differentiation of malignancy. The cytomorphological features and background inflammation were also studied at both primary and metastatic site. Of 362 malignant cases diagnosed on FNA smears, in 11 cases (3.09%), tumor cells showed neutrophil phagocytosis. The background showed increase in polymorphs in all cases. All the cases were associated with metastasis at presentation and were high-grade tumors cytologically. There were three cases of anaplastic carcinoma, two cases of adenocarcinoma, two cases of carcinoma breast, two cases of anaplastic non-Hodgkins lymphoma, one case each of squamous cell carcinoma and small cell carcinoma from larynx and lung, respectively. Phagocytic activity by tumor cells is uncommon and usually seen in high-grade/poorly differentiated malignancies. It is frequently associated with metastatic disease. On cytology smears, true phagocytosis of neutrophils by tumor cells has to be distinguished from superimposed inflammatory cells from the background. The tumor cells also need to be distinguished from histiocytes displaying phagocytosis.     

Value of scoring system in classification of proliferative breast disease on fine needle aspiration cytology

Fine-needle aspiration (FNA) cytology is successful in identification of benign and malignant breast lesions, but its role in proliferative breast lesions which increase cancer risk is poorly defined. We have analyzed the cytomorphologic features of proliferative breast lesions in conjunction with cytologic scoring system proposed by Masood et al and with histopathology. Sixty two patients (14 cases of fibroadenoma, 15 cases of fibroadenoma with atypia, 11 cases of proliferative breast disease (PBD), 8 cases of PBD with atypia and 14 cases of carcinoma) diagnosed on routine FNA were subjected to scoring following Masood's criteria. All cases with the cytologic diagnosis of fibroadenoma were confirmed on histology. Of 11 cases of PBD on FNA, 10 were PBD without atypia on histology. One case, which showed atypical hyperplasia on histology, was missed by both the scoring system and cytomorphology and one case was over-diagnosed as PBD with atypia by the scoring system. FNA cytology correctly identified all the carcinoma cases, while the scoring system under-diagnosed 2 cases as PBD with atypia. Hence, in cases not suspected to be atypical or confirmed to be cancer on routine cytology, scoring added no information over and above cytomorphology and was not useful. All fourteen cases of fibroadenoma with atypia suspected on routine cytology were fibroadenoma on histology. Scoring system correctly placed 11/14 of these cases as PBD without atypia. Similarly 3/8 cases thought to be PBD with atypia were correctly placed as PBD without atypia by scoring. Only 2/8 cases thought to be PBD with atypia on cytology were confirmed to have atypical hyperplasia on histology. Scoring improved the diagnostic yield to 2/5. Hence, in cases of fibroadenoma or PBD, suspected on FNAC to have cytological atypia, Masood scoring gives additional information by eliminating benign cases and improving diagnostic yield. Application of scoring in a step-wise manner, on atypical aspirates, can help in selection of cases suitable for biopsy.     

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.     

Fine Needle Aspiration cytology versus Fine Needle Sampling without aspiration. A prospective study of 200 cases

In the present prospective study of 200 patients with superficial swelling of various sites, FNS followed by FNA were performed. Fifteen cases were excluded due to inadequate material. In the 80 lymph node cases, FNS was diagnostic in 85% cases as compared to FNA in 87.5%. The diagnostic accuracy was higher for FNA (87.5%) than for FNS (81.25%). However FNS smears were much superior qualitatively than FNA smears and for the diagnosis of malignant conditions FNS was found to be much better. Regarding the 68 thyroid swellings, FNS obtained a diagnosis in 82.4% cases while FNA got it in 77.9%. The diagnostic accuracy with FNS (89%) was much better compared to FNA (75%). Of the 27 breast cases FNS yielded diagnostic material in 70.38% cases while FNA was diagnostic in 85.19%, thus establishing definite superiority. However FNS seemed to be better for diagnosing malignant lesions while FNA appeared better for diagnosing benign ones. In the 5 salivary gland lesions and 5 miscellaneous lesions both FNS and FNA fared equally well. On the whole FNS technique was much more patient friendly and gave high class "text book" quality smears while FNA smears gave quantitatively more adequate material. Both the techniques therefore would be complementary to each other.     

The estimation of mean nuclear volume in the diagnosis of breast carcinoma.

Sixty-two cases of breast pathology were randomly selected from the files of the Dunedin Public Hospital for evaluation of mean epithelial nuclear volume. The cases were comprised of both benign and malignant ductal epithelial disease, diagnosed in cytological smears or in histological sections. Nuclear volume in histological preparations was estimated by the stereological technique of point-line intercept measurements to derive volume-weighted mean volumes (vV). An index of the nuclear volume (Vi) of cytology smears was calculated from measurements of nuclear areas by either image analysis Vi(e) or point-line intercepts Vi(p). By all methods of analysis a clear distinction of nuclear volume was found between the benign [means for the cytology were 148 microns 3 (Vi(e)) or 246 microns 3 (Vi(p)), and 203 microns 3 (Vv) for the histology specimens] and malignant diseased cases [means for cytology: 524 microns 3 (Vi(e)) or 886 microns 3 (Vi(p)), and 587 microns 3 (vV) for the histology specimens].     

Evaluation of fine needle aspiration cytology of salivary glands: an analysis of 141 cases

141 salivary gland lesions that were subjected to fine needle aspiration (FNA) cytology at the University Hospital, Kuala Lumpur, from January 1993 to October 2000 were reviewed with a view to assess the sensitivity and utility of cytological diagnosis in diseases of salivary glands. The highest number of cases was seen in the sixth decade of life. There was no gender preponderance in salivary gland neoplasms except in Warthin's tumours that occurred predominantly in males. The parotid gland was the most frequent salivary gland needled. Seven cases (5%) presented with bilateral salivary gland enlargement. Cytological study yielded a neoplastic diagnosis in 74.5% cases. Of the neoplastic lesions, 71.4% could be definitely designated as benign and 25.7% as clearly malignant. Pleomorphic adenoma and acinic cell carcinoma were the most common benign and malignant neoplasms diagnosed respectively. 53 cases had histological correlation; of these, 49 (92.5%) were neoplastic. The overall diagnostic accuracy of FNA cytological diagnosis in salivary gland lesions was found to be 73.6%.     

Diagnostic significance of signet ring cells in fine-needle aspirates of the breast

Fine-needle aspiration (FNA) is a reliable and cost-effective procedure in the evaluation and management of breast lesions. One diagnostic dilemma that may sometimes arise is the finding of signet ring cells. The isolated finding of such cells in aspirate smears may be particularly problematic in cases of low cellularity or those with otherwise benign features. Although it is generally held that such cells are almost exclusively associated with carcinoma (particularly the lobular subtype), their significance in FNA smears has never been systematically evaluated. To establish their diagnostic utility, we evaluated aspirate smears from 150 cases of histologically proven benign (77) and malignant (73) breast lesions for the presence of signet ring cells, defined as those containing a prominent intracytoplasmic vacuole with nuclear displacement. Signet ring cells were identified in 71% of malignant cases (75% of ductal carcinomas and 71% of lobular carcinomas), mostly as single cells or within small, loosely cohesive tissue fragments. Such cells were also present in 6% of histologically proven benign lesions, most commonly within large tissue fragments. Many of these cells were proven to be vacuolated myoepithelial cells, based on histologic correlation and immunostaining results using anti-muscle-specific actin. On the basis of these findings, we conclude that (1) the presence of signet ring cells within small loose tissue fragments or as single cells in FNA smears should prompt close clinical follow-up (including repeat FNA and perhaps surgical biopsy), regardless of smear cellularity, (2) the presence of signet ring cells in cases of adenocarcinoma does not predict a particular tumor subtype, and (3) rare benign breast lesions may contain signet ring cells, particularly within large tissue fragments, and do not, in isolation, warrant surgical biopsy to exclude malignancy. Diagn. Cytopathol. 16:117–121, 1997. © 1997 Wiley-Liss, Inc.     

Correlation of fine needle aspiration cytology and frozen section biopsies in the diagnosis of thyroid nodules.

AIMS: To evaluate the correlation of fine needle aspiration (FNA) cytology and frozen section biopsy in the diagnosis of thyroid nodules. METHODS: The medical records of 662 patients who underwent FNA cytology of the thyroid and thyroid surgery were analysed. Frozen section biopsies were taken from 586 of the 662 patients. The diagnostic correlations of FNA cytology, frozen section, and both FNA cytology and frozen section with definitive histological assessment were evaluated. RESULTS: Among the 662 patients who received FNA cytology, there were 356 cases (53.8%) diagnosed as benign, 114 cases (17.2%) as malignant, 148 cases (22.4%) as indeterminate, and 44 cases (6.6%) as unsatisfactory. The positive predictive value for the detection of malignancy by FNA cytology was 92.1% and the negative predictive value was 95.2%. The incidence of malignancy in the indeterminate cytological diagnosis was 23%. The diagnosis from frozen sections was benign in 445 cases (75.9%), malignant in 134 cases (22.9%), and deferred in 7 cases (1.2%). By frozen section, the positive and negative predictive values were 97% and 95.5%, respectively. Diagnostic accuracy up to 98% was achieved when FNA cytology and frozen section diagnoses were in agreement. No false positives were observed when FNA cytology and frozen sections were both positive for malignancy. When FNA cytology and frozen section diagnoses were discordant, frozen section showed a higher accuracy (78.9%) than FNA cytology (21.1%). In the face of an indeterminate or unsatisfactory cytological diagnosis, the diagnostic accuracy of frozen sections reached 92.6%. CONCLUSIONS: The results confirm that FNA cytology is a useful tool in the initial evaluation of thyroid nodules. Intraoperative frozen section is a valuable procedure to confirm the cytological diagnosis and identify malignancy in patients with indeterminate or unsatisfactory cytological diagnosis. With reliance on frozen sections as an intraoperative guide of thyroid surgery, the possibility of unnecessary extensive surgery and the need for the second operation are considerably lower.     

Fine‐needle aspiration in myxofibrosarcoma: Experience of Institut Curie

Myxofibrosarcoma (MFS) is a well‐established nosologic entity different from the myxoid variant of malignant fibrous histiocytoma. In an attempt to better define the representative cytologic criteria of MFS, we undertook a review and a reanalysis of a series of 14 cytology samples in 12 patients whose tumors were diagnosed as MFS. Using FNA technique and reviewing the original diagnoses, 11 cases were diagnosed as malignant and three as benign tumors. The cytologic diagnosis of MFS was accurate in seven cases (2 primary tumors, 4 recurrences, and 1 metastasis). Four cases were classified malignant myxoid sarcoma (1 primary and 3 recurrences), whereas three cases (2 primary and 1 recurrence) were false‐negative. The smears were cell‐rich in 12 cases and cell‐poor in two cases. They were constantly composed of isolated and regular small spindle‐shaped and stellated cells with elongated nuclei containing small inconspicuous nucleoli. Cytoplasm was pale with elongated processes. Clusters of wavy spindle‐shaped cells, round cells without specific pattern, moderate cytonuclear atypia, and abundant myxoid background as well as curvilinear vascular structures were always seen. In the vast majority of cases, the cytologic distinction of MFS from other low‐grade myxoid lesions is difficult. Entities such as myxoid MFH, myxoid liposarcoma (MLP), myxoid DFSP, and myxoma should be considered in the differential diagnosis. The cytological misdiagnosis is of limited clinical consequence because FNA findings suggestive of a myxoid tumor will be indicative for a surgical removal followed by the histopathological analysis. Diagn. Cytopathol. 2010. © 2009 Wiley‐Liss, Inc.     

Study of a manual method of liquid-based cervical cytology

We report a study of a manual liquid-based cytology (MLBC) method. Slides are prepared by using a polymer solution and allowing it to dry, forming a membrane. The aims of the study were to prepare cervical cytology smears using the manual method, observe morphology, compare with direct scrape smears and correlate with histopathology wherever possible. Out of 105 cases, the membrane was intact, indicating a good MLBC preparation, in 97 cases. Simultaneous conventional smears were taken in 81 patients. There was an 88.8% agreement in the diagnoses of general category in both groups. The diagnosis of negative for intraepithelial lesion or malignancy (NILM) in both groups was made in 70 cases. The MLBC preparation was unsatisfactory in two cases which showed high grade squamous intraepithelial lesion and low grade squamous intraepithelial lesion, respectively, on the conventional smear. One MLBC smear diagnosed as atypical squamous cells of undetermined significance was reported as NILM on conventional smear. Cytohistologic correlation was done in nine cases, all of which showed cervicitis on histopathology. The MLBC method was found to be comparable to the conventional scrape smear. Further study of this method as a cost-effective alternative to the mechanized methods would be worthwhile.     

Spindle cell lipoma of the breast: A case report and literature review

Fine-needle aspiration cytology (FNA) was performed on a breast lump in a 66-year-old female, clinically thought to be a carcinoma. The cytological findings were reported as suspicious of malignancy. Subsequent histological examination showed a tumour macroscopically and microscopically identical with six other cases previously described as benign spindle cell tumours of the breast. This report highlights yet another diagnostic pitfall in FNA cytology of the breast. The presence of floret cells in this case has not been previously reported but supports the concept that this lesion is the same as a spindle cell lipoma, from which it is virtually indistinguishable on light microscopy. The lesion affects both mate and female breast, is predominantly single but may be multiple, and follows a benign course. Local excision is curative.     

ER,PR, and Her2 immunocytochemistry on cell‐transferred cytologic smears of primary and metastatic breast carcinomas: A Comparison Study With Formalin‐Fixed Cell Blocks and Surgical Biopsies

The use of formalin‐fixed cell blocks (CBs) for detection of ER, PR, and Her2 status of primary and metastatic breast carcinomas sampled by fine‐needle aspiration (FNA) has been extensively used in clinical practice; however, CBs sometimes lack adequate cellularity even when direct smears are cellular. The aim of this study is to assess the reliability of ER, PR, and Her2 status as demonstrated by immunocytochemical staining (ICC) on alcohol‐fixed direct smears using the cell transfer (CT) technique. FNA cases diagnosed as primary or metastatic breast carcinoma in which the status of ER, PR, and Her2 had been determined either on CB or concurrent biopsy were identified over a period of 18 months. ICC for ER, PR, and Her2 was performed on alcohol‐fixed direct smears using the CT technique. Results were compared with those reported for the corresponding formalin‐fixed tissue. A total of 47 FNA specimens from 46 patients were included in this study. ICC results were excluded from analysis if the CT smear contained fewer than 50 cells. Correlation between the ICC performed on the CT smears and the corresponding CB or biopsy revealed a sensitivity rate for ER, PR, and Her2 of 95%, 90%, and 88%, respectively with a specificity of 100% for all three markers. ICC performed on the FNA smears using the CT technique is a reliable method for assessment of the ER, PR, and Her2 status of breast carcinomas, especially when the direct smears are highly cellular and the CB lacks adequate cellularity. Diagn. Cytopathol. 2013. © 2012 Wiley Periodicals, Inc.     

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.