Ultrasonographically and stereotactically guided fine-needle aspiration cytology of non-palpable breast lesions: cyto-histological correlation

Objective:  To determine the diagnostic accuracy of ultrasonographically (US) and stereotactically guided fine needle aspiration cytology (FNAC) for the diagnosis of non-palpable breast lesions.
Patients and methods:  From January 2002 to December 2004, 470 women with 478 mammographically detected non-palpable breast lesions had US or stereotactically guided FNAC of the breast lesion. Subsequent histological evaluation of the same lesion was performed at the Institute of Oncology Ljubljana, Slovenia. The correlation between the original cytological and histological diagnosis was assessed and the sensitivity, specificity, positive predictive value and negative predictive value were calculated.
Results:  Among US-guided FNACs, 144 (53.5%) were histologically verified benign lesions and 125 (46.5%) were carcinomas. Cytological diagnoses were: true positive (TP) in 63 cases (50.4%), suspicious in 35 (28%), false negative (FN) in eight (6.4%), and in 19 (15.2%) cases, the material was inadequate for diagnosis. In the stereotactically guided FNAC group, there were 209 women with 209 lesions, with 95 (45%) histologically proven carcinomas and 114 (55%) benign lesions. Cytological diagnoses were TP in 49 (51.6%) cases, true suspicious in 21 (22.1%), FN in nine (9.5%), and in 16 (16.8%) cases, the material was not adequate for the diagnosis.
Conclusion:  The sensitivity of 88.7% and specificity of 98.6% for US-guided FNAC and 84.5% and 100% for stereotactically guided FNAC, respectively, suggest that clinicians can rely upon cytological diagnosis for planning further management of women with non-palpable breast lesions.     

Characteristic cytological features of histological grade one (G1) breast carcinomas in fine needle aspirates

Objective:  To analyse the spectrum of nuclear features as well as dissociation pattern found in fine needle aspirates (FNAC) from histological grade 1 breast carcinomas and evaluate the critical cytological features of these lesions.
Material and methods:  The material consisted of FNAC smears from 494 histologically confirmed grade 1 breast carcinomas. All smears were revaluated for cell dissociation pattern, nuclear size, cell uniformity, nucleoli, nuclear margin and chromatin pattern. All features were compared with the histological subtype and cytological grading.
Results:  73.9% of the cases were cytological grade 1, 24.3% were grade 2 and 1.8% were grade 3. The majority of the cases had a cell dissociation pattern showing both a population of single carcinoma cells and cell clusters (65.9%). Practically all tumours had a granular chromatin pattern (94.7%) and a slightly irregular nuclear margin with folds and grooves (94%) irrespective of histological subtype and cytological grading. Nucleoli were mostly indistinct or small (74%), whereas 24.3% were noticeable and 1.7% abnormal. Practically all cases revealed some degree of pleomorphism with 74.3% showing mild and 22.4% a distinct pleomorphism. A small subgroup of IDC was classified as monomorphic (3.3%). Almost all tumours had nuclear sizes in the range of 2–4 × RBC (96.9%).
Conclusion:  Not all histological grade 1 carcinomas are cytological grade 1. About 25% were grade 2, and a small subpopulation reached grade 3. The typical/average findings in FNAC from grade 1 breast carcinomas were a population of both groups and single cells showing mild pleomorphism, granular chromatin, slightly irregular nuclear margin, indistinct nucleolus and nuclear size 2–4 × RBC.     

Diagnostic pitfalls in the evaluation of fine needle aspiration cytology of the thyroid: correlation with histopathology in 260 cases

Objectives:  Fine needle aspiration cytology (FNAC) of the thyroid is a non-invasive, cost-effective screening procedure that is valuable for distinguishing neoplastic lesions from non-neoplastic nodules. The aim of this study was to determine the diagnostic accuracy of FNACs performed at our institution by correlating FNAC results with histopathological diagnoses.
Methods:  Two hundred and seventy-one aspiration cytology specimens followed by thyroidectomy were included in the study, and the results of 260 adequate FNACs were compared with their histological diagnoses.
Results:  The sensitivity and specificity of thyroid FNAC for detecting neoplasia were 92.6% and 91.6%, respectively. There were 15 (5.7%) false positives and six (2.3%) false negatives.
Conclusions:  The results showed that follicular cells that exhibit some of the features of papillary carcinoma could be observed in a cytology slide of Hashimoto's thyroiditis, leading to a diagnostic pitfall. In addition, cellularity and overlapping cytological criteria in hyperplasia might lead to a false diagnosis.     

P-2COMPLETING THE AUDIT CYCLE OF NON-GYNAECOLOGIC CYTOLOGY TURNAROUND TIMES

Introduction:  The authors initiated the use of Liqui-PREP™ (LGM International Inc., Fort Lauderdale, FL, USA) in August, 2005. Cytotechnologists received extensive (one month) training by cytopathologists experienced in Liquid-based cytology. The Liqui-PREP™ direct-to-vial procedure (LP) was compared to the conventional Pap smears in a routine screening population.
Methods:  Data derived from 26 178 LP cervical-vaginal (CV) specimens were compared to data derived from 218 548 conventional Pap smears (CS). Both data sets reflect patient samples collected concurrently (August–December, 2005) by 117 participating outpatient medical practices from a well-defined geographic area. There were no significant personnel changes during the study period. The diagnostic results, classified according to Bethesda criteria were calculated.
Results:   

     

Fine needle aspiration cytology of thyroid nodules: how accurate is it and what are the causes of discrepant cases?

Fine-needle aspiration cytology (FNAC) is widely accepted as the most accurate, sensitive, specific and cost-effective diagnostic procedure in the assessment of thyroid nodules and helps to select people preoperatively for surgery. The purpose of this study was to evaluate the results of thyroid FNAC in our institution and to determine the reasons for discrepancies between the cytological and histological diagnosis. We evaluated the cytological and histological results of 254 FNACs obtained from 231 patients who underwent subsequent thyroid surgery. All of the material was blindly reviewed for quality control, by one experienced cytopathologist. All FNACs were carried out under ultrasound guidance. The cytological diagnosis was classified as benign, suspicious, malignant or unsatisfactory. The definitive histological study showed benign lesions in 195 of the 231 patients (84%). A benign diagnosis based on FNAC was correct in 105 of the 108 benign cases (97%). FNACs diagnosed as 'suspicious' resulted in a distribution of 49 benign (79%) and 13 malignant (21%) diagnoses. FNAC showed malignancy in 34 cases (13%) and in only one case did the final histology differ from cytology (correlation 97%). The percentage of FNACs that were inadequate for diagnosis was 20%. Review of cytological and histological slides did not lead to any change in the original diagnosis. Our study revealed a cytological-histological discrepancy (2%) in only 4 out of 231 cases over a period of 10 years, due to either a diagnostic or sampling error.     

O-2"ARTISTIC" TRIAL: BASELINE DATA

Recent reviews of glandular reports have confirmed a wide variation in specificity.^1–3 We have reviewed our performance over the last 10 years and evaluated the effect of conversion to Liquid Based Cytology (LBC) on our reporting rates and accuracy. Audit revealed an upward trend in ability to accurately detect glandular lesions, with particular improvement in identification of Cervical Glandular Intraepithelial Neoplasia (CGIN).
 

     

Pre‐operative features of non‐invasive follicular thyroid neoplasms with papillary‐like nuclear features: An analysis of their cytological,Gene Expression Classifier and sonographic findings

Objective

To investigate the corresponding cytological diagnoses, Gene Expression Classifier (GEC) results and ultrasound features of thyroid nodules diagnosed as non‐invasive follicular thyroid neoplasms with papillary‐like nuclear features (NIFTP), as well as any coexisting pathology.

Methods

We performed a retrospective review of thyroid nodules histologically diagnosed as NIFTP at our institution between 1^st April 2016 and 1^st April 2017. The following data points were collected: demographics, nodule size, ultrasound features, cytological diagnosis, GEC results, origin of sample (in‐house vs outside hospital) and any additional pathology identified in the resection specimen.

Results

The case cohort included 87 nodules diagnosed as NIFTP (size range: 1‐7 cm, mean: 2.5 cm) from 82 patients (age range: 22‐82, mean age: 50.4, M:F—1:4.1). Corresponding FNA results were available for 72 nodules (82.8%) and were categorised as follows: benign (n = 5, 6.9%), atypia of unknown significance/follicular lesion of undetermined significance (n = 29, 40.3%), follicular neoplasm/suspicious for follicular neoplasm/follicular neoplasm with oncocytic features (n = 27, 37.5%), suspicious for papillary thyroid carcinoma (n = 6, 8.3%) and malignant (n = 5, 6.9%). GEC results were available for 32 (44.4%) nodules, with the majority of cases classified as suspicious (81.3%). On ultrasound, most of the nodules were predominantly solid (81.8%), vascular (93.8%), non‐calcified (86.5%), and either hypoechoic (44.9%) or isoechoic (38.8%). In addition to NIFTP and other benign findings in the background thyroid, 75 separate malignant tumours were identified in 38 (46.3%) patients, many of which were papillary thyroid microcarcinomas (86.5%) with lymph node metastases present in two cases.

Conclusions

The majority of thyroid nodules histologically diagnosed as NIFTP have indeterminate cytology (77.8%) and are classified as suspicious (81.3%) by GEC testing. Taken together, these findings can guide clinicians toward a more conservative therapeutic approach.

     

Cytomorphological changes after ultrasound-guided percutaneous ethanol injection in benign thyroid nodules

Objective:  To characterize the cytomorphological changes after percutaneous ethanol injection (PEI) in benign thyroid nodules, we compared the cytological features of fine needle aspiration cytology (FNAC) samples before and after PEI.
Methods:  Fifty-five cases diagnosed with adenomatous goitre (group 1, 35 cases) or cystic changes only (group 2, 20 cases) were included. In all cases, FNACs were performed by the pathologists before and after PEI. PEI was performed in all cases by a diagnostic radiologist according to the ultrasound guidelines. The following cytological features were evaluated by two pathologists: cellularity of follicular epithelial cells, background, cellular pleomorphism, nuclear/cytoplasmic (N/C) ratio, chromatin pattern, presence of nucleoli, macrophages, multinucleated giant cells, and mitosis.
Results:  In group 1, 19 cases (54%) showed changes in cellularity after PEI, with reduced cellularity in 13 cases (37%) and increased cellularity in six cases (17%). No necrotic background was observed before PEI; however, 14 cases (40%) developed necrotic background after PEI ( P  < 0.0001). Multinucleated giant cells were observed in 18 cases (51%) after PEI, which is in contrast to four cases (11%) before PEI ( P  = 0.001). In group 2, necrotic background was seen in 11 cases (55%, P  < 0.0001) and multinucleated giant cells were observed in four cases (20%) after PEI.
Conclusions:  Necrotic background and presence of multinucleated giant cells are indicative of tissue damage caused by PEI in the FNAC specimens of benign thyroid nodules. In contrast to other modalities including chemotherapy or radiation treatment for malignant tumour, no unusual cytological change is observed after PEI.     

P-14CERVICAL DYSPLASIA AND RISK FACTORS IN NORTHERN IRELAND SLE PATIENTS

Introduction:  An increased risk of cervical dysplasia has previously been reported in lupus. The role of traditional related risk factors are unclear. Persistent infection with certain genotypes of Human Papilloma Virus termed high risk (HR-HPV) is considered a prerequisite for the development of cervical cancer.
Methods:  A total of 141 SLE patients fulfilling the ACR criteria for lupus were enrolled into the study. They were compared to 138 control patients who were due to attend for a routine cervical smear. Each patient completed a cervical cancer risk factor questionnaire. A cervical smear was taken and residual material used to test for the presence of HR-HPV using a hybridisation microplate assay. Positive samples were then genotyped.
Results:   

     

P-13CERVICAL SMEAR REPORTING IN NORTHERN IRELAND SLE PATIENTS

Introduction:  SLE is an autoimmune disease with the potential for multi-organ involvement. It has been suggested that SLE patients may be at increased risk of cervical dysplasia. We studied a cohort of Northern Ireland Lupus patients and compared them to controls within the same geographical location assessing their cervical smear histories and performing an up-to-date cervical smear.
Methods:  A total of 141 SLE patients fulfilling the ACR criteria for lupus were enrolled into the study. They were compared to 138 control patients who were due to attend for a routine cervical smear within the same geographical location. Each patient gave written consent to be involved in the study including access to medical records and pathology data.
Results:   

     

Ultrasound-guided fine needle aspiration cytology in the diagnosis and management of thyroid nodules

OBJECTIVE: To examine the accuracy of fine needle aspiration cytology (FNAC) in the diagnosis of thyroid nodules and compare the inadequacy rates for ultrasound-guided and freehand FNAC. METHODS: A retrospective study of 434 patients with thyroid nodules who underwent diagnostic FNAC over a 2-year period. Cytological diagnoses have been compared with the histological assessment of resection specimens in 69 cases. RESULTS: The inadequacy rate was significantly lower from ultrasound guided FNAC (24/373 cases, 6.4%) than from freehand FNAC (8/61 cases, 13.1%) (P = 0.043). Seventy-six percentage of patients had a non-neoplastic cytological diagnosis and, after multidisciplinary review, the patients were reassured and assigned to clinical follow-up. Sixty-seven patients had a resection for cytological appearances consistent with non-neoplastic disease (n = 34), suspicious of follicular neoplasia (n = 23), or suspicious of malignancy (n = 10), and two patients had resections following inadequate cytology with ultrasound appearances suspicious of a neoplasm. The overall accuracy of FNAC analysis for malignancy was 97.0%, with sensitivity 83.3%, specificity 98.0%, positive predictive value 71.4% and negative predictive value 98.4%. The overall accuracy of FNAC analysis for the prediction of neoplasia was 97.5%, with sensitivity 80.5%, specificity 97.8%, positive predictive value 89.2% and negative predictive value 95.9%. Difficulties in cytological diagnosis were associated with lymphoid infiltrates and with degenerative changes in follicular adenomas. CONCLUSION: Ultrasound-guided FNAC has a significantly lower yield of inadequate aspirates than palpable FNAC. The ability of FNAC to predict neoplasia in 89% patients and to exclude neoplasia in 95.9% patients makes an important contribution to the multidisciplinary assessment of patients.     

Randomized study comparing endoscopic ultrasound-guided Trucut biopsy and fine needle aspiration with high suction

H. Gerke, M. K. Rizk, A. D. Vanderheyden and C. S. Jensen
Randomized study comparing endoscopic ultrasound-guided Trucut biopsy and fine needle aspiration with high suction
Objectives:  Endoscopic ultrasound (EUS)-guided Trucut biopsy (TCB) enables acquisition of tissue cores for histological assessment. Because of the rigid needle and the spring mechanism, tissue acquisition can be difficult from regions that require sharp angulation of the echoendoscope. Fine needle aspiration with high suction (FNAHS) has been proposed as a method to obtain histological tissue cores while affording the flexibility to obtain specimens even with extreme endoscope angulation. The objective was to compare prospectively these two methods in their ability to obtain specimens for histological assessment and in their diagnostic accuracy, including cytological diagnosis when achieved.
Methods:  Eighty lesions in 77 patients were amenable to transoesophageal, transgastric or transrectal biopsy and were randomized to TCB ( n  = 44) or FNAHS ( n  = 36). Each specimen was assessed for adequacy (scoring system where a score of 0 was no material, 1–2 was considered cytological, and 3–5 was considered histological). Follow-up information was obtained to establish a gold standard final diagnosis.
Results:  The median histological scores for FNAHS and TCB were 2 and 5, respectively. Histological cores were obtained in 95.3% of TCB, as opposed to 27.8% in the FNAHS group ( P  < 0.0001). Although the diagnostic accuracy for TCB was greater than that for FNAHS (88.3% and 77.8%, respectively), this was not statistically significant ( P  = 0.24).
Conclusion:  If histological information is required, TCB is superior to FNAHS. The difference in diagnostic accuracy did not reach statistical significance due to low numbers and the fact that FNAHS often enabled a cytological diagnosis.     

The role of liquid-based cytology in the investigation of thyroid lesions

Objective:  This study investigates the role of liquid-based cytology by ThinPrep^® technique in the detection of thyroid lesions.
Methods:  In all, 252 specimens from 157 patients for pre-operative evaluation of thyroid nodules, prepared by the ThinPrep^®, were examined. In all cases thyroidectomy followed the initial cytological evaluation. All cytological diagnoses were correlated to the histological ones.
Results:  According to our findings, a sensitivity of 87.80%, a specificity of 99.50%, a positive predictive value of 97.30%, a negative predictive value of 97.56% and an overall accuracy of 97.52% were observed in fine needle aspiration cytology in correlation to the histological diagnosis after thyroidectomy.
Conclusions:  ThinPrep^® technique is a valid method for the pre-operative cytological diagnosis of thyroid nodules, offering the possibility of ancillary techniques, such as immunocytochemical and molecular methods and can, therefore, be potentially complementary to histological evaluation for further investigation of follicular lesions.     

Comparative validation of c-kit exon 11 mutation analysis on cytology samples and corresponding surgical resections of gastrointestinal stromal tumours

Objective:  Studies have shown that c-kit mutation analysis of gastrointestinal stromal tumours (GISTs) obtained by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) can be routinely performed. We validated c-kit exon 11 mutational analysis on cell block material obtained from fine needle aspiration cytology (FNAC) for diagnostic purposes and compared it with the same analysis in formalin-fixed paraffin-embedded full sections of the corresponding resection specimens.
Methods:  c-kit mutation analysis was done on cell block material obtained from ten cases encountered in our department from 1999 to 2008 on which FNAC was attempted pre-operatively. The findings were compared with analysis on full paraffin section of the corresponding resected tumours in seven cases where patients opted for resection. c-kit exon 11 was examined via bidirectional nucleic acid sequencing.
Results:  Our results showed 100% concordance for the presence and type of exon 11 mutation in the resected and aspirated tumours in all seven cases. These mutations had diagnostic value when compared with other neoplasms that are part of the cytomorphological differential diagnosis, such as leiomyosarcoma or gastric adenocarcinomas.
Conclusion:  Molecular cytopathology is a powerful tool that can complement morphology and immunohistochemical assessment of cytological material in routine practice for the diagnosis and prognostication of GISTs. We briefly discuss the advantages and limitations of the fine needle method of obtaining tissue for the diagnosis and prognostication of GISTs, and its current therapeutic strategies.     

Cytology of benign multicystic peritoneal mesothelioma in peritoneal washings

Objective:  To describe the cytological aspect of peritoneal washings in benign multicystic peritoneal mesothelioma (BMPM).
Methods:  Three peritoneal washing specimens stained by standard cytological and histological procedures and analysed by light microscopy.
Results:  The specimens showed an abundance of monomorphous mesothelial cells devoid of atypia or mitoses. The mesothelial cells were calretinin positive. They also showed numerous squamous metaplastic cells arranged in flat sheets or isolated cells. The background contained some inflammatory cells.
Conclusion:  The combination of cytology of the peritoneal washing, histology (cell block and surgical specimen) and clinical history allow differentiation of BMPM from other cystic lesions (cystic lymphangioma and malignant mesothelioma).     

Signet ring cells in fine needle aspiration cytology of breast carcinomas: review of the cytological findings in ten cases identified by histology

Objective:  To establish whether the presence of signet ring cells (SRCs) in histology sections of breast carcinoma cases was reflected by their presence in fine needle aspiration cytology (FNAC) smears, correlating to the histological type of breast carcinoma.
Methods:  We reviewed the FNAC findings of ten cases that had been diagnosed as primary breast carcinoma with SRCs on histological sections between 1998 and 2007. Slides and histological sections were obtained from the archives of Ege University Hospital.
Results:  FNA smears were reviewed for the following cytomorphological features: background, cellularity, architecture, nuclear pleomorphism and the presence of SRCs. The background was bloody in eight cases, necrotic in one, and clean in one. There was no mucinous material in any of the cases. Cellularity was prominent in five cases (hypercellular), moderate in three (cellular) and low in two (hypocellular). Loosely cohesive groups of tumour cells of varying size were observed in all cases. A plasmacytoid appearance to some of the tumour cells was seen in all cases and discohesive tumour cells were present in eight. Nuclear pleomorphism was high in six cases and moderate in four. SRCs were observed in seven of the ten cases. Two of these seven cases also had a tubular pattern and one had tumour giant cells.
Conclusions:  FNAC should be evaluated carefully regarding the presence of SRCs when cells with a plasmacytoid appearance are observed in either hyper- or hypocellular smears. The presence of single SRCs in FNACs with hypercellularity, high nuclear grade and tubular formation or tumour giant cells may be a clue in favour of ductal carcinoma. The presence of single SRCs in FNACs with hypocellularity and mild to moderate nuclear grade may be suggestive of lobular carcinoma. However, larger studies would be needed to establish the predictive value of the presence of SRCs on FNAC.     

Inter- and intraobserver reproducibility of thyroid fine needle aspiration cytology: an analysis of discrepant cases

OBJECTIVE: To determine the inter- and intraobserver reproducibility and analyse the discrepant cases of fine needle aspiration cytology (FNAC) of the thyroid. METHODS: Cases of thyroid FNAC with a corresponding histological diagnosis were reviewed regarding the original cytological diagnoses by two observers. The final cytological diagnoses (FCD) included both concordant and consensus diagnoses. The inter- and intraobserver reproducibility and efficacy of thyroid FNAC were calculated based on the FCD. RESULTS: A total of 97 FNAC cases with corresponding histopathological specimens were analysed. Although inter- and intraobserver disagreement in the cytological diagnoses occurred in about one-quarter of the cases analysed (24.7% and 23.7%, respectively), a substantial level of diagnostic interobserver (kappa = 0.71) and intraobserver (kappa = 0.66) reproducibility was observed. The efficacy of the method was 94.4%. Disagreement in the diagnosis was detected in 24 cases (24.7%), most of them (41.7%) for follicular lesions. Discordant cytological diagnoses between the two observers were represented by six (16.2%) of the 37 cases with an FCD of colloid nodule, five (41.7%) of the 12 cases of cellular follicular lesion, all three cases of follicular neoplasm, in two (6.3%) of the 32 cases of PTC, one (16.7%) of six cases of follicular neoplasm with a predominance of Hürthle cells and in one case of poorly differentiated neoplasia. Similarly, major disagreement in intraobserver cytological diagnoses was observed for the diagnosis of follicular lesions: 18 (78.3%) of a total of 23 discordant cases. CONCLUSION: As discrepancies in the cytopathological diagnosis can have repercussions in the management of patients, all cases with a cytological diagnosis of follicular lesions/neoplams should be reviewed in multidisciplinary meetings thus minimizing interobserver variability.     

Initial axillary staging of breast cancer using ultrasound‐guided fine needle aspiration: a liquid‐based cytology study

A. Schiettecatte, C. Bourgain, C. Breucq, N. Buls, V. De Wilde and J. de Mey
Initial axillary staging of breast cancer using ultrasound‐guided fine needle aspiration: a liquid‐based cytology study Objective: To evaluate the preoperative detection of axillary metastasis combining ultrasound (US)‐guided fine needle aspiration cytology (FNAC) and liquid‐based cytology (Surepath^®) to reduce sentinel node procedures. Methods: In total, 148 patients with clinically negative lymph nodes and no preoperative therapy were included. All patients underwent preoperative ultrasound of the axilla with FNAC if suspicious lymph nodes were found. Complete axillary lymph node dissection was performed at primary surgery when FNAC was positive. All other patients underwent a sentinel node procedure. Results: US‐guided FNAC of the axilla revealed metastasis in 34 (23.0%) of the 148 patients. These 34 patients were 53.1% of all patients (n = 64) with proven axillary lymph node involvement. In 66 patients (44.6%), both ultrasound and histopathology were negative. Overall sensitivity of US‐guided FNAC was 50.0%, specificity 100%, positive predictive value 100% and negative predictive value 70.2%. In T1 tumours, all patients referred for sentinel node procedure were node‐negative. The correlation between malignant FNAC and histopathology was 100%. US‐guided liquid‐based FNAC in patients with no clinically positive lymph nodes reduced the necessity for a sentinel node procedure by 23.0%. Conclusions: We advocate that US‐guided fine needle aspiration (FNA) combined with liquid‐based cytology of axillary lymph nodes should be included in the preoperative staging of breast cancer.