Peripheral endothelial cells are not reliable in differentiating primary benign and malignant hepatocellular lesions in fine needle aspirates of the liver

The distinction of hepatocellular carcinoma (HCC) from benign lesions of the liver in fine needle aspiration (FNA) specimens can be problematic. In an attempt to separate well-differentiated HCC from benign hepatocellular lesions, the presence of tissue fragments displaying peripheral endothelial cells (PE) has been proposed in a previous study as a useful feature in favour of malignancy. In this study, we evaluated slides from 59 cases of liver masses undergoing FNA (19 HCC, 40 benign) and evaluated them for the presence of tissue fragments containing PE. We found that 90% of cases of HCC contained tissue fragments in which PE were either focally present or abundant. However, 68% of cases containing only benign hepatocytes also contained tissue fragments in which PE were at least focally present. In addition, it appears that within the group of benign lesions, the presence of PE was related to the overall cellularity of the specimen rather than the specific nature of the lesion. Thus, the presence of PE in tissue fragments does not, in isolation, appear to be a useful morphological feature for the separation of benign and malignant hepatocellular lesions in FNA material.     

Diagnostic difficulties in the interpretation of fine needle aspirates of salivary gland lesions: the problem revisited

Diagnostic difficulties in the interpretation of he needle aspirates of salivary gland lesions: the problem revisited
Cases of salivary gland lesions ( n =325), mainly neoplastic but including a small number of non-neoplastic lesions, investigated by fine needle aspiration (FNA) and with histological correlation, are reviewed. The review identified a number of differential diagnostic problems which are discussed in some detail. One false-positive and eight false-negative diagnoses had been made resulting in a 99.5% specificity and a 85.5% sensitivity. If type-specific diagnoses are made only when all defined diagnostic criteria are present and if any uncertainty is clearly conveyed to the clinician, FNA is a safe and accurate tool in the investigation of salivary gland lesions.     

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.     

Cytoplasmic colloid inclusions in thyroid lesions: a cytomorphological study based on fine needle aspiration

INTRODUCTION: Intracytoplasmic lumens (ICL) with or without magenta material and transgressing vessels are features of Hürthle cell neoplasms (HCN). After detection of intracytoplasmic colloid inclusions (CIs) including targetoid (magenta) body-like structures in the Hürthle cells (HC) in a case of Hashimoto's thyroiditis (HT), we reviewed cases of HT, thyroid neoplasms, hyperplastic nodules (HN) and colloid goitres to determine the frequency of these structures. Further, an attempt was made to find out the significance of CIs. METHODS: FNA smears of 120 HT, 101 colloid goitres, 11 HN, and 76 neoplastic goitres were examined. The presence of CIs and empty ICL were noted in epithelial cells in these lesions. An attempt was made to find out the difference between HT with and without CIs in respect of various cytomorphologic features. The groups were compared using the Fisher's exact test of probability. RESULTS: The CIs were present in 36 (30.0%) of HT, 26 (34.2%) of neoplastic goitres, 3 (27.3%) of HN, and 4 (4.0%) colloid goitres. As compared to colloid goitres, CIs were present in a significant higher number of cases in HN (P = 0.0202), neoplastic goitres (P < 0.0001), and HT (P < 0.0001). Among neoplasms the frequency of CIs in HCN (75.0%) was significantly higher than that of papillary thyroid carcinoma (PTC) (33.3%, P = 0.0466), and follicular neoplasm (14.3%, P = 0.0083). The CIs were more frequent in HC in HT and HCN but in follicular cells (FC) in other lesions. The HT cases with CIs differed significantly from those without CIs in respect of HC and their cellularity, cellularity of reactive lymphoid cells, extracellular colloid and empty ICL. CONCLUSION: Care should be taken not to diagnose HT cases with an excessive Hürthle cell component and CIs, and PTC cases with Hürthlization and CIs, as HCN in FNA smears. Based on review of the literature and our findings, it is suggested that the Hürthle cell metaplasia in HT is a survival response of FC and the presence of CIs in Hürthle cell may represent their limited ability to synthesize colloid.     

Follow‐up of atypia and follicular lesions of undetermined significance in thyroid fine needle aspiration cytology

N. Dincer, S. Balci, A. Yazgan, G. Guney, R. Ersoy, B. Cakir and G. Guler
Follow‐up of atypia and follicular lesions of undetermined significance in thyroid fine needle aspiration cytology Objective: To report our experience of atypia of undetermined significance (AUS)/follicular lesion of undetermined significance (FLUS) rate and outcome. Methods: Among 7658 patients with 19 569 nodules, 524 (2.7%) nodules were diagnosed as AUS/FLUS on fine needle aspiration (FNA). After exclusion of patients with simultaneous nodules that were suspicious for follicular neoplasm or malignancy or that were malignant, 368 (4.8%) patients were diagnosed as AUS/FLUS. The outcome of 146 patients who had undergone surgery or repeated fine needle aspirate at the time of preparation of this study was evaluated. The original FNAs were matched to repeated FNAs and thyroidectomy or diagnostic lobectomy specimens. Results: Seventy‐two (19.6%) of the 368 patients had directly undergone surgery, either a lobectomy or a thyroidectomy: of these, 27 (37.5%) had neoplastic nodules (21 were malignant). Seventy‐four (20.1%) of the 368 patients had repeat FNA. On second FNA, 47 of 74 (63.5%) were benign, three were suspicious for follicular neoplasm, one was malignant and 23 (31.1%) were non‐diagnostic. Four patients had a third FNA: two were AUS/FLUS, one was malignant and one non‐diagnostic. One patient had a fourth FNA, which was diagnosed as AUS/FLUS. Sixteen (21.6%) of 74 patients with repeat FNA had surgery: three of these had neoplastic nodules (two were malignant). Overall, 88 of the 368 (23.9%) patients had a thyroidectomy of which 30 (34.1%) were neoplastic and 23 (26.1%) malignant. The neoplastic rate for patients who were once diagnosed with AUS/FLUS was 8.2% and the malignancy rate 6.3%. The malignancy rate for patients on follow‐up at the time we prepared the study was 15.7% (23/146); 222 remained on follow‐up without surgery or repeat FNA or were managed elsewhere. Conclusions: Although in this category repeat FNA is expected rather than excision, we suggest evaluation of all AUS/FLUS patients in multidisciplinary meetings to decide management and recommend follow‐up of all patients with this diagnosis.     

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.     

Role of fine needle aspiration cytology in the diagnosis of soft tissue tumours and tumour-like lesions

In this study, we evaluated the usefulness of fine needle aspiration cytology (FNAC) in the diagnosis of soft tissue tumours. We have also assessed the various pitfalls of FNAC of soft tissue tumours. This was a retrospective study and here we analysed only 82 histopathology proven cases of FNAC of soft tissue tumours diagnosed in a five and half year period. On histopathological examination, 55 of these cases were malignant and 27 were benign. There was a total of 15 recurrences and histopathology was available prior to FNAC in only eight of these cases. Therefore, excluding these eight cases, malignant tumours were primarily diagnosed by FNAC in 47 cases. The sensitivity, specificity and positive predictive value of FNAC in diagnosis of soft tissue tumours were 91.5%, 92.5% and 95.5%, respectively. Only 22 of 47 cases (46.8%) were correctly categorized. There were two false-positive and four false-negative cases. One case each of fibromatosis and schwannoma were reported as sarcoma. False-negative cases were fibrosarcoma (1), malignant nerve sheath tumour (2) and haemangiopericytoma (1). FNAC was very useful in distinguishing benign from malignant soft tissue tumours. However, it was not so effective in exact categorization of tumours.     

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.     

CD44v6编码蛋白与Thrombodulin／TM在腹水胃癌细胞的鉴别诊断

观察转移相关黏附分子拼接变异体CD44v6在腹水胃癌细胞中的表达率,评价CD44v6是否作为腹水胃癌细胞特异性标志物,探讨胃癌细胞的转移机理.用TM区分腹水中胃癌细胞与间皮细胞.并与Melano-cyte/MC进行了敏感性、特异性对比.从腹水液基薄层细胞涂片中筛查出53例胃癌细胞,28例间皮细胞进行常规细胞石蜡包埋切片,采用鼠抗人CD44v6,TM,MC特异性抗体,对53例胃癌细胞.28例间皮细胞进行了免疫组化检测,应用χ2检验.CD44v6在腹水胃癌细胞中的检出丰为96.2%(51/53),间皮细胞中的检出率为7.14%(2/28);TM,MC在间皮细胞中的检出率分别为96.4%(27/28),92.9%(26/28),胃癌细胞中的检出率为7.55%(4/53)22.6%(12/53);TM,MC对间皮细胞敏感性分别为96.4%(27/28)、92.9%(26/28);TM,MC对间皮细胞特异性为92.5%(49/53)、77.4%(41/53).薄层细胞涂片、石蜡包埋技术能够有效地开展细胞免疫化学检测,并且具有广阔发展前景.CD44v6在胃癌细胞中的检出率明显高于间皮细胞,提示参与了胃癌细胞的浸润转移,可作为胃癌细胞的标志物.TM对间皮细胞检测的敏感性、特异性要高于MC.CD44v6协同TM对于胃癌细胞和间皮细胞的鉴别诊断有重要的意义.     

MOC-31和CD44v6在良恶性腹水鉴别诊断中的应用

目的探讨检测肿瘤标志物MOC-31和CD44v6对鉴别良恶性腹水的诊断价值。方法利用液基薄层细胞学自动涂片技术方法筛查出查到肿瘤细胞的恶性腹水标本390例以及良性腹水标本100例,分别采用酶联免疫吸附法(ELISA)和免疫细胞化学染色检测MOC-31和CD44v6的含量和表达情况。结果 ELISA结果显示MOC-31和CD44v6在良性腹水中的含量分别为21±4ng/ml和291±32ng/ml,在恶性腹水中的含量分别为98.1±19.3ng/ml和891±116ng/ml,差异均具有显著性(P<0.05);免疫细胞化学染色显示MOC-31在恶性腹水细胞中阳性表达250例,良性腹水细胞中阳性表达5例;CD44v6在恶性腹水细胞中阳性表达266例,良性腹水细胞中阳性表达3例,差异均具有显著性(P<0.05)。结论 MOC-31和CD44v6可以做为良恶性腹水鉴别诊断的重要指标,值得在临床病理工作中推广应用。     

双歧杆菌脂磷壁酸对结肠癌细胞CD44v6和MMP-2表达的影响

目的研究双歧杆菌脂磷壁酸(LTA)对结肠癌细胞中CD44v6与基质金属蛋白酶2(MMP-2)表达的影响,探讨其在抑制结肠癌转移中的作用。方法结肠癌LoVo细胞及HT-29细胞用含50 mg/L双歧杆菌LTA的培养液培养24 h后,RT-PCR和免疫细胞化学染色检测CD44v6和MMP-2在结肠癌细胞中的表达变化。结果结肠癌LoVo细胞及HT-29细胞中CD44v6和MMP-2的mRNA和蛋白质均呈高表达,经双歧杆菌LTA处理后,其表达均明显下降,与对照组比较,差异有非常显著性(P0.01)。结论双歧杆菌LTA可能通过下调CD44v6和MMP-2的表达来抑制结肠癌的转移。     

胃癌中CD44v6 表达及与微血管密度和生物学行为的关系

目的:探讨CD44v6在胃癌中的表达及其与微血管密度(microvessel density,MVD)和生物学行为的关系。方法:采用免疫组化法检测80例胃癌组织CD44v6、CD34的表达,以CD34标记肿瘤微血管,并在显微镜下计数微血管密度(MVD)。结果:CD44v6在胃癌组织中的表达与肿瘤浸润深度、临床分期、淋巴结转移相关(P<0.05),CD44v6强阳性表达组中MVD明显高于CD44v6阴性表达组(P<0.05)。结论:CD44v6的表达和MVD计数是反映胃癌生物学特性的良好的指标,对判断胃癌的浸润转移具有一定的临床意义。     

非小细胞肺癌中E-钙粘素和CD44v6的表达及其意义

为了探讨E-钙粘素(E-cadherin,E-cad)和白细胞分化抗原变异型6(CD44v6)在非小细胞肺癌(NSCLC)中的表达及临床意义,采用免疫组织化学(SP法)对65例NSCLC和20例癌旁组织中E-cad和CD44v6的表达进行研究。结果显示E-cad在肺癌组织中的阳性表达率(32.31%)显著低于癌旁组织(75.00%)(P<0.01),且与NSCLC的TNM分期、淋巴结转移呈负相关(P<0.05),与分化程度呈正相关(P<0.01),而与组织分型无关(P>0.05);CD44v6的阳性表达率与组织分型和分化程度无关(P>0.05),而与TNM分期和淋巴结转移呈正相关(P<0.05,<0.01)。两者在NSCLC中的表达显著相关(P<0.05)。因此检测E-cad和CD44v6的共同表达将是指导临床治疗及估计预后的有意义指标,可应用于临床预后的综合评价。     

Evaluation of fine needle aspiration (FNA) cytology in the diagnosis of thyroid nodules

FNA cytology of 112 patients with thyroid nodules seen in a 5-year period in a general hospital setting, and the histology obtained from the 53 operated patients, were retrospectively analysed. the inadequacy rate of FNA cytology was 11%, sensitivity was 84% (16/19), specificity was 52% (15/29), positive predictive value was 53% (16/30) and negative predictive value was 83% (15/18). Extrapolating these figures to the whole study group a negative predictive value of 95% is put forward as a more realistic figure. the results and the clinical pitfalls of the use of FNA cytology in diagnosing thyroid nodules are discussed. the authors conclude that FNA cytology is a reliable first diagnostic step in the diagnosis of thyroid nodules, even in a general hospital setting.     

Searching for RET/PTC rearrangements and BRAF V599E mutation in thyroid aspirates might contribute to establish a preoperative diagnosis of papillary thyroid carcinoma

OBJECTIVE: Searching for multiple molecular markers in thyroid aspirates appears to be a promising approach for establishing a preoperative diagnosis of papillary thyroid carcinoma (PTC). METHODS: Based on this hypothesis, a total of 63 samples from 55 patients, were collected at random. RNA was extracted from the residue cells inside the needle used for fine needle aspiration cytology (FNAC) and thereafter molecular analysis was carried out both for RETrearrangements (type 1, 2, 3) and BRAF codon 599 mutation molecule. Results were compared with the cytological and histopathological diagnoses in 24 patients submitted to surgery. RESULTS: 58% PTCs presented a genetic alteration either RET/PTC rearrangement, BRAF V599E mutation or both: three cases of PTCs (25%) presented a RET/PTC rearrangement; three cases of PTCs (25%) presented a BRAF V599E mutation and in one case (8%) both alterations were identified. CONCLUSIONS: The present results suggest that searching for multiple molecular markers in thyroid aspirates may enhance the accuracy of FNAC and refine preoperative diagnosis of PTC.     

Reduced expression of Claudin-7 in fine needle aspirates from breast carcinomas correlate with grading and metastatic disease

OBJECTIVE: To study the immunocytochemical expression of the tight junction protein Claudin-7 in smears from breast carcinomas and correlate with grading, nodal status, locoregional and distant metastases and the cellular cohesion. METHODS: The material consisted of 52 air-dried smears from fine needle aspirates of breast carcinomas, both primary and metastatic and smears from seven benign lesions. A primary antibody to Claudin-7 was used for immunocytochemical staining. The degree of staining was recorded as negative, reduced or full, with full expression meaning equivalent to the staining pattern found in the fibroadenomas used as benign control. Staining intensity and the percentage of stained cells were evaluated. The control smears revealed a strong membrane and cytoplasmic positivity in all luminal epithelial cells. Cellular cohesion was graded as: (1) mainly cohesive groups, (2) groups and single cells and (3) mainly single cells. RESULTS: All primary and recurrent/metastatic breast lesions expressed Claudin-7. Full expression was demonstrated in 46% of the cases. Reduced expression was found in 54%. In cases with reduced expression, the percentage of stained cells were usually high, and no smear showed <50% stained tumour cells. The staining pattern was heterogeneous and always mixed membrane/cytoplasmic. Claudin-7 expression showed a significant correlation (P < 0.05) with grading, locoregional and distant metastases, nodal involvement and cellular cohesion in invasive carcinomas, but not with tumour size or subtype. CONCLUSION: Reduced expression of Claudin-7 correlated with higher tumour grade, metastatic disease, including loco-regional recurrences and with cellular discohesion.     

EMMPRIN (CD147) expression and differentiation of papillary thyroid carcinoma: implications for immunocytochemistry in FNA cytology

Y. Aratake, K. Marutsuka, K. Kiyoyama, T. Kuribayashi, T. Miyamoto, K. Yakushiji, S. Ohno, Y. Miyake, T. Sakaguchi, T. K. Kobayashi, A. Okayama, K. Tamura and E. Ohno
EMMPRIN (CD147) expression and differentiation of papillary thyroid carcinoma: implications for immunocytochemistry in FNA cytology Objective: Extracellular matrix metalloproteinase inducer (EMMPRIN) and its induced matrix metalloproteinases (MMPs) play a crucial role in tumour progression, invasion and metastasis. EMMPRIN expression has been demonstrated in several tumours, but its expression profile in thyroid cancer remains unclear. Methods: We evaluated the expression profile of EMMPRIN at various stages of differentiation of thyroid carcinoma, including 20 cases of well‐differentiated papillary carcinoma (WDPC), 15 cases of papillary carcinoma with a poorly differentiated carcinoma component (PC/PDC) and four cases with an undifferentiated carcinoma (UDC) component, using paraffin‐embedded sections for immunohistochemical stains. Also, we used 32 fine needle aspiration cytology and imprint smears from the same cases for immunocytochemical stains. The staining results were evaluated with a scoring system. Results: Immunohistochemical staining showed that EMMPRIN expression was absent or weak in almost all WDPC specimens, whereas it was moderate or strong in PDC and UDC components. In tumours that showed a gradual morphological transformation from WDPC to PDC components, the expression of EMMPRIN was progressively stronger from the areas of WDPC to those of PDC. WDPC, PC/PDC and UDC had expression scores of 4.9, 45.0 and 245.7, respectively. Results of immunocytochemical staining showed almost the same staining profile as those of immunohistochemical staining. The cytological atypia of EMMPRIN‐positive cells was greater than that of negative cells. Conclusion: These results indicated that EMMPRIN expression correlates significantly with the degree of dedifferentiation of thyroid carcinoma. This study demonstrates the feasibility of expression of EMMPRIN using fine needle aspiration samples. Therefore, immunocytochemical analysis of EMMPRIN may be a novel aid to evaluate the differentiation of thyroid carcinoma.