Myelomatous meningitis diagnosed by cerebrospinal fluid cytology examination.

Myelomatous meningitis diagnosed by CSF cytology. The combined use of cytology with immunocytochemistry can identify the presence of multiple myeloma cells in cerebrospinal fluid specimens.

An unexpected cause of recurrent pneumothorax.

The thoracic district is the most frequent visceral location of synovial sarcoma, generally involving lung and pleura as a large solid mass. We present herein a 57-year-old man with recurrent pneumothorax and a localized bulla at the lingula. The lesion was excised by a Video-Assisted-Thoracoscopic-Surgery (VATS) wedge resection and surprisingly consisted of a unilocular cyst with fibrous wall intermingled by a longitudinal proliferation of bland-looking, dense, monomorphic spindle cells diffusely expressing EMA, CD99, CD56 and focally staining with cytokeratins. Fluorescent in situ hybridization demonstrated the presence of SYT rearrangement and a diagnosis of pulmonary cystic monophasic synovial sarcoma was made. Only few similar cases have been reported in literature, mainly occurring in young male adults. A meticulous examination of all resected tissue from pneumothorax is the prerequisite to suspect this extremely challenging condition, while immuno-molecular studies are mandatory to achieve the correct diagnosis.

Cytopathology of Follicular Cell Nodules.

The detection of thyroid nodules, consisting of different diseases, represents a common finding in population. Their evaluation and diagnosis are mostly achieved with fine-needle aspiration cytology (FNAC). Even though the majority of thyroid nodules are correctly diagnosed, a total of 25% to 30% of them are classified "indeterminate" comprising lesions with varying risk of malignancy and different types of management. Although the number of thyroid FNACs, including small lesions, is increasing due to the reliance upon sonographic and cytologic interpretations, there are issues concerning cytomorphologic interpretation and interobserver reproducibility. Different classification systems have tried to better define the criteria for inclusion in specific categories and to therefore reduce the rate of indeterminate diagnoses such as atypia of undetermined significance, follicular neoplasms, and suspicious for malignancy. However, the support of ancillary techniques (eg, immunocytochemistry and molecular analysis) are reshaping morphologic diagnoses made on materials obtained from FNAC.

Immunohistochemistry for Claudin-4 and BAP1 in the Differential Diagnosis between Sarcomatoid Carcinoma and Sarcomatoid Mesothelioma.

(1) Background. In the differential diagnosis between sarcomatoid carcinoma (SC) and sarcomatoid mesothelioma (SM), we aimed to investigate the role of Claudin-4 and BAP1, a panel recently used to distinguish conventional carcinoma from epithelioid mesothelioma. (2) Methods. We collected 41 surgical pleural biopsies of SM, 46 surgical resections of SC from different sites and 49 pleural biopsies of normal/hyperplastic mesothelium. All the cases were tested for Claudin-4 and BAP1 using immunohistochemistry. The statistical calculations of the sensitivity, specificity and positive and negative predictive values were performed. (3) Results: Claudin-4 was negative in 41/41 SMs, while it was positive in 18/36 (50.1%) SCs (eight diffusely, 10 focally) within their sarcomatous component. BAP1 was lost in 23/41 SMs, while it was regularly expressed in 46/46 SCs. All the cases of the normal/hyperplastic mesothelium were negative for Claudin-4 and retained the regular expression of BAP1. The Claudin-4 expression was useful for detecting SC (sensitivity, 39.1%; specificity, 100%) and the BAP1 loss was useful for diagnosing SM (sensitivity, 56.1%; specificity, 100%). (4) Conclusions. The staining for Claudin-4 and BAP1 exhibited a low/moderate sensitivity in diagnosing SC and SM (39.1% and 56.1%, respectively), but a very high specificity (100%). Claudin-4 was expressed only in SC and BAP1 loss was noted only in SM.

Pathologic comparison of conventional video-assisted thoracic surgical (VATS) biopsy versus non-intubated/"awake" biopsy in fibrosing interstitial lung diseases.

Surgical lung biopsy remains the standard procedure for the subset of patients with fibrosing interstitial lung disease (F-ILD) who require a lung biopsy to secure a confident diagnosis. Little is known about the pathologic features of samples obtained via non-intubated/"awake" surgical lung biopsy and the diagnostic accuracy of awake biopsy in patients with F-ILD. Two expert thoracic pathologists blinded to the type of lung biopsy compared the clinical-pathologic features of 120 conventional VATS biopsies with those of 21 consecutive non-intubated/"awake" VATS biopsies. No statistically significant differences between the two procedures were observed with regard to identification of histopathological features. Biopsy length, average of sampled lobes and mean number of slides were similar with the two procedures, while the width of the biopsies was significantly deeper with conventional VATS (31.5 mm versus 25.6 mm; p = 0.01). By contrast, the mean age of patients (69.5 versus 64.5 years; p = 0.02) and the level of diagnostic confidence (100% versus 75%; p = 0.007) were significantly higher among patients undergoing the "awake" procedure. Diagnostic yield was 100% in both groups, with a similar distribution of ILD diagnoses. Non-intubated/"awake" biopsy has the potential to become the standard surgical procedure in patients with F-ILD requiring a histological confirmation of their diagnosis. However, larger prospective studies are needed to validate the safety and diagnostic yield of "awake" compared to conventional VATS.

The "Brescia panel" (Claudin-4 and BRCA-associated protein 1) in the differential diagnosis of mesotheliomas with epithelioid features versus metastatic carcinomas.

BACKGROUND: The distinction between mesothelioma with epithelioid features and metastatic carcinoma may be challenging, particularly on cytology. A novel 2-hit Claudin-4 and BRCA-associated protein 1 (BAP1) panel was investigated. METHODS: The objective of this study was to determine the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the panel on cytology from pleural effusions and matched biopsies, including 49 malignant mesotheliomas on cytology with 43 matched biopsies, 49 normal/reactive mesothelial proliferations, and 49 pleural metastatic carcinomas from different primaries with 21 matched pleural biopsies. The diagnostic role of the 4 categories obtained by crossing the immunostaining results was analyzed. RESULTS: Claudin-4 strongly stained all metastatic carcinomas and tested completely negative in normal mesothelium, benign reactive mesothelial hyperplasia, and malignant mesothelioma. All normal and benign mesothelial proliferations and all carcinomas except 1 were immunoreactive for BAP1, whereas BAP1 loss was observed in 88% of malignant mesotheliomas. The expression of Claudin-4 alone excluded all benign and malignant mesothelial growth, consistently characterizing all metastatic carcinomas. Double negativity was evident in all malignant mesotheliomas, and double positivity was observed in all metastatic carcinomas. BAP1-positive/Claudin-4-negative status was observed only in malignant mesotheliomas and benign mesothelial proliferations. A single metastatic anal squamous cell carcinoma had BAP1-negative/Claudin-4-positive staining. CONCLUSIONS: Claudin-4 expression was completely specific and sensitive for metastatic carcinoma, excluding mesothelial proliferations. BAP1 staining characterized 98% of metastatic carcinomas and 100% of benign mesothelial proliferations, whereas negativity was observed almost exclusively in mesotheliomas. This 2-hit panel is probably the best compromise for differentiating malignant mesothelioma and metastatic carcinoma on either cytology or biopsy specimens.

Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP): Implications for the risk of malignancy (ROM) in the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC).

BACKGROUND: The introduction of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) affects the risk of malignancy (ROM) mostly in the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) categories. In this multi-institutional, retrospective study, the authors investigated variations in the impact of an NIFTP diagnosis on the associated ROM for each TBSRTC category with an emphasis on the influence of pathologist and institutional diagnostic thresholds on the ROM. METHODS: Baseline data on cytology and histology diagnostic categories were collected over a 3-year period at 3 academic center hospitals (institutions A, B, and C). Histology slides for all cases diagnosed as follicular variant of papillary thyroid carcinoma (FVPTC) were re-reviewed at each institution, and those that qualifying as NIFTP were separated from other PTCs. RESULTS: The collective case cohort from the 3 institutions included 15,973 thyroid fine-needle aspiration cytology (FNAC) specimens and 5090 thyroid surgical resection specimens. Significant differences in baseline cytology and histology data were noted among the 3 institutions. The number of cases classified as NIFTP compared with FVPTC was highly variable (institution A, 14%; institution B, 39%; and institution C, 12%). For 3250 resected thyroid nodules with a previous FNAC diagnosis, the average decrease in ROM after the exclusion of NIFTP for all TBSRTC categories was as follows: institution A, 9.8%; institution B, 3.9%; and institution C, 1.3%. CONCLUSIONS: The institutional frequency of NIFTP histopathology diagnosis and cytology baseline data will impact the ROM associated with specific FNAC diagnoses, especially among the indeterminate TBSRTC categories. The range of ROM for each TBSRTC diagnostic category is reflective of the inherent diagnostic thresholds and interobserver and interinstitutional variability in the diagnosis of thyroid lesions. Cancer Cytopathol 2018;126:20-6. © 2017 American Cancer Society.

Clinicopathological analysis of mixed endometrial carcinomas: clinical relevance of different neoplastic components.

Mixed endometrial carcinomas (MECs) refer to tumors characterized by 2 or more distinct histotypes mostly that comprised endometrioid (EC) and serous/clear cell carcinomas (SC/CC). The specific quantification of these distinct components represents a challenging and critical point for both prognosis and management. Herein, we analyze a large series of MEC and compare them with EC and SC/CC. We evaluated a series of 69 MECs between January 2002 and December 2015. We compared the MEC series with 186 ECs (including 117 endometrioid G3), 31 SCs, and 38 CCs. The prognostic implication of the percentage of each component was analyzed. Among the 69 MECs, those patients older than 45 years represent the significant population, with 52.2% of them with stage III-IV disease. A similar result was found among pure SC. The comparative analysis of some prognostic parameters (multifocality, vascular invasion, and lymph node metastasis) underlined that MECs with a type II component larger than 5% represent a more aggressive entity. However, relapse, disease-free survival, mortality, and overall survival are statistically significant (P<.05) in EC-SC (SC<5%or >5%) and in EC-CC (CC<5%or >5%), whereas they are not significant (P>.05) in SC-CC (SC/CC<%or >5%). MECs, including also cases with less than 5% of SC/CC, show features as aggressive as those of pure SC/CC. In this perspective, MEC should be followed by personalized and tailored managements. The presence of different components suggests different pathogenic and metastatic processes when compared with pure carcinomas.

The Role of Liquid Based Cytology and Ancillary Techniques in the Peritoneal Washing Analysis: Our Institutional Experience.

BACKGROUND: The cytological analysis of peritoneal effusions serves as a diagnostic and prognostic aid for either primary or metastatic diseases. Among the different cytological preparations, liquid based cytology (LBC) represents a feasible and reliable method ensuring also the application of ancillary techniques (i.e immunocytochemistry-ICC and molecular testing). METHODS: We recorded 10348 LBC peritoneal effusions between January 2000 and December 2014. They were classified as non-diagnostic (ND), negative for malignancy-NM, atypical-suspicious for malignancy-SM and positive for malignancy-PM. RESULTS: The cytological diagnosis included 218 ND, 9.035 NM, 213 SM and 882 PM. A total of 8048 (7228 NM, 115SM, 705 PM) cases with histological follow-up were included. Our NM included 21 malignant and 7207 benign histological diagnoses. Our 820 SMs+PMs were diagnosed as 107 unknown malignancies (30SM and 77PM), 691 metastatic lesions (81SM and 610PM), 9 lymphomas (2SM and 7PM), 9 mesotheliomas (1SM and 8SM), 4 sarcomas (1SM and 3PM). Primary gynecological cancers contributed with 64% of the cases. We documented 97.4% sensitivity, 99.9% specificity, 98% diagnostic accuracy, 99.7% negative predictive value (NPV) and 99.7% positive predictive value (PPV). Furthermore, the morphological diagnoses were supported by either 173 conclusive ICC results or 50 molecular analyses. Specifically the molecular testing was performed for the EGFR and KRAS mutational analysis based on the previous or contemporary diagnoses of Non Small Cell Lung Cancer (NSCLC) and colon carcinomas. We identified 10 EGFR in NSCCL and 7 KRAS mutations on LBC stored material. CONCLUSIONS: Peritoneal cytology is an adjunctive tool in the surgical management of tumors mostly gynecological cancers. LBC maximizes the application of ancillary techniques such as ICC and molecular analysis with feasible diagnostic and predictive yields also in controversial cases.

Somatic mutations in solid tumors: a spectrum at the service of diagnostic armamentarium or an indecipherable puzzle? The morphological eyes looking for BRAF and somatic molecular detections on cyto-histological samples.

This review article deals with the analysis and the detection of the morphological features associated with somatic mutations, mostly BRAFV600E mutation, on both cytological and histological samples of carcinomas. Few authors demonstrated that some architectural and specific cellular findings (i.e. polygonal eosinophilic cells defined as "plump cells" and sickle-shaped nuclei) are able to predict BRAF V600E mutation in both cytological and histological samples of papillary thyroid carcinoma (PTC) as well as in other carcinomas. In the current review article we evaluated the first comprehensive analysis of the morphological prediction of BRAFV600E and other somatic mutations in different malignant lesions with the description of the possible mechanisms beneath these morphologic features. The detection of predictive morphological features, mostly on FNAC, may add helpful information to the stratification of the malignant risk and personalized management of cancers. Additionally, the knowledge of the molecular mechanism of different oncogenic drivers can lead to the organ-specific triaging selection of cases and can provide significant insight for targeted therapies in different malignant lesions.

The expression of monocarboxylate transporters in thyroid carcinoma can be associated with the morphological features of BRAF V600E mutation.

BRAF V600E mutation, usually performed by DNA techniques, is one of the most common diagnostic markers in papillary thyroid carcinoma. Few papers have demonstrated that plump cells (eosinophilic cytoplasms and papillary thyroid carcinoma nuclei) and peculiar sickle-shaped nuclei represent morphological features of BRAF V600E on papillary thyroid carcinomas. These features seem to be linked to glycolytic phenotype whereby monocarboxylate transporters 1-4 are hypothesized to have a dominant role as lactate transporters. We investigated the association between these morphological features and monocarboxylate transporters 1 and 4 in 48 cyto-histological samples diagnosed as "positive for malignancy-favoring papillary thyroid carcinoma". These cases were processed with liquid-based cytology and underwent BRAF V600E mutational analysis (pyrosequencing) on liquid-based cytology and monocarboxylate transporters immunostaining on histology. The expression of monocarboxylate transporter 1, monocarboxylate transporter 4, glucose trasporter-1 and carbonic anhidrase were scored semi-quantitatively with expression from 0 to 3+ (strong positivity). The 33 mutated and 15 wild type cases showed 100 % cyto-histological concordance. The cytological evaluation revealed plump cells and sickle nuclear shape in 100 % mutated cases. Monocarboxylate transporter 1 yielded 76 % positivity in the mutated cases especially in both the plump cells and sickle-shaped nuclei, whereas the wild types showed 13.3 % positive monocarboxylate transporter 1 (p = 0.00013). Monocarboxylate transporter 4 resulted in 100 % positivity in mutated and 40 % in wild types (p < 0.005). Furthermore, 20 % of the wild types showed weak monocarboxylate transporter 1 nuclear expression associated to a less aggressive behavior. The analysis of glucose trasporter-1 and carbonic anhidrase did not highlight any statistical significance (p > 0.05). This is the first report analyzing the association between monocarboxylate transporter expression and the morphological features of BRAF V600E mutated papillary thyroid carcinomas suggesting the possible involvement of lactate in the morphological features.

FNA biopsy of secondary nonlymphomatous malignancies in salivary glands: A multi-institutional study of 184 cases.

BACKGROUND: Secondary malignancies of salivary glands (SMSGs) are among the most common malignant neoplasms to involve the salivary glands. Fine-needle aspiration biopsy (FNAB) of SMSG can present diagnostic challenges. The current report presents the largest such FNAB series to date. METHODS: A search of the pathology database from 6 academic institutions identified 184 FNAB cases of nonlymphomatous SMSG. RESULTS: Of the 184 cases, 171 were of the parotid glands, and 13 were of the submandibular glands; 130 patients were men, and 54 were women, and the mean patient age at diagnosis was 68 years. Metastatic squamous cell carcinoma (SCC) from all sites (n = 87) and melanoma (n = 67) constituted the majority of SMSGs. Less frequent SMSGs were comprised of metastatic carcinomas from distant organs (n = 16), including sites in the breast, lung, kidney, thyroid, pancreatobiliary, prostate, and bladder. Other uncommon SMSGs, including nasopharyngeal carcinoma (n = 3), sarcoma (n = 4), other metastatic skin-derived carcinomas (n = 6), and metastatic chordoma (n = 1), also were observed. Ancillary tests were performed on 37 FNAB specimens (20.1%) to aid the evaluation. One hundred forty-seven specimens (79.9%) had a definitive diagnosis with accurate tumor subtyping, 21 (11.4%) had a definitive malignant diagnosis but without specifying subtype, 9 (4.9%) had an indeterminate diagnosis, and 7 (3.8%) had a false-negative diagnosis. CONCLUSIONS: SMSGs originate predominately from the head and neck and are more common in older men. Overall, the FNAB diagnosis of SMSG is accurate, but diagnostic challenges can be encountered, especially in SCC types of SMSG. Ancillary studies are needed for the definitive diagnosis of challenging cases. Cancer Cytopathol 2017;125:91-103. © 2016 American Cancer Society.

Comparison between cytospin and liquid-based cytology in urine specimens classified according to the Paris System for Reporting Urinary Cytology.

BACKGROUND: The current study compared ThinPrep urinary cytology and conventional cytospin urinary cytology in the diagnosis of bladder cancer, applying the Paris System for Reporting Urinary Cytology. METHODS: Between January 2010 and December 2011, a total of 3659 urine samples were processed using conventional cytospin methods. Between January 2012 and December 2013, a total of 4186 urine cytological cases were analyzed using ThinPrep methods. In 131 cases (65 processed by conventional cytospin and 66 processed by ThinPrep), a subsequent biopsy was performed. The authors reclassified these cases according to the Paris System and an analysis between the 2 methods with regard to bladder biopsies was performed. RESULTS: No significant differences were observed in terms of sensitivity and specificity between the 2 methods in cases with positive cytology for high-grade carcinoma. According to the Paris System, cases of atypical urothelial cells (AUC) and atypical urothelial cells suspicious for high-grade carcinoma (AUC-H) that were processed using cytospin did not correlate with urothelial carcinoma or with negative biopsies; conversely, the AUC cases processed using ThinPrep appeared to correlate with negative histological biopsies or low-grade urothelial carcinoma. CONCLUSIONS: The results of the current study demonstrated that according to the Paris System, there were no significant differences in sensitivity or specificity for the diagnosis of high-grade urothelial carcinoma or AUC-H between the 2 methods. Cases of AUC should be easy to recognize using Thin Prep rather than cytospin and only AUCs diagnosed with ThinPrep were found to be statistically linked to negative cases for carcinoma or with low-grade urothelial carcinoma. Cancer Cytopathol 2016;124:519-23. © 2016 American Cancer Society.

The impact of FNAC in the management of salivary gland lesions: Institutional experiences leading to a risk-based classification scheme.

BACKGROUND: Fine-needle aspiration cytology (FNAC) has proven its value as an essential step in the diagnosis of salivary gland lesions. Although the majority of salivary gland lesions, especially those that are common and benign, can be diagnosed with ease on FNAC, limited cellularity and morphologic lesion heterogeneity can pose diagnostic challenges and lead to false-positive and false-negative diagnoses. This study presents the institutional experience of FNAC of salivary gland lesions from 2 academic centers. METHODS: A retrospective analysis was conducted on 1729 salivary gland FNAC specimens that were diagnosed over an 8-year period from January 2008 to March 2015. All samples were processed either with liquid-based cytology alone or in combination with air-dried, Diff-Quik-stained or alcohol-fixed, Papanicolaou-stained smears. RESULTS: Surgical excision was performed in 709 of 1749 FNACs (41%) that were diagnosed as nondiagnostic/inadequate (n = 29), benign (n = 111), neoplasm (n = 453), atypical (n = 15), suspicious for malignancy (n = 28), and malignant (n = 73). The overall concordance between cytologic and histologic diagnoses was 92.2%, with 91.8% concordance in the benign category and 89.5% concordance in cases diagnosed as suspicious for malignancy and malignant. The most frequent benign and malignant lesions were pleomorphic adenoma and squamous cell carcinoma, respectively. There were 46 false-negative and 13 false-positive results, leading to an overall specificity of 97.6% and diagnostic accuracy of 91.3%. CONCLUSIONS: FNAC is a reliable diagnostic modality for the diagnosis and management of salivary gland lesions based on its high specificity and diagnostic accuracy. Cancer Cytopathol 2016;124:388-96. © 2016 American Cancer Society.

The role of fine-needle aspiration in the thyroid nodules of elderly patients.

We assess the role of thyroid fine needle aspiration cytology(FNAC) in our series of elderly patients. The growing subset of people aged older than 70 years has shown an increased incidence of thyroid diseases which need to be studied in order to reduce the percentage of surgical treatments in patients with higher likelihood of co-morbidities and associated life risk. We compared Follicular/Indeterminate Neoplasms(FN) and suspicious of malignancy(SM) with pediatric and adult cohorts. We discussed the role of immunocytochemistry-ICC to refine diagnoses. Four hundred and eighty out of 3539FNACs(13.5%) in elderly patients, were surgical followed-up. They included: 35Inadequate, 188benign(BL), 164FN/AUS, 49SM and 44positive for malignancy (PM). All PM and 95.7%BL were histological confirmed. The malignant rate was 24.3% mostly diagnosed as papillary thyroid carcinomas. An ICC panel (HBME-1 and Galectin-3) was carried out on liquid based cytology (LBC) and performed on FN/AUS, SM and PM.We found concordant positive ICC in 69.3%malignancies and concordant negative ICC in 97.6%benign follicular adenomas. Among FNs, 42.9%malignant histologic cases had concordant positivity whilst 97.4%benign histology had negative panel.Thyroid FNAC shows high feasibility in elderly patients. ICC helps in reducing the number of useless thyroidectomies and providing a more adequate clinical and/or surgical selection in elderly patients.

The evaluation of miRNAs on thyroid FNAC: the promising role of miR-375 in follicular neoplasms.

Fine needle aspiration cytology (FNAC) plays an essential role in the evaluation of thyroid nodules especially for the category of follicular neoplasms (FN) representing 25 % of all thyroid cases including different neoplastic entities. Hence, one of the most promising areas is the application of molecular tests to FNAC. Among them, microRNAs (miRNA),identified as negative (post-transcriptional) gene expression regulators involved in tumor development, are likely to discriminate among FNs. Limited data explored the use of miRNAs on FNAC as well as their role in the malignant risk stratification. We aimed to define whether liquid-based cytology (LBC) is a valid method for miRNA evaluation. From June 2014 to March 2015, we enrolled 27FNs with histological follow-up. In the same reference period, 13 benign nodules (BN) and 20 positive for malignancy (PM) were selected as controls. Histologically, FNs resulted in 14 malignancies (3 papillary thyroid carcinoma-PTC and 11 follicular variant of PTC-FVPC) and 13 follicular adenomas (FA). The 20 PMs included two FVPC, 16 PTC and two medullary thyroid carcinoma (MTC). Five miRNAs (10b, 92a, 221/222 cluster, and 375) were studied on LBC and quantified by real-time PCR. Only miR-375 was over-expressed in the FNs diagnosed as carcinomas and in the PMs. A cut-off of 12 miR-375/U6 relative ratio recognized all BNs and 95 % PMs. Specifically, in each category, FVPCs and PTCs did not show any difference while MTCs had the highest value. miR-375 shows 97.1 % sensitivity, 100 % specificity, 96.3 % negative predictive value (NPV), 100 % positive predictive value (PPV), and 98.3 % diagnostic accuracy. LBC is suitable for miRNAs evaluation. miR-375 resulted over-expressed in all malignant FNs and 95 % PMs. It may represent a valid aid in ruling out BNs and supporting PTCs and/or FVPCs.

Young investigator challenge: The morphologic analysis of noninvasive follicular thyroid neoplasm with papillary-like nuclear features on liquid-based cytology: Some insights into their identification.

BACKGROUND: Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) represents a challenge for the diagnosis and management of thyroid carcinoma. Some authors have proposed histological criteria that are able to distinguish NIFTPs from invasive follicular variant of papillary thyroid carcinoma (I-FVPTC). Hence, NIFTPs may have repercussions in the diagnostic categories on fine-needle aspiration. In the current study, the authors evaluated the criteria for NIFTPs on liquid-based cytology samples. METHODS: The authors recorded all 61 liquid-based cytology samples proved to be histological FVPTC between January 2013 and March 2016 and analyzed the architectural, cytoplasmic, and nuclear parameters. They compared them with a cohort of 40 PTC cases and 20 follicular adenoma cases. RESULTS: The authors reported 37 NIFTP cases and 24 I-FVPTC cases at histology. The cytological diagnoses of follicular nodules in the NIFTP cases were twice those found in the I-FVPTC cases (54.1% vs 29.2%). The number of positive for malignancy cases among the NIFTPs were approximately half those of I-FVPTC cases. When compared with I-FVPTCs, 70% of the NIFTP cases demonstrated a nuclear size <20 µm (P = .025) and rarely exhibited grooves (13% vs 42%; P = .009). The authors found 100% of cases with wild-type BRAF gene in NIFTP cases versus 38.4% in mutated I-FVPTC cases (P = .046). The cytoplasmic features might help to discriminate NIFTPs from follicular adenomas but not from I-FVPTCs (P>.05). A predominant microfollicular pattern was recognized in both NIFTPs and I-FVPTCs (97.3% vs 100%). CONCLUSIONS: The majority of NIFTPs appear to be devoid of nuclear pseudoinclusions and papillary structures, thereby allowing the inclusion in the follicular nodule cases. Nuclear size and microfollicular clusters may suggest the discrimination between NIFTPs and I-FVPCs. Cancer Cytopathol 2016;124:699-710. © 2016 American Cancer Society.

The role of liquid-based cytology and ancillary techniques in pleural and pericardic effusions: an institutional experience.

BACKGROUND: Fine-needle aspiration cytology (FNAC) of serous membrane effusions may fulfil a challenging role in the diagnostic analysis of both primary and metastatic disease. From this perspective, liquid-based cytology (LBC) represents a feasible and reliable method for empowering the performance of ancillary techniques (ie, immunocytochemistry and molecular testing) with high diagnostic accuracy. METHODS: In total, 3171 LBC pleural and pericardic effusions were appraised between January 2000 and December 2013. They were classified as negative for malignancy (NM), suspicious for malignancy (SM), or positive for malignancy (PM). RESULTS: The cytologic diagnoses included 2721 NM effusions (2505 pleural and 216 pericardic), 104 SM effusions (93 pleural and 11 pericardic), and 346 PM effusions (321 pleural and 25 pericardic). The malignant pleural series included 76 unknown malignancies (36 SM and 40 PM effusions), 174 metastatic lesions (85 SM and 89 PM effusions), 14 lymphomas (3 SM and 11 PM effusions), 16 mesotheliomas (5 SM and 11 SM effusions), and 3 myelomas (all SM effusions). The malignant pericardic category included 20 unknown malignancies (5 SM and 15 PM effusions), 15 metastatic lesions (1 SM and 14 PM effusions), and 1 lymphoma (1 PM effusion). There were 411 conclusive immunocytochemical analyses and 47 molecular analyses, and the authors documented 88% sensitivity, 100% specificity, 98% diagnostic accuracy, 98% negative predictive value, and 100% positive predictive value for FNAC. CONCLUSIONS: FNAC represents a primary diagnostic tool for effusions and a reliable approach with which to determine the correct follow-up. Furthermore, LBC is useful for ancillary techniques, such as immunocytochemistry and molecular analysis, with feasible diagnostic and predictive utility.

A meta-analytic review of the Bethesda System for Reporting Thyroid Cytopathology: Has the rate of malignancy in indeterminate lesions been underestimated?

BACKGROUND: The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) provides a 6-tier diagnostic framework using uniform criteria in reports of thyroid aspirates. One of the major advantages of this framework is its association with defined risks of malignancy, allowing standardized management algorithms for each diagnosis. The objective of the current meta-analysis was to demonstrate the feasibility of using TBSRTC among specimens in the atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS) and follicular neoplasm or suspicious for neoplasm (FN/SFN) categories. The authors also evaluated both the morphologic features and the risk of malignancy in the presence of Hurthle cells. METHODS: A literature search was performed of the PubMed, Scopus, and Web of Science databases for English-language studies published from January 2008 to December2014. Studies were considered eligible only if they evaluated the risk of malignancy for specimens in the AUS/FLUS and/or FN/SFN categories and included surgical follow-up. RESULTS: In total, 51 articles were identified that used TBSRTC criteria and provided data for a total of 145,928 fine-needle aspiration (FNA) specimens. Of these, FNAs that had surgical follow-up were selected among the AUS/FLUS (N = 4475) and FN/SFN (N = 3202) specimens. The overall rate of malignancy was 27% for the AUS/FLUS category and 31% for the FN/SFN category. CONCLUSIONS: The AUS category was characterized by limited reported follow-up and surgical outcome. The data demonstrated that FNAs with an AUS diagnosis had a higher risk of malignancy than the risk according to published TBSRTC criteria, whereas the percentage of malignancy in FNAs with an FN/SFN diagnosis did not differ from that according to TBSRTC. Hurthle cell lesions represent a challenging category, underlying the importance of further studies to define whether they can be diagnosed in the AUS/FLUS category rather than the FN/SFN category.