Patrizia Straccia

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

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.

DIAGNOSTIC AND PROGNOSTIC VALUE OF IMMUNOCYTOCHEMISTRY AND BRAF MUTATION ANALYSIS ON LIQUID BASED BIOPSIES OF THYROID NEOPLASMS SUSPICIOUS FOR CARCINOMA

OBJECTIVE In the field of fine-needle aspiration cytology, the category of suspicious for malignancy (SM) thyroid lesions, that bears 55-85% risk of malignant histology, is a challenging topic in which morphology alone is not always able to make a correct diagnosis. Recently, immunocytochemistry (ICC) has been referred to as helpful in differentiating low- and high-malignant risk lesions and BRAF activating mutations have been identified in a significant amount of papillary thyroid carcinomas (PTC). The introduction of the liquid-based cytology (LBC) may simplify the application of these techniques to thyroid cytology. DESIGN Our aim is to evaluate the diagnostic and prognostic role of both ICC and BRAF mutation for the SM category on LBC. METHODS From October 2010 through June 2011, 113 LBC cytological cases (including 37 SM and 76 PTC) underwent surgery. All cases were studied for BRAF mutation and ICC. RESULTS ICC resulted positive in 26 (86.6%) histologically malignant SM with 15 of which (40.5%) expressing a BRAF mutation. Overall, 63 cases showed a BRAF mutation resulting in PTC. Concerning the prognostic role of BRAF mutation for the two categories, we reported a significant correlation with multifocality, nodal involvement and extra-capsular invasion (P<0.0001). CONCLUSIONS Special techniques such as ICC and molecular markers might be successfully carried out on LBC-processed material. For both categories, ICC is more sensitive whereas BRAF analysis is an interesting support due to its high specificity adding a prognostic value in both SM and PTCs.

Analysis of immunocytochemical and molecular BRAF expression in thyroid carcinomas: A cytohistologic institutional experience

It has been generally demonstrated that the valine‐to‐glutamic acid substitution at position 600 (V600E) in the v‐Raf murine sarcoma viral oncogene homolog B1 (BRAF) gene is an effective diagnostic/prognostic marker mainly for papillary thyroid carcinoma (PTC). The detection of this mutation typically has been achieved using DNA‐based techniques. The recently introduced monoclonal V600E antibody (clone VE1) is likely to be an alternative strategy for detecting this mutation in thyroid lesions. The authors investigated molecular and immunocytohistochemical BRAF analyses in a prospective series of samples from patients with PTC.

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

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.

Diagnostic and prognostic role of HBME-1, galectin-3, and β-catenin in poorly differentiated and anaplastic thyroid carcinomas.

Aim:Thyroid cancer represents the first endocrine malignant neoplasm, accounting for 1% of human malignancy. The majority of which are well-differentiated cancer representing up to 90% of thyroid cancer and pursuing a favorable clinical course. The groups of poorly differentiated thyroid cancer (PDC) and anaplastic thyroid cancer (ATC) have a poor outcome and need a strict clinical surveillance. Materials and Methods:Thirty-four cases including 23 PDC/insular cancer and 9 ATC were examined for the expression of an immunohistochemical panel made up by HBME-1, galectin-3, and &bgr;-catenin and correlated either with histologic prognostic parameters or the overall surveillance. Results:HBME-1 and galectin-3 were expressed in 100% of the PDC/insular cases and in none of the ATC cases. The data for &bgr;-catenin pointed out an 80% expression (12/15) in the PDCs and only a focal and nonspecific positivity in the ATCs. A &bgr;-catenin-positive expression was found in all patients with a worse outcome/death and in the presence of vascular invasion and metastatic disease. All 3 PDC patients with &bgr;-catenin negativity are alive, whereas only 41% (5/12) are alive in the &bgr;-catenin-positive group. Conclusions:Our data set up the idea that PDC represents an intermediate step in the biological process of dedifferentiation of thyroid tumors toward ATC. This shift is underlined by the &bgr;-catenin expression, which seems to be related to a worse prognostic behavior. HBME-1 and galectin-3 show a similar pattern in PDC compared with well-differentiated carcinoma, whereas they are not expressed, as well as &bgr;-catenin, in anaplastic carcinomas.

The cytologic category of oncocytic (Hurthle) cell neoplasm mostly includes low-risk lesions at histology: an institutional experience

DESIGN The cytological diagnosis of oncocytic/Hurthle cell neoplasms (OCN) represents a challenge with which cytopathologists face up to in their practice. The majority of these lesions undergo surgery for a definitive characterization of the nature mainly due to their more aggressive behavior than other malignant follicular lesions. In this study, we aimed at the evaluation of the effective malignant rate in a large cohort of OCNs. METHODS From January 2008 to December 2011, we analyzed 150 cyto-histological OCNs and 64 benign oncocytic/Hurthle lesions (BOL). Both groups of patients were analyzed for clinical and cyto-histological parameters. All the nodules were sampled under sonographic guidance and processed with the liquid-based cytological method. RESULTS In agreement with literature, we found a significant correlation only with female gender in both OCN (P=0.0160) and BOL groups. The 64 BOLs were histologically diagnosed as 15 Hashimoto thyroiditis (HT), 45 hyperplastic nodules in HT, and four papillary thyroid carcinomas (PTC, 6.2%). The 150 OCNs resulted in 141 (94%) oncocytic adenomas and nine (6%) malignant lesions. The latter group included five oncocytic carcinomas (OCC), three oncocytic variants of PTC, and one macrofollicular PTC featured by mild nuclear clearing with a dispersive cellular pattern. The malignant rate was respectively 6.2% in BOLs without any OCC whereas 3.3% OCC diagnosed in the OCN category. CONCLUSIONS Our OCNs mostly resulted in histological adenomas with a lower rate of malignancy than in other series. Some morphological parameters (nuclear clearing, dysplasia, and dispersive cellular pattern) might be helpful in stratifying OCN patients into different risks of malignancy.

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

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.

The potential of liquid‐based cytology in lymph node cytological evaluation: the role of morphology and the aid of ancillary techniques

Our aim was to evaluate the feasibility and diagnostic accuracy of liquid‐based cytology (LBC) on lymph node fine needle aspiration (FNA). FNA may fulfil a challenging role in the evaluation of the majority of primary (benign and malignant) diagnoses as well as metastatic lymph node lesions. Although the morphological features may be quite easily recognized, cytological samples with a scant cellular component may raise some issues.

Large non-functioning parathyroid cysts: our institutional experience of a rare entity and a possible pitfall in thyroid cytology.

Large non‐functioning parathyroid cysts represent a rare entity with a benign clinical course. They may be misdiagnosed as thyroid cystic neoplasms on fine needle aspiration cytology (FNAC), resulting in inappropriate surgical treatment. We evaluated our institutional experience in the diagnosis of large parathyroid cystic lesions underlining all the differential diagnoses and pitfalls.

Detection of ectopic thyroid remnants: a serious diagnostic dilemma. When molecular biology and immunohistochemistry can solve the problem.

The presence of ectopic thyroid tissue is a frequent diagnostic feedback related to a possible histogenetic abnormality or a result of post-surgical seeding. The important challenge is the diagnostic definition of its nature, which could lead to a different therapeutic approach. We describe a case with all the possible implications and differential diagnoses supported by the application of immunohistochemistry and BRAF-V600E molecular detection. A 36-year-old girl with a left thyroid nodule underwent surgery with a diagnosis of angio-invasive tall cell variant of papillary carcinoma without lymph-node metastases. The patient history revealed a previous right lobectomy in another institution ten years before. The right neck dissection was histologically characterized by the presence of thymic residual and evidence of microfollicular microfoci (less than 1mm) of thyroid tissue. Thyroid tumor cells were positive for thyroglobulin, TTF-1, HBME-1 and Galectin-3, while the residual ectopic thyroid tissue showed positivity only for TTF-1 and thyroglobulin. The molecular tests on the thyroid nodule revealed the presence of BRAF-V600E mutation, but wild type BRAF in the ectopic tissue. The histo-morphological definition of these remnants plays the most important role, but the application of immunohistochemistry and molecular biology may help to reach a conclusive diagnosis.