Secretory carcinoma of the salivary gland, a rare entity: An international multi-institutional study.

BACKGROUND: Secretory carcinoma (SC) of the salivary gland is a rare entity with limited published literature on cytomorphology. The authors present the largest cohort to date of SC fine-needle aspiration (FNA) cases. METHODS: FNA cases of histologically confirmed SC were retrospectively retrieved from 12 academic institutions in the United States, Italy, Finland, and Brazil. The collated data included patient demographics, imaging findings, cytopathologic diagnoses according to the Milan System for Reporting Salivary Gland Cytopathology, cytomorphologic characteristics, and immunohistochemical/molecular profiles. RESULTS: In total, 40 SCs were identified (male-to-female ratio, 14:26) in patients with a mean age of 52 years (age range, 13-80 years). Ultrasound imagining revealed a hypoechoic, ovoid, poorly defined, or lobulated mass. The most common primary site was the parotid gland (30 of 40 tumors). Regional lymph node metastasis (9 patients) and distant metastasis (4 patients; brain, liver, lungs, and mediastinum) were noted. Two patients died of disease. FNA smears were cellular and demonstrated mainly large, round cells with intracytoplasmic vacuoles or granules and round-to-oval nuclei with smooth nuclear contour, minimal irregularities, and prominent nucleoli arranged predominantly in clusters, papillary formations, and single cells. The background was variable and contained inflammatory cells, mucin, or proteinaceous material. The diagnoses were malignant (19 of 38 tumors; 50%), suspicious for malignancy (10 of 38 tumors; 26%), salivary gland neoplasm of uncertain malignant potential (7 of 38 tumors; 18%), and atypia of undetermined significance (2 of 38 tumors; 6%) according to the Milan System for Reporting Salivary Gland Cytopathology. Two malignant cases (2 of 40 tumors; 5%) were metastases. The neoplastic cells were immunoreactive for S100 (23 of 24 tumors), mammaglobin (18 of 18 tumors), GATA-3 (13 of 13 tumors), AE1/AE3 (7 of 7 tumors), and vimentin (6 of 6 tumors). ETV6-NTRK3 fusion was detected in 32 of 33 tumors by fluorescence in situ hybridization (n = 32) and next-generation sequencing (n = 1). CONCLUSIONS: Familiarity with cytomorphologic features and the immunohistochemical/molecular profile of SC can enhance diagnostic accuracy.

Thyroid paraganglioma: A diagnostic pitfall in thyroid FNA.

BACKGROUND: Thyroid paragangliomas are extremely rare and often are misdiagnosed by preoperative fine-needle aspiration (FNA) because their cytologic features overlap with those of other thyroid neoplasms. The objective of this study was to review the cytomorphology in a series of thyroid paragangliomas and correlate the findings with histopathology. METHODS: Five thyroid paraganglioma cases that underwent FNA were reviewed. Their clinical presentation, radiology features, cytomorphology, ancillary tests, and histopathology were analyzed. RESULTS: All patients were women with an average age of 49 years (age range, 35-61 years) and presented with an asymptomatic, solitary thyroid nodule. Radiologically, these nodules (size range, 1.8-3.0 cm) were well circumscribed, hypoechoic, and hypervascular. FNA smears showed clusters of loosely cohesive, medium-to-large epithelioid cells with clear-to-eosinophilic and occasionally foamy cytoplasm that had indistinct cytoplasmic borders. The nuclei were round to oval with focal nuclear membrane irregularities, inconspicuous nucleoli, focal marked anisonucleosis, and occasional intranuclear pseudoinclusions. Naked nuclei, variable numbers of plasmacytoid cells, multinucleated giant cells, and sustentacular cells were present in the background along with blood vessels and lymphocytes. Cytology diagnoses were incorrect and included follicular neoplasm (n = 4) and follicular lesion of undetermined significance (n = 1). Final histopathology with immunohistochemistry revealed conventional paraganglioma (n = 3) or sclerosing paraganglioma with invasive features (n = 2). CONCLUSIONS: All thyroid paragangliomas were misdiagnosed on FNA as follicular neoplasms, in part because of the rarity of these tumors in this location and cytomorphology mimicking follicles. The absence of colloid, the presence of naked nuclei, focal marked anisonucleosis, and the presence of sustentacular cells are important cytology clues.

A Call for Universal Acceptance of the Milan System for Reporting Salivary Gland Cytopathology.

OBJECTIVES: The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) established a standardized, tiered reporting system for salivary gland fine-needle aspiration (FNA) that has gained international acceptance among cytologists. Our goal was to review the key features of the MSRSGC to familiarize the surgical community with this system and its application to the FNA evaluation of salivary gland masses. METHODS: A comprehensive review of the MSRSGC and its application in clinical practice. RESULTS: The MSRSGC consists of six major diagnostic categories: 1) nondiagnostic, 2) non-neoplastic, 3) atypia of undetermined significance, 4) neoplasm (benign or salivary gland neoplasm of uncertain malignant potential), 5) suspicious for malignancy, and 6) malignant. Each diagnostic category is associated with an implied risk of malignancy with implications for clinical management. CONCLUSIONS: The MSRSGC is similar to the system used for reporting thyroid FNA, which is familiar to most otolaryngologists and head and neck surgeons. As this reporting system continues to gain popularity among pathologists, widespread understanding by surgeons will be important to standardize communication and classification of salivary gland cytopathology to improve clinical care. Laryngoscope, 130:80-85, 2020.

Ultrasound-guided FNA cytology of groin lymph nodes improves the management of squamous cell carcinoma of the vulva: Results from a comparative cytohistological study.

BACKGROUND: Lymph node metastases represent the most important negative prognostic predictor in vulvar carcinoma. Therefore, an accurate preoperative assessment of suspicious lymph nodes would be fundamental for a personalized therapy. The aim of this article was to assess the reliability of ultrasound-guided fine-needle aspiration cytology (FNAC) in the preoperative assessment of nodal metastatic disease in 43 patients with vulvar cancer. METHODS: In total, 43 FNAC specimens of clinicoradiologically suspicious lymph nodes with corresponding nodal resection specimens were collected from 2016 to 2018 at Catholic University Hospital in Rome. Cytohistologic correlation was performed. Patients were treated with wide local excision of the vulvar mass followed by bilateral inguinofemoral lymphadenectomy and radiotherapy if the tumor involved a lymph node or the vulvar margins. RESULTS: Cytologic examination agreed with histology in 37 of 43 cases (86.04%). The authors observed a positive FNAC result in 14 of 20 histologically confirmed metastatic lymph nodes, 6 false-negative cases, and no false-positive results. The sensitivity and specificity of cytological examination were 76.92% and 100%, respectively. All patients with FNAC-positive results showed metastatic disease in other surgically resected inguinofemoral nodes. Eleven of 29 patients (37.9%) with FNAC-negative results also showed metastatic disease in subsequent lymphadenectomy specimens, but the extent of metastases was always <1 cm (range, 0.1-0.6 cm). CONCLUSIONS: FNAC of suspicious lymph nodes represents a useful tool in the management of patients with vulvar cancer. A positive result enables the surgeon to immediately perform a bilateral inguinofemoral lymphadenectomy thus avoiding an unnecessary sentinel lymph node sampling. Finally, FNAC can also predict the presence and extent of metastatic disease in other surgically resected inguinofemoral lymph nodes.

Application of the Milan System for Reporting Submandibular Gland Cytopathology: An international, multi-institutional study.

BACKGROUND: The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) is a 6-tier diagnostic category system with associated risks of malignancy (ROMs) and management recommendations. Submandibular gland fine-needle aspiration (FNA) is uncommon with a higher frequency of inflammatory lesions and a higher relative proportion of malignancy, and this may affect the ROM and subsequent management. This study evaluated the application of the MSRSGC and the ROM for each diagnostic category for 734 submandibular gland FNAs. METHODS: Submandibular gland FNA cytology specimens from 15 international institutions (2013-2017) were retrospectively assigned to an MSRSGC diagnostic category as follows: nondiagnostic, nonneoplastic, atypia of undetermined significance (AUS), benign neoplasm, salivary gland neoplasm of uncertain malignant potential (SUMP), suspicious for malignancy (SM), or malignant. A correlation with the available histopathologic follow-up was performed, and the ROM was calculated for each MSRSGC diagnostic category. RESULTS: The case cohort of 734 aspirates was reclassified according to the MSRSGC as follows: nondiagnostic, 21.4% (0%-50%); nonneoplastic, 24.2% (9.1%-53.6%); AUS, 6.7% (0%-14.3%); benign neoplasm, 18.3% (0%-52.5%); SUMP, 12% (0%-37.7%); SM, 3.5% (0%-12.5%); and malignant, 13.9% (2%-31.3%). The histopathologic follow-up was available for 333 cases (45.4%). The ROMs were as follows: nondiagnostic, 10.6%; nonneoplastic, 7.5%; AUS, 27.6%; benign neoplasm, 3.2%; SUMP, 41.9%; SM, 82.3%; and malignant, 93.6%. CONCLUSIONS: This multi-institutional study shows that the ROM of each MSRSGC category for submandibular gland FNA is similar to that reported for parotid gland FNA, although the reported rates for the different MSRSGC categories were variable across institutions. Thus, the MSRSGC can be reliably applied to submandibular gland FNA.

Mucoepidermoid carcinoma, acinic cell carcinoma, and adenoid cystic carcinoma on fine-needle aspiration biopsy and The Milan System: an international multi-institutional study.

BACKGROUND: We evaluated the diagnostic accuracy (DA), risk of neoplasm (RON), and risk of malignancy (ROM) for the commonly encountered malignant salivary gland tumors mucoepidermoid carcinoma (MECa), acinic cell carcinoma (ACCa), and adenoid cystic carcinoma (ADCa) applying The Milan System for Reporting Salivary Gland Cytology (MSRSGC). MATERIALS AND METHODS: The cytology archives from 2007 to 2017 of 9 academic institutions were searched for salivary gland FNAs for the following key words mentioned either in the principal and/or differential diagnosis: MEC, ACCa, and ADCa. The original cytology diagnosis was retrospectively classified according to the MSRSGC. Patient demographics, biopsy site, and available surgical follow-up were recorded. The final analysis included only cases with surgical follow-up. RESULTS: A total of 212 salivary gland FNAs were included. Based on retrospective reclassification according to MSRSGC, 97 of 212 (46%) FNA cases carried a diagnosis of malignancy specific for either MECa, ACCa, or ADCa. In the remaining 115 cases, 24 of 212 (11%) were reclassified as suspicious for malignancy (SM) and 91 of 212 (43%) as salivary gland neoplasm of uncertain malignant potential (SUMP). The DA for MECa, ACCa, and ADCa was 78.7%, 75% and 89%, respectively. The RON was 100% for all 3 tumors and the ROM was 93.6% for MECa, 96.8% for ACCa, and 94.4% for ADCa. CONCLUSIONS: The DA of 78.7% for MECa, 75% for ACCa, and 89% for ADCa is reasonable in FNA specimens. Although the management of definitive cases of malignancy remains unchanged, the MSRSGC provides a ROM for SM and SUMP categories, which can improve patient management.

The immunocytochemical expression of VE-1 (BRAF V600E-related) antibody identifies the aggressive variants of papillary thyroid carcinoma on liquid-based cytology.

BACKGROUND: The recently introduced monoclonal V600E antibody (clone VE1) is likely to be an alternative strategy for detecting this mutation in thyroid lesions. Although VE1 immunostaining and molecular methods used to assess papillary thyroid carcinoma in surgical specimens are in good agreement, evaluation of VE1 in cytology and cell block samples is rarely performed, and its diagnostic value in cytology has not been well established. In this study, we sought to determine if VE1 is suitable for fine needle aspiration (FNA) and cell block methods. METHODS: A total of 86 patients who had BRAF V600E mutations were investigated with molecular and immunocytochemical (ICC) analysis in 45 FNA and 41 cell blocks. In total, 83 (96.5%) patients underwent surgical treatment. Assessment of BRAF V600E mutation status was performed in 72 (83.7%) cases. RESULTS: Among the 72 cases analysed, 54 cases agreed (ICC+/BRAF+ or ICC-/BRAF-), seven cases were false positive (ICC+/BRAF-) and 11 cases were false negative (ICC-/BRAF+). False negative cases were not detected in the cell block method. The statistical analysis showed that sensitivity and specificity of ICC for detecting the BRAF V600E mutation were 61% and 77% in FNA samples and 100% and 73% in cell block. CONCLUSION: The use of antibody VE-1 is a reliable method and a negative result of VE1 immunostaining might help to save time and money, restricting the molecular test to antibody-positive cases only. The identification of the aggressive variants of papillary carcinoma might be enabled by the expression of the antibody in neoplastic cells with tall cell features.

Salivary Gland Fine Needle Aspiration and Introduction of the Milan Reporting System.

Fine needle aspiration (FNA) is a well-established procedure for the diagnosis and management of salivary gland lesions despite challenges imposed by their diversity, complexity, and cytomorphologic overlap. Until recently, the reporting of salivary gland FNA specimens was inconsistent among different institutions throughout the world, leading to diagnostic confusion among pathologists and clinicians. In 2015, an international group of pathologists initiated the development of an evidence-based tiered classification system for reporting salivary gland FNA specimens designated the "Milan System for Reporting Salivary Gland Cytopathology" (MSRSGC) that culminated with the publication of the MSRSGC Atlas in February 2018. The MSRSGC consists of 6 diagnostic categories, which incorporate the morphologic heterogeneity and overlap among various non-neoplastic, benign, and malignant lesions of the salivary glands. In addition, each diagnostic category is associated with a risk of malignancy and management recommendations. The main goal of the MSRSGC is to improve communication between cytopathologists and treating clinicians, while also facilitating cytologic-histologic correlation, sharing of data from different laboratories for quality control, and research. Herein, we review the current status of salivary gland cytology and the role of MSRSGC in providing a framework for reporting salivary gland lesions.

34BetaE12 and Alfa-Methylacyl Coenzyme A Racemase (AMACR) Antibodies Better Than p63 Antibody Distinguish Normal and Neoplastic Glands in Prostatic Tissue With Thermal Artifacts.

The occurrence of inked margins with crush artifact derived from the electrocauterization in radical prostatectomy and/or the presence of crushed areas with distorted glands in prostatic samples after transurethral resection of prostate (TURP) can induce a significant interobserver variability during histopathologic evaluation of specimens. The specific immunostaining for basal cell markers 34BetaE12 and p63 and for alfa-methylacyl coenzyme A racemase (AMACR) in neoplastic cells is commonly used as an ancillary tool to establish benign and malignant glands. In this study we carried out the immunohistochemical reactions for p63, 34BetaE12, and AMACR on 3 different and successive paraffin sections to discriminate malignant and benign prostatic glands, distorted and crushed by the thermal artifacts in 60 radical prostatectomies and 50 TURP samples. All prostatic acinar adenocarcinoma showed the loss of basal cell markers and expression of AMACR, whereas p63 failed to stain the basal cell layer in benign crushed prostatic glands. The same cauterized glands were steadily positive for 34BetaE12. The high percentage of p63 false negative cases in benign distorted and crushed glands could be explained by the thermal artifacts which might cause lack of p63 antigenicity. In contrast, the antigenicity of 34BetaE12 and AMACR seem not to be affected by cautery artifacts. Thus, in cauterized suspicious prostatic glands an immunohistochemistry panel including, p63, 34BetaE12, and AMACR or only 34BetaE12 is recommended. In addition, after the first evaluation with only p63, we suggest that a separate and confirmatory staining for 34BetaE12 is strongly recommended.

Nodular fasciitis of the parotid gland: A challenging diagnosis on FNA.

BACKGROUND: Nodular fasciitis (NF) is a clonal, self-limited proliferation that has only rarely been described in the parotid gland. Because of its potential to mimic benign and malignant parotid neoplasms clinically, radiographically, and cytomorphologically, NF is often managed with unnecessary surgery, which is associated with a risk for significant surgical complications. The purpose of this study is to present the clinical and cytomorphologic findings for NF of the parotid gland by fine-needle aspiration (FNA). METHODS: The pathology archives of the authors' respective institutions were searched for salivary gland FNA cytology specimens with a confirmed diagnosis of NF. The clinical history, pathologic diagnosis, cytomorphologic findings, and immunocytochemical results were recorded. RESULTS: A total of 15 cases were identified; the average age was 37 years, and 10 patients (66.7%) were female. Five cases (33.3%), all treated surgically, showed recurrence within an average timeframe of 1.6 months. Only 3 cases (20.0%) were classified as definitive, probable, or suggestive of NF. On average, smears were composed of predominantly single (69.2%), spindled cells (100.0%) with short unipolar (76.9%) and/or bipolar processes (38.5%), round (61.5%) or elongated (84.6%) nuclei, and inconspicuous nucleoli (53.8%). In 69.2%, a tissue-culture appearance was shown, and 76.9% contained myxoid stroma. In 46.2%, a minimal amount of cytologic atypia was shown. CONCLUSIONS: Keeping NF in the differential for any bland, single, spindled cell proliferation with elongated cytoplasmic processes and bland nuclei may prompt the clinician to consider more conservative management in the correct clinical context.

One-Step Nucleic Acid Amplification (OSNA): A fast molecular test based on CK19 mRNA concentration for assessment of lymph-nodes metastases in early stage endometrial cancer.

INTRODUCTION: The aim of the current study is to evaluate the detection rate of micro- and macro-metastases of the One-Step Nucleic Acid Amplification (OSNA) compared to frozen section examination and subsequent ultra-staging examination in early stage endometrial cancer (EC). MATERIAL AND METHODS: From March 2016 to June 2016, data of 40 consecutive FIGO stage I EC patients were prospectively collected in an electronic database. The sentinel lymph node mapping was performed in all patients. All mapped nodes were removed and processed. Sentinel lymph nodes were sectioned and alternate sections were respectively examined by OSNA and by frozen section analysis. After frozen section, the residual tissue from each block was processed with step-level sections (each step at 200 micron) including H&E and IHC slides. RESULTS: Sentinel lymph nodes mapping was successful in 29 patients (72.5%). In the remaining 11 patients (27.5%), a systematic pelvic lymphadenectomy was performed. OSNA assay sensitivity and specificity were 87.5% and 100% respectively. Positive and negative predictive values were 100% and 99% respectively, with a diagnostic accuracy of 99%. As far as frozen section examination and subsequent ultra-staging analysis was concerned, we reported sensitivity and specificity of 50% and 94.4% respectively; positive and negative predictive values were 14.3% and 99%, respectively, with an accuracy of 93.6%. In one patient, despite negative OSNA and frozen section analysis of the sentinel node, a macro-metastasis in 1 non-sentinel node was found. CONCLUSIONS: The combination of OSNA procedure with the sentinel lymph node mapping could represent an efficient intra-operative tool for the selection of early-stage EC patients to be submitted to systematic lymphadenectomy.

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.

Well-differentiated thyroid cancer with a minor poorly differentiated component: clonal heterogeneity through the prognostic role of CXCR4 and BRAF analysis.

Well-differentiated carcinoma (WDC) accounts for up to 90% of all thyroid cancers. The presence of a minor poorly differentiated (PD) component (mainly insular pattern) might represent an additional critical parameter for patients' prognosis and outcome. The role of both CXCR4 (a chemokine inducing cytoskeletal rearrangement and cell adhesion) and BRAF mutation have been studied in WDC (mainly papillary thyroid cancer and its variants), highlighting their critical role in tumor progression, local infiltration, and metastases. We discussed the clonal heterogeneity through the prognostic role of CXCR4 and BRAF mutation in WDC with a minor PD/insular component. Of our 16 WDC cases with a PD/insular component, up to 40% underwent surgery. The cases were subclassified according to the PD percentage as (1) <20% PD and (2) 20% to 40% PD, and were studied for CXCR4 expression and BRAF mutation. CXCR4 and molecular testing were distinctly performed on both components of each lesion. The majority of the cases (69%) showed an extrathyroid and metastatic dissemination. Regardless of the 2 categories, we had 8/16 (50%) patients with disease-free status. CXCR4 was negative in all 16 cases, whereas 3 of them (19%) had a mutated BRAF only in the WDC component of the lesion. WDCs with a minor PD pattern, even when <20%, showed more aggressive features than pure WDCs and should be entirely considered as PD carcinoma. The absence of CXCR4 expression and BRAF mutation in cancers with a minor PD component underlined different pathogenic and metastatic processes in comparison with WDCs.

Detection of common and less frequent EGFR mutations in cytological samples of lung cancer.

OBJECTIVE: Lung cancer represents the leading cause of cancer death. EGFR mutations, detected in 10-40% of lung adenocarcinomas, are an essential key to therapeutic management. EGFR-activated mutations comprise mainly deletions in exon 19 and point mutations in exon 21. Although histology is the traditional method of detection, we investigated the role of cytology in EGFR mutations. STUDY DESIGN: A total of 774 lung cancers were studied for EGFR mutations (676 histological and 98 cytological samples), including 424 adenocarcinomas, 326 non-small cell lung carcinomas not otherwise specified, and 24 squamous cell carcinomas. RESULTS: We had a total of 164 (21.2%) cases of mutations. Common mutations were short in-frame deletions in exon 19 (53.7%) and single-nucleotide substitutions in exon 21 (34.1%); less frequent mutations included single-nucleotide substitutions in exon 18 (3.7%) and in-frame insertions/deletions in exon 20 (8.5%). Histologically, EGFR mutations in exons 19 and 21 occurred in 19.4% and in exons 18 and 20 in 2.2%, while the rates cytologically were 13.3% for exons 19 and 21 and 5.1% for exons 18 and 20. CONCLUSIONS: The sensitivity for the detection of EGFR mutations in cytological samples overlaps histology, so the use of cytological material constitutes an adequate approach for treatment selection in patients with locally advanced or metastatic lung cancer.

Thyroglossal duct cyst cancer most likely arises from a thyroid gland remnant.

Thyroglossal duct cancer is a rare entity, occurring in 1.5 % of all thyroglossal duct cysts (TDC). A definitive consensus about its neoplastic origin has not been established as two contrasting theories exist, one proposing an origin in extra-thyroid remnants and the other a metastatic localization of a primary thyroid cancer. We compare morphological and molecular characteristics of both thyroglossal and thyroid carcinomas in a case series from our institute. We evaluated histology of 80 TDC. In 12 cases, prior cytological evaluation had been performed by liquid-based cytology (LBC). The BRAF gene was examined for mutations, and the histology of both thyroglossal duct and synchronous thyroid carcinoma was reevaluated. In 9 out of 80 (11 %) TDC cases, a papillary thyroid cancer (PTC) was diagnosed. In five out of nine (56 %) thyroglossal carcinomas, a synchronous thyroid cancer was diagnosed: 3 PTC and 2 follicular variant PTC (FVPC). In five thyroglossal carcinomas, mutated BRAF (V600E) was found, three in PTC and in thyroglossal as well as in the synchronous tumor in the thyroid. All the patients are in a disease-free status and still alive. Our results suggest that the majority of thyroglossal carcinomas most likely develop as a primary malignancy from a thyroid remnant. Neither the presence of V600E BRAF mutations nor that of a well-differentiated thyroid carcinoma changed the outcome or disease-free survival. We suggest that a diagnosis of thyroglossal carcinoma should be followed by a detailed evaluation of the thyroid gland. In the absence of clinical and radiological thyroid alterations, follow-up as for thyroid cancer is the correct management.

Diagnostic and prognostic role of HBME-1, galectin-3, and ß-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 ß-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 ß-catenin pointed out an 80% expression (12/15) in the PDCs and only a focal and nonspecific positivity in the ATCs. A ß-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 ß-catenin negativity are alive, whereas only 41% (5/12) are alive in the ß-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 ß-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 ß-catenin, in anaplastic carcinomas.

Surgical treatment of thyroid diseases in elderly patients.

BACKGROUND: We evaluated the safety of thyroid surgery in elderly patients, in whom surgical procedures usually are considered more hazardous than in younger patients. METHODS: The medical records of all the patients who were aged 70 years or older who had undergone thyroid surgery between January 1998 and June 2008 were reviewed. RESULTS: A total of 320 patients were included. The preoperative diagnosis was multinodular goiter in 171 cases, toxic goiter in 59 cases, suspicious or indeterminate thyroid nodule in 60 cases, and thyroid carcinoma in 30 patients. Total thyroidectomy was performed in 283 patients, thyroid lobectomy in 15 patients, and a completion thyroidectomy was performed in 22 patients. The final histology showed thyroid cancer in 86 patients and benign disease in 234. CONCLUSIONS: Thyroid surgery in patients aged 70 years or older is safe and the relatively high rate of thyroid carcinoma and toxic goiter may justify an aggressive approach.

Immunocytochemical evaluation of thyroid neoplasms on thin-layer smears from fine-needle aspiration biopsies.

BACKGROUND: Fine-needle aspiration biopsy (FNAB) is the most reliable diagnostic tool for thyroid nodules. A difficult cytologic diagnosis may be supported by an immunocytochemical study. The efficacy of a panel made up of RET, HBME-1, and Galectin-3 antibodies was evaluated in smears processed by thin-layer cytology (TLC). DESIGN: Thyroid FNABs (n = 99) with both conventional (CS) and thin-layer cytology (TLC) smears were studied. The cases were diagnosed as follows: 5 benign lesions (BL), 13 papillary carcinomas (PC), and 81 follicular proliferations (FP). The category of FP was divided into three subgroups according to nuclear features of follicular cells: Follicular neoplasm (FN NOS), oxyphilic follicular neoplasm (OFN), and follicular lesion with nuclear pleomorphism (FLWNP). Immunostains for HBME-1, Galectin-3, and RET were carried out on TLC slides. RESULTS: Among 49 cases undergoing surgery, all 10 PC and 2 BL were histologically confirmed, whereas 15 out of 37 FP (40.5%) were malignant. The complete immunocytochemical panel (ICCP) was positive in 9 of 10 malignancies (90%) and negative in both BLs. Out of 37 FP, the ICCP yielded positive in 15 cases (4 benign, 11 malignant) and negative in 11 (all benign). In the FLWNP subgroup, the ICCP was positive in 11 (84.6%) and negative in 2 histologically benign cases. CONCLUSION: The combined panel of antibodies and the nuclear pleomorphism of follicular cells were effective in distinguishing between thyroid nodules requiring surgery from thyroid nodules requiring just follow-up.

Does the fine-needle aspiration diagnosis of "Hürthle-cell neoplasm/follicular neoplasm with oncocytic features" denote increased risk of malignancy?

The thyroid fine-needle aspiration (FNA) diagnosis of Hürthle-cell neoplasm (HCN)/follicular neoplasm with oncocytic features (FNOF) does not differentiate between Hürthle-cell adenoma and carcinoma. A majority of cases diagnosed as HCN undergo surgical excision for definite characterization. The aim of this study was to determine the risk of malignancy in cases diagnosed as HCN and identify clinical features that may help in predicting malignancy in patients with FNA diagnosis of HCN. We reviewed a cohort of 206 cases of thyroid FNA diagnosed as HCN; histological follow-up was available in 169 (82%) cases. The cases were evaluated for patient's age, sex, and size of the nodule and histological diagnosis. One hundred and sixty-six were female patients and 40 were male patients (age range, 12-83 yr). The histological diagnoses were benign in 93 (93/169, 55%) cases and malignant in 76 (76/169, 45%) cases. The malignant histological diagnoses were Hürthle-cell carcinoma (HCC), 53 cases; papillary thyroid carcinoma, 19 cases; follicular carcinoma, 3 cases; and medullary carcinoma, 1 case. The risk of malignancy was greater in nodules measuring > or =2 cm (55% vs. 45%; P value < 0.0001) in patients who were > or =40 yr old (82% vs. 18%, P value < 0.0001) than in patients <40 yr. The risk of malignancy was found greater in male patients than in female patients (61% vs. 43%); however, the difference was not statistically significant. The diagnosis HCN/FNOF carries a higher risk of malignancy as compared with a diagnosis of follicular lesion/neoplasm (20% malignancy rate from previously published studies). Clinical features including size of the nodule, age, and possibly sex of the patient can be a part of the decision analysis in selecting a patient for surgery.