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Concept: Needle aspiration biopsy

172

A progressive increase in the incidence of thyroid cancer (TC) has been reported over the last few decades. This either reflects the increased number of newly discovered and accurately selected thyroid nodules with more sensitive technologies and a relative more potent carcinogenic effect of pathogenetic factors in malignant, but not benign nodules. This observational time-trend study addresses this issue by analysing the proportion of TC within 8411 consecutive thyroid nodule (TN) patients evaluated in Pisa by the same pathology Department and individual clinician over a four-decade period. From 1972 to 1979 surgery was used to detect TC among the TN patients: 1140 TN patients were operated on and 35 cancers were detected (3.1% of all the TN patients). Subsequently, needle aspiration techniques were used to select TN for surgery. From 1980 to 1992, 5403 TN patients were examined, 483 were selected for surgery, and 150 cancers were found (2.8% of all the TN patients). From 1993 to 2010, 1568 TN patients were examined, 143 were selected for surgery, and 46 cancers were found (2.9% of all the TN patients). Therefore, in the University Hospital of Pisa, and independent of preoperative TN selection protocols, these proportions of TN eventually found to harbor TC remained statistically unchanged over 40 years (p = 0.810). This finding suggests that pathogenic risk factors and more sensitive diagnostic technologies did not differentially affect the incidence of TN and TC.

Concepts: Epidemiology, Cancer, Oncology, Pathology, Hospital, Needle aspiration biopsy, Selection, Carcinogen

163

The diagnosis of breast lesions is usually confirmed by fine-needle aspiration cytology (FNAC) or histological biopsy. Although there is increasing literature regarding the advantages and limitations of both modalities, there is no literature regarding the accuracy of these modalities for diagnosing breast lesions in high-risk patients, who usually have lesions detected by screening. Moreover, few studies have been published regarding the cytopathology of mammary tumors in cats despite widespread use of the animal model for breast cancer formation and inhibition. The objective of the present study was to evaluate the diagnostic interest of cytological and histopathological analysis in feline mammary tumours (FMTs), in order to evaluate its possible value as an animal model.

Concepts: Cancer, Breast cancer, Pathology, Anatomical pathology, Breast, Needle aspiration biopsy, Mammary gland, Mammary tumor

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The accident at the Fukushima Daiichi Nuclear Power Plant occurred after the Great East Japan Earthquake on 11 March 2011, releasing a large amount of radioactive materials into the atmosphere. Questions were raised regarding the health effects of radiation exposure, which led to increased anxiety among the Fukushima residents about the possible development of thyroid cancer. Thus, thyroid ultrasound examinations began for those who were from the areas where the radiation doses were highest, and will continue for the long term. In total, 300 476 subjects aged 18 years or younger at the time of the disaster were screened from 9 October 2011 to 31 March 2014. The participation rate was 81.7% of the total population of this age and in the affected area. Among them, the proportions of those who fell into the categories A1 (no nodules or cysts present), A2 (nodule ≤ 5 mm or cyst ≤ 20 mm diameter), B (nodule > 5 mm or cyst > 20 mm diameter) and C (immediate need for further investigation) were 51.5, 47.8, 0.8 and 0%, respectively; 2294 subjects in categories B and C were recommended to undergo a confirmatory examination; 113 were subsequently diagnosed with malignancy or suspected malignancy by fine needle aspiration cytology. The full-scale survey (second round survey) began in April 2014, and was completed by 30 June 2015, and comprised 169 455 subjects (participation rate; 44.7%). The proportions of those who fell into the categories A1, A2, B and C were 41.6, 57.6, 0.8 and 0% (no case), respectively; 1223 subjects in category B were recommended to undergo a confirmatory examination, 25 of these were subsequently diagnosed with malignancy or suspected malignancy by fine needle aspiration cytology. The thyroid cancers identified in this survey so far are unlikely to be due to radiation exposure, and are more likely to be the result of screening using highly sophisticated ultrasound techniques. However, it would be advisable to continue long-term screening to determine whether the risk of childhood and adolescent thyroid cancer due to radiation exposure increases or not.

Concepts: Cancer, Ionizing radiation, Biopsy, Chernobyl disaster, Radioactive decay, Needle aspiration biopsy, Nuclear power, Nuclear safety

35

The development of stabilized recombinant HIV envelope trimers that mimic the virion surface molecule has increased enthusiasm for a neutralizing antibody (nAb)-based HIV vaccine. However, there is limited experience with recombinant trimers as immunogens in nonhuman primates, which are typically used as a model for humans. Here, we tested multiple immunogens and immunization strategies head-to-head to determine their impact on the quantity, quality, and kinetics of autologous tier 2 nAb development. A bilateral, adjuvanted, subcutaneous immunization protocol induced reproducible tier 2 nAb responses after only two immunizations 8 weeks apart, and these were further enhanced by a third immunization with BG505 SOSIP trimer. We identified immunogens that minimized non-neutralizing V3 responses and demonstrated that continuous immunogen delivery could enhance nAb responses. nAb responses were strongly associated with germinal center reactions, as assessed by lymph node fine needle aspiration. This study provides a framework for preclinical and clinical vaccine studies targeting nAb elicitation.

Concepts: Immune system, Antibody, Neutralizing antibody, Lymph node, Vaccination, Adaptive immune system, Antigen, Needle aspiration biopsy

28

To determine the degree of variation in the handling of prostate needle biopsies (PBNx) in laboratories across Europe.

Concepts: Cancer, Biopsy, Pathology, University, Medical tests, Needle aspiration biopsy

28

Abstract Objective. This study aimed to survey current Swedish practices for performing and handling transrectal ultrasound-guided prostate biopsies. Material and methods. A Swedish Urology Network (SUNe) was organized for the distribution of information, survey studies and research collaborations. A web-based questionnaire was distributed to the members in 2011. Results. In this first SUNe survey, 137 (91%) of the 151 members replied. All used antibiotic prophylaxis (84% ciprofloxacin, 12% trimethoprim-sulfamethoxazole), most commonly (63%) as a single dose of ciprofloxacin. Local anaesthesia was used by 87%. Half of the respondents only used a “side-fire” probe, whereas 17% always used an “end-fire” probe. Most (84%) routinely took 10 or more biopsy cores. About three-quarters started with the right base of the prostate and did not routinely take midline biopsies. More than one-third never or rarely sampled the anterior part of the prostate. There was great variability in how biopsy location was reported, but 71% considered a national standardized coordinate system desirable. Fine-needle aspiration was used occasionally by 39%, in more than 10% of cases by 6% and always by 2%. Most urologists mounted the biopsy cores on paper before fixation (78%), put only one core per jar (75%) and used flat-bottomed jars (70%). Conclusions. Most routines for handling of prostate biopsies, antibiotic prophylaxis, local anaesthesia and number of cores were uniform. However, there is still a need for standardization of the performance of ultrasound-guided biopsies. Although the method used to specify biopsy location varied greatly, most urologists would prefer a national standardized system.

Concepts: Biopsy, Pathology, Surgery, Prostate cancer, Local anesthesia, Medical tests, Needle aspiration biopsy, Benign prostatic hyperplasia

28

OBJECTIVES/HYPOTHESIS: Lymphoma of the parotid gland (LPG) is a rare disease. Clinical diagnosis is difficult, due to a lack of specific symptoms and findings. The aim of this study is to evaluate the diagnostic workup based on the analysis of our cases of LPG and to present the stage-dependent treatment outcome. STUDY DESIGN: Retrospective case-control study. METHODS: From 1992 to 2008, 697 patients at our institution underwent surgery because of a parotid tumor. Among 246 malignancies, an LPG was found histologically in 28 cases (4%). Staging was performed according to the Ann Arbor classification, and treatment was performed by radiotherapy and/or chemo/immunotherapy. The patients were retrospectively analyzed. RESULTS: No specific symptoms were found, with the main finding being a unilateral, painless, slowly progressing parotid mass. The sensitivities of imaging and fine-needle aspiration cytology in detecting LPG were 41% and 12%, respectively. Histology was the key to diagnosis, and frozen sections often revealed the diagnosis during surgery, which obviated the need for more extensive surgery in 89% of cases. The 5-year disease-specific survival estimates were 100% and 75% for early tumor stages (I and II) and advanced stages (III and IV), respectively. CONCLUSIONS: When the precise nature of a parotid mass remains obscure after fine-needle aspiration cytology and imaging, but LPG is clinically suspected, surgical tissue sampling with frozen sections appears to be a valid option and can prevent the need for more extensive surgery. The treatment outcome for LPG is favorable.

Concepts: Epidemiology, Cancer, Surgery, Needle aspiration biopsy, Case-control study, Study design, Parotid gland, Warthin's tumor

28

Context: Graves' disease (GD) and Hashimoto´s thyroiditis (HT) are the most common autoimmune thyroid diseases (AITD). The exact etiology of the immune response to the thyroid is still unknown. MicroRNAs (miRNAs) critically control gene-expression. It has become evident that some miRNAs play an important role in regulating the immune response, as well as immune cell development. However, data on the role of miRNAs in autoimmune thyroid diseases are lacking. Objective: The aim of this study was to determine levels of key immunoregulatory miRNAs in thyroid glands of AITD patients and healthy controls Design: Several miRNAs were amplified by a semiquantitative TaqMan PCR from fine needle aspiration biopsies of thyroid tissue of 28 patients with GD, HT, and healthy controls. Results: miRNA 146a1 is significantly decreased in the thyroid tissue of GD (mean relative expression 5,17 in GD group vs. 8,37 in controls, p = 0.019) whereas miRNA 200a1 is significantly decreased (mean 8,30 in HT group vs. 11,20 in controls, p = 0.001) and miRNA 155 2 is significantly increased (mean 12,02 in HT group vs. 8,01 in controls, p = 0.016) in the thyroid tissue of HT compared to controls. Conclusion: Although limited by small sample size and some other limitations (e.g. missing matching for age and medication), our preliminary data open up a new field of research concerning miRNAs in thyroid diseases. Further studies in this interesting field are clearly warranted.

Concepts: Immune system, Medicine, Immunology, Thyroid disease, Hyperthyroidism, Thyroid, Graves' disease, Needle aspiration biopsy

26

The distinction between benign and malignant thyroid nodules has important therapeutic implications. Our objective was to develop an assay that could classify indeterminate thyroid nodules as benign or suspicious, using routinely prepared fine needle aspirate (FNA) cytology smears.

Concepts: Needle aspiration biopsy, Thyroid nodule

26

Among several ultrasound patterns, thyroid nodule hypoechogenicity, spot microcalcifications, and an absent halo sign are used for predicting increased risk of thyroid malignancy. The predictive value of ultrasound, however, increases at the expense of its sensitivity, and malignancy is predicted with high specificity only when multiple ultrasound features are simultaneously present. Ultrasound features are important in determining the strength of the indication for carrying out fine needle aspiration. To this end, a system for standardization of ultrasound features (Thyroid Imaging Reporting and Data System) aids in establishing risk of malignancy. Ultrasound elastosonography is a technique that assesses hardness as an indicator of malignancy risk. It has been carried out in selected studies of patients with thyroid nodules, and has been shown to have a high predictive value for malignancy, which is also maintained in cytologically indeterminate and non-diagnostic nodules. Although conventional ultrasound maintains its pivotal role in defining which nodules are candidates for ultrasound elastosonography characterization, the latter seems to have considerable potential in the diagnosis, or exclusion, of thyroid cancer. This especially concerns thyroid nodules with indeterminate cytology at fine-needle aspiration.

Concepts: Biopsy, Negative predictive value, Pathology, Future, Needle aspiration biopsy