Fine-Needle Aspiration of the Thyroid: Correlating Suspicious Cytology Results with Histological Outcomes

Purpose

Fine-needle aspiration cytology (FNAC) assists the diagnosis of thyroid malignancy. A ‘suspicious for malignancy’ on FNAC creates a management dilemma. The aims of this study were to investigate the malignancy rate for patients with suspicious cytology, and to describe a management approach for those with a suspicious result.

Methodology

A retrospective review of prospectively collected data in an endocrine surgery database was undertaken. Patients undergoing thyroidectomy with preoperative FNAC from 1992 to 2012 were analysed.

Results

Preoperative FNAC was undertaken in 2,692 patients, and the FNAC result was ‘suspicious for malignancy’ in 94 (3.5 %) patients. Of these, 53 (56.4 %) were malignant, with the majority 44 (83.0 %) being papillary thyroid cancer. 48 patients went straight to total thyroidectomy, 40 patients had an initial diagnostic hemithyroidectomy, and 1 patient had a diagnostic isthmusectomy. 5 patients required reoperative total thyroidectomy as an initial procedure. Of the 94 suspicious cases, 55 were reported by an unknown, presumably non-expert, thyroid cytopathologist. 38 of these cases were available for review and re-reporting by an experienced cytopathologist. On review, 28 (73.7 %) were reclassified as cytologically malignant, and all of these were confirmed as malignant on subsequent histopathology.

Conclusions

Suspicious cytology has a high risk of malignancy. Expert thyroid cytopathology can improve diagnostic accuracy and a preoperative malignant diagnosis should be pursued to enable one-stage surgery where possible.     

Novel prion protein gene mutation in an octogenarian with Creutzfeldt-Jakob disease

BACKGROUND: The transmissible spongiform encephalopathies constitute a fascinating and biologically unique group of invariably fatal neurodegenerative disorders that affect both animals and humans. Creutzfeldt-Jakob disease (CJD), Gerstmann-Straussler-Scheinker syndrome, and fatal familial insomnia represent the more common human phenotypes. Excluding the small number of iatrogenically transmitted cases, approximately 85% to 90% of patients develop CJD without identifiable explanation, with an increasing number of different mutations in the prion protein gene (PRNP) recognized as probably causative in the remainder. OBJECTIVE: To report on an 82-year-old woman with pathologically confirmed CJD found unexpectedly to harbor a novel mutation in PRNP. METHODS: Routine clinical investigations were undertaken to elucidate the cause of the rapidly progressive dementia and neurological decline manifested by the patient, including magnetic resonance imaging of the brain, electroencephalography, and cerebrospinal fluid analysis for the 14-3-3 beta protein. Standard postmortem neuropathological examination of the brain was performed, including immunocytochemistry of representative sections to detect the prion protein. Posthumous genetic analysis of the open reading frame of PRNP was performed on frozen brain tissue using polymerase chain reaction and direct sequencing. RESULTS: Concomitant with the exclusion of alternative diagnoses, the presence of characteristic periodic sharp-wave complexes on the electroencephalogram in combination with a positive result for 14-3-3 beta protein in the cerebrospinal fluid led to a confident clinical diagnosis of CJD, confirmed at autopsy. There was no family history of dementia or similar neurological illness, but patrilineal medical information was incomplete. Unexpectedly, full sequencing of the PRNP open reading frame revealed a single novel mutation consisting of an adenine-to-guanine substitution at nucleotide 611, causing alanine to replace threonine at codon 188. CONCLUSIONS: In addition to expanding the range of PRNP mutations associated with human prion diseases, we believe this case is important for the following reasons. First, from an epidemiological perspective, the avoidance of occasional incorrect classification of patients manifesting neurodegenerative disorders that may have a genetic basis requires systematic genotyping, particularly when there are uncertainties regarding the family history. Second, the incidence of spongiform encephalopathy in elderly patients beyond the typical age range may be underestimated and does not preclude a genetic basis. Finally, as a corollary, this case highlights problematic issues in human transmissible spongiform encephalopathies, as illustrated by disease penetrance and age of onset in genotype-phenotype correlations.     

Cytoskeletal protein mRNA expression in the chick utricle after treatment in vitro with aminoglycoside antibiotics: effects of insulin, iron chelators and cyclic nucleotides

In birds, spontaneous recovery of the hair cells of the inner ear can occur after damage induced by aminoglycoside antibiotics. The factors that influence this recovery and the process of hair cell regeneration itself have until recently been investigated largely by morphological and histological methods. The aim of this work was to use a molecular biological approach to the analysis of hair cell regeneration by measuring the changes that occur in expression of mRNA for hair cell-specific cytoskeletal proteins fimbrin and class III beta-tubulin, along with that for beta-actin, in the utricle of chicks after hair cell damage both in vitro and in vivo. Utricles were removed from 1-day-old chicks and incubated with the aminoglycoside antibiotics gentamicin or neomycin (both 1 mM), or chicks were injected intraperitoneally with 100 mg/kg gentamicin or neomycin for 4 consecutive days. At the end of the treatment periods, total RNA was extracted from single utricles, reverse transcribed to cDNA and the cDNA amplified by PCR with primers for beta-actin, fimbrin and class III beta-tubulin. Co-amplification allowed quantitative comparison of mRNA between fimbrin, or class III beta-tubulin and beta-actin from the same utricle. Both aminoglycosides, either after 48 h in vitro or immediately after treatment in vivo, caused a significant decrease in the expression of fimbrin mRNA and class III beta-tubulin mRNA, relative to beta-actin mRNA, which itself increased. Light and electron microscopy confirmed that this corresponded to loss of, and damage to, hair cells. The relative expression of fimbrin and class III beta-tubulin mRNAs was partly restored almost to control levels 4 days after cessation of treatment in vivo and fully normalised by 4 weeks, by which time hair cells appeared normal. However, their relative expression remained depressed 4 days after removal of antibiotic in vitro. The iron chelator desferrioxamine (100 microM) in vitro prevented the aminoglycoside-induced reduction in relative expression of mRNA for both fimbrin and class III beta-tubulin. Neither insulin (5 microM) nor a combination of dibutyryl cyclic AMP (5 mM) and the phosphodiesterase inhibitor IBMX (0.5 mM) prevented the decrease in relative expression of the mRNAs for the hair cell-specific proteins, but both treatments allowed their partial recovery in vitro during the 4-day-period after removal of aminoglycoside. It is concluded that the cells of the sensory epithelium of the chick utricle subjected to aminoglycoside-induced damage undergo a process in which mRNA expression is switched away from the production of functional proteins and towards proteins necessary for structural re-organisation. The restoration of mRNA expression to a normal pattern is promoted by the growth factor insulin and by cyclic AMP.     

Scottish national bronchoscopy audit: a prospective multicentre study of 3316 cases against agreed standards. Scottish Thoracic Society

INTRODUCTION: Bronchoscopy guidelines address issues of patient and operator safety but do not give guidance on the expected yield of the procedure. Realistic standards for several outcome measures of bronchoscopy for investigating bronchial carcinoma have been derived by Scottish clinicians from a published national study. The present study describes the use of these agreed standards in prospective audit. METHODS: All Society members in Scotland (population 5.1 million) were invited to participate. Data were collected for 1 year and coded anonymously. STANDARDS: 1. Supervising bronchoscopist to have completed at least 100 procedures; 2. histology to be positive in 80% of cases where tumour seen; 3. 35%-55% of bronchoscopies to reveal a diagnosis; 4. 60% of patients admitted for bronchoscopy to be day cases; 5. 80% of day case patients to be in hospital for less than 6 h; 6. 90% of male patients and 80% of female patients willing to have repeat bronchoscopy. RESULTS: Three thousand, three hundred and sixteen bronchoscopies were performed by 45 senior pulmonologists at 22 centres. One centre reached all the standards and five centres met five standards. There was wide national variation in histological spectrum, incidence of small cell cancer ranged from 12% to 25% between centres. Participants found their own data helpful in identifying local areas for improvement. CONCLUSION: Bronchcoscopy standards set locally by practising pulmonologists can be used in collaborative audit to identify areas for improving practice. Variation in histology may be accounted for by case-mix or pathology techniques.     

Inflammatory cellular kinetics in sympathetic ophthalmia a study of 29 traumatized (exciting) eyes

An immunohistochemical study was conducted on 29 cases of sympathetic ophthalmia (SO). Monoclonal antibodies against T, B, NK cells, macrophages, and MHC class II antigen (HLA-DR) were used. The choroidal infiltrate in 20 eyes was predominantly T cell while B cell predominated in four cases. All eyes with a B cell predominance came from males. A predominance of B cells was correlated to a longer duration of the disease (> 9 months) and in eyes showing phthisical changes. There was no correlation between a predominance of B cells with age, race, corticosteroid treatment or histological type (typical or atypical). These findings suggest that, although SO is a T cell mediated disease, the predominance of B cells in some cases may represent the end stage of the disease process, or seems a secondary pathological process. The kinetic change in cell populations during the disease may have therapeutic implication.     

Communication profiles of two types of gesture using nonverbal persons with severe to profound mental retardation

A structured communication sampling procedure was used to measure the form and function characteristics of intentional communication acts produced by nonverbal adults with severe mental retardation. Four "contact" subjects (who communicated only with contact gestures) and 4 "distal" subjects (who used distal as well as contact gestures) participated in this study. All subjects produced communication acts that were coded as initiations, and all subjects produced protoimperative-type communication acts. However, contact subjects produced no protodeclarative-type communication acts, whereas all distal subjects produced some protodeclaratives. Distal subjects also produced significantly more repair/recast acts than did contact subjects. Other findings included a tendency for distal subjects to communicate at a higher rate, to initiate more communication acts, and to produce more accompanying wordlike vocalizations than contact subjects. These results are discussed in light of Werner and Kaplan's (1984) concept of distancing as central to symbolization. Implications for future research and for clinical practice are also discussed.     

Qualities attributed to an ideal educator by medical students: should faculty take cognizance?

Since teaching is a fundamental activity of tertiary institutions, measures need to be in place to assess the teaching quality of individual academic staff members. Few faculties, however, have objective criteria for assessing this quality. In the present study, for second-year medical students, being a good communicator was identified as the most important asset a teacher could have. Personal qualities, such as being approachable, helpful and friendly, were more highly regarded than technical issues such as being punctual and having organized lectures. This suggests that students value the teacher-learner relationship. Since the global trend of medical education is towards a more humanistic approach to patient care, medical teachers need to become educators, interacting with individual students. Educators might also have to become role models for students in terms of attitudes and ethics. Students will therefore be in the best position to judge the impact of individual educators on their development.