Pediatric thyroid nodules: management in the era of fine needle aspiration

BACKGROUND/PURPOSE: Thyroid nodules are rare in children. The need to uncover malignancy is the most challenging dilemma in management. The aim of this report was to determine whether management of pediatric thyroid nodules has changed in the era of fine-needle aspiration (FNA) cytology. METHODS: Twenty-four children with thyroid nodules comprised the study group. Demographic characteristics, clinical manifestations, imaging results, FNA cytology results, surgical therapy, complications, and pathological reports were reviewed retrospectively. FNA cytology results were categorized as either benign, malignant, suspicious, or insufficient. RESULTS: Girls outnumbered boys (five to one) with a mean age of 14.9 years. Nineteen nodules were benign and five malignant. Malignancy was characterized by localized tenderness, multiglandular appearance, and fixation to adjacent tissues. Ultrasound scans and nuclear scans gave no clue toward management because cystic, hot, and warm nodules figured among malignant cases. FNA in 18 children achieved 80% accuracy, 60% sensitivity, 90% specificity, 75% positive, and 81% negative predictive value. Physical examination findings, persistence of the nodule, and progressive growth decided for surgery in most children. CONCLUSIONS: FNA is a safe adjunctive test that plays a minor role in the decision to withhold surgery. Its greatest strength is to resolve, in case of suspicious or malignant cytology, that a more radical procedure will be needed. Clinical judgement as determined by serial physical findings continues to be the most important factor in the management of thyroid nodules in children.     

How I study thyroid pathology using ultrasonography-guided needle biopsy

From a retrospective study of 259 files, the authors stress the value of US-guided thyroid cytoponction and its essential role in case of thyroid cancer suspicion. This very specific and inexpensive method fits perfectly into the other exploration techniques. It is the deciding factor in the thyroid nodule differential diagnostic and therapeutic planning.     

Role of ultrasound-guided fine-needle aspiration biopsy in evaluation of nonpalpable thyroid nodules

To determine the role of ultrasound-guided fine-needle aspiration biopsy (US-FNAB) in the evaluation of incidentally diagnosed nonpalpable thyroid nodules (NP-TN), we compared the diagnostic yield of US-FNAB in NP-TN larger than 10 mm in diameter, with palpation-guided (P-FNAB) in palpable thyroid nodules (P-TN) in the same hospital setting. Of 108 consecutive patients with NP-TN (female/male: 97/11, age: 55.2 +/- 14.3, mean +/- SD), malignancy was identified in 8 patients (7 with thyroid papillary carcinoma, 4 of which had extrathyroidal spread, and 1 patient had metastasis of pulmonary adenocarcinoma). Male gender was associated with higher prevalence of malignancy (p = 0.09) while calcification and/or cystic degeneration of the nodule did not predict the cytological findings. Malignancy was identified in 16 of 151 consecutive patients with P-TN (female/male: 139/12, age: 44.1 +/- 9.5, mean +/- SD) indicating a similar rate of malignancy in both NP-TN and P-TN. In the P-TN group thyroid cancer was more common in males (p = 0.007), and the US properties of the nodule did not predict its cytological diagnosis. In conclusion, because similar rates of cancer are detected by FNAB in both NP-TN and P-TN, an FNAB is recommended for NP-TN larger than 10 mm.     

Histocytological correlation in fine needle aspiration biopsy of the thyroid gland]

Monoclonal antibodies are useful probes for analyzing cells at the molecular level at various developmental stages. Although identification of the genes encoding tissue- and stage-specific antigens could be informative for further molecular analysis, gene cloning is usually a time-consuming step, particularly when a monoclonal antibody is the only probe available. We describe here an immunocytochemical method for preliminary and immediate analysis of the regulation of antigen-coding genes. mRNAs purified from stage 27 and 38 Xenopus tadpoles were fractionated by size and injected into newt oocytes, from which frozen sections were prepared for immunostaining with tissue-specific monoclonal antibodies. Both of the antigens we tested, which are early markers for differentiating epidermal cells of Xenopus tadpoles, were detected in mRNA injected oocytes, but not in control oocytes. Immunostaining for each of the antigens showed that their relative levels in stage 27 and 38 tadpole tissue were reflected in those oocytes injected with mRNA purified from tadpoles of the respective stages. We suggest that this oocyte translation system combined with immunostaining provides for rapid analysis of changes in levels of antigen coding mRNAs throughout development.     

The use of fine needle aspiration biopsy in the management of thyroid disease

Fine needle aspiration biopsy is now a first line investigation in thyroid disease. The purpose of this study was to evaluate the results of this technique in comparison with routine histopathology. A total of 593 aspirations over a four year period were included. There were 390 (65.7%) solitary nodules, 124 (20.9%) multinodular goiters, 66 (11.1%) diffuse goitres and 13 (2.2%) recurrent post thyroidectomy nodules. Radioisotope scanning in 386 cases showed 325 (84.2%) cold nodules, 54 (14.0%) warm nodules and 7 (1.8%) hot nodules. There were 458 (77.2%) colloid goitres and cysts, 14 cases of thyroiditis (2.2%) and 30 malignancies diagnosed on fine needle aspiration biopsy. In 19 cases (3.2%) a diagnosis of follicular neoplasm and in 29 cases (4.9%) a diagnosis of suspicious aspirate was made. Histological results were available in 176 cases. In 108 cases findings of histology and FNAB were compared with radioisotope scanning. A sensitivity of 92.8% and 42.8%, a specificity of 90.1% and 98.7% and accuracy index of 90.3% and 94.3% was found, when considering suspicious cases alternatively as positives and negatives. Surgery was recommended in all suspicious cases to prevent reduction in sensitivity of the technique. Fine needle aspiration biopsy was found to be a highly effective procedure which can obviate a lot of unnecessary surgery in thyroid lesions.     

Management of thyroid nodules

Clinically apparent thyroid nodules occur in about 5 percent of the population. Because most patients with thyroid nodules present initially to their primary care physician, family physicians should have a thorough understanding of the diagnosis and treatment of thyroid nodules. The history and physical examination may be helpful in detecting thyroid nodules but are not useful in predicting malignancy. Furthermore, laboratory studies, ultrasonography and nuclear medicine scans do not reliably differentiate between benign and malignant thyroid nodules. In most cases, fine-needle aspiration biopsy can accurately identify malignant thyroid nodules. Fine-needle aspiration biopsy is safe and can be performed in an office setting.     

Suppressive therapy with levothyroxine for solitary thyroid nodules: a double-blind controlled clinical study and cumulative meta-analyses

Levothyroxine suppressive treatment of solitary thyroid nodules is controversial. A 1-yr prospective randomized placebo-controlled trial was conducted to evaluate the effect of T4 on nodule volume and bone mineral density, and meta-analyses were performed to examine the quantitative synthesis of data from similar designed controlled trials. Forty-five euthyroid patients (42 females, age range: 19-73 yr) with single, colloid nodules were randomized to T4 (21 patients, 2.7 +/- 0.3 microg/kg, TSH < 0.3 microIU/mL) and placebo. Ultrasonography and densitometry were performed at baseline and repeated after treatment. Mean nodule volume or bone mineral density did not change. Nodule reduction more than 50% was observed in 6 of 21 treated patients and 2 of 24 placebo patients (P = 0.12). This study and another 6 prospective controlled trials (minimum 6 months, ultrasonographic nodule evaluation) were included in cumulative meta-analyses (risk-difference method). Nodule volume decreased more than 50% in a significantly higher percentage of patients in the T4 groups (risk difference, 16.7%; 95% confidence intervals, 5.8-27.6%). Four trials evaluated nodule growth with homogeneous results (Q = 0.42). Nodule volume increased more than 50% in a significantly smaller percentage of patients treated with T4 (risk difference, 9.7%; 95% confidence intervals, 2.0-17.4%). In conclusion, T4 treatment is associated with decreased nodule volume in 17% of patients and may inhibit growth in another 10%.     

Prevalence of thyroid cancer in hot nodules

Five parkinsonian patients with motor fluctuations and dyskinesia after long-term treatment with levodopa were treated with subcutaneous lisuride infusion (0.24-0.42 mg/day) together with oral levodopa for a mean period of 27 (range 13-36) months. All 5 patients showed marked initial improvement in mobility. Mild psychiatric side effects were observed in three patients; however, these side effects disappeared with reduction in the dosage of lisuride to 0.06 mg per day without a significant increase in motor fluctuations. A low dose of subcutaneous lisuride infusion with oral levodopa is an effective treatment for fluctuations of motor performance in parkinsonian patients without adverse psychiatric effects.     

Clinical significance of clonality in thyroid nodules

BACKGROUND: Many different neoplastic and hyperplastic thyroid diseases present with clinically apparent thyroid nodules. Clonality analysis indicates whether a nodule arises from the polyclonal proliferation of a group of cells or forms a clone from a genetically altered cell and thus provides objective information on the origin of the thyroid nodules. Clonality was studied in thyroid nodules using the polymerase chain reaction (PCR) assay in the X-linked human androgen receptor (HUMARA) gene by random X chromosome inactivation in women. METHODS: DNA samples were obtained from 28 nodules in 21 women. All nodules and non-tumour thyroid tissues were fractioned selectively under a cryostat. Genomic DNA was isolated and digested with HhaI. PCR amplification of the HUMARA locus was performed using PCR mixtures containing [alpha-32P]2'-deoxycytidine 5'-triphosphate. The PCR products were analysed by denaturing gel electrophoresis. RESULTS: The HUMARA alleles were heterogeneous in 18 of 21 patients. Among the 23 nodules from 18 patients, all of the eight papillary thyroid carcinomas were monoclonal. Two solitary nodules from follicular adenomas were monoclonal. Of the 13 follicular nodules from nodular goitres, ten were polyclonal and three were monoclonal. The monoclonal follicular nodules were larger in size (3.5 versus 2.0 cm, P< 0.05) and had a tendency towards more cystic changes than polyclonal nodules. CONCLUSION: PCR-based clonality study of thyroid nodules may help to distinguish hyperplastic from neoplastic nodules.     

Macrofollicular variant of papillary thyroid carcinoma diagnosed by fine needle aspiration biopsy: a case report

BACKGROUND: Macrofollicular variant of papillary thyroid carcinoma (PTC) is an uncommon, recently described thyroid tumor. By frozen section it can be confused easily with goiter or macrofollicular adenoma. CASE: A 41-year-old female presented with a huge mass in the right thyroid lobe, cold on scintigraphy. By fine needle aspiration fluid was obtained. Smears of the sediment of the fluid showed epithelial cells with morphologic features diagnostic of PTC. Frozen section diagnosis was benign. CONCLUSION: This is the first reported case of macrofollicular variant of PTC diagnosed preoperatively by cytology. In our case the cytology was similar to that of cystic PTC.     

Jamshidi needle biopsy of bone lesions

The technique and advantages of using a Jamshidi needle for skeletal biopsies are described, together with the results of 50 consecutive biopsies. A combined clinical, radiological and pathological approach to the lesions can provide the diagnosis in the majority of patients.     

Transcutaneous needle biopsy of the lung

Spinal muscular atrophy (SMA) is a frequent autosomal recessive neurodegenerative disorder leading to weakness and atrophy of voluntary muscles. The survival motor neuron gene (SMN) is a strong candidate for SMA and present in two highly homologous copies (telSMN and cenSMN) within the SMA region (5q11.2-q13.3). More than 90% of SMA patients show homozygous deletions of at least exon 7 of telSMN, whereas absence of cenSMN seems to have no clinical consequences. In 23 non-deleted SMA patients, we searched for intragenic mutations of the SMN genes in exons 1-7 and the promotor region by single strand conformation analysis. We identified two different missense mutations, S2621 and T2741, in exon 6 of telSMN in three independent SMA families, providing further evidence for the telSMN gene as a SMA determining gene. Both mutations, as well as two previously described mutations (Y272C and G279V) are located within a highly conserved interval from codon 258 to codon 279 which seems to be an important functional domain of the telSMN protein. Recently, this region has been shown to contain a tyrosine/glycine-rich motif, which is also present in various RNA binding proteins, suggesting a potential role of SMN in RNA metabolism. Missense mutations might be useful for in vivo and transgenic experiments and further investigations on understanding the function of the telSMN protein.     

Percutaneous needle muscle biopsy in the horse

The use of the technique of percutaneous needle biopsy in obtaining skeletal muscle samples in the horse is described. The biochemical, ultrastructural and histochemical investigations that can be carried out on this biopsy specimen are outlined. Analyses performed on the specimen may be used to obtain information on racing potential and state of fitness. These studies on normal horses will provide information for future investigations into the structural and biochemical alterations in muscle disorders in the equine.     

Hormonal suppressive therapy of thyroid nodules

In this article we report on a 43-year-old man, who had been treated with two cortisone injections containing soja bean oil for epicondylitis humeri radialis. Four weeks after the second injection necrotized fat which had been extracted surgically was sent to us for histological examination. We could show a calcifying collagen fibre necrosis being cleared by a granulomatous reaction and resorbed by granulation tissue. The calcifying necrosis of collagen fibres might have been induced by soja bean oil which were used as carrier of the drug.     

Reliability of skin biopsy pathology

BACKGROUND: The diagnosis of skin disease by histologic examination is regarded as the reference standard upon which therapy and follow-up are determined. Our study investigated the reliability of skin biopsy diagnosis requested by family physicians and physicians' assistants. METHODS: Biopsy diagnoses by a community-based pathology group were reinterpreted by our study dermatopathologist on a sample of 119 skin biopsies randomly selected from the 1844 biopsies performed by family physicians and physicians' assistants at a large Washington State health maintenance organization during a 4 1/2-year period. RESULTS: There were 107 exact matches and 3 mismatches of premalignant lesions and 6 mismatches of benign diagnoses. In addition, two melanomas diagnosed by the community-based pathologists were interpreted as benign by our study dermatopathologist. A third melanoma diagnosed by the community-based group was interpreted as a poorly differentiated squamous cell cancer by the university dermatopathologist. The weighted kappa, 0.83, indicated excellent interrater agreement. CONCLUSION: Although our study showed excellent interrater concordance of skin biopsy interpretation, there was disagreement about three melanomas between a community-based general pathology group and our study dermatopathologist. The melanoma disagreement is consistent with previous studies that found poor interrater agreement for early melanomas. The community-based pathologists were uncertain about two of these melanomas, and as part of their quality control and review procedures requested confirmation by an expert pathologist, who agreed with the melanoma diagnosis. Family physicians are justified in requesting a second opinion (if not automatically requested by a community laboratory) when the histopathologic diagnosis is not in concordance with the clinical history or impression or when the pathologist is unsure of the diagnosis.