Combination of ultrasound and molecular testing in malignancy risk estimate of Bethesda category IV thyroid nodules: results from a single-institution prospective study.

PURPOSE: Malignancy prediction in indeterminate thyroid nodules is still challenging. We prospectively evaluated whether the combination of ultrasound (US) risk stratification and molecular testing improves the assessment of malignancy risk in Bethesda Category IV thyroid nodules. METHODS: Ninety-one consecutively diagnosed Bethesda Category IV thyroid nodules were prospectively evaluated before surgery by both ACR- and EU-TIRADS US risk-stratification systems and by a further US-guided fine-needle aspiration cytology (FNAC) for the following molecular testing: BRAFV600E, N-RAS codons 12/13, N-RAS codon 61, H-RAS codons 12/13, H-RAS codon 61, K-RAS codons 12/13, and K-RAS codon 61 point-mutations, as well as PAX8/PPARγ, RET/PC1, and RET/PTC 3 rearrangements. RESULTS: At histology, 37% of nodules were malignant. No significant association was found between malignancy and either EU- or ACR-TIRADS. In total, 58 somatic mutations were identified, including 3 BRAFV600E (5%), 5 N-RAS 12/13 (9%), 13 N-RAS 61 (22%), 7 H-RAS 12/13 (12%), 11 H-RAS 61 (19%), 6 K-RAS 12/13 (10%), 8 K-RAS 61 (14%) mutations and 2 RET/PTC1 (4%), 0 RET/PTC 3 (0%), 3 PAX8/PPARγ (5%) rearrangements. At least one somatic mutation was found in 28% and 44% of benign and malignant nodules, respectively, although malignancy was not statistically associated with the outcome of the mutational test. However, the combination of ACR-, but not EU-, TIRADS with the presence of at least one somatic mutation, was significantly associated with malignant histology (P = 0.03). CONCLUSION: US risk stratification and FNAC molecular testing may synergistically contribute to improve malignancy risk estimate of Bethesda category IV thyroid nodules.

Can misdiagnosis in pre-operative FNAC of thyroid nodule influence surgical treatment?

BACKGROUND: Pre-operative cytology in thyroid disease remains the most appropriate diagnostic test for defining the nature of a thyroid nodule before surgical excision. MATERIALS AND METHODS: We selected the most recent 825 surgical thyroid procedures performed in our institution from January 2004 to June 2007; 776 were total thyroidectomies, 23 were lobe-isthmectomies, and 26 were radical neck dissections. We distributed the data based on pre-operative cytology. Each cytological diagnosis was compared to results obtained by definitive histology. Tumors were called incidentalomas if they consisted of a neoplastic focus with a low grade of aggressiveness, as demonstrated by dimension <5 mm, non-aggressive histological subtype. RESULTS: Of the 541 cases of benign disease, 417 were confirmed as benign. The other 124 cases are listed as follows: 29 follicular adenoma; 76 papillary carcinoma (35 found as incidentalomas), and 19 follicular carcinoma (3 incidentalomas). Cytology suggestive of papillary carcinoma was correct in 95.2% of cases (119/125). The 135 tumors termed "follicular neoplasm" were staged on pathology thus: 56 adenoma (41.4%), 26 carcinoma (19.2%), 13 (9.6%) absence of follicular proliferation, 38 (28.1%) papillary follicular variant, 2 (1.4%) undifferentiated cells. Medullary carcinomas were both confirmed. The "suspicious group" exhibited no malignancy on fine needle aspiration cytology (12 of 21; 57%). CONCLUSIONS: Cytology has good reliability in malignant lesions. Incidental tumors occurring in benign disease have little impact on clinical and surgical management; "follicular neoplasm" posed two problems - the impossibility of identifying the nature of the tumor, as well as the newer difficulty in distinguishing papillary follicular subtype.

Oncocytic mucoepidermoid carcinoma of a submandibular gland: a case report and review of the literature.

This report describes the first recognized case of oncocytic mucoepidermoid carcinoma of a submandibular gland, and emphasizes the role of immunohistochemical study in the correct diagnosis of this tumour. This is only the second case in which this tumour has appeared as a completely cystic lesion. A review of the literature was carried out to clarify the clinical and pathological features of this rare malignancy.

Ultrasound-guided fine-needle capillary biopsy of thyroid nodules, coupled with on-site cytologic review, improves results.

Fine-needle aspiration biopsy represents the most reliable test for cytologic evaluation of thyroid nodules. However, inadequate samples may occur leading to a repetition of the procedure with the consequence of patients' discomfort and poor compliance. In this paper, we present results from biopsy of thyroid nodules obtained by combining: (1) ultrasound (US) guidance, (2) no-aspiration technique, and (3) on-site review of specimens. A total of 465 nodules were biopsied in 307 patients. Solitary nodules and multinodular goiter were present in 36.8% and 63.1% of patients, respectively. After collection, each sample was smeared in duplicates, one of which was stained with hematoxylin and checked on-site by a cytopathologist. In cases of inadequate smears, biopsies were immediately repeated. All slides were then processed for final cytologic results, which were reported as benign in 427 nodules (91.8%), malignant in 12 nodules (2.5%), with follicular proliferation or suspicious for malignancy in 23 nodules (4.9%). Inadequate final cytology was reported in 3 nodules (0.6%). No statistically significant relationship was found between nodule size and adequacy of specimens. We conclude that the combination of US guidance, capillary collection with no-aspiration technique, and on-site review of slides, characterizes an advantageous method for thyroid nodule fine-needle biopsy.

[Breast carcinoma in accessory gland: a case report]. / Il carcinoma mammario insorto su tessuto ghiandolare soprannumerario: a proposito di un caso.

The Authors we report the case of a 50 year old woman with accessory breast cancer in the thoracic region. The examination revealed a mass of 1 cm diameter and a tumorectomy showed a ectopic breast with an intraductal carcinoma. Nodal dissection, chemo-, radio- and hormonal therapy there performed. The follow up didn't show a relapse of breast carcinoma after 5 years.

Effects of vitamin A administration on serum thyrotropin concentrations in healthy human subjects.

Retinoids play an important role in the regulation of normal growth and development. Their biological action is mediated by a nuclear receptor that belongs to the steroid/thyroid hormone receptors superfamily. Retinoic acid has been shown to inhibit the secretion and synthesis of thyrotropin (TSH); however, little is known on the effects of retinoids on TSH secretion in normal human subjects. In the present study, we evaluated serum TSH concentration following both vitamin A (vit A) and the combined vit A and triiodothyronine (T(3)) administration. Basal and thyrotropin-releasing hormone (TRH)-stimulated TSH serum concentrations were measured in healthy young subjects in the following experimental conditions: (1) after 10 days of treatment with vit A orally administered as retinol at a dose of 50,000 IU/d; (2) after 10 days of oral placebo (PL) treatment; (3) after 1 hour from the administration of 40 mg T(3) at the end of 10 days of PL treatment; and (4) after 1 hour from the administration of 40 mg T(3) at the end of 10 days of vit A treatment. Serum TSH concentrations were also measured during vit A administration in healthy elderly subjects according to the following protocol: (1) after 10 days of treatment with PL; and (2) after 10 days of treatment with vit A at the same dose used for young subjects. In young subjects, basal serum TSH levels were found to be similar in the 4 different treatment conditions. In the same group of subjects, each of the 4 experimental conditions induced an increase in serum TSH, which rose from basal values of 1.80 +/- 0.31 to a peak of 11.92 +/- 1.75 microIU/mL (P <.001) during the PL treatment, from basal values of 1.81 +/- 0.22 to a peak of 10.81 +/- 1.00 microIU/mL (P <.001) during vit A treatment, from basal values of 1.72 +/- 0.28 to a peak of 9.92 +/- 1.10 microIU/mL (P <.001) during PL + T(3) treatment, and from basal values of 1.79 +/- 0.30 to a peak of 9.51 +/- 1.12 microIU/mL (P <.001) during vit A + T(3) treatment. The 2-way repeated measure analysis of variance revealed no significant differences among treatments. In old subjects, basal serum TSH levels were similar in the 2 experimental conditions and were not different from those observed in young subjects. In these subjects, serum TSH levels increased significantly in response to the TRH stimulus from basal values of 2.16 +/- 0.3 to a peak of 10.27 +/- 0.55 microIU/mL (P <.001) during PL treatment and from basal values of 2.10 +/- 0.51 to a peak of 7.82 +/- 1.4 microIU/mL (P <.001) during vit A treatment. No significant effects of treatment were found in this group of subjects on TRH-induced TSH levels; however, TSH responses were somewhat lower during vit A treatment with a difference close to statistical significance. These results suggest that TSH secretion is poorly affected by vit A administration in healthy human subjects; the data also indicate that any cooperation between T(3) and vit A is unlikely to occur in the regulation of TSH secretion.

[Stereotactic fine-needle aspiration biopsy (FNAB) of nonpalpable breast lesions: cyto-histological correlations]. / Agoaspirazione (FNAB) mediante centratura stereotassica di lesioni mammarie non palpabili: correlazioni cito-istologiche.

There are not complete consensus if mammographically guided FNABs of nonpalpable breast lesions can replace open biopsy. To elucidate this problem, we have reviewed the efficacy of stereotactic FNAB in a series of 502 cases of nonpalpable lesions observed in a period from 1990 to 1994, with a immediate cytologic control of adequacy of material. In 144 patients of the lesion is achieved with 4% sterile coal localisation and an open biopsy of the area performed. In each case cytologic findings, with a brief description of probable histotype of the lesion, are correlate with surgical pathologic diagnosis, with a comparison between two time period (1990-92; 1993-94). In our study particularly ductal and lobular hyperplasia (with or without atypia) restrict the efficiency of the FNAB. In fact the specificity varies from 83.3% to 90.3%, the sensitivity from 78.7% to 77.8%, positive predictive value from 86.0% to 90.3%, negative predictive value from 75.6% to 70% and diagnostic accuracy from 80.0 to 82.4%, considering ductal and lobular hyperplasias as true negatives or true suspects. Cytologically we have 2 false positive in the first period of time, 3 false suspects in the second period of time and 7 false negatives. However benign/malign biopsy ratio is well (0.97). Moreover histopathologic informations of cytological diagnosis is variable according the histotype of the lesion. In conclusion our study confirm that FNAB is an reliable method that avoid unnecessary biopsy but is insufficiently sensitive to replace open biopsy of nonpalpable breast lesions, also with an immediate cytological control of adequacy of aspirate.