Thyroid nodules are a common clinical problem, and fine-needle aspiration biopsy (FNAB) is widely used for its evaluation. Only 5% are malignant, being papillary carcinoma (PC) the most frequent neoplasia. Approximately 20% are classified as indeterminate or suspicious for malignancy. Gene-expression pattern may be useful for diagnosing PC in difficult or ambiguous cases. In our prior study, we were able to apply RT-PCR method in a series of routinely performed FNAB of thyroid nodules using individual, residual samples. In this study, a total of 70 thyroid samples were evaluated for the expression of MPPED2, H/HBA2, MET, FN1, GALE, and QPCT genes, including 24 cases of frozen thyroid tissue, 12 nodular hyperplasia and 12 PC, and the 46 consecutive thyroid FNAB samples, previously analyzed (3 positive, 10 indeterminate and 32 negative for malignancy, and 1 insufficient). FN1, GALE, MET, and QPCT mRNA expression were significantly different in benign and malignant samples, with similar pattern of overexpression in aspirates compared to frozen tissue. H/HBA2 and MPPED2 expression varied. Histological correlation was possible in five indeterminate cases, revealing one PC and four benign lesions. In conclusion, FN1, GALE, MET, and QPCT were significantly overexpressed in thyroid PC. RT-PCR method could be applied to routine FNAB, showing a similar pattern of overexpression. Despite the small number of cases evaluated, our results suggest that molecular analysis may be of assistance in patients with indeterminate/suspicious cytology, adding elements for preoperative diagnosis and better management of these patients.
images in clinical medicineT h e n e w e ng l a n d j o u r na l o f m e dic i n e n engl j med 367;9 nejm.org august 30, 2012 850A 42-year-old man had acute respiratory failure after receiving all-trans retinoic acid for the treatment of acute promyelocytic leukemia. Computed tomography (CT) of the chest revealed multiple nodular lesions (Panel A), which on biopsy showed invasive aspergillus species. The patient was treated with antifungal therapy and received mechanical ventilation. His clinical condition was improving when he had an episode of sudden and severe hemoptysis, followed by cardiac arrest. He was resuscitated, but subsequently a severe neurologic deficit developed. A brain CT scan revealed cerebral air embolism, especially in the anterior arterial-circulation territory, with accompanying cerebral edema (Panel B). Cerebral air embolism can be caused by positive-pressure maneuvers performed during cardiac resuscitation, lung biopsy, and the placement of venous catheters in the presence of a patent foramen ovale. Lung biopsy was not performed in this patient, and venous catheters were already in place. Cardiac resuscitation maneuvers were the likely cause of the condition in this patient. Diffuse cerebral edema developed, and the patient was declared brain dead on the fifth day after diagnosis.
Thyroid nodules are frequent in clinical practice and fine-needle aspiration biopsy (FNAB) is widely used for its evaluation, but approximately 20% of the cases are diagnosed as indeterminate for malignancy. Aspirates from thyroid nodules can be used for ancillary methods, but molecular techniques are not routinely applied to these specimens. Forty-six consecutive, routinely performed, FNAB of thyroid nodules were evaluated for the feasibility of applying RT-PCR method. RNA was extracted from 1 of 3 fresh residual samples and analyzed to determine its pureness, integrity, and concentration. Cellularity was adequate in all 46, except one, specimens analyzed, scored as 0, 1+, 2+, 3+, and 4+ in 1, 10, 14, 9, and 8 cases, respectively. Thirty-three nodules measured less than 1.5 cm. Cytological diagnosis was positive for malignancy in 3 cases, indeterminate for malignancy in 3, most probably benign follicular lesion in 7, negative for malignancy in 32, and suggestive of benign follicular lesion in 1. Good quality RNA was successfully isolated in 45/46 (97.8%) samples, with an average RNA concentration of 14 ng/microl and detection of B2M mRNA in 97.7% (44/45). There was no significant correlation between RNA concentration and nodule size or specimen cellularity. In conclusion, molecular analysis using individual, residual samples of thyroid nodules aspirates is feasible and could be employed for molecular preoperative studies in the future, adding elements for final cytological diagnosis of indeterminate cases, without altering the routine procedure.
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