Early diagnosis by FNA cytology should not influence the outcome of differentiated thyroid cancer.

In oncology, the early cancer detection is recognized as associated with good patient's prognosis. Then, one could expect that differentiated thyroid carcinoma (DTC) undergone fine-needle aspiration cytology (FNA) early have better outcome. Aim of this study was to investigate if DTC prognosis is improved by early FNA diagnosis. DTCs followed-up at our institution were included. Information about initial management of thyroid lesion, FNA, surgery, and postoperative follow-up was collected. Cytologies were classified according to British Thyroid Association (BTA). The final series comprised 219 DTCs, of which 22 (10%) recurred. The length of time between nodule appearance and cancer treatment was significantly (p<0.0001) shorter in patients who had undergone FNA than those who had not. In the FNA group, 73 patients underwent biopsy within six months, 25 at 7-12 months, and 43 after at least one year. Regardless of this highly significant (p<0.0001) difference, the results of TNM staging and cancer recurrence rate were no different between these three subgroups. This result was confirmed in DTCs larger than 1 cm submitted to FNA within 12 months or later. When we evaluated the impact of nodule's presentation on DTC outcome, clinically discovered cancers were significantly associated with relapse (OR 2.81) and advanced TNM stages (p=0.03). These data show a lack of clinical impact of the delayed diagnosis of DTC. Also, the postoperative outcome of these patients should not be influenced by the timing of FNA. Instead, DTC patients with preoperative clinical nodule appearance should be considered at higher risk of relapse.

Detection rate of FNA cytology in medullary thyroid carcinoma: a meta-analysis.

BACKGROUND: The early detection of medullary thyroid carcinoma (MTC) can improve patient prognosis, because histological stage and patient age at diagnosis are highly relevant prognostic factors. As a consequence, delay in the diagnosis and/or incomplete surgical treatment should correlate with a poorer prognosis for patients. Few papers have evaluated the specific capability of fine-needle aspiration cytology (FNAC) to detect MTC, and small series have been reported. This study conducts a meta-analysis of published data on the diagnostic performance of FNAC in MTC to provide more robust estimates. RESEARCH DESIGN AND METHODS: A comprehensive computer literature search of the PubMed/MEDLINE, Embase and Scopus databases was conducted by searching for the terms 'medullary thyroid' AND 'cytology', 'FNA', 'FNAB', 'FNAC', 'fine needle' or 'fine-needle'. The search was updated until 21 March 2014, and no language restrictions were used. RESULTS: Fifteen relevant studies and 641 MTC lesions that had undergone FNAC were included. The detection rate (DR) of FNAC in patients with MTC (diagnosed as 'MTC' or 'suspicious for MTC') on a per lesion-based analysis ranged from 12·5% to 88·2%, with a pooled estimate of 56·4% (95% CI: 52·6-60·1%). The included studies were statistically heterogeneous in their estimates of DR (I-square >50%). Egger's regression intercept for DR pooling was 0·03 (95% CI: -3·1 to 3·2, P = 0·9). The study that reported the largest MTC series had a DR of 45%. Data on immunohistochemistry for calcitonin in diagnosing MTC were inconsistent for the meta-analysis. CONCLUSIONS: The presented meta-analysis demonstrates that FNAC is able to detect approximately one-half of MTC lesions. These findings suggest that other techniques may be needed in combination with FNAC to diagnose MTC and avoid false negative results.

Calcitonin measurement in aspiration needle washout fluids has higher sensitivity than cytology in detecting medullary thyroid cancer: a retrospective multicentre study.

OBJECTIVE: Only few studies analysed the capability of cytology in detecting medullary thyroid cancer (MTC), and they reported a low accuracy of this diagnostic technique. Recently, calcitonin (CT) measurement in aspiration needle washout (FNA-CT) of thyroid and neck lesions has been reported as a sensitive tool for MTC. The aim of this study is to compare the sensitivity of FNA-CT and cytology in detecting MTC and to assess a cut-off value of FNA-CT for clinical practice. PATIENTS: Thirty-eight MTC lesions from 36 patients were retrospectively studied, diagnosed and treated in four different centres. Furthermore, 52 nonmedullary lesions from subjects undergone biopsy following increased serum CT were collected as a control group. RESULTS: Cytology detected MTC in 21/37 lesions with 56·8% sensitivity. The median FNA-CT value was 2000 pg/ml (range 58-10 000 pg/ml) in MTC and 2·7 pg/ml (range <2-13 pg/ml) in controls (P < 0·001). Using a cut-off of 39·6 pg/ml, MTC lesions could be identified with 100% sensitivity and specificity. As the most important finding, 14 histologically proved MTC lesions could be detected by FNA-CT, despite they were cytologically diagnosed as benign or nonconclusive. CONCLUSIONS: This study shows, as the first in a multicentre series, that FNA-CT sensitivity is higher than that of cytology in diagnosing MTC. To avoid false-negative MTC by cytology, CT measurement in aspiration needle washout is to be performed in all patients undergoing biopsy following high serum CT.

The use of core needle biopsy as first-line in diagnosis of thyroid nodules reduces false negative and inconclusive data reported by fine-needle aspiration.

BACKGROUND: The reported reliability of core needle biopsy (CNB) is high in assessing thyroid nodules after inconclusive fine-needle aspiration (FNA) attempts. However, first-line use of CNB for nodules considered at risk by ultrasonography (US) has yet to be studied. The aim of this study were: 1) to evaluate the potential merit of using CNB first-line instead of conventional FNA in thyroid nodules with suspicious ultrasonographic features; 2) to compare CNB and FNA as a first-line diagnostic procedure in thyroid lesions at higher risk of cancer. METHODS: Seventy-seven patients with a suspicious-appearing, recently discovered solid thyroid nodule were initially enrolled as study participants. No patients had undergone prior thyroid fine-needle aspiration/biopsy. Based on study design, all patients were proposed to undergo CNB as first-line diagnostic aspiration, while those patients refusing to do so underwent conventional FNA. RESULTS: Five patients refused the study, and a total of 31 and 41 thyroid nodules were subjected to CNB and FNA, respectively. At follow-up, the overall rate of malignancy was of 80% (CNB, 77%; FNA, 83%). However, the diagnostic accuracy of CNB (97%) was significantly (P < 0.05) higher than that of FNA (78%). In one benign lesion, CNB was inconclusive. Four (12%) of the 34 cancers of the FNA group were not initially diagnosed because of false negative (N = 1), indeterminate (N = 2) or not adequate (N = 1) samples. CONCLUSIONS: CNB can reduce the false negative and inconclusive results of conventional FNA and should be considered a first-line method in assessing solid thyroid nodules at high risk of malignancy.

Papillary thyroid carcinoma: ≤ 10 mm does not always mean pN0. A multicentric real-world study.

The incidence of papillary thyroid carcinoma (PTC) is increasing and PTC ≤ 10 mm (PTMC) accounts for most new diagnoses. PTMCs are not always low risk, as detection of lymph nodes metastasis (LNM) may occur. The purpose of the study was to analyze the clinical pattern, frequency, and independent risk factors of patients with PTMC and LNM. From January 2022 to June 2023, PTCs managed at CTO Hospital, Rome; Policlinico Vanvitelli, Naples; and Garibaldi Nesima Hospital, Catania were included. PTC management followed the same diagnostic-therapeutic procedures according to the ATA guidelines. Variables such as age, sex, maximum diameter, histologic evidence of LNM (HELNM +), Hashimoto's thyroiditis (HT), multifocality, capsule invasion, and histological subtype were considered. PTCs were divided according to HELNM and size. Two hundred ninety-eight PTCs were included. PTMCs were 136 (45.6%) and LNM occurred in 27.2% of them. In the HELNM + group, analysis of PTMC vs 'MacroPTC' (PTC > 10 mm) did not show any statistical difference. Multivariate regression revealed that young age (OR 0.93; CI 95% 0.90-0.96; p < 0.01) and male sex (male OR 3.44; CI 95% 1.16-10.20; p = 0.03) were the only independent risk factors for HELNM + in PTMC. The risk of LNM in PTMC is not negligible; therefore, a careful evaluation by an expert thyroidologist is mandatory for patients with small thyroid nodule, especially in younger and male patients before excluding surgery. In the future, new tools are needed to detect early PTMC with LNM before surgery.

SARS-CoV-2-Related Olfactory Dysfunction: Autopsy Findings, Histopathology, and Evaluation of Viral RNA and ACE2 Expression in Olfactory Bulbs.

BACKGROUND: The COVID-19 pandemic has been a health emergency with a significant impact on the world due to its high infectiousness. The disease, primarily identified in the lower respiratory tract, develops with numerous clinical symptoms affecting multiple organs and displays a clinical finding of anosmia. Several authors have investigated the pathogenetic mechanisms of the olfactory disturbances caused by SARS-CoV-2 infection, proposing different hypotheses and showing contradictory results. Since uncertainties remain about possible virus neurotropism and direct damage to the olfactory bulb, we investigated the expression of SARS-CoV-2 as well as ACE2 receptor transcripts in autoptic lung and olfactory bulb tissues, with respect to the histopathological features. METHODS: Twenty-five COVID-19 olfactory bulbs and lung tissues were randomly collected from 200 initial autopsies performed during the COVID-19 pandemic. Routine diagnosis was based on clinical and radiological findings and were confirmed with post-mortem swabs. Real-time RT-PCR for SARS-CoV-2 and ACE2 receptor RNA was carried out on autoptic FFPE lung and olfactory bulb tissues. Histological staining was performed on tissue specimens and compared with the molecular data. RESULTS: While real-time RT-PCR for SARS-CoV-2 was positive in 23 out of 25 lung samples, the viral RNA expression was absent in olfactory bulbs. ACE2-receptor RNA was present in all tissues examined, being highly expressed in lung samples than olfactory bulbs. CONCLUSIONS: Our finding suggests that COVID-19 anosmia is not only due to neurotropism and the direct action of SARS-CoV-2 entering the olfactory bulb. The mechanism of SARS-CoV-2 neuropathogenesis in the olfactory bulb requires a better elucidation and further research studies to mitigate the olfactory bulb damage associated with virus action.

Primary Thyroid Lymphoma: How Molecular Biology and Ancillary Techniques Can Help the Cytopathologist Overcome This Diagnostic Challenge.

Primary thyroid lymphoma (PTL) occurs rarely, its diagnosis is a challenge, and the prognosis of these patients depends on the time of diagnosis. Even though fine-needle aspiration cytology (FNAC) is recognized as the most accurate tool for detecting thyroid malignancies, its sensitivity for PTL is poor. Both clinical and ultrasound presentation of PTL can be atypical, and laboratory tests fail to furnish relevant data. Consequently, the reliability of a cytopathologist facing PTL can be poor, even when he is aware of its clinical information. In addition, the cases described in the literature are extremely rare and fragmentary, and consequently, the molecular data currently available for this neoplasm are practically negligible. Here, we present a case report in order to discuss the intrinsic limitations in achieving a final diagnosis of PTL and how using molecular diagnostics to identify potential mutational models can improve the evaluation of this neoplasm.

Testing for BRAF (V600E) Mutation in Thyroid Nodules with Fine-Needle Aspiration (FNA) Read as Suspicious for Malignancy (Bethesda V, Thy4, TIR4): a Systematic Review and Meta-analysis.

In patients with thyroid fine-needle aspiration (FNA) report of suspicious for malignancy (SFM), both lobectomy and thyroidectomy might be considered. BRAF mutation analysis could guide towards accurate surgical therapy. The primary outcome was the reliability of BRAF (V600E) in detecting malignancy in nodules with FNA reading of SFM. The secondary outcome was to analyze its positive predictive value (PPV) and negative predictive value (NPV) considering the surgical histology as gold standard. A literature search of online databases was performed in June 2019. BRAF prevalence among thyroid nodules with FNA read as SFM according to the most popular classification systems (i.e., Bethesda V, Thy4, TIR4 category) was searched. The random-effects model was used. Three hundred sixty original articles were identified and 34 were finally included in the study. There were 1428 thyroid nodules with FNA read as SFM and 1287 (90.1%) lesions underwent surgery with a cancer rate 89.6%. The pooled prevalence of BRAF (V600E) mutation among all nodules with SFM cytology was 47% (95% CI = 40 to 54, I2 = 85.5%). Pooled PPV and NPV of BRAF testing were 99% (95% CI, 97-99) and 24% (95% CI, 16-32), respectively. BRAF (V600E) mutation was found in about one in two nodules with thyroid FNA read as SFM, its PPV to detect cancers was excellent, and its NPV was very poor. The routine BRAF testing in FNA read as SFM cannot be recommended. BRAF (V600E) test may be useful to extend surgical approach in selected cases with further suspicious clinical/ultrasound features.

Morphometric analysis of atypical glandular cells correctly classifies normal, reactive, and atypical cells in cervical smears.

The 2014 Bethesda System diagnostic criteria for atypical glandular cells (AGC) aid in the classification of atypical cells in cervical cytology. Anyway, AGC diagnosis remains challenging, due to low frequencies of this finding (approximately 0.5%-1% of Pap test results), abundance of AGC mimics, and significant interobserver variability. We developed an algorithm based on nuclear areas parameter that can help to differentiate AGC from Normal and Reactive glandular cells. Nuclear areas and perimeters were measured on 16 Pap smears with AGC and 18 with Reactive glandular cells of women aged between 30 and 77. Glandular cells from nonpathological Pap smears were used as controls. For each case, the means, medians, standard deviations, and the minimum and maximum values of both nuclear areas and perimeters of the cells of interest were calculated. The nuclear area analysis showed a 100% specificity in discriminating Normal from Altered cells (either Reactive or AGC), whereas the nuclear perimeter analysis showed a lower specificity (87.5%). Both nuclear area and perimeter variability analysis resulted in high specificity values in distinguishing Reactive cells from AGC. Therefore, a stepwise two-step algorithm using nuclear areas to discriminate Normal from Altered cells, and nuclear area variability to distinguish Reactive from AGC, allowed us to reliably classify the cells into these three categories. The morphometric analysis of nuclear area is a valuable and reliable aid in AGC diagnosis and standardization, easily integrable into common automatic algorithms.

Use of fine-needle aspirate calcitonin to detect medullary thyroid carcinoma: A systematic review.

BACKGROUND: The measurement of calcitonin in washout fluids of thyroid nodule aspirate (FNA-calcitonin) has been reported as accurate to detect medullary thyroid carcinoma (MTC). The results from these studies have been promising and the most updated version of ATA guidelines quoted for the first time that "FNA findings that are inconclusive or suggestive of MTC should have calcitonin measured in the FNA washout fluid." Here we aimed to systematically review published data on this topic to provide more robust estimates. RESEARCH DESIGN AND METHODS: A comprehensive computer literature search of the medical databases was conducted by searching for the terms "calcitonin" AND "washout." The search was updated until April 2015. RESULTS: Twelve relevant studies, published between 2007 and 2014, were found. Overall, 413 thyroid nodules or neck lymph nodes underwent FNA-calcitonin, 95 were MTC lesions and 93 (97.9%) of these were correctly detected by this measurement regardless of their cytologic report. CONCLUSIONS: The present study shows that the above ATA recommendation is well supported. Almost all MTC lesions are correctly detected by FNA-calcitonin and this technique should be used to avoid false negative or inconclusive results from cytology. The routine determination of serum calcitonin in patients undergoing FNA should improve the selection of patients at risk for MTC, guiding the use of FNA-calcitonin in the same FNA sample and providing useful information to the cytopathologist for the morphological assessment and the application of tailored ancillary tests.

Serum markers measured in FNA fluids of medullary thyroid carcinoma occurring as a cyst.

BACKGROUND: Diagnosis of medullary thyroid carcinoma (MTC) is still a challenge, and the measurement of calcitonin in fine-needle aspiration (FNA) washout has been recently introduced. Rarely, MTC presents as a cyst and its preoperative detection is difficult. METHODS: A 66-year-old woman was referred to us with high serum calcitonin. Ultrasound evaluation showed one cystic and one solid nodule. FNA was performed in both nodules and calcitonin, procalcitonin and CEA were measured in the aspirate fluids. RESULTS: The markers showed elevated levels in the FNA washout of the cyst and the patient was operated on. Final histology demonstrated MTC of the cystic nodule. Four weeks later, all serum markers were undetectable. CONCLUSIONS: In the presence of a cystic thyroid lesion the diagnosis of MTC should be taken into account, and measuring calcitonin in FNA fluid is relevant. The determination in FNA of other markers is technically feasible but its role should be evaluated in larger series.

Galectin-3 and HBME-1 improve the accuracy of core biopsy in indeterminate thyroid nodules.

Core needle biopsy (CNB) has been recently described as an accurate second-line test in thyroid inconclusive cytology (FNA). Here we retrospectively investigated the potential improvement given by Galectin-3, Cytokeratin-19, and HBME-1 on the accuracy of CNB in thyroid nodules with prior indeterminate FNA report. The study included 74 nodules. At CNB diagnosis, 15 were cancers, 40 were benign, and 19 had uncertain/non-diagnostic CNB report. The above immunohistochemical (IHC) panel was analyzed in all cases. After surgery, 19 malignant and 55 benign lesions were found. All 15 cancers and all 40 benign nodules diagnosed at CNB were confirmed at final histology. Regarding the uncertain CNB group, 4 (21 %) were malignant and 15 (79 %) benign. When we considered all the series, the most accurate IHC combination was Galectin-3 plus HBME-1, while HBME-1 was the most sensitive marker in those nodules with uncertain CNB report. The combination of CNB plus IHC could indentify 19/19 cancers and 53/55 benign lesions. Sensitivity and specificity of CNB increased from 79 to 100 % and from 73 to 96 %, respectively, by adding IHC. CNB can diagnose the majority of thyroid nodules with previous indeterminate FNA cytology, while the accuracy of CNB is increased by adding Galectin-3, Cytokeratin-19, and HBME-1 panel. We suggest to adopt CNB as a second-line approach to indeterminate thyroid FNA, and apply IHC in those lesions with uncertain/non-diagnostic CNB report. This approach should improve the pre-surgical diagnosis of patients. These results should be confirmed in larger prospective series.

Differentiated thyroid cancer patients with a previous indeterminate (Thy 3) cytology have a better prognosis than those with suspicious or malignant FNAC reports.

The prognosis of differentiated thyroid cancers (DTC) read at cytology as indeterminate and classified as Thy 3 according to the British Thyroid Association has recently been suggested to be good. To obtain robust information about this potential novelty, in this study we retrospectively reviewed DTC with a prior fine-needle aspiration cytology (FNAC) of Thy 3, Thy 4 or Thy 5 presently followed up at two institutes. Patients with no FNAC before surgery were excluded and a series of 284 DTC was enrolled in the study. Of these, 53 had Thy 3, 108 Thy 4, and 123 had Thy 5 prior to surgery. At histology, 280 (98.6 %) papillary and 4 follicular (1.4 %) cancers were found. Overall, the less aggressive cancer forms were prevalent in all three groups. The lower TNM stages (I and II) were more frequent in the Thy 3 group (96.2 %) than in the other cases (76.6 %) (p < 0.001). Neck lymph node metastasis at diagnosis was found in 3.8 % of Thy 3, 18.5 % of Thy 4, and 26 % of Thy 5 cases. At follow-up, a 16.2 % recurrence rate was recorded, ranging from 1.9 % in Thy 3 group to 19.5 % for Thy 4 and Thy 5 (p < 0.001). According to the Kaplan-Meier curve, Thy 3 was thus a favorable prognostic factor compared with Thy 4 and Thy 5 (OR = 0.079, p < 0.001, 95 %CI 0.01-0.59). At multivariate analysis, Thy 3 was an independent predictor of good prognosis (OR = 0.06, p = 0.03, 95 %CI 0.01-0.80). In conclusion, DTC with a preoperative Thy 3 cytology have a better prognosis than those with Thy 4 and Thy 5 due to less aggressive tumor types and lower TNM stage at diagnosis.

A cost analysis of thyroid core needle biopsy vs. diagnostic surgery.

BACKGROUND: Twenty percent of thyroid fine needle aspiration (FNA) is indeterminate. Because 3 in 4 of these are actually benign, a method of clarifying the pathology could help patients to avoid diagnostic thyroidectomy. Recently, core needle biopsy (CNB) has been proven to be highly reliable for this purpose. However, there are no reports of any potential cost benefit provided by CNB. Here we analyzed the impact on management costs of CNB compared with traditional diagnostic surgery in indeterminate FNA. METHODS: Over 24 months, 198 patients with thyroid indeterminate cytology underwent CNB at Ospedale Israelitico of Rome or diagnostic surgery at the Department of Surgery of Sapienza University of Rome. We tabulated costs of the medical instruments, operating theater, surgical team, patient recovery, and pathologic examination for each method. RESULTS: In CNB group, 42.4% of patients had benign lesions and avoided surgery, 20.8% was cancer, and the remaining 36.8% uncertain. The malignancy rate in CNB group was 26.4%, and mean cost of CNB per nodule was 1,032€. In diagnostic surgery group, 24.7% had cancer and 75.3% had benign lesions, and mean expense for each thyroidectomy was 6,364€. In an ideal cohort of 100 patients with indeterminate FNA, the cost of CNB is 33.8% lower than that of diagnostic surgery. CONCLUSIONS: CNB can detect a large proportion of the benign thyroid nodules that are classified as indeterminate by FNA. These patients can avoid diagnostic thyroidectomy and hospitals can reduce their surgical costs by one-third.

Patient's comfort with and tolerability of thyroid core needle biopsy.

Recently, the core needle biopsy (CNB) has been proposed as a complementary test for thyroid nodules with inconclusive cytology by fine-needle aspiration (FNA). However, there have been no reports regarding patient comfort during and after CNB or tolerability of this procedure. Here we aimed to investigate and compare comfort with and tolerability of the CNB and FNA procedures. A 21 gauge needle was used for collection in CNB procedures, and a 23 gauge needle was used for collection in FNA procedures. Sixty-one consecutive patients underwent both biopsies and were asked to evaluate their comfort during and after these procedures by a structured questionnaire. A total of 58 (95 %) patients reported local pain during both biopsies. Two patients reported pain only during CNB, and one reported no pain. Mild pain was reported in 87 % of CNB cases. Local pain after biopsy was reported in 29 % of FNA and 45 % of CNB. The occurrence of pain in the first minutes following CNB was significantly higher than FNA (p = 0.008), while there was not a significant difference in pain at later time points after the procedures. Finally, patients were asked to evaluate the degree of tolerability of the two sampling techniques, and FNA and CNB were reported as tolerable in 82 and 83 %, respectively. The results from a questionnaire evaluating patients' comfort level showed no significant difference between the tolerability of CNB and FNA. This finding suggests that CNB may be performed with a reasonable level of patient comfort.

Clinical characteristics as predictors of malignancy in patients with indeterminate thyroid cytology: a meta-analysis.

Indeterminate thyroid nodules (ITN) constitute the gray zone of thyroid fine-needle aspiration cytology (FNAC). About 70-80 % of ITN are later diagnosed as benign; therefore, it is very important to identify the predictors of malignancy. Aim of the study was to summarize published data about clinical risk factors for malignancy in patients with ITN and thereby provide more robust estimates of the effect of these risk factors. Sources comprised studies published through December 2012. Original articles that investigated clinical parameters as potential predictors of malignancy in ITN were identified. Two authors performed the data extraction independently. A meta-analysis of 19 relevant studies was conducted that included 3,494 patients with ITN according to FNAC. The pooled prevalence of malignancy was 28 % (95 % CI 23-33), 26 % in females and 34 % in males. The pooled OR was 1.51 (95 % CI 1.2-1.83) for males and 0.68 (95 % CI 0.53-0.88) for females. Regarding the nodule's size, the pooled OR was 2.10 (95 % CI 1.26-3.50) for nodules >4 cm in diameter. Analysis of the patient age as a risk factor was not feasible because of marked difference found between the studies. In patients with indeterminate thyroid nodules diagnosed at FNAC, the pooled rate of malignancy from 19 studies was 28 %. Patients that are male and have ITN greater than 4 cm in diameter should be considered at higher risk of cancer.

Ultrasound features of medullary thyroid carcinoma correlate with cancer aggressiveness: a retrospective multicenter study.

BACKGROUND: Poor prognosis of medullary thyroid cancer (MTC) with suspicious ultrasound (US) features has been reported. The aim of the study was to investigate the association between preoperative US presentation and aggressiveness features of MTC. Also, US features of MTC were compared with those previously reported. METHODS: Study group comprised 134 MTC from nine different centers. Based on US presentation the nodules were stratified in "at risk for malignancy" (m-MTC) or "probably benign" (b-MTC) lesions. RESULTS: Eighty nine (66.4%) m-MTC and 45 (33.6%) b-MTC were found. Metastatic lymph nodes (p = 0.0001) and extrathyroid invasiveness (p < 0.0001) were more frequent in m-MTC. There was statistically significant correlation (p = 0.0002) between advanced TNM stage and m-MTC with an Odds Ratio 5.5 (95% CI 2.1-14.4). Mean postsurgical calcitonin values were 224 ± 64 pg/ml in m-MTC and 51 ± 21 in b-MTC (p = 0.003). CONCLUSIONS: This study showed that sonographically suspicious MTC is frequently associated with features of aggressiveness, suggesting that careful preoperative US of MTC patients may better plan their surgical approach.

Thin core biopsy should help to discriminate thyroid nodules cytologically classified as indeterminate. A new sampling technique.

Indeterminate neoplasms (IN) represent the gray zone of thyroid cytology in which malignant and benign tumors cannot be discriminated. Recently, the approach by thin core needle biopsy has been proposed. Here we report a new thin core needle biopsy approach in 40 consecutive patients with thyroid IN at cytology. In this study, a 21-G needle was inserted into the nodule, advanced within the lesion, and moved ahead reaching extranodular tissue. The resulting sample allowed to evaluate the cytomorphology of nodular tissue, its relationship with extranodular parenchyma, and the nodule's capsule when present. All biopsies were adequate for diagnosis but one. Of the 39 adequate samples, 5 cases were papillary cancer as confirmed at histology, while 14 nodules avoided surgery because of Hürthle cell hyperplasia in thyroiditis (n = 6) and microfollicular adenomatous hyperplasia (n = 8). The remaining 20 cases were assessed as follicular neoplasms because of encapsulation and were evaluated by immunohistochemistry. Of these, 6 had positive markers in different degree and 1/6 has follicular cancer at histology, while the other 14 were benign after surgery. Overall, this approach by thin core needle biopsy identified benignancy in 14/40 (35 %) IN avoiding surgery. As a conclusion, thin core biopsy should help to discern the nature of thyroid lesions cytologically classified as indeterminate, and it should be used as a complementary test in thyroid nodule assessment.

Poly(ADP-ribose)polymerase activity is reduced in circulating mononuclear cells from type 2 diabetic patients.

Poly(ADP-ribose)polymerase (PARP-1), a nuclear enzyme activated by DNA strand breaks, is involved in DNA repair, aging, inflammation, and neoplastic transformation. In diabetes, reactive oxygen and nitrogen species occurring in response to hyperglycemia cause DNA damages and PARP-1 activation. Because circulating mononuclear cells (MNCs) are involved in inflammation mechanisms, these cells were chosen as the experimental model to evaluate PARP-1 levels and activity in patients with type 2 diabetes. MNCs were isolated from 25 diabetic patients (18 M, 7 F, age, 63.5 +/- 10.2 years, disease duration 17.7 +/- 8.2 years) and 11 age and sex matched healthy controls. PARP-1 expression and activity were analyzed by semi-quantitative PCR, Western and activity blot, and immunofluorescence microscopy. PARP-1-mRNA expression was increased in MNCs from all diabetic patients versus controls (P < 0.01), whereas PARP-1 content and activity were significantly lower in diabetic patients (P < 0.0001). To verify whether low PARP-1 levels and activity were due to a proteolytic effect of caspase-3 like, the latter activation was measured by a fluorimetric assay. Caspase-3 activity in MNCs was significantly higher in diabetic patients versus control subjects (P < 0.0001). The different PARP-1 behavior in MNCs from patients with type 2 diabetes could therefore be responsible for the abnormal inflammation and infection responses in diabetes.