Leopoldo Rubaltelli

Differential Diagnosis of Benign and Malignant Thyroid Nodules at Elastosonography

PURPOSE Ultrasound of the neck detects a large number of non-palpable thyroid nodules in the population, but it offers poor diagnostic accuracy (the presence of microcalcifications is the only statistically significant criterion indicative of malignancy). The aim of this study is to evaluate elastography, a technique which allows differentiation between pathological and normal tissue by determining its hardness and which could also prove useful in the characterisation of thyroid nodules. MATERIALS AND METHODS In this prospective study, 51 thyroid nodules in 40 consecutive patients were examined (25 women, 15 men, mean age +/- SD, 54 +/- 13.4). Elastosonography was performed by real-time, free-hand technique, using Logos HiVision equipment with a 10 MHz transducer and lesions were classified and scored in 4 classes of hardness. All patients were also examined by grey scale high frequency ultrasound and colour Doppler. Final diagnoses were obtained from cytological and/or histological evaluation. RESULTS Final diagnoses revealed 11 malignant and 40 benign nodules. Only in two cases ultrasound demonstrated signs useful for a differential diagnosis (intrinsic microcalcifications). Correct differentiation of malignant from benign nodules was obtained by elastosonography in 43 / 51 cases with 5 false positives (FP) and 3 false negatives (FN). Specificity, sensitivity and accuracy were 87.5 %, 81.8 % and 86.2 %, respectively. Predictive negative value (PNV) and predictive positive value (PPV) were 94.5 % and 64 % area under the curve (AUC) 0.86. CONCLUSION Elastosonography provides an interesting contribution to the differentiation of malignant and benign thyroid nodules. Particularly worthy of mention is that an entirely elastic nodule pattern was observed only in relation to benign nodules, a result which would suggest that immediate recourse to FNAB might be avoided.

Evaluation of Lymph Node Perfusion Using Continuous Mode Harmonic Ultrasonography With a Second-Generation Contrast Agent

Objective. To evaluate the contribution of continuous mode contrast‐enhanced harmonic ultrasonography (CE‐HUS) with a second‐generation contrast agent to the characterization of superficial lymphadenopathies with respect to conventional ultrasonographic techniques (B‐mode and power Doppler). Methods. Fifty‐six lymph nodes from 45 patients were studied both by conventional techniques and by CE‐HUS. The dimensions, intranodal architecture, margins, and location of vessels were evaluated. Subsequently, all the lymph nodes were examined by CE‐HUS, and enhancement of echogenicity was evaluated. The diagnoses obtained by means of fine‐needle aspiration cytologic examination, surgical biopsy, or both were compared with those obtained by ultrasonography. Results. Of the lymph nodes examined, 30 were benign and 26 were malignant (18 metastases and 8 non‐Hodgkin lymphomas). The study using CE‐HUS showed intense homogeneous enhancement in 28 of 30 reactive lymph nodes; perfusion defects in 17, of which 15 were neoplastic and 2 were inflammatory; intense but inhomogeneous speckled enhancement in the early arterial phase in 5 cases of lymphoma; and, last, scarce or absent intranodal enhancement in 4 metastases. The specificity, sensitivity, and accuracy of conventional techniques in differentiation between benign and malignant lymph nodes were 76%, 80%, and 78% versus 93%, 92%, and 92.8% for CE‐HUS. The increase in correct diagnoses was significant (P = .05) when conventional ultrasonography was tested against CE‐HUS. Conclusions. Superficial lymph nodes can be characterized as being neoplastic or benign with a high degree of diagnostic accuracy on the basis of the perfusion characteristics evaluated by CE‐HUS. This technique has been shown to afford a higher degree of accuracy than currently obtainable by any other ultrasonographic technique.

Synovial effusion and synovial fluid biomarkers in psoriatic arthritis to assess intraarticular tumor necrosis factor-α blockade in the knee joint.

IntroductionThe purpose of this study was theevaluation of synovial effusion (SE), synovial fluid (SF) and synovial tissue (ST) biomarkers in relation to disease activity indexes to assess the response to intraarticular (IA) tumor necrosis factor (TNF)-α blockers in psoriatic arthritis (PsA).MethodsSystemic and local disease activity indexes (disease activity score (DAS); the Ritchie articular index (mRAI), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP); Thompson articular (THOMP) and joint articular (KJAI)-Index ) and ST samples were assessed at baseline, throughout treatment, and during the follow-up in 14 patients affected with PsA who underwent IA injections (0.5 ml to 12.5 mg) in the knee joint of etanercept (E) or placebo (P) once every two weeks for a 10-week period. Total SF white blood cell (WBC) counts (WBC/μl) and SF cytokine/chemokine (CK/CCK) levels were measured before IA-E at baseline, after IA-E, and as long as there were adequate amounts of SF for knee aspiration (post). Characterization of synovial mononuclear cell infiltration and synovial vessels was carried out in 8 out of 14 knees by staining serial sections of synovial tissue biopsies for CD45, CD3, CD68, CD31 and CD105.ResultsAt baseline, CRP and/or ESR were significantly correlated with SF-CK (interleukin- (IL-)1β, IL-1Ra, IL-6, IL-8) and CCK (CCL3). Post-IA injections, there was a decrease in SE in the knees in which aspiration following IA-E injection was possible as well as a significant reduction in SF WBC/μl and in SF-CK (IL-1β, IL-1Ra, IL-6 and IL-22). Pre- and post-IA-E injections, there were significant correlations between ST markers and SF-CK (IL-1β with CD45; IL-1β and IL-6 with CD31) and between SF-CCK (CCL4 and CCL3 with CD3). At the end of the study, there was a significant reduction in disease activity indexes (CRP, DAS, RAI, THOMP, KJAI) as well as in the ST markers (CD45; CD3).ConclusionsSynovial effusion regression is a reliable indicator of the response to IA TNF-α blockers in PsA patients as it is confirmed by the correlation between SF biomarkers to disease activity and synovial tissue inflammation.

MRI in the assessment of muscular pathology: a comparison between limb-girdle muscular dystrophies, hyaline body myopathies and myotonic dystrophies.

PurposeThe continuous discovery of new subtypes of neuromuscular disorders demands more accurate imaging analyses. We set out to establish the specific patterns of muscular involution using magnetic resonance imaging (MRI).Materials and methodsA systematic clinical evaluation based on the Medical Research Council scale and MRI was completed in ten patients with calpainopathy [limb-girdle muscular dystrophy (LGMD)-2A], 16 with dysferlinopathy (LGMD-2B), ten with hyaline body myopathy (HBM), six with myotonic dystrophy (MD) types 1 and 5 with MD type 2. Severity of fibroadipose degeneration was specifically staged using T1-weighted sequences. Turbo inversion recovery magnitude (TIRM) sequences were used to assess oedema-like changes.ResultsT1 scans showed recurrent patterns of fibroadipose replacement, whereas TIRM images revealed differences in oedema-like changes between the various diseases. In LGMD, the posterior compartments are more vulnerable to degeneration. In HBM, fatty muscle degeneration and oedema are allocated to muscles of the posterior compartments of the leg. In MD, fatty muscle degeneration and oedematous changes are allocated to muscles of the anterior thigh and posterior lower leg.ConclusionsImaging examination suggests a characteristic pattern of muscle involvement. MRI represents an important diagnostic technique useful in differential diagnosis, thanks to the distinctive patterns observed in the distribution of muscular changes between the different muscular diseases.RiassuntoObiettivoLa continua scoperta di nuovi sottotipi di patologie neuromuscolari rende necessaria un’analisi di imaging adeguata. Ci si prefigge di descrivere specifici modelli di involuzione muscolare con la risonanza magnetica (RM).Materiali e metodiLa valutazione clinica, basata sulla scala del Medical Research Council, e la RM sono state eseguite su 10 pazienti con calpainopatia (LGMD2A), 16 con disferlinopatia (LGMD2B), 10 con miopatia a corpi ialini (HBM), 6 con distrofia miotonica di tipo 1 (MD1) e 5 con il tipo 2 (MD2). La severità della degenerazione fibroadiposa è stata valutata con sequenze pesate in T1. Le sequenze turbo inversion recovery (TIRM) sono state usate per valutare l’edema.RisultatiLe immagini T1-pesate hanno mostrato modelli ricorrenti di sostituzione fibro-adiposa, mentre le immagini TIRM hanno rivelato differenze nell’interessamento edematoso dei muscoli. Nella LGMD i compartimenti muscolari posteriori sono più vulnerabili alla degenerazione. Nella HBM, l’involuzione adiposa e l’edema sono appannaggio dei muscoli dei compartimenti posteriori dell’arto inferiore. Nella MD, l’involuzione adiposa del muscolo ed i segni di edema interessano soprattutto i muscoli della coscia anteriore e della gamba posteriore.ConclusioniL’esame di diagnostica per immagini suggerisce un modello caratteristico di coinvolgimento muscolare. La RM rappresenta un’importante tecnica diagnostica utile nella diagnosi differenziali grazie ai diversi pattern di interessamento muscolare.Purpose. The continuous discovery of new subtypes of neuromuscular disorders demands more accurate imaging analyses. We set out to establish the specific patterns of muscular involution using magnetic resonance imaging (MRI). Materials and methods. A systematic clinical evaluation based on the Medical Research Council scale and MRI was completed in ten patients with calpainopathy [limb-girdle muscular dystrophy (LGMD)-2A], 16 with dysferlinopathy (LGMD-2B), ten with hyaline body myopathy (HBM), six with myotonic dystrophy (MD) types 1 and 5 with MD type 2. Severity of fibroadipose degeneration was

Contrast-Enhanced Ultrasound for Characterizing Lymph Nodes With Focal Cortical Thickening in Patients With Cutaneous Melanoma

OBJECTIVE The aim of this study was to ascertain the utility of contrast-enhanced ultrasound in assessing the significance of focal cortical thickening in the lymph nodes of patients followed up after surgery for cutaneous melanoma. MATERIALS AND METHODS Ultrasound was used to examine 460 consecutive patients to identify nodes with focal hypoechoic cortical thickening. Patients whose nodes revealed these features underwent contrast-enhanced ultrasound and ultrasound-guided fine-needle aspiration cytology (FNAC) focusing on the area of cortical thickening. Enhancement in the arterial and parenchymal phases was evaluated: A generalized homogeneous or intense enhancement was considered benign and the presence of a perfusion defect was considered metastatic. RESULTS After exclusion of 24 patients with frank signs of malignancy at gray-scale ultrasound, the study included 436 patients. Focal hypoechoic cortical thickening was seen in 44 of 436 nodes in as many patients. In 29 nodes, the area of focal thickening showed contrast enhancement similar to that of the remaining cortex on contrast-enhanced ultrasound. In 15 nodes, the area of cortical thickening was less well vascularized than the adjacent parenchyma in the arterial phase and there were areas with perfusion defects that were more evident in the parenchymal phase. FNAC focusing on the areas of focal cortical thickening identified 13 metastatic nodes and 31 nodes with benign features. Contrast-enhanced ultrasound compared with FNAC correctly classified 42 of 44 nodes, showing a sensitivity of 100% and a specificity of 99.5%. CONCLUSION Although our findings need to be confirmed in larger series, they indicate that contrast-enhanced ultrasound can be useful in clinical practice for characterizing focal cortical thickening in lymph nodes. The exclusion or identification of regional lymph node metastases is of fundamental importance in oncologic staging because this issue directly influences both the prognosis and the choice of therapeutic strategy.

Infantile recurrent sialectatic parotitis: the role of sonography and sialography in diagnosis and follow-up

The results of a clinical, sonographic and sialographic study in 10 children (aged 4-10 years) with recurrent sialectatic parotitis are presented. Alteration in the sonographic pattern of the parotid glands, consisting of multiple hypoechogenic areas in the parenchyma, were found in four cases; milder nonhomogeneity was seen in four cases, and an almost normal pattern in two cases. Sonographic follow-up in two children showed a parallel reduction in non-homogeneity with symptomatic improvement. A probable therapeutic action following sialography using fat-soluble contrast medium was observed in four of the 10 children. The familial nature of the disease, which has not previously been described, is documented.

Automated quantitative evaluation of lymph node perfusion on contrast-enhanced sonography

OBJECTIVE The aim of this study was to assess the performance of experimental software (Qontraxt) intended to provide automated quantification of sonographic signal intensity, which is related to the contrast enhancement of lymph node tissue, to differentiate benign from malignant lymph nodes. SUBJECTS AND METHODS In 31 patients (age range, 24-86 years; mean age +/- SD, 53.6 +/- 14.4 years) a single lymph node per patient was evaluated on sonography after the administration of sulfur hexafluoride-filled microbubbles. The stored sonographic images were analyzed and processed into chromatic maps that had numeric values related to the amount of contrast. The lymph node regions in which the increase of signal intensity values with respect to baseline were highest (maximum signal intensity value [SImax]) and lowest (minimum signal intensity value [SImin]) were identified, and the corresponding numeric data were stored. Statistical analyses were performed by means of the Students t test; a p value of less than 0.05 was considered to be statistically significant. RESULTS Histopathologic analysis revealed metastatic lesions in 12 of the 31 lymph nodes; the remaining 19 were benign (16 reactive lymph nodes, two cases of granulomatous lymphadenitis, and one case of tubercular lymphadenitis). Values obtained from the SImax regions showed no consistent difference between benign and malignant lymph nodes; on the other hand, values from the SImin regions comparing baseline and maximal contrast-enhanced values were significantly different in the two groups (p < 0.001). Confidence for characterization of malignancy was significant using the difference between values from SImax and SImin regions, with the higher diagnostic value from 24 to 31 inclusive: sensitivity, 92% (11/12); specificity, 89% (17/19); positive predictive value, 85% (11/13); and accuracy, 90% (28/31). CONCLUSION The software being tested proved to be useful in differentiating benign from metastatic lymph nodes on the basis of the quantitative data it provided.

Blockade of intra-articular TNF in peripheral spondyloarthritis: its relevance to clinical scores, quantitative imaging and synovial fluid and synovial tissue biomarkers.

OBJECTIVES This open-label study is based on a translational approach with the aim of detecting changes in the clinical condition as well as in imaging and synovial biological markers in both synovial fluid (SF) and synovial tissue (ST) in peripheral spondyloarthritis (SpA) patients following intra-articular (IA) blockade of TNF-α by serial etanercept injections. METHODS Twenty-seven SpA patients with resistant knee synovitis underwent four biweekly IA injections of etanercept (E) (12.5 mg). The primary outcome of Thompsons Knee Index (THOMP), and secondary outcomes of Knee Joint Articular Index (KJAI), C-reactive protein (CRP), HAQ-Disability Index (HAQ-DI), maximal synovial thickness (MST) according to ultrasonography (US) and contrast-enhanced magnetic resonance (C+MR) imaging, ST-CD45+ mononuclear cells (MNC) and ST-CD31+ vessels, IL-1β, IL-1Ra and IL-6 levels in SF were assessed at baseline and at the end of the study. RESULTS At the study end, clinical and imaging outcomes as well as ST and SF biological markers were significantly reduced compared to baseline. There were significant correlations between clinical, imaging and biological markers (CRP with either THOMP, or KJAI, or HAQ-DI or SF-IL-1Ra; US-MST with KJAI, ST-CD45+ with either THOMP, or KJAI, or ST-CD31+, or SF-IL-1β; SF-IL-6 with either THOMP, or KJAI, or SF-IL-1β, or IL-1Ra). CONCLUSIONS The proof of concept study revealed early improvement either in local and systemic clinical scores, in synovial thickness measures by C+MR and US, or expression of synovial biological markers. CD45+, CD31+ in ST and IL-6 and IL-1β in SF may be considered potential biomarkers of the peripheral SpA response to IA TNF-α blocking.

Molecular pathways involved in synovial cell inflammation and tumoral proliferation in diffuse pigmented villonodular synovitis.

Diffuse-type tenosynovial giant cell tumors, also known as pigmented villonodular synovitis, are unique mesenchymal lesions that arise from the synovial tissue of the joints. They are predominantly intraarticular, aggressive, infiltrative processes, characterized by both inflammatory or neoplastic properties and local destructive progression. The pattern of synovial gene and protein expressions in pigmented villonodular synovitis, similar to those in activated macrophages in rheumatoid arthritis, and the phenotype of multinucleated giant cells, characteristic of osteoclasts, suggest that there is a common autocrine mechanism in osteoclast differentiation in both diseases and indicate the potential utility of tumor necrosis factor (TNF)-alpha blockade. High synovial colony stimulating factor 1 (CSF1) messenger RNA (m RNA) expression in pigmented villonodular synovitis, unrelated to a chromosomal translocation involving CSF1 locus, may indicate that there is a synergic paracrine loop mediated by TNF-alpha and CSF1, as shown in both inflammatory and neoplastic conditions. The effects of a new therapeutic approach consisting in intraarticular TNF-alpha blockade were studied in four pigmented villonodular synovitis knees. Knee injections produced a rapid reduction in clinical and sonographic indexes and immunohistological alterations, confirmed by arthroscopic synovectomy. A delayed relapse in one of the four knees and unaltered synovial CSF1 expression were other important findings. In the light of these observations, CSF1/CSF1R interaction probably represents a more sensible therapeutic target than TNF-alpha blockade in the diffuse form of pigmented villonodular synovitis.

Sentinel node biopsy and ultrasound scanning in cutaneous melanoma: clinical and technical considerations

1.5 mm and in all cases with two metastatic SNs, further positive additional nodes were found. The mean counts per 10 s (CP10S) ratio for SN and non-SN values was 5.62 (1.29-23.51) and 3.09 (1.03-10.99) in the intra-operative and extra-operative phases, respectively. US scanning and preoperative lymphoscintigraphy associated with PBD allows preoperative patient selection and accurate SN(s) identification. Breslow thickness and the number of metastatic SN(s), but not their type, are correlated with disease spread; CP10S contributed to the differentiation amongst the nodes and the determining of procedures completion.