Cytologic, flow cytometry, and molecular assessment of lymphoid infiltrate in fine-needle cytology samples of Hashimoto thyroiditis.

BACKGROUND: The thyroidal lymphoid infiltrate (TLI) in Hashimoto thyroiditis (HT) represents the substrate from which thyroid lymphoma may arise. The objective of the current study was to classify the TLI in HT by comparing the cytologic features with flow cytometry (FC) data and evaluating the kappa/lambda light chain ratio and its molecular assessment. METHODS: Fine-needle aspiration cytology (FNAC) was performed in 34 patients with HT with nodular or diffuse palpable enlargement of the gland. Two or 3 passes were performed to prepare traditional smears, FC, and immunophenotyping, and RNAlater suspensions for molecular assessment. FC was performed using the following antibodies: CD3, CD5, CD4, CD8, CD10, CD19, and kappa and lambda light chains. In 4 cases, high molecular weight DNA was extracted and used for polymerase chain reaction (PCR) to amplify the variable diversity joining region of the heavy chain immunoglobulin (Ig) genes (IgH). Statistical analysis was performed to evaluate possible associations between clinical ultrasound presentation, cytologic pattern, and TLI phenotype. Light chain expression was evaluated as the percentage of the expressing cells (20%) and as the kappa/lambda ratio. RESULTS: Smears were classified as "lymphocytic," "lymph node-like," or "mixed." FC demonstrated T cells (CD3 positive [+], CD5+) in all cases, and T cells and B cell (CD19+, CD10+/-) lymphocytes in 22 cases. Light chains were expressed in 30 cases (in <20% of the gated cells in 13 cases and in >20% of the gated cells in 17 cases). Five cases demonstrated small kappa/lambda ratio imbalances and PCR analysis demonstrated diffuse bands in the gel and Gaussian curves at the heteroduplex. Statistical analysis indicated significant associations between the "lymphocytic" pattern and T-cell phenotype and between the "lymph node-like" pattern and B-cell phenotype. A significant association also was observed between light chain restriction and low light chain expression (P < .005). CONCLUSIONS: The cytologic pattern of TLI in HT is quite representative of the clinical presentation and phenotypic cell type. Small light chain imbalances are not sustained by heavy chain Ig gene (IgH) rearrangements. FNA coupled with FC may contribute to making the distinction between florid TLI and non-Hodgkin lymphoma.

Fine-needle aspiration cytology in the follow-up of Hodgkin lymphoma.

Hodgkin lymphoma (HL) is characterized by long survival and risk of relapse and second neoplasm. The aim of this study is to evaluate the possibility of improving the accuracy of fine-needle cytology (FNC) in HL follow-up using Power Doppler ultrasound (US) assistance and immediate microscopic evaluation (ICE). The study was performed in two consecutive groups of 200 FNC in HL patients. In the first group FNC of palpable lymph-nodes or extra lymph-nodal masses were performed without US assistance except for impalpable and/or deep located masses (nonassisted group); In the second group, all the FNC were performed under Power Doppler US assistance with ICE and immediately repeated in inadequate cases (assisted group). Cytological diagnoses were controlled by histology (61) or clinical follow-up (69); sensitivity and specificity were calculated in the two groups and to evaluate the effect of Power Doppler alone, adequate cases were compared with the total number of FNC in each of the two groups.FNC identified 90 negative cases, 3 false negatives, 70 HL relapse, 16 inadequate and 14 suspicious; second neoplasia were diagnosed in 12 cases and all histologically confirmed. Sensitivity and specificity were 64 and 84% in the nonassisted group and 86 and 94% in the assisted group and there were significant differences between the number of adequate cases v.s. the total number of FNC in each of the two groups. Sensitivity and specificity in assisted FNC are higher than in nonassisted ones. The main advantage of assisted FNC in the follow-up of HL is to produce accurate diagnoses avoiding invasive biopsies.

Long-term cardiovascular effects of levothyroxine therapy in young adults with congenital hypothyroidism.

CONTEXT: Congenital hypothyroidism (CH) is the most prevalent endocrine disorder in the newborn and is routinely treated with life-long levothyroxine replacement therapy. Although several studies have demonstrated that such therapy may impact on the cardiovascular system, little is known with regard to the effects of long-term levothyroxine administration in patients with CH. OBJECTIVE: The aim of the current study was to evaluate whether long-term levothyroxine replacement therapy in young adults with CH is associated with cardiovascular abnormalities. PATIENTS AND METHODS: Thirty young adults with CH aged 18.1 +/- 0.2 yr and 30 age- and sex-matched controls underwent cardiac and carotid Doppler ultrasound and symptom-limited cardiopulmonary exercise testing. Hypothyroidism was diagnosed by neonatal screening, and levothyroxine treatment was initiated within the first month of life and carefully adjusted to maintain TSH levels in the normal range and free T(4) in the high-normal range. RESULTS: Compared with controls, hypothyroid patients exhibited left ventricular diastolic dysfunction, impaired exercise capacity, and increased intima-media thickness. At multiple regression analysis, the number of episodes of plasma TSH levels less than 0.5 mU/liter and greater than 4.0 mU/liter from the age of 1 yr onward, and mean TSH plasma levels during puberty were independent predictors of diastolic filling and cardiopulmonary performance indexes (multiple r values: 0.61-0.75). CONCLUSIONS: Long-term levothyroxine treatment in young adults with congenital hypothyroidism is associated with impaired diastolic function and exercise capacity and increased intima-media thickness.

Burden of smoking and occupational exposure on etiology of chronic obstructive pulmonary disease in workers of Southern Italy.

OBJECTIVE: This study evaluates the burden of smoking and occupational exposure on chronic obstructive pulmonary disease (COPD). METHODS: Two thousand nineteen workers underwent a diagnostic protocol for COPD at the baseline and after 5 and 10 years. Taking into account individual and occupational exposures the sample was divided in four groups. Prevalence, incidence of COPD, differences among groups, and logistic regression were calculated. RESULTS: Higher COPD prevalence and incidence were observed in the group with combined exposures. Smoking habits and occupational exposure were confirmed as risk factors for COPD and an interaction between smoking and occupational exposure was found. CONCLUSIONS: Workers exposed to both risk factors have to be considered in COPD high-risk class. Smoking cessation programs could play an important role particularly in activities where effects of smoking have a positive interaction with occupational exposure.

High prevalence of non-HFE gene-associated haemochromatosis in patients from southern Italy.

Hereditary haemochromatosis is an autosomal recessive disorder of iron regulation that results in abnormal intestinal iron absorption with progressive iron overloading of parenchymal cells. Two specific, single point mutations of the HFE gene (C282Y and H63D) have been described in haemochromatosis patients. Epidemiological studies have revealed a strict association between hereditary haemochromatosis and C282Y homozygosis or C282Y/H63D compound heterozygosis, suggesting that these mutations may provide a useful tool for diagnosis. However, recent investigations from southern Europe have reported lower allelic frequencies of the C282Y mutation among haemochromatosis patients, apparently depending on the geographical area of the population analysed. To assess the predictive value of the detection of the C282Y and H63D HFE mutations in our geographical area, we have evaluated their occurrence in 46 haemochromatosis patients from southern Italy. We found that only 19.6% of our patients were homozygous for the C282Y mutation and 21.7% were compound C282Y/H63D heterozygotes. Among the remaining 59%, approximately 40% did not display any of the known HFE mutations. We conclude that, in southern Italy, another genetic determinant/s must be responsible for many haemochromatosis cases and that a genetic screening for the C282Y and H63D HFE mutations is not sufficient for hereditary haemochromatosis diagnosis.

Expression of cyclin-D1 in uveal malignant melanoma.

BACKGROUND: Uveal malignant melanoma (MM) is characterized by a marked variability in biological behavior and by an unpredictable clinical course. Therefore the search for reliable prognostic parameters is active. In this study we investigated the immunohistochemical expression of cyclin D1, a cell cycle regulatory molecule, to analyze the possible significance of the protein in the prognostic evaluation of these neoplasms. MATERIALS AND METHODS: Forty-five selected uveal MM were incubated with the anti-cyclin D-1 antibody; the findings were compared with the follow-up data, with the cell type and with the largest tumor dimension. RESULTS: The overexpression of cyclin D1 was found to be inversely related to disease-free interval (p < 0.001) and to the spindle A/B tumors with good prognosis (p = 0.05). On the other hand, a direct correlation was found with epithelioid/spindle B melanomas with poor clinical course (p = 0.05) and with sclera infiltration (p = 0.01). No statistically significant relation emerged between cyclin D1 expression and LTD. CONCLUSION: These data may suggest a possible role of the overexpression of cyclin D1 in the tumorigenesis of uveal MM and in the prognostic evaluation of these tumors, representing a useful tool to subclassify lesions with similar morphological features.

Influence of body surface area on serum peak thyrotropin (TSH) levels after recombinant human TSH administration.

Recombinant human TSH (rhTSH) has been proposed as an alternative method to the withdrawal of thyroid hormones in the follow-up of differentiated thyroid cancer. The aim of the present study was to evaluate the influence of several demographic and anthropometric parameters [age, body weight, height, body mass index, and body surface area (BSA)] on serum peak TSH levels after rhTSH administration. rhTSH was administered to 112 patients with differentiated thyroid carcinoma according to the conventional two-dose schedule (0.9 mg/d). Serum TSH levels were measured 24 h before and after the first administration of rhTSH, and then 24, 48, and 72 h after the second administration of rhTSH. In one severely obese patient, serum peak TSH values did not reach a valid stimulation range. Serum peak TSH levels were negatively related to body weight (r = -0.69; P < 0.0001), body mass index (r = -0.51; P < 0.0001), and BSA (r = -0.72; P < 0.0001). In a multivariate regression analysis including demographic and anthropometric variables, only BSA was independently associated to serum peak TSH concentrations (standardized beta coefficient = -0.721; P < 0.0001). In conclusion, body size seems to influence serum peak TSH levels after rhTSH administration. Future studies should evaluate the possibility of using personalized rhTSH doses, adjusted in relation to BSA.