Filip Gabalec

Benign fine-needle aspiration cytology of thyroid nodule: to repeat or not to repeat?

CONTEXT Fine-needle aspiration cytology (FNAC) is the gold standard for evaluating thyroid nodules. It has a sensitivity rate of about 95%, i.e. false negative results represent up to 5% of cases. The value of repeated FNAC during follow-up is still controversial. OBJECTIVE To evaluate the usefulness of repeating the FNAC for initially benign nodules. DESIGN AND METHODS All 5017 patients who underwent FNAC of the thyroid nodule in years 1991-2008 were retrospectively evaluated. RESULTS Repeated FNAC was performed in 574 nodules with initially benign results. The number of repetitions varied from one to six. Repeatedly benign results were found in 498 cases, and malignant/suspicious results with initially benign cytology were found in 76 nodules (13.2%). Carcinoma was present in 13 out of the 58 surgically treated malignant/suspicious results of initially benign cytology. CONCLUSIONS A change from a benign FNAC result to a malignant/suspicious one was present in more than 13% of the patients with initially benign cytology; malignancy has been recognised on the basis of repeated FNAC in 2.3% patients. In the majority of cases, the repetition corrected wrong cytological interpretation of results other than colloidal goitre, especially Hashimotos thyroiditis and regressive changes. We believe that repeating FNAC in patients with benign cytology in about a 1-year horizon can reduce the rate of undiagnosed tumours.

Dopamine 2 receptor expression in various pathological types of clinically non-functioning pituitary adenomas

Clinically non-functioning pituitary adenomas account for about one-third of pituitary tumors. The majority of them are pathologically classified as gonadotropinomas or null-cell adenomas without hormonal expression. The rest represent silent corticotroph adenomas and plurihormonal tumors. Conservative therapy with dopamine agonists is effective in some cases only depending on the expression of dopamine 2 receptors (D2R). The aim of this study was to quantitatively estimate D2R expression in clinically non-functioning pituitary adenomas and correlate the results with adenoma type according to pathological classification. Out of the 87 adenomas investigated, 63 expressed gonadotropins, 7 were silent corticotroph adenomas, 7 were plurihormonal tumors, and only 6 did not express any pituitary hormone on immunohistochemical investigation. With the use of the reverse transcriptase PCR technique, D2R mRNA was expressed in all adenomas with very heterogeneous quantity. The expression was very low in corticotroph adenomas (relative median quantity after normalization to housekeeping gene 0.01) and lower in plurihormonal tumors (median 0.4) than in gonadotroph (median 1.3) and null-cell adenomas (median 1.9). The difference between corticotroph adenomas and plurihormonal tumors in comparison with other pathological types was statistically significant. The expression of D2R did not depend on the presence or absence of gonadotropins. We conclude that D2R expression is very low in corticotroph adenomas and significantly lower in plurihormonal tumors. The positivity of gonadotropins does not predict the D2R quantity.

Pneumocystis pneumonia during medicamentous treatment of Cushing's syndrome--a description of two cases.

Only a few cases of pneumocystis pneumonia (PCP) in Cushings syndrome have been published in the literature so far. In the majority of these patients, the pneumonia occurred after reduction of the hypercortisolism with medicamentous treatment. We report two cases of PCP during conservative treatment of hypercortisolism. We describe clinical, imaging and laboratory findings in two patients and review published cases of pneumocystits pneumonia in Cushings syndrome. A 60-year-old woman and 20-year-old man with Cushings syndrome due to ectopic ACTH syndrome were treated at our department. Both developed pneumocystis pneumonia early after treatment with ketoconazole and ethomidate bromide had been introduced and the levels of cortisol rapidly decreased. PCP prophylaxis in patients with high cortisolemia should be started before treatment of hypercortisolism in current practice. Gradual lowering of plasma cortisol should also reduce the risk of infection by Pneumocystis jiroveci.

Follicular variant of papillary carcinoma presenting as a hyperfunctioning thyroid nodule.

In this study, we describe a case of papillary carcinoma in a 15-year-old girl who presented with a hyperfunctioning (hot) thyroid nodule and discuss it in the context of current management guidelines for patients with thyroid nodules. In adults, hot nodules rarely require cytologic or histologic evaluation, and hyperthyroidism is often treated with radioiodine (131I). However, in children and adolescents, the malignancy rate for nodules (both cold and hot) is higher and surgery is often necessary. Surgery may serve as a therapy, as well as a diagnostic tool, to treat hot nodules in children and adolescents.

Impact of Hashimoto's thyroiditis, TSH levels, and anti-thyroid antibody positivity on differentiated thyroid carcinoma incidence.

INTRODUCTION The relationship between Hashimotos thyroiditis (HT) and thyroid cancer (TC) is controversial. While most surgical studies report a high incidence of malignancy among patients with HT, cytological studies do not. The role of autoantibodies in the incidence of malignancy is unclear. MATERIAL AND METHODS A single-centre retrospective observational study was conducted in patients evaluated for thyroid nodules by US-guided fine-needle aspiration cytology (FNAC) and, if indicated, by surgery. The levels of thyroid-stimulating hormone (TSH) and anti-thyroid antibodies were measured at the time of FNAC. RESULTS Of 4947 patients, 599 (12.1%) were diagnosed with HT. A malignant/suspicious cytological result was found in 14.2% of the patients with HT and in 15.2% of the others. The odds ratio (OR) for malignancy in HT was 0.921 (0.716-1.183, p = 0.51). Of 1603 patients who underwent surgery, differentiated thyroid carcinoma was found in 29.5% of the HT patients and in 15.2% of the others (OR 2.33, 95% confidence interval CI, 1.403-3.854, p < 0,001). Low TSH (< 0.4 mIU/L) decreased the malignancy rate in the entire patient population, both when considering the cytological results and the surgical results. This was not confirmed in the subgroup diagnosed with HT. No relationship was observed between autoantibodies against thyroid peroxidase (ATP) or thyroglobulin (ATG) and malignancy rate. CONCLUSIONS No association between HT and thyroid cancer was observed cytologically; a positive relationship in histological series was caused by selection bias. Low TSH levels decreased the risk of TC in patients with nodular goitre, but this has not been proven in patients with HT.

Expression profiles of somatostatin, dopamine, and estrogen receptors in pituitary adenomas determined by means of synthetic multilocus calibrators

AIMS Pituitary adenomas (PA) are non-invasive benign tumors with a high autopsy prevalence. They are classified according to the type of hormone secreted (prolactin, growth hormone, adrenocorticotropin, thyrotropin, folitropin, or luteinizing hormone). Clinically non-functioning adenomas (CNFA) lacking the typical hypersecretion of hormones make up a significant portion of PA. The aim of the study was to determine the complete expression profiles of somatostatin receptors (SSTR1-SSTR5), dopamine receptors type 2 (D2R), and estrogen receptors (ER1) in various types of PA. METHODS Adenoma specimens were obtained from 206 patients during transsphenoidal resection. For quantitative analysis, reverse transcription and consequent real-time PCR with synthetic multilocus calibrators (SMC) were used. The obtained data were normalized to the number of transcripts of the beta-glucuronidase gene. RESULTS The use of SMC enabled the alignment of individual calibration functions for all the receptors. No relationships between the expression of the receptors and the tumor size, site of extension, gender or age at diagnosis were significant. In growth hormone-secreting adenomas, D2R and SSTR2 transcripts were extensively expressed, followed by ER1, SSTR5, SSTR3, and SSTR1. In patients with macroprolactinomas, transsphenoidal resection was indicated because dopamine agonists did not normalize prolactin levels. D2R, ER1 and SSTR1 transcripts were significantly transcribed. Corticotroph adenomas showed high levels of D2R and ER1 transcripts and lower amounts of SSTR2 and SSTR1 transcripts. SSTR5 transcripts were very low. Subjects with CNFA dominantly expressed D2R and ER1, followed by SSTR2 and SSTR3 mRNA. CONCLUSION We evaluated SSTR1-SSTR5, D2R, and ER1 expressions in a large group of pituitary adenomas and we found that determining their individual expression profiles could help when choosing the optimal postoperative treatment.

Detection of cytomegalovirus DNA in fecal samples as a method for CMV enterocolitis diagnosis after allogeneic stem cell transplantation

BACKGROUND Cytomegalovirus enterocolitis is a rare but potentially life threatening complication after allogeneic stem cell transplantation. Its early diagnosis and treatment are essential for a successful outcome. OBJECTIVE To determine the potential benefit of fecal CMV DNA detection in the diagnosis of CMV colitis among stem cell transplant recipients. STUDY DESIGN Biopsies from the lower gastrointestinal tract, taken during 69 episodes of diarrhea, were compared with fecal samples previously examined for CMV DNA in 45 patients after allogeneic stem cell transplantation. RESULTS Six confirmed cases of CMV colitis were observed, with 16 out of 69 (23%) fecal samples proving positive for CMV DNA. Only one positive sample correlated with histologically confirmed CMV colitis, and 15 samples were evaluated as false positive. These results provide a 16.7% sensitivity and 76.2% specificity in the diagnosis of CMV enterocolitis. CONCLUSION The examination of fecal samples for the presence of CMV DNA has very low potential in the diagnosis of CMV enterocolitis after allogeneic stem cell transplantation; therefore, a biopsy of the gastrointestinal mucosa is still warranted for correct diagnosis.

Ciprofloxacin prophylaxis during autologous stem cell transplantation for multiple myeloma in patients with a high rate of fluoroquinolone-resistant gram-negative bacteria colonization

BACKGROUND Ciprofloxacin prophylaxis used to be a standard precaution during autologous stem cell transplantation. Its benefit, with a high prevalence of fluoroqinolone resistance in the population, has recently been under scrutiny. OBJECTIVE To evaluate the impact of cessation of ciprofloxacin prophylaxis during stem cell transplantation for multiple myeloma. PATIENTS AND METHODS Data from 104 patients with multiple myeloma transplanted during the period from January 2013 to April 2015 were retrospectively reviewed. 67 received standard ciprofloxacin prophylaxis (group A) and 37 received no antibacterial prophylaxis (group B). RESULTS Febrile episodes during neutropenia, bloodstream infection (BSI) and mortality in these two cohorts were evaluated. Gram negative BSI was assessed for the colonization of quinolone-resistant gram-negative pathogens. Secondary Clostridium difficile enterocolitis presence was determined in both cohorts. There were 42 (63%), 7 (10%), and 0 febrile episodes, BSI and gram-negative BSI respectively in group A, and 34 (92%), 12 (32%), and 4 (11%) respectively in group B. The differences in the number of febrile episodes (P=0.0011) and deaths (P=0.0427) were statistically significance. Mortality was 0 and 3 (8%) in group A and group B, respectively. There was no significant difference in colonization with quinolone-resistant gram negative pathogens (25 (37%) versus 11 (30%)) between groups. The occurrence of Clostridium difficile colitis was the same in both groups. CONCLUSION We resumed ciprofloxacin prophylaxis for the following reasons. There was a significant reduction in febrile episodes, and consequently a sparing effect of antibiotics used for treatment of this condition. No difference in Clostridium difficile colitis occurred and the mortality rate of 8% in group B was unacceptably high.

Risk and Prognostic Factors in Cerebral Venous Thrombosis

Objective and design: Cerebral venous thrombosis (CVT) differs from deep venous thrombosis (DVT) in prognosis, risk factors and treatment. We analyzed data gathered in our prospective CVT single-center registry in search of risk and prognostic factors. Data from 73 patients were available.Results: JAK2 mutation (11%) and Leiden mutation of factor V (11%) were the most common among genetic risk factors. The most common acquired risk factor was the use of combined hormonal contraception (COC) or hormonal replacement therapy (HRT) in 64% of female patients. No specific cause was found in 22% of cases. Complete recanalization was present in 44% of cases, more often in female than in male (p=0.0287) and in younger patients (p=0.045). We found final mRS score one and higher in 29% of patients. These patients did not use COC/HRT (p=0.021) or did not achieve complete recanalization (p=0.0058). Patients with higher mRS score tend to be older (p=0.081).Conclusions: COC/HRT use and complete recanalization can be considered when adjusting the length of anticoagulation therapy. JAK2 mutation should be screened in all patients with CVT.

Treatment of Multifocal Multisystem BRAF Positive Langerhans Cell Histiocytosis with Cladribine, Surgery and Allogenic Stem Cell Transplantation

Langerhans cell histiocytosis (LCH) is a very rare disease in adults and as well a very rare cause of sellar expansion. The clinical presentation can be heterogeneous, from a single bone lesion to potentially fatal, widespread disease. We describe the difficulties with the diagnosis and treatment of LCH as well as successful treatment with cladribine chemotherapy and allogeneic stem cell transplantation.