TERT Promoter Mutations Are a Major Indicator of Poor Outcome in Differentiated Thyroid Carcinomas

Context: Telomerase promoter mutations (TERT) were recently described in follicular cell-derived thyroid carcinomas (FCDTC) and seem to be more prevalent in aggressive cancers. Objectives: We aimed to evaluate the frequency of TERT promoter mutations in thyroid lesions and to investigate the prognostic significance of such mutations in a large cohort of patients with differentiated thyroid carcinomas (DTCs). Design: This was a retrospective observational study. Setting and Patients: We studied 647 tumors and tumor-like lesions. A total of 469 patients with FCDTC treated and followed in five university hospitals were included. Mean follow-up (±SD) was 7.8 ± 5.8 years. Main Outcome Measures: Predictive value of TERT promoter mutations for distant metastasization, disease persistence at the end of follow-up, and disease-specific mortality. Results: TERT promoter mutations were found in 7.5% of papillary carcinomas (PTCs), 17.1% of follicular carcinomas, 29.0% of poorly differentiated carcinomas, and 33.3% of anaplastic thyroid carcinomas. Patients with TERT-mutated tumors were older (P < .001) and had larger tumors (P = .002). In DTCs, TERT promoter mutations were significantly associated with distant metastases (P < .001) and higher stage (P < .001). Patients with DTC harboring TERT promoter mutations were submitted to more radioiodine treatments (P = .009) with higher cumulative dose (P = .004) and to more treatment modalities (P = .001). At the end of follow-up, patients with TERT-mutated DTCs were more prone to have persistent disease (P = .001). TERT promoter mutations were significantly associated with disease-specific mortality [in the whole FCDTC (P < .001)] in DTCs (P < .001), PTCs (P = .001), and follicular carcinomas (P < .001). After adjusting for age at diagnosis and gender, the hazard ratio was 10.35 (95% confidence interval 2.01–53.24; P = .005) in DTC and 23.81 (95% confidence interval 1.36–415.76; P = .03) in PTCs. Conclusions: TERT promoter mutations are an indicator of clinically aggressive tumors, being correlated with worse outcome and disease-specific mortality in DTC. TERT promoter mutations have an independent prognostic value in DTC and, notably, in PTC.

Mycoplasma pneumoniae and Chlamydia pneumoniae in calcified nodules of aortic stenotic valves

Aortic Valve Stenosis (AVS) has been explained as an atherosclerotic process of the valve as they often exhibit inflammatory changes with infiltration of macrophages, T lymphocytes and lipid infiltration. The present study investigated whether the bacteria Chlamydia pneumoniae (CP) and Mycoplasma pneumoniae (MP), detected previously in atherosclerotic plaques, are also present in AVS. Ten valves surgically removed from patients with AVS were analyzed by immunohistochemistry, in situ hybridization, and electron microscopy. The mean and standard deviation of the percentage areas occupied by CP antigens and MP - DNA were respectively 6.21 +/- 5.41 and 2.27 +/- 2.06 in calcified foci; 2.8 +/- 3.33 and 1.78+/- 3.63 in surrounding fibrotic areas, and 0.21 +/- 0.17 and 0.12 +/- 0.13 in less injured parts of the valve. There was higher amount of CP and MP in the calcified foci and in the surrounded fibrosis than in more preserved valvular regions. In conclusion, the fact that there were greater amounts of CP and MP in calcification foci of AVS favors the hypothesis that AS is not an inevitable degenerative process due to aging, but rather that it may be a response to the presence of these bacteria, similarly to the morphology detected in atherosclerosis damage.

Disseminated nocardiosis due to Nocardia farcinica: diagnosis by thyroid abscess culture

A previously healthy 75-year-old white male dentist presented with a 6-month history of low-back pain treated with chronic steroid therapy had a Nocardia farcinica infection diagnosed by aspirate of thyroid abscess and six blood cultures. Despite the treatment with parenteral combination of trimethoprim/sulfamethoxazole, the patient failed to respond and died after two days of therapy. Autopsy revealed disseminated nocardiosis, involving lungs with pleural purulent exudate in both sides, heart, thyroid, kidneys, brain, bones, and lumbosacral soft tissue with destruction of L2-L4.

Histoplasmosis presenting with multiple pulmonary nodules. A case mimicking radiological features of pulmonary metastasis

We present a case of histoplasmosis with multiple pulmonary nodules in a patient with a history of melanoma. This case closely simulated malignancy, including the presence of feeding vessel sign, which occurs in pulmonary metastasis. We emphasize the need to be aware of this infection in areas where histoplasmosis is endemic.

MULTIPLE PULMONARY NODULES CAUSED BY Corynebacterium striatum IN AN IMMUNOCOMPETENT PATIENT

Nondiphtherial corynebacteria are ubiquitous in nature and commonly colonize the skin and mucous membranes of humans, however they rarely account for clinical infection. We present the first reported case of multiple pulmonary nodules caused by Corynebacterium striatum. The infection occurred in a 72-year-old immunocompetent female, and the diagnosis was obtained by Gram's stain and culture of lung biopsy. C. striatumshould be recognized as a potential pathogen in both immunocompromised and normal hosts in the appropriate circumstances.

IgG4-Related Hashimoto's Thyroiditis - A New Variant of a Well Known Disease

Hashimoto's thyroiditis (HT) has been characterized for many years as a well-defined clinicopathologic entity, but is now considered a heterogeneous disease. IgG4-related HT is a new subtype characterized by thyroid inflammation rich in IgG4-positive plasma cells and marked fibrosis. It may be part of the systemic IgG4-related disease. We report a case of a 56-year-old Portuguese man who presented with a one-month history of progressive neck swelling and dysphagia. Laboratory testing revealed increased inflammatory parameters, subclinical hypothyroidism and very high levels of thyroid autoantibodies. Cervical ultrasound (US) demonstrated an enlarged and heterogeneous thyroid gland and two hypoechoic nodules. US-guided fine needle aspiration cytology was consistent with lymphocytic thyroiditis. The patient was submitted to total thyroidectomy and microscopic examination identified typical findings of HT, marked fibrosis limited within the thyroid capsule and lymphoplasmacytic infiltration, with >50 IgG4-positive plasma cells per high-power field and an IgG4/IgG ratio of >40%. After surgery, serum IgG4 concentration was high-normal. Symptoms relief and reduction in laboratory inflammatory parameters were noticed. Thyroid function is controlled with levothyroxine. To our knowledge we report the first case of IgG4-related HT in a non-Asian patient. We also perform a review of the literature regarding IgG4-related disease and IgG4-related HT. Our case highlights this new variant of the well known HT, and helps physicians in recognizing its main clinical features, allowing for proper diagnosis and treatment.

Macrofilaricidal effects of chloroquine on adult Onchocerca volvulus by local infiltration of palpable onchocercal nodules

The macrofilaricidal effects of local infiltration of high concentrations of chloroquine into the capsule of onchocercal nodules on adult worms of Onchocerca volvulus was determined. Six weeks post infiltration, histological examination of single nodules showed all adult worms to be dead. With nodule conglomerates, there was localized action of chloroquine only on the adult worms in the infiltrated nodule, with no diffusion of the drug to adjacent nodules. Chloroquine infiltration of young, recently formed nodules to reduce the adult worm load of infected individuals may be an alternative method to costly nodulectomy.

Multiple lymphoid nodules in bone marrow biopsy in immunocompetent patient with cytomegalovirus infection: an immunohistochemical analysis

In Brazil, a high prevalence of cytomegalovirus (CMV) infection has been documented. In immunocompetent adults CMV infection is usually asymptomatic and therefore morphologic and immunophenotypic bone marrow changes have rarely been described. The authors report the case of a previously healthy patient who developed fever of undetermined origin. The diagnosis of acute CMV infection was based on serological testing. A computed tomographic scan showed mediastinal lymphadenopathy. A bone marrow biopsy revealed a hypercellular haematopoiesis with eosinophilia and large mixed T- and B-cell lymphoid aggregates. In spite of bcl-2 positivity, their reactive nature was demonstrated. Polymerase chain reaction (PCR) and immunohistochemistry were unable to detect CMV-DNA in paraffin-embedded bone marrow sections. Much like in other systemic disorders, the lymphoid nodules in this case seemed to be caused by immunological mechanisms, possibly due to cytokines released in response to the systemic infectious process.

Testicular schistosomiasis as differential diagnosis for testicular nodules: a case report

AbstractDespite its infrequent occurrence, testicular schistosomiasis forming pseudo-tumors can be considered in the differential diagnosis of testicular tumors, especially in areas where the parasitic disease is endemic. In this report, we present a case of testicular schistosomiasis caused by Schistosoma mansoni and mimicking a testicular neoplasm. We describe the patterns of a testicular nodule on ultrasonography and magnetic resonance images in a 46-year-old man. The nodule was removed after a pre-operative diagnosis of a non-malignant lesion. Histology demonstrated granulomas with epithelioid macrophages and eosinophils around S. mansoni eggs within a fibrous tissue that formed a nodular structure.

Parasitic thyroid nodule in a patient with Hashimoto's chronic thyroiditis

A case of parasitic thyroid nodule is presented. The patient was a non symptomatic 53-year-old white woman, on irregular course of L-thyroxine to treat hypothyroidism due to Hashimoto's thyroiditis. Without a history of thyroid trauma or surgery, she presented a 1.6 x 0.7 x 0.5cm right pre-laryngeal lymph node-like mass which, on ultrasonography, appeared distinct from the gland. TSH, thyroid peroxidase antibody and thyroglobulin antibody serum levels were elevated and T4-free level was normal. Thyroid and total body 99mTc isonitrile scintiscan showed a topic thyroid without radionuclide uptake in the nodule. Fine-needle aspiration of the nodule showed epithelial cells with nuclear atypia and oncocytic changes plus intense lymphoid infiltration and germinative center formation, simulating lymph node metastasis of papillary thyroid carcinoma. Conventional biopsy revealed a parasitic thyroid nodule with Hashimoto's chronic thyroiditis. Parasitic thyroid nodule must always be remembered so that unnecessary surgical assessment and undesirable sequels may be avoided.

The importance of the ligation of the inferior thyroid artery in parathyroid function after subtotal thyroidectomy

We prospectively studied the effects of the ligation of the inferior thyroid artery (ITA) on postoperative hypoparathyroidism in 48 patients who underwent functional subtotal thyroidectomy. Patients were randomized into two groups: A, with bilateral ligation of the ITA and B, without ligation of the ITA. Parathyroid function was checked preoperatively and after surgery by clinical examination and measurement of total calcium, intact PTH, urinary calcium, and AMPc. RESULTS: A significant incidence of postoperative hypocalcemia occurred: 17% in group A and 13% in B on the 4th postoperative day. Six months later, the incidence was 5% in Group A and 0% in Group B. These differences were not statistically significant between the two groups, and neither were any of the other clinical and laboratory observations. CONCLUSION: The ligation of the ITA was not an important causal factor for the occurrence of postoperative hypocalcemia after subtotal thyroidectomy.

Relationship between the recurrent laryngeal nerve and the inferior thyroid artery: a study in corpses

The anatomical relationship between the recurrent laryngeal nerve (RLN) and the inferior thyroid artery (ITA) was studied in 76 embalmed corpses, 8 females and 68 males. In both sexes, the RLN lay more frequently between branches of the ITA.; it was found in this position in 47.3% of male corpses and 42.8% of female ones. On the right, RLN was found between branches of the ITA in 49.3% of the cases, anterior to it in 38.04%, and posterior in 11.26%. On the left, the RLN lay between branches of the ITA in 44.45%, posterior to the ITA in 37.05%, and anterior to it in 18.05% of the cases. In 62.68% of the cases, the relationship found on one side did not occur again on the opposite side. There was a significant difference (p<0.05) in the distribution of the 3 types of relationships between the RLN and the ITA, on the right and on the left. Racial variations could contribute to an explanation of the differences observed by authors of different countries in the relationship between the RLN and the ITA.