Hürthle cell carcinoma: diagnostic and therapeutic implications

Background  

Hürthle cell carcinoma is a variant of follicular cell carcinoma of thyroid. It may present as a low-grade tumour or as a more aggressive type. Prognosis depends upon the age of the patient, tumour size, extent of invasion and initial nodal or distant metastasis.     

Fine needle aspiration of poorly differentiated oxyphilic (Hürthle cell) thyroid carcinoma: a case report

BACKGROUND: Poorly differentiated oxyphilic (Hürthle cell) carcinomas are a more recently described variant of poorly differentiated thyroid carcinoma and are characterized by a prominent Hürthle cell component in a solid or trabecular arrangement. Clinically, poorly differentiated oxyphilic carcinomas behave more aggressively as compared to classic Hürthle cell carcinomas, which have a predominantly follicular pattern. Although the histology of these rare thyroid tumors has been reported in the literature, the cytologic features on fine needle aspiration biopsy have not been described before. CASE: A 73-year-old man with a long history of radioactive iodine and levothyroxine therapy for multinodular goiter presented with a painful, rapidly expanding, 6-cm, left thyroid mass with aggressive radiologic features. Fine needle aspiration biopsy of the mass yielded extremely cellular smears with a dual population of medium-sized follicular cells and numerous Hürthle cells. Subsequent thyroidectomy confirmed the malignant nature of this Hürthle cell-rich tumor, warranting a diagnosis of poorly differentiated oxyphilic (Hürthle cell) thyroid carcinoma. CONCULSION: Poorly differentiated oxyphilic thyroid carcinoma is an aggressive variant of Hürthle cell carcinomas and must enter the differential diagnosis when fine needle aspiration biopsy of a radiologically aggressive thyroid mass yields extremely hypercellular smears with a prominent Hürthle cell component.     

Hürthle cell carcinoma of the thyroid presenting as thyrotoxicosis

ObjectiveTo report a case of hyperthyroidism associated with Hülllnnvl-ürthle cellcarcinoma and to review the literature regarding this relationship.MethodsWe describe the clinical, biochemical, radiologic, and pathologic data of a patient with Hürthle cellcarcinoma associated with thyrotoxicosis and reversible heart failure. We discuss the mechanistic aspects and review previously reported cases of functionalHürthle cellcarcinomas.ResultsA 43-year-old womanpresented with thyrotoxicosis and nonischemic cardiomyopathy. She had a “hot” nodule inthe left lobe of the thyroid onsodium pertechnetate scan. She underwent a left hemithyroidec-tomy and isthmusectomy. Pathologic findings revealed a minimally invasive Hürthle cellcarcinoma. Onfollow-up, the dilated cardiomyopathy had resolved. The associationof thyroid carcinoma with thyrotoxicosis is rare.ConclusionsSome Hürthle cellcarcinomas canbe functionaland lead to thyrotoxicosis. To our knowledge, we present the first case of reversible dilated cardiomyopathy due to thyrotoxicosis originating from Hülll-ürthle cellcarcinoma. (Endocr Pract. 2012;18:e5-e9)     

Hürthle cell Thyroid Carcinoma Presenting as A “Hot” Nodule

ObjectiveTo report an unusual clinical scenario and a rare histopathologic finding of Hürthle cell thyroid carcinoma in a patient with an autonomous thyroid nodule.MethodsWe describe the presentation and clinical course leading to the surprising histopathologic diagnosis of Hürthle cell carcinoma in a pediatric patient who was diagnosed with hyperthyroidism presenting as a solitary toxic nodule.ResultsA 13-year-old white girl presented with a recent history of a palpable thyroid nodule during a routine primary care clinic visit. She was asymptomatic, and thyroid function tests revealed a suppressed thyrotropin concentration, high-normal free thyroxine concentration, and elevated triiodothyronine concentration. The patient underwent dedicated thyroid ultrasonography revealing a 3.5-cm complex mass in the left lobe with increased central vascularity. Iodine 123 imaging of the thyroid demonstrated homogenous, hyperintense activity in the left lobe. The right lobe was not visualized. A solitary toxic nodule was diagnosed, and, considering her age, she was referred for surgical management. The patient underwent a left lobectomy with isthmusectomy. Pathologic examination revealed a 5-cm, encapsulated, well-differentiated Hürthle cell carcinoma with negative margins and no lymphovascular invasion. The patient underwent subsequent completion thyroidectomy with no evidence of residual carcinoma in the right thyroid lobe.ConclusionsMalignancy in autonomously functioning thyroid nodules is rare. Most of the thyroid nodules presenting as “hot” on radioiodine scintigraphy are benign follicular adenomas. However, this case represents a rare clinical entity, and it highlights the need for clinicians to be vigilant and aware that occasionally carcinomas can masquerade as scintigraphic “hot” nodules. (Endocr Pract. 2011;17:e68-e72)     

Could a strong alkali deproteinization replace the standard lysis step in alkaline single cell gel electrophoresis (comet) assay (pH > 13)?

The alkaline version of single cell gel electrophoresis (comet) assay is widely used for evaluating DNA damage at the individual cell level. The standard alkaline method of the comet assay involves deproteinization of cells embedded in agarose gel using a high salt–detergent lysis buffer, followed by denaturation of DNA and electrophoresis using a strong alkali at pH > 13 [N.P. Singh, M.T. McCoy, R.R. Tice, E.L. Schneider, A simple technique for quantitation of low levels of DNA damage in individual cells, Exp. Cell. Res. 175 (1988) 184–191]. However, a recent report showed that a strong alkali treatment results in simultaneous deproteinization of cells and denaturation of genomic DNA [P. Sestili, C. Martinelli, V. Stocchi, The fast halo assay: an improved method to quantify genomic DNA strand breakage at the single cell-level, Mutat. Res. 607 (2006) 205–214]. This study was carried out to test whether the strong alkali deproteinization of cells could replace the high salt–detergent lysis step used in the standard method of the alkaline comet assay. Peripheral blood lymphocytes from 3 healthy individuals were irradiated with gamma rays at doses varying between 0 and 10 Gy. Following irradiation, the comet assay was performed according to the standard alkaline method (pH > 13) and a modified method. In the modified method, agarose embedded cells were treated with a strong alkali (0.3 M NaOH, 0.02 M Trizma and 1 mM EDTA, pH > 13) for 20 min to allow deproteinization of cells and denaturation of DNA. This was followed by electrophoresis using the same alkali solution to obtain comets. DNA damage expressed in terms of comet tail length, percentage of DNA in comet tail and tail moment obtained by the standard alkaline method and the modified method were compared. In both methods, DNA damage showed a good correlation with the dose of gamma ray. The results indicate a satisfactory sensitivity of the modified method in detecting radiation-induced DNA damage in human peripheral blood lymphocytes.     

Oncocytic-type intraductal papillary mucinous neoplasm (IPMN)-derived invasive oncocytic pancreatic carcinoma with brain metastasis ¿ a case report

ABSTRACT: Pancreatic cancer is a lethal disease without effective treatments at present. It ranks as s as 4th and 5th in cancer-related mortality in the western countries and worldwide. Locally advanced pancreatic duct carcinoma (PDAC) and metastatic PDAC, usually found the metastases over liver, peritoneum, or lung, have been shown to be with dismal prognosis. Brain metastasis is a rare entity and most cases reported before were found post-mortem. Intraductal papillary mucinous neoplasms of the pancreas (IPMN) has been deemed as a precursor of PDAC with very slow progression rate. Here we reported a case diagnosed with IPMN-derived PDAC with brain metastasis. After surgeries for PDAC and brain metastasis, subsequent chemotherapy and radiotherapy were also given. One and half year after surgery, this patient is still living with good performance status, which may warrant individualization of therapeutic strategy for PDAC with only brain metastasis.     

Nuclear targeting with cell-specific multifunctional tricarbonyl M(I) (M is Re, <Superscript>99m</Superscript>Tc) complexes: synthesis,characterization, and cell studies

Abstract  

Auger-emitting radionuclides such as ^99mTc have been the focus of recent studies aiming at finding more selective therapeutic approaches. To explore the potential usefulness of ^99mTc as an Auger emitter, we have synthesized and biologically evaluated novel multifunctional structures comprising (1) a pyrazolyl-diamine framework bearing a set of donor atoms to stabilize the [M(CO)₃]⁺ (M is Re, ^99mTc) core; (2) a DNA intercalating moiety of the acridine orange type to ensure close proximity of the radionuclide to DNA and to follow the internalization and subcellular trafficking of the compounds by confocal fluorescence microscopy; and (3) a bombesin (BBN) analogue of the type X-BBN[7-14] (where X is SGS, GGG) to provide specificity towards cells expressing the gastrin releasing peptide receptor (GRPr). Of the evaluated ^99mTc complexes, Tc ³ containing the GGG-BBN[7-14] peptide showed the highest cellular internalization in GRPr-positive PC3 human prostate tumor cells, presenting a remarkably high nuclear uptake in the same cell line. Live-cell confocal imaging microscopy studies with the congener Re complex, Re ³ , showed a considerable accumulation of fluorescence in the nucleus, with kinetics of uptake similar to that exhibited by Tc ³ . Together, these data show that the acridine orange intercalator and the metal fragment are colocalized in the nucleus, which indicates that they remain connected despite the lysosomal degradation of Tc ³ /Re ³ . These compounds are the first examples of ^99mTc bioconjugates that combine specific cell targeting with nuclear internalization, a crucial issue to explore use of ^99mTc in Auger therapy.     

Valbro : un nouveau site à vertébrés de l’Oligocène inférieur (MP 22) de France (Quercy). II – Oiseaux (Aves)

The bird remains from Valbro belong only to three taxa, Paraortyx lorteti, Archaeotrogon venustus, and A. zitteli. This association makes it possible to ascribe to this locality an early Oligocene age, reference-levels MP 22 or MP 23, which is in agreement with the age given by the mammals.     

Mitochondria-targeted antioxidant SkQ1 (10-(6′-plastoquinonyl)decyltriphenylphosphonium bromide) inhibits mast cell degranulation <Emphasis Type="Italic">in vivo</Emphasis> and <Emphasis Type="Italic">in vitro</Emphasis>

The therapeutic effect of mitochondria-targeted antioxidant 10-(6′-plastoquinonyl)decyltriphenylphosphonium bromide (SkQ1) in experimental models of acute inflammation and wound repair has been shown earlier. It was suggested that the antiinflammatory activity of SkQ1 is related to its ability to suppress inflammatory activation of the vascular endothelium and neutrophil migration into tissues. Here, we demonstrated that SkQ1 inhibits activation of mast cells (MCs) followed by their degranulation and histamine release in vivo and in vitro. Intraperitoneal injections of SkQ1 in the mouse air-pouch model reduced the number of leukocytes in the air-pouch cavity and significantly decreased the histamine content in it, as well as suppressing MC degranulation in the air-pouch tissue. The direct effect of SkQ1 on MCs was studied in vitro in the rat basophilic leukemia RBL-2H3 cell line. SkQ1 inhibited induced degranulation of RBL-2H3 cells. These results suggest that mitochondrial reactive oxygen species are involved in the activation of MCs. It is known that MCs play a crucial role in regulation of vascular permeability by secreting histamine. Suppression of MC degranulation by SkQ1 might be a significant factor in the antiinflammatory activity of this mitochondria-targeted antioxidant.     

Paradox of Bcl‐2 (and p53): why may apoptosis‐regulating proteins be irrelevant to cell death?

Although the Bcl-2 family members and p53 are involved in the regulation of apoptosis, the status of apoptotic machinery (eg caspases) plays a major role in determining the mode and timing of cell death. If the apoptotic machinery is lost, inhibited, or intrinsically inactivated, the "death stars", Bcl-2 and p53, may become irrelevant to cell death. In this light, high levels of Bcl-2 may indicate that downstream apoptotic pathways are still functional. This explains why Bcl-2 overexpression can be a marker of chemosensitivity and favorable prognosis in certain cancers and why retention of wild-type p53 may manifest inactivation of caspases in aggressive cancers.     

Assessment of proliferative activity of thyroid Hürthle cell tumors using PCNA, Ki-67 and AgNOR methods

We have undertaken an attempt to compare the application efficacy of the proliferative activity markers in differential diagnosis of thyroid Hürthle cell tumors (HCT) using the PCNA and Ki-67 labeling and AgNOR visualisation techniques. The present work is a retrospective analysis of 78 Hürthle cell tumors: 20 Hürthle cell carcinomas (HCC), 32 Hürthle cell adenomas (HCA) and 26 hyperplastic nodules with Hurthle cell metaplasia (HCM). Five microm sections were stained according to AgNOR technique and labeled with antibodies against PCNA and Ki-67. AgNOR dot count in the nucleus and proliferative index (PI - percentage of cells expressing PCNA and Ki-67) in randomly chosen nuclei (100 in case of AgNOR and over 1000 in case of PI) were evaluated in each slide. The mean values of AgNOR dot count, PI-PCNA and PI-Ki-67 in HCC, HCA and HCM were respectively: 5.1, 61.3 and 54.9; 3.4, 42.4 and 38.6 and 2.5, 39.3 and 34.3. Statistically significant difference was found in all the proliferative activity markers between malignant and benign tumors: HCC:HCA (p<0.01) and HCC:HCM (p<0.001). There was no statistically significant difference between HCA and HCM.     

XLMR protein related to neurite extension (Xpn/KIAA2022) regulates cell–cell and cell–matrix adhesion and migration

X-linked mental retardation (XLMR) is a common cause of moderate to severe intellectual disability in males. XLMR protein related to neurite extension (Xpn, also known as KIAA2022) has been implicated as a gene responsible for XLMR in humans. Although Xpn is highly expressed in the developing brain and is involved in neurite outgrowth in PC12 cells and neurons, little is known about the functional role of Xpn. Here, we show that Xpn regulates cell–cell and cell–matrix adhesion and migration in PC12 cells. Xpn knockdown enhanced cell–cell and cell–matrix adhesion mediated by N-cadherin and β1-integrin, respectively. N-Cadherin and β1-integrin expression at the mRNA and protein levels was significantly increased in Xpn knockdown PC12 cells. Furthermore, overexpressed Xpn protein was strongly expressed in the nuclei of PC12 and 293T cells. Finally, depletion of Xpn perturbed cellular migration by enhancing N-cadherin and β1-integrin expression in a PC12 cell wound healing assay. We conclude that Xpn regulates cell–cell and cell–matrix adhesion and cellular migration by regulating the expression of adhesion molecules.     

Sinularia leptoclados (Ehrenberg, 1834) (Cnidaria,?Octocorallia) re-examined

Sinularia leptoclados (Ehrenberg, 1834) is re-described. Sinularia leptoclados var. gonatodes Kolonko, 1926 is synonymized with Sinularia maxima Verseveldt, 1977. Two new species of Sinularia with digitiform lobules, leptoclados-type surface clubs and unbranched interior spindles, are described. An updated maximum likelihood tree of Sinularia species with leptoclados-type clubs (clade 5C) based on two mitochondrial genes (mtMutS, COI) and a nuclear gene (28S rDNA) is presented.     

The duality of epidermal growth factor receptor (EGFR) signaling and neural stem cell phenotype: cell enhancer or cell transformer?

Recruitment of neural stem cells (NSCs) represents an elegant strategy for replacing adult central nervous system (CNS) cells lost to injury or disease. However, except in the rostral migratory stream to the olfactory bulb, the adult CNS harbors a relatively non permissive environment for motility of neural stem cells. This opens the possibility of therapeutic enhancement of NSC motility towards sites of CNS injury or disease. The Epidermal Growth Factor Receptor (EGFR) is involved in the activation of a number of downstream pathways that regulate the phenotype of progenitor cells. Activated EGFR tyrosine kinase activity enhances NSC migration, proliferation, and survival. However, EGFR signaling is also known to play a role in the most malignant and highly invasive of human tumors, glioblastoma multiforme (GBM). Recent evidence supports the theory that GBM derives from a 'cancer stem cell' and that EGFR signals are commonly altered in these precursor cells. This article will review the role of EGFR signaling as it relates to neural stem cell motility and invasion. The duality of altered EGFR signaling in neural progenitor cells is discussed and opportunities for enhancing the recruitment of adult progenitors, and consequences of altering EGFR signaling in progenitor cells will be highlighted.     

Fine needle aspiration biopsy of anaplastic thyroid carcinoma developing from a Hürthle cell tumor: a case report

BACKGROUND: Anaplastic thyroid carcinoma is a highly malignant tumor in elderly people with a long history of multinodular goiter and is usually associated with a rapidly fatal clinical evolution. The tumor often develops as a result of anaplastic transformation of a slowly growing papillary carcinoma or follicular neoplasm. CASE: An 85-year-old woman had a multinodular goiter and had been asymptomatic, with a normal white blood cell count and chest radiograph three months prior to her hospital admission for the treatment. The tumor presented with low grade fever, leukocytosis, multiple metastatic lung nodules and enlargement of the intrathoracic thyroid in a period of three months, causing compression of the esophagus and trachea. Despite a total thyroidectomy, the tumor recurred within one month and caused dysphagia and death. CONCLUSION: FNAB permitted the diagnosis of an anaplastic thyroid carcinoma arising from an intrathoracic Hürthle cell tumor.     

Oxygen uptake rate regulation during cell growth phase for improving avermectin B<Subscript>1a</Subscript> batch fermentation on a pilot scale (2 m<Superscript>3</Superscript>)

Avermectin B_1a batch fermentation of Streptomyces avermitilis in a 2 m³ fermentor was investigated by oxygen uptake rate (OUR) regulation during cell growth phase. OUR was controlled by adjusting of aeration and agitation. Result showed that OUR strongly affected cell growth and antibiotics production. Avermectin B_1a biosynthesis could be effectively enhanced when OUR was stably regulated at an appropriate level in batch fermentation of S. avermitilis. Avermectin B_1a yield reached 5568 ± 111 mg/l by controlling maximal OUR between 15 and 20 mmol/l/h during cell growth phase, which was increased by 21.8% compared with the control (maximal OUR above 20 mmol/l/h). The stimulation effect on avermectin B_1a production could be attributed to the improved supply of propionic acid and acetic acid, the precursors of avermectin B_1a, in the cells. Hence, this OUR control method during cell growth phase may be a simple and applicable way to improve industrial production of avermectin.