ABSTRACT
<b><br>Introduction:</b> Primary hyperparathyroidism (PHPT) is mainly caused by parathyroid adenoma (PA). Rare variants of PA, weighing >2.0-3.5 g are called "large" or "giant" adenomas and account for about 1.5% of all PA.</br> <b><br>Aim:</b> The aim of this study was to compare normal-sized and large parathyroid lesions identifying risk factors for severe hypercalcemia.</br> <b><br>Materials and methods:</b> 27 patients with PHPT and parathyroid lesion ≥2.0 cm3 (study group) were compared with 73 patients with PHPT and lesion < 2.0 cm<sup>3</sup> (control group). In both groups, the majority were women (81.5% - study group, 90.5% - control group, gender ratios 4.4:9.1, respectively). The patients were examined preoperatively and postoperatively: PTH, creatine, calcium, and phosphate serum and urine concentrations, and calcidiol serum levels were assessed. Preoperative ultrasonography (US) was performed.</br> <b><br>Results:</b> Patients with larger parathyroid lesions had signifficantly higher PTH and calcium serum concentrations and lower serum phosphate and calcidiol concentrations. There were no statistically significant differences in the concentration of creatine in serum and urine, calciuria, or tubular reabsorption of phosphorus (TRP). US relatively underestimated the parathyroid volume by about 0.3-0.4 mL (10% in larger lesions and 43% in smaller ones).</br> <b><br>Conclusions:</b> Due to higher PTH and calcium levels, larger parathyroid adenomas may constitute a higher risk of severe hypercalcemia. In general, US underestimated the parathyroid volume.</br>.
Subject(s)
Adenoma , Hypercalcemia , Parathyroid Neoplasms , Humans , Hypercalcemia/etiology , Hypercalcemia/blood , Hypercalcemia/diagnosis , Parathyroid Neoplasms/surgery , Parathyroid Neoplasms/complications , Parathyroid Neoplasms/blood , Female , Male , Middle Aged , Adenoma/surgery , Adenoma/complications , Adenoma/blood , Adult , Aged , Risk Factors , Hyperparathyroidism, Primary/surgery , Hyperparathyroidism, Primary/blood , Hyperparathyroidism, Primary/complications , Calcium/blood , ParathyroidectomyABSTRACT
BACKGROUND Brown and jaw tumors are rare entities of poorly understood etiology that are regarded as end-stage of bone remodeling in patients with long-lasting and chronic hyperparathyroidism. Jaw tumors are mainly diagnosed in jaw tumors syndrome (HPT-JT syndrome) and are caused by mutation in the CDC73 gene, encoding parafibromin, a tumor suppressing protein. The aim of this work is to present 4 cases of patients in whom the genetic mutation of the CDC73 gene and clinical presentation coexist in an unusual setting that has not yet been described. CASE REPORT We present cases of 4 patients with primary hyperparathyroidism. Three were diagnosed with brown tumors (located in long bones, ribs, iliac, shoulders) and 1 with brown and jaw tumors. Expression of parafibromin in affected parathyroid tissues were analyzed. In patients without positive parafibromin staining, we searched for CDC73 mutation using next-generation sequencing. Parafibromin staining was positive in 1 patient with brown tumors and was negative in 2 individuals with brown tumors and 1 with brown and jaw tumors. CDC73 mutation was detected in two-thirds of patients (60%) with negative staining for parafibromin and brown tumors. MEN1 mutation was found in the patient with brown tumor and positive staining for parafibromin. CONCLUSIONS Patients with hyperparathyroidism and coexistence of brown tumors or jaw tumors might have decreased expression of parafibromin in parathyroid adenoma tissue, which might be caused by CDC73 mutation and suggest a genetic predisposition. Further research on much larger study groups is needed.
Subject(s)
Fibroma , Hyperparathyroidism, Primary , Jaw Neoplasms , Parathyroid Neoplasms , Humans , Hyperparathyroidism, Primary/diagnosis , Hyperparathyroidism, Primary/genetics , Tumor Suppressor Proteins/genetics , Jaw Neoplasms/genetics , Jaw Neoplasms/complications , Jaw Neoplasms/pathology , Parathyroid Neoplasms/complications , Parathyroid Neoplasms/genetics , Parathyroid Neoplasms/diagnosis , Transcription FactorsABSTRACT
BACKGROUND Parathyroid carcinoma (PC), accounting for 0.005% of all cancers, is responsible for less than 1% of all cases of primary hyperparathyroidism, and equally affects males and females, usually in 4th or 5th decades of life. PC can occur sporadically and can be associated with congenital genetic syndromes such as hyperparathyroidism-jaw tumor syndrome (HPT-JT), isolated familial hyperparathyroidism, or multiple endocrine neoplasia 1 and 2 syndromes. Surgery is the main treatment, with a limited role of radio- and chemotherapy, which allows 49-77% of patients to survive 10 years. In this work we report the case of a patient with parathyroid carcinoma, whose treatment required 13 surgeries over a period of 27 years, together with radiotherapy and pharmacological treatment. CASE REPORT A 51-year-old woman was first diagnosed with primary hyperparathyroidism in 1993 at the age of 23. From 1993 to present, she underwent 13 surgeries and 33 courses of radiotherapy due to recurrent lesions, which initially had a character of parathyroid adenomas, then parathyromatosis, and finally were diagnosed as parathyroid carcinoma. The patient also required and currently requires complex pharmacological treatment to control the calcemia and manage the complications of the primary disease. Supervision by the multidisciplinary professional medical team allows the patient to lead a normal life with good control of the disease. CONCLUSIONS Parathyroid carcinoma is a rare disease with a number of complications; however, obtaining satisfactory long-term survival with acceptable quality of life is achievable.
Subject(s)
Hypercalcemia , Hyperparathyroidism, Primary , Jaw Neoplasms , Parathyroid Neoplasms , Female , Humans , Hypercalcemia/diagnosis , Hypercalcemia/etiology , Hyperparathyroidism, Primary/complications , Hyperparathyroidism, Primary/diagnosis , Male , Middle Aged , Parathyroid Neoplasms/complications , Parathyroid Neoplasms/diagnosis , Quality of LifeABSTRACT
Brown tumours, known also as osteitis fibrosa cystica, are benign osteolytic lesions found in 5-15% of patients with hyperparathyroidism, and commonly located in mandibles, the shafts of long bones, the pelvis or ribs. As they compromise bone strength, pathological fractures can be a typical effect of their presence; but given the complex nature of the disease process in this case, such fractures require an interdisciplinary approach directed at orthopaedic treatment, plus management of the underlying hyperparathyroidism. In this paper, we present the case of a 36-year-old female patient with bilateral anophthalmia, hyperparathyroidism and nephrolithiasis, in whom a fall led to her sustaining a pathological fracture of the proximal third of the femoral shaft in the place of an osteolytic lesion, as well as second pathological fracture of the left patella also changed by multiple examples of such lesions. Parathyroidectomy on account of adenoma had been performed 2 weeks prior to the trauma. The femoral shaft fracture was treated surgically, the patella fracture conservatively, and a sample brown tumour was found in tissue. As the parathyroid showed no parafibromin expression, a diagnosis of HPT-JT (hyperparathyroidism and jaw tumour) was arrived at, with this condition given as caused by CDC73 mutation. This disease is able to account for brown tumours, hyperparathyroidism, benign or malignant tumours of kidneys, intestinal tract, and lungs. The approach combining treatment of the fractures with intervention over the parathyroid adenoma proved a successful one, with complete bone union ensuing, and no relapse into hyperparathyroidism 2 years on from the surgery. This case indicates the importance of an interdisciplinary approach to the treatment of brown tumours, as well as the necessity for a diagnosis to be extended when incidental brown tumours are found.
ABSTRACT
BACKGROUND: Mechanisms that are responsible for positive 99mTc-MIBI uptake in parathyroid glands are not clearly understood, some authors suggest there is a correlation between 99mTc MIBI accumulation and oxyphil cell content or parathyroid gland volume. The aim of our work was to assess the relationship between the pathological structure of parathyroids, their volume, oxyphil cell content and parathyroid 99mTc-MIBI retention. MATERIAL AND METHODS: A total of 62 hyperfunctioning parathyroid glands in 46 patients were retrospectively analyzed. Preoperative 99mTc-MIBI scintigraphy was performed according to the double-phase and subtraction protocol. After surgery all glands were evaluated histologically, oxyphil cell content was assessed and volume of each excised gland was calculated. RESULTS: Scintigraphy was positive in 41 of 62 parathyroid glands (66%). The median volume of positive glands was larger than that of negative glands (1.33 ml vs 0.7 ml, p = 0.015). Of the parathyroid lesions, there were 14 (22.6%) cases of nodular hyperplasia, 23 (37.1%) cases of diffuse hyperplasia, and 25 (40.3%) cases of adenomas. A high (≥ 25%) oxyphil cell content was found in 16 glands (25.8%) and a low ( < 25%) oxyphil cell content in 46 (74.2%) glands. Histopathology of parathyroid glands was related to the scintigraphy result (p = 0.002), but not to the 99mTc-MIBI uptake pattern (p = 0.868). The overall result of scintigraphy was not related to the oxyphil cell content (p = 0.797). 99mTc-MIBI uptake pattern wasn't related to the oxyphil cell content (p = 0.833). In general, parathyroid lesions with low oxyphil cell content were larger than parathyroid glands with high oxyphil cell content (1.33 ml vs 0.5 ml, respectively; p = 0.01). The median volume of parathyroids containing a high number of oxyphil cells and having a prolonged 99mTc-MIBI retention was larger than those without prolonged 99mTc-MIBI retention (1.62 ml vs 0.3 ml, respectively; p = 0.008). The median volume of parathyroids with low oxyphil cells content and showing prolonged 99mTc-MIBI retention was larger than those without prolonged 99mTc-MIBI retention (1.95 ml vs 1.07 ml, respectively; p = 0.014). CONCLUSIONS: Our findings suggest that a positive scintigraphy result depends on parathyroid histopathology and gland volume and does not depend on the presence of oxyphil cells. Prolonged 99mTc-retention is not related to the parathyroid gland histopathology and the presence of oxyphil cells but to the gland volume.
Subject(s)
Oxyphil Cells/pathology , Parathyroid Glands/diagnostic imaging , Parathyroid Glands/pathology , Female , Humans , Male , Middle Aged , Organ Size , Radionuclide Imaging , Retrospective Studies , Technetium Tc 99m SestamibiABSTRACT
BACKGROUND: Literature on non-neoplastic adrenal pseudocysts (NNAPC) remains limited and to date no large series have been reported. The pathogenesis of these lesions remains poorly defined, however a vascular origin is most often suggested in the literature. We aimed to evaluate the clinicopathological features and the spectrum of vascular changes within NNAPC, in order to better understand the mechanisms and circumstances of their pathogenesis. METHODS AND RESULTS: We reviewed 44 cases of surgically resected NNAPC. There were 30 females and 14 males ranging from 23 to 82â¯years (median, 53â¯years). On the basis of histopathologic and immunohistochemical analysis of the vascular changes the following types were defined: pseudocysts with lymphatic-related changes (type 1, nâ¯=â¯16), pseudocysts with large vein-related changes (type 2, nâ¯=â¯15) and pseudocysts with blood vessel microvasculature-related changes (type 3, nâ¯=â¯13). The median patient age of the latter group was higher than that of type 1 and 2 (64â¯years versus 51 and 50â¯years, respectively; pâ¯=â¯0.0002). Type 3 pseudocysts were more frequently associated with a history of systemic vascular and vascular-related disorders than type 1 and type 2 pseudocysts (92% versus 33% and 64%, respectively; pâ¯=â¯0.008). Type 1 pseudocysts were more frequently connected with a history of previous intra-abdominal surgical procedures than type 2 and 3 pseudocysts (60% versus 7% and 25%, respectively; pâ¯=â¯0.0079). CONCLUSIONS: NNAPC are clinically heterogenous and can arise on a background of various vascular changes. They may represent end-stage processes related to lymphangiomatous lesions, changes in adrenal venous structures or microvasculature.
Subject(s)
Adrenal Gland Neoplasms/pathology , Adrenal Glands/pathology , Cysts/pathology , Microvessels/pathology , Pseudopregnancy/pathology , Adrenal Gland Neoplasms/diagnosis , Adrenal Gland Neoplasms/metabolism , Adult , Aged , Aged, 80 and over , Female , Humans , Immunohistochemistry/methods , Male , Middle Aged , Young AdultABSTRACT
Gliomas are the most frequent type of primary brain tumours. Low grade gliomas (LGGs, WHO grade II gliomas) may grow very slowly for the long periods of time, however they inevitably cause death due to the phenomenon known as the malignant transformation. This refers to the transition of LGGs to more aggressive forms of high grade gliomas (HGGs, WHO grade III and IV gliomas). In this paper we propose a mathematical model describing the spatio-temporal transition of LGGs into HGGs. Our modelling approach is based on two cellular populations with transitions between them being driven by the tumour microenvironment transformation occurring when the tumour cell density grows beyond a critical level. We show that the proposed model describes real patient data well. We discuss the relationship between patient prognosis and model parameters. We approximate tumour radius and velocity before malignant transformation as well as estimate the onset of this process.
Subject(s)
Brain Neoplasms/pathology , Cell Transformation, Neoplastic/pathology , Glioma/pathology , Models, Theoretical , Cell Proliferation , Computer Simulation , Disease Progression , Humans , Magnetic Resonance Imaging , Models, Biological , PrognosisABSTRACT
Epithelial- lined (true) cysts are rare lesions and until now the only information we had about their histogenesis was based on the analysis of a few cases. We retrospectively reviewed 8 cases of cysts with a true epithelial lining (confirmed immunohistochemically). The pathological findings and immunohistochemical analysis of the epithelial linings allowed for categorization of the cysts into 3 groups. Five cysts had pure mesothelial lining, which was flattened to cuboidal, and demonstrated a positive reaction for mesothelial markers (eg. calretinin, WT1), and a negative reaction for EpCAM, EMA, PAX8 and ER. Two cysts had cuboidal to flattened lining, the cells of which were diffusely or focally positive for mesothelial markers, for some epithelial markers (eg. EpCAM and EMA) and despite a lack of müllerian-type epithelium demonstrated a positive reaction for PAX8 and focally for ER. A cyst derived from adreno-hepatic fusion (AHF)-related intra-adrenal bile ductules was diagnosed in a right adrenal gland which was directly adherent to the liver, microscopically features of AHF were visible with intermingling of adrenal and liver parenchymal cells. The immunoreactivity pattern was similar among the preserved cells of the cyst-lining, the intra-adrenal bile ductules and the normal bile ductules in the adjoining liver parenchyma. On the basis of this case series from a single institution (8 presented now and 1 reported before) we propose a new histogenetic categorization of adrenal epithelial cysts into: 1. pure mesothelial cysts (the most common type), 2. mesothelial cysts with incomplete or complete müllerian metaplasia 3. AHF-related cysts.
Subject(s)
Adrenal Gland Diseases/classification , Adrenal Gland Diseases/pathology , Cysts/classification , Cysts/pathology , Adult , Aged , Female , Humans , Male , Middle Aged , Retrospective Studies , Young AdultABSTRACT
INTRODUCTION: Many clinicians consider chronic gastritis to be equivalent to Helicobacter pylori infection. However, it is known that there are numerous other causes of the condition. AIM: Determination of the incidence of gastritis in patients with dyspepsia referred for diagnostic endoscopy of the upper part of the digestive tract, identification of the parts of the stomach most frequently affected by the inflammation, as well as the impact of an insufficient number of collected samples on the correct diagnosis. MATERIAL AND METHODS: Upper gastrointestinal endoscopy due to dyspepsia was performed in 110 patients. In the course of gastroscopy two biopsy specimens were collected for histopathological examination and towards H. pylori infection from the lesser and greater curvature in the antrum 3 cm from the pyloric sphincter, in the body - 4 cm proximally to the stomach angular incisure on the lesser curvature, and in the middle of the greater curvature, as well as in the subcardiac region on the side of the lesser and greater curvature. RESULTS: In patients with dyspepsia H. pylori-negative chronic gastritis is more common than gastritis with accompanying H. pylori infection. Collection of too small a number of biopsy specimens results in failure to detect inflammatory changes and/or H. pylori infection, which may be limited to one part of the stomach. Biopsy specimens of gastric mucosa should be collected in compliance with the assumptions of the Sydney System. Helicobacter pylori infection in people with dyspepsia is now being reported more rarely than in the past (36%). CONCLUSIONS: In patients with dyspepsia chronic H. pylori-negative gastritis is more common than gastritis with an accompanying H. pylori infection. Helicobacter pylori infection is not always equivalent to the presence of chronic gastritis.
ABSTRACT
PURPOSE: Five germline genetic variants (rs116909374, rs965513, rs944289, rs966423, and rs2439302) have been associated in genome-wide association studies (GWAS) with increased risk of differentiated thyroid cancer (DTC), but their role in mortality of patients has not been established. Also, no preoperative marker of the clinical outcome of thyroid cancer had yet been identified. The aim of the study was to investigate the relationship between the variants and overall mortality in patients with DTC. EXPERIMENTAL DESIGN: Retrospective study of 1,836 patients (1,643 women, 193 men) with median age at diagnosis of 49 years and overall median follow-up time of 8.7 years after initial treatment at a single comprehensive cancer center between 1990 and 2013. RESULTS: Among 5 variants, rs966423 was associated with increased mortality, which was 6.4% (33 of 518) versus 3.7% (47 of 1,259) in TT carriers versus CC/CT carriers (P = 0.017). The HR of TT versus TC/CC carriers was 1.6 [95% confidence interval (CI), 1.02-2.49; P = 0.038] after adjustment for age at diagnosis and sex. Importantly, the association of rs966423 with mortality remained valid when clinicopathologic risk factors were included in the model (HR, 1.89; 95% CI, 1.14-3.13; P = 0.014). Higher rs966423-associated patient mortality of TT versus CC/CT carriers was also observed in interaction with angioinvasion (adjusted HR, 3.48; 95% CI, 1.67-7.22; P < 0.001), lymph node metastasis (adjusted HR, 3.47; 95% CI, 1.16-10.4; P = 0.018), extrathyroidal invasion (adjusted HR, 2.07; 95% CI, 1.15-3.73; P = 0.013). CONCLUSIONS: The presence of the rs966423-TT genotype was associated with a significant increase in overall mortality of patients with DTC. Contrary to BRAF mutation and other somatic changes, the status of germline rs966423 is known before the treatment and might be used in the management of mortality risk by means of modification of therapy.
Subject(s)
Genetic Predisposition to Disease , Genome-Wide Association Study , Polymorphism, Single Nucleotide/genetics , Thyroid Neoplasms/genetics , Adult , Aged , Female , Genotype , Humans , Lymphatic Metastasis , Male , Middle Aged , Mutation , Proto-Oncogene Proteins B-raf/genetics , Risk Factors , Thyroid Neoplasms/mortality , Thyroid Neoplasms/pathologyABSTRACT
Low-grade gliomas (LGGs) are a group of primary brain tumours usually encountered in young patient populations. These tumours represent a difficult challenge because many patients survive a decade or more and may be at a higher risk for treatment-related complications. Specifically, radiation therapy is known to have a relevant effect on survival but in many cases it can be deferred to avoid side effects while maintaining its beneficial effect. However, a subset of LGGs manifests more aggressive clinical behaviour and requires earlier intervention. Moreover, the effectiveness of radiotherapy depends on the tumour characteristics. Recently Pallud et al. (2012. Neuro-Oncology, 14: , 1-10) studied patients with LGGs treated with radiation therapy as a first-line therapy and obtained the counterintuitive result that tumours with a fast response to the therapy had a worse prognosis than those responding late. In this paper, we construct a mathematical model describing the basic facts of glioma progression and response to radiotherapy. The model provides also an explanation to the observations of Pallud et al. Using the model, we propose radiation fractionation schemes that might be therapeutically useful by helping to evaluate tumour malignancy while at the same time reducing the toxicity associated to the treatment.
Subject(s)
Brain Neoplasms/radiotherapy , Disease Progression , Glioma/radiotherapy , Models, Theoretical , Treatment Outcome , HumansABSTRACT
CONTEXT: A single microRNA gene may give rise to several mature products that differ in length, called isomiRs. IsomiRs are known to be tissue specific and functionally relevant. The microRNA sequence heterogeneity of the thyroid gland has yet to be determined. OBJECTIVE: The objective of the study was to provide a comprehensive view of the microRNA transcriptome in normal thyroid and papillary thyroid carcinoma (PTC). DESIGN: We used next-generation deep sequencing to analyze microRNA length heterogeneity and expression profiles of PTC tumors (n = 14), unaffected tissue adjacent to tumors (n = 14), and control, noncancerous thyroid tissue (n = 14). The results were validated with a microarray on an additional set of 9 PTC tumor/normal tissue pairs. RESULTS: Eighty-nine microRNAs were significantly deregulated in PTC compared with normal thyroid tissue (false discovery rate < 0.05, fold change 0.13-20.7). Top deregulated miRNAs included miR-146b-5p, miR-221-3p, miR-7-3p, miR-551b-3p, miR-486-3p, and miR-144-3p, confirming previous microarray profiling. The expression of miRNAs did not depend on the BRAF mutation status. Interestingly, 85% of the most abundant microRNAs consisted of isoforms that differed from the standard reference sequence deposited in miRBase. Moreover, the reference microRNAs were completely absent in 42.4% and 35.9% of the microRNAs expressed in normal thyroid and PTC tumors, respectively. Numerous isomiRs had altered seed sequences, which led to a different set of target genes. For highly deregulated miR-146b-5p, we detected 6 isoforms (tumor/normal fold change 14.4-28.7, false discovery rate < 0.002) that varied at their 5' ends with a 1-nt difference that created 2 alternative seeds. The target genes for those 2 seeds overlapped in only 13.1% of genes. CONCLUSIONS: Almost all microRNAs exhibit isoforms of variable length and potentially distinct function in thyroid tumorigenesis.
Subject(s)
Carcinoma/genetics , MicroRNAs/physiology , Thyroid Gland/metabolism , Thyroid Neoplasms/genetics , Transcriptome , Carcinoma/etiology , Carcinoma, Papillary , Gene Expression Regulation , Humans , Mutation , Oligonucleotide Array Sequence Analysis , Proto-Oncogene Proteins B-raf/genetics , Thyroid Cancer, Papillary , Thyroid Neoplasms/etiologyABSTRACT
Bacterial thyroiditis is a rare disease, and one of which the clinical symptoms and signs are frequently misleading. On the other hand, prompt diagnosis is crucial for successful treatment. We report the case of an 82 year-old man with diabetes mellitus type 2 and a history of steroid treatment who presented with severe odynophagia and dysphagia associated with fever, chills, sore throat and right ear pain. Based on the clinical picture, radiological studies, thyroid cytology, blood and thyroid aspirate culture, suppurative thyroiditis caused by Salmonella enteritidis was diagnosed. The patient was successfully treated with antibiotics and surgical drainage.
Subject(s)
Salmonella Infections/complications , Salmonella enteritidis/pathogenicity , Thyroiditis, Suppurative/etiology , Aged, 80 and over , Anti-Bacterial Agents/therapeutic use , Diabetes Mellitus, Type 2/complications , Drainage/methods , Humans , Male , Salmonella Infections/therapy , Thyroidectomy/methods , Thyroiditis, Suppurative/therapy , Treatment OutcomeABSTRACT
INTRODUCTION: Estimation of malignancy in thyroid follicular neoplasms is a common diagnostic problem, thus revealing of differences in expression of some antigens in both benign and malignant lesions seems to be essential. The aim of this study is to evaluate the immunohistochemical expression of CD15, galectin-3 and HBME-1 in follicular adenomas and carcinomas. MATERIAL AND METHODS: Samples of 38 follicular adenomas (23 "classical", 5 with intracapsular invasion, 10 oncocytic) and 15 follicular carcinomas (9 "classic", 6 oncocytic) were stained immunohistochemically with anti-CD15, galectin-3 and HBME-1. RESULTS: In the whole group we found statistically significant differences in CD15 expression between follicular adenomas and carcinomas. "Classic" follicular carcinomas (without oncocytic tumors) showed stronger CD15 and HBME- 1 expression than "classic" adenomas. Adenomas with intracapsular invasion differed from "classic" adenomas only in HBME-1 expression. In oncocytic tumors the expression of examined antigens was similar. CONCLUSIONS: 1. In the group of nonoxyphilic tumors positive reaction with HBME-1 was more common in adenomas with intracapsular invasion and carcinomas, but positive reaction with anti-CD15--only in carcinomas. We suggest that reactivity with these antibodies could mark malignancy. 2. Oncocytic tumors had similar expression of CD15 and HBME-1 and galectin-3.
Subject(s)
Adenoma/chemistry , Biomarkers, Tumor/analysis , Carcinoma, Papillary, Follicular/chemistry , Galectin 3/analysis , Lewis X Antigen/analysis , Thyroid Neoplasms/chemistry , Adenoma/pathology , Carcinoma, Papillary, Follicular/pathology , Diagnosis, Differential , Humans , Immunohistochemistry , Neoplasm Invasiveness , Thyroid Neoplasms/pathologyABSTRACT
Sialylation of cell components is an important immunomodulating mechanism affecting cell response to hormones and adhesion molecules. To study alterations in sialic acid metabolism in Graves' disease (GD) we measured the following parameters in various human thyroid tissues: lipid-bound sialic acid (LBSA) content, ganglioside profile, total sialyltransferase activity, and the two major sialyltransferase mRNAs for sialyltransferase-1 (ST6Gal I) and for sialyltransferase-4A (ST3Gal I). Fragments of toxic thyroid nodules (TN), nontoxic thyroid nodules (NN) and nontumorous tissue from patients with nodular goiter or thyroid cancer were used as a control (C). The LBSA content and sialyltransferase activity were the highest in the GD group (164 +/- 4.44 versus 120 +/- 2.00 nmoL/g, p = 0.005 and 1625 +/- 283.5 versus 324 +/- 54.2 cpm/mg of protein, p < 0.005 compared to control group C). Ganglioside profile in the GD group was similar to that in control tissues. Sialyltransferase- 1 mRNA and sialyltransferase-4A mRNA levels were significantly higher in the GD group than in the control group (12.52 +/- 6.90 versus 2.54 +/- 1.24 arbitrary units, p < 0.005 and 2,49 +/- 1.16 versus 1.23 +/- 0.46 arbitrary units, p < 0.05, respectively). There was a positive correlation between the increased sialyltransferase-1 mRNA level and the TSH-receptor antibody titer determined by the TRAK test. These results indicate that sialyltransferases expression and activity are increased in GD. Exact mechanism of this upregulation remains unknown, though one of possible explanations is the activation of the thyrotropin (TSH) receptor.
Subject(s)
Graves Disease/metabolism , Graves Disease/physiopathology , Sialyltransferases/genetics , Thyroid Gland/enzymology , Adolescent , Adult , Aged , Female , Gangliosides/metabolism , Gene Expression Regulation, Enzymologic , Humans , Male , Middle Aged , N-Acetylneuraminic Acid/metabolism , RNA, Messenger/metabolism , Receptors, Thyrotropin/metabolism , beta-D-Galactoside alpha 2-6-Sialyltransferase , beta-Galactoside alpha-2,3-SialyltransferaseABSTRACT
UNLABELLED: Hepatoid differentiation in neoplastic tumors occurs not only in primary hepatic carcinoma but also in other malignant tumors, especially carcinomas. Stomach is the most frequent site of such tumors. Usually, at the time of diagnosis liver metastases are found and it is difficult to establish what was the primary site of hepatoid-like carcinoma. CASE REPORT: 83-year-old man was admitted to the hospital due to upper gastrointestinal haemorrhage. Beside weight loss (11 kg during the period of 3 months) he did not complain of any symptoms. Urgent gastroscopy revealed in the middle portion of the gastric corpus two ulcers 12 and 3 mm in diameters and just above them polyp 1.5 cm in diameter. The other parts of gastrointestinal tract were normal. Neoplastic infiltration of the whole thickness of the gastric wall was found in the histopathologic examination of the specimens taken from all these lesions. The lesion consisted of the hepatocyte-like cells with the droplets of bile visible among them. Morphological examination and immunohistochemical results (CKMNF+, CKhepatocyte+, Vimentin and CD68 negative) were consistent with very rare hepatoid type of gastric cancer--carcinoma hepatoides. The following investigations (USG, CT) showed tumor in the II, III and IV segments of the liver and thromboses in the left branch of vena porta and middle hepatic vena. The serum level of AFP was high (5837 ng/l). The possibility of gastric infiltration by primary hepatic tumor and primary gastric hepatoides carcinoma were considered in the differential diagnosis. CONCLUSION: Morphological characteristics of primary hepatic carcinoma may be identical with primary gastric hepatoides carcinoma. When the biopsy specimens are very small even immunohistochemical examination does not allow to establish the diagnosis.