Correlation between stromal Th and Tc lymphocytes and PD-L1 expression in early breast cancer tumors.

INTRODUCTION: Prognostic and predictive value of PD-L1 as a biomarker in breast cancer remains controversial. While some studies suggest its association with negative prognostic parameters, others reported a highly significant association between PD-L1 expression and tumor-infiltrating lymphocytes, which are known to be an independent favorable prognostic factor. The aim of present study is to examine the relationship between immune response markers and PD-L1 expression in early breast cancer. MATERIAL AND METHODS: Immunohistochemical expression of PD-L1, along with density and composition of stromal lymphocytic infiltrate and peritumoral lymphoid aggregates was analyzed in 95 samples of invasive breast cancer. RESULTS: A strong positive correlation between PD-L1 expression and the density of stromal lymphocytic infiltrate and peritumoral lymphoid aggregates was identified and a cut-off value of 53% coverage of tumor stroma by lymphocytes, with which PD-L1 positivity can be predicted with excellent diagnostic accuracy, was determined for the first time using statistical methods. Additionally, PD-L1 positivity was observed significantly more often in tumors with higher absolute number of both CD4 and CD8 T-lymphocytes in the stromal infiltrate. No significant correlation with molecular subtype of breast cancer was found. CONCLUSIONS: Our results indicate that the density of stromal lymphocytic infiltrate might be a better predictor of PD-L1 positivity in early breast cancer than the molecular subtype and that the key to the optimization of PD-L1 as a biomarker in breast cancer lies in its interpretation in the context of other immune response markers.

Expression of CD105 but not of E-cadherin is associated with malignancy recurrence and disease-free interval in laryngeal cancer in men.

INTRODUCTION: In this study we analyzed CD105 (endoglin) and E-cadherin expression in laryngeal squamous cell carcinoma (LSCC) to evaluate their clinicopathologic significance. MATERIAL AND METHODS: Expression of CD105 and E-cadherin was examined immunohistochemically using paraffin-embedded archival tissues of 72 (35 glottic and 37 supraglottic) previously untreated LSCC male patients. The mean value of the positively-stained microvessels for CD105 counted in four hot spots for each case was used as the final intratumoralmicrovessel density (MVD). A staining score of E-cadherin was calculated based on the percentage of cells stained (0-100%). RESULTS: MVD was significantly higher in patients with advanced TNM stage (P = 0.004) and younger than 65 (P = 0.008). Nodal metastases were more frequent in the cases with low E-cadherin expression (P = 0.000). Tumor recurrence was associated with advanced TNM stage (P = 0.035) and high MVD (P = 0.002). A high MVD was an independent predictor of malignancy recurrence (P = 0.021). The log-rank test showed a significant difference in the disease-free interval in patients stratified according to the MVD value (P = 0.016). Spearman's rank correlation test did not show a significant correlation between E-cadherin and CD105 expression. CONCLUSIONS: CD105-assessed MVD and expression of E-cadherin are promising prognostic factors for the outcome of patients with LSCC. Increased expression of CD105 could help predict patients with an increased risk of developing loco-regional recurrence after surgical treatment. Decreased E-cadherin expression is a potential predictor of lymph node metastases.

Rare benign lung tumours presenting with high clinical suspicion for malignancy: a case series and review of the literature.

INTRODUCTION: Incidentally discovered lung nodules can be worrisome for both the patient and their physicians. Although 95% of solitary lung nodules are benign, it is important to distinguish which nodules have high clinical suspicion for malignancy. Existing clinical guidelines do not apply to patients with signs and symptoms related to the lesion and with an increased baseline risk of lung cancer or metastasis. This paper highlights the vital role of pathohistological analysis and immunohistochemistry in the definitive diagnosis of such incidentally discovered lung nodules. MATERIAL AND METHODS: The three cases presented were selected based on their similar clinical presentations. A review of the literature was performed using the online database PubMed, for articles published in the period between January of 1973 to February of 2023 using the following medical subject headlines: "primary alveolar adenoma," "alveolar adenoma," "primary pulmonary meningioma," "pulmonary meningioma," and "pulmonary benign metastasizing leiomyoma." Results (Case Series). The case series consists of three incidentally discovered lung nodule(s). Although they presented with high clinical suspicion for malignancy, detailed workup confirmed the diagnosis of three rare benign lung tumours: primary alveolar adenoma, primary pulmonary meningioma, and benign metastasizing leiomyoma. CONCLUSIONS: Clinical suspicion for malignancy in the presented cases arose from previous and current medical history of malignancy, family history of malignancy, and/or specific radiographic findings. This paper highlights the need for a multidisciplinary approach in the management of incidentally discovered pulmonary nodules. Excisional biopsy and pathohistological analysis remain the gold standard in confirming the presence of a pathologic process and determining the nature of the disease. Common features of the diagnostic algorithm utilized among the three cases include multi-slice computerized tomography, excisional biopsy via atypical wedge resection (if the nodule is peripherally located), and lastly, pathomorphological analysis using haematoxylin and eosin staining and immunohistochemistry.

The role of miRNA in colorectal cancer diagnosis: A pilot study.

Despite recent advances in diagnosis and treatment, colorectal cancer (CRC) remains the third most common cancer worldwide, and has both a poor prognosis and a high recurrence rate, thus indicating the need for new, sensitive and specific biomarkers. MicroRNAs (miRNAs/miRs) are important regulators of gene expression, which are involved in numerous biological processes implicated in tumorigenesis. The objective of the present study was to investigate the expression of miRNAs in plasma and tissue samples from patients with CRC, and to examine their potential as CRC biomarkers. Using reverse transcription-quantitative PCR, it was revealed that miR-29a, miR-101, miR-125b, miR-146a and miR-155 were dysregulated in the formalin-fixed paraffin-embedded tissues of patients with CRC, compared with the surrounding healthy tissue, and these miRNAs were associated with several pathological features of the tumor. Bioinformatics analysis of overlapping target genes identified AGE-RAGE signaling as a putative joint regulatory pathway. miR-146a was also upregulated in the plasma of patients with CRC, compared with the healthy control group, and had a fair discriminatory power (area under the curve, 0.7006), with 66.7% sensitivity and 77.8% specificity. To the best of our knowledge, this distinct five-miRNA deregulation pattern in tumor tissue, and upregulation of plasma miR-146a, were shown for the first time in patients with CRC; however, studies on larger patient cohorts are warranted to confirm their potential to be used as CRC diagnostic biomarkers.

The Relationship between Diabetes Mellitus and Pancreatic Cancer-Diabetes Mellitus as a Red Flag for Pancreatic Cancer.

The relationship between diabetes mellitus (DM) and pancreatic cancer is complex-DM is both a risk factor and early sign of pancreatic cancer. DM is a risk factor for pancreatic cancer because it increases insulin resistance, intrapancreatic concentrations of insulin, and the bioavailability of IGF, subsequently promoting ductal cell proliferation. Accordingly, treatment targeting the insulin/IGF pathway is the focus of many researchers. Antidiabetic drugs modify the risk for pancreatic cancer-metformin's antineoplastic effect being most notable and indicating potential clinical use in pancreatic cancer. New-onset DM can also be the first manifestation of pancreatic cancer. There are several theories for the pathogenesis of DM in pancreatic cancer, the most important being that DM is a paraneoplastic syndrome caused by diabetogenic factors. As a consequence of this intricate relationship, new-onset DM after the age of 50 is considered a red flag for pancreatic cancer, prompting the need for screening in this patient population. Multiple clinical studies are currently underway exploring this matter. A better understanding of the relationship between DM and pancreatic cancer could aid in developing novel screening and treatment strategies for pancreatic cancer. This could ultimately improve the prognosis and quality of life of patients with pancreatic cancer.

Prognostic significance of a panel of two biomarkers (E-cadherin and CD105) in laryngeal cancer.

This study aimed to evaluate the clinicopathologic significance of the combined immunohistochemical expression of the epithelial-mesenchymal transition marker E-cadherin and the angiogenesis marker CD105 in laryngeal squamous cell carcinoma and assess correlation of their expression. Eighty-five patients who underwent complete resection as primary treatment were selected for this study. E-cadherin and CD105 expression levels were determined by immunohistochemistry. The receiver operating curve approach was applied to determine the cut-off value and separate patients with high and low expression of markers. The high-risk group ("CD105 high" and "E-cadherin low" expression) showed statistically significant correlations with age less than 66 years (p = 0.039), advanced T-status (T3-4) (p = 0.046), aggressive TNM stage (stage III-IV) (p = 0.003) and locoregional recurrence of disease (p = 0.004). In the Kaplan-Meier analyses, the high-risk group had significantly worse prognoses than other risk groups (log-rank test 2 = 9.415, p = 0.024). Spearman's correlation coefficient analysis showed a nonsignificant negative correlation between the expression of E-cadherin and CD105 (rho = -0.073, p = 0.505). Simultaneous consideration of E-cadherin and CD105 is a simple panel of markers to determine aggressive tumour phenotype with a higher risk of disease recurrence in patients with laryngeal cancer.

Prevalence and clinical implications of the HPV16 infection in oral cancer in Montenegro - Evidence to support the immunization program.

Oral squamous cell carcinoma (OSCC) makes 85-95% of all malignances in the oral cavity. Increasing evidence shows that the Human Papillomaviruses (HPVs) are preferentially associated with some oropharyngeal and OSCCs, namely the genotype 16. The aim of the present study was to determine the prevalence and clinical implications of HPV16 infection in oral squamous cell carcinoma in population of Montenegro.This study included 60 patients with OSCC (localized on the lower lip, tongue or/and floor of the mouth), surgically treated at the Clinical Centre of Montenegro from 2012 to 2018. Surgically obtained formalin-fixed and paraffin-embedded specimens were used for histopathological analysis and HPV16 genome detection using standard Polymerase Chain Reaction (primers for detection of E6 gene). Each individual was further followed up for the period of three years and for different clinico-pathological characteristics, including disease free interval (DFI).The prevalence of HPV16 infection in OSCCs was 23.3% and the infection was significantly more common in female patients (P = 0.038). No significant correlation was detectable between HPV16 infection and the patients' age (P = 0.302), tumor site (P = 0.125), tumor grade (P = 0.363) and disease stage (P = 0.995). Observing the total sample the DFI was not significantly different for HPV16-positive versus HPV16-negative patients (P = 0.427), but a gender-based difference in DFI was observed, with the significantly shorter DFI (Log Rank test, P = 0.003) in HPV16 positive female patients compared to male patients (P = 0.003).The results obtained in this study provide scientific evidence for the development of national HPV vaccination program in Montenegro.

Fibrothecoma in a Virgo Intacta Adolescent with Elevated Levels of CA 125 and B-hCG: A Case Report.

Ovarian fibromas are benign tumors that consist of spindle cells in bundles or storiformly arranged with collagen fibers in the stroma. Thecomas resemble theca interna ovarian cells, and there is lipid material in their cytoplasm. There is an overlap in histological and immunohistochemical characteristics of these two benign tumors, and the term "fibrothecoma" was coined to describe such cases. Their incidence is extremely rare in adolescents. The subject of our study is a 15-year-old, unmarried, virgo intacta patient who was referred to us due to profuse vaginal bleeding and the loss of consciousness. A right ovary ultrasound examination exposed the formation of a hyperechoic tumor with a diameter of 41.2 mm × 29.5 mm. Findings of cancer antigen 125 (CA 125) in the amounts of 621.1 U/mL and 142.87 mIU/mL of the B-human chorionic gonadotropin (B-hCG) serum were determined. After preoperative preparation, we operated on the patient to remove a tumor with a diameter of 37 mm × 30 mm × 22 mm, smooth outer surface, solid cross-section, and yellowish white color. The diagnosis of fibrothecoma was made based on pathohistological examination. An unusual finding of fibrothecoma in a virgo intacta adolescent with profuse vaginal bleeding and increased levels of CA 125 and B-hCG may serve as a basis for broader thinking about the pathology of juvenile bleeding.

Comparison of Dako HercepTest and Ventana PATHWAY anti-HER2 (4B5) tests and their correlation with silver in situ hybridization in lung adenocarcinoma.

BACKGROUND: Discordant results exist about the role of human epidermal growth factor receptor 2 (HER2) overexpression and/or HER2 amplification in lung adenocarcinoma. We aimed to compare the performance of HercepTest and PATHWAY anti-HER2 (4B5) by correlating immunohistochemistry (IHC) results with silver in situ hybridization (SISH) in adenocarcinoma lung specimens. METHODS: A total of 148 surgically resected adenocarcinoma lung specimens were included. RESULTS: HER2 overexpression was found in 7.4% patients for HercepTest Dako and in 2.7% patients for 4B5 antibody. The overall coincidence between these two types of antibodies equals 93.9%. The incidence of HER2 amplification in lung adenocarcinoma was 17.6%, of which in 2.7% of the cases high-grade amplification was present. HER2 amplification was present in 90.9% of patients with overexpression of HER2, obtained by using HercepTest Dako and 75% patients using 4B5 antibody. A significant correlation between overexpression of HER2 receptors obtained by HercepTest Dako and 4B5 antibody and HER2 amplification was shown. CONCLUSION: The research of the efficiency of targeted molecular therapies with an HER2 antibody may serve as a basis for the introduction of routine HER2 status determination in lung adenocarcinoma, dictating the need for the standardized protocol for HER2 status determination in such pathology.

Low-grade chondrosarcoma of the larynx: A case report.

BACKGROUND: Chondrosarcomas of the larynx are malignant tumours that most commonly originate from the hyaline cartilage. Chondrosarcoma of the larynx, the most common type of low-grade tumour, accounts for 1% of all laryngeal neoplasms. CASE SUMMARY: We present the case of a 60-year-old female patient who developed progressive hoarseness and shortness of breath over a 2-mo period. The patient had undergone resection of a laryngeal tumour 14 years before the aforementioned symptoms occurred, and histopathological analysis indicated that it was a chondroma. During the assessment of the patient, a submucosal, oval-shaped tumour was detected that was predominantly located on the left side of the larynx and was approximately 6 cm in size. The decision to perform left partial vertical laryngectomy was made. A pathohistological diagnosis of low-grade chondrosarcoma was made. Considering the results of pathohistological analysis and the positive margins of the resection, a total laryngectomy was performed. During the 12-mo follow-up, no local relapse or regional or distant metastases was detected. CONCLUSION: Chondrosarcoma of the larynx must be considered in the differential diagnosis of laryngeal submucosal tumours. It is crucial to carefully sample of tumour tissue, differentiate chondroma and chondrosarcoma, and consider the possibility of malignant changes from chondroma to chondrosarcoma.

Ovarian female adnexal tumor of probable Wolffian origin - Case report.

BACKGROUND: During embryonic development in women, a regression of temporary embryonic structures - mesonephric (Wolffian) ducts occurs. Adnexal tumors of Wolffian duct origin (FATWO) are rare. CASE REPORT: We presented the case of a 64-year-old female patient who was diagnosed with FATWO. After the surgical treatment, the uterus with bilateral adnexal structures was submitted for histopathological analysis. The left ovary was occupied by a tumor measuring 80 × 60 × 50 mm, with smooth, shiny, whitish surface. Tumor cells were medium-sized, relatively uniform, round, and polygonal, with eosinophilic cytoplasm and centrally laid nucleus with fine chromatin, organized into solid, trabecular, and tubular formations. Tumor cells were positive for pancytokeratin (CK), CK7, CD10, neuron-specific enolase (NSE), synaptophysin, calretinin, progesterone, estrogen, and epithelial membrane antigen (EMA). CONCLUSION: This case adds a report of a rare tumor to the literature. We must think of it in the differential diagnostic algorithm to make an accurate diagnosis for selecting the best treatment modality.

Prognostic value of IMP3 immunohistochemical expression in triple negative breast cancer.

Triple negative breast cancer (TNBC) account for 12% to 17% of all breast cancers. It is a heterogeneous group of tumors associated with aggressive clinical course. Insulin-like growth factor II mRNA binding protein 3 (IMP3) belongs to a family of insulin-like growth factor type II (IGF2), which plays a key role in the transmission and stabilization of mRNA, cell growth, and migration during embryogenesis. Increased expression of IMP3 is associated with aggressive behavior of different tumor types, advanced clinical stage, distant metastasis, and shorter overall survival (OS).The study included 118 patients with breast carcinoma diagnosed as TNBC and immunohistochemical staining for estrogen receptors (ER), progesterone receptors (PR), epidermal growth factor receptor 2 (HER2/neu), Ki-67, and IMP3 was performed. Correlations between categorical variables were studied using the chi-square and the Mann-Whitney U test. For survival analysis, the Kaplan-Meier method, log-rank test and the Cox proportional hazard regression model were used.Positive expression of IMP3 protein was present in 35.6% of TNBC. The presence of basal morphology was observed in 46.6% of TNBC. Positive IMP3 expression was connected with larger size of tumor, higher clinical stage, and basal morphology (P = .039, P = .034, P < .001). Disease-free survival and OS were significantly shorter in IMP3 positive TNBC.According to results of our study IMP3 expression can be used as negative prognostic factor for triple negative breast carcinomas. Targeting IMP3 molecule could be an effective approach to the management of a triple negative breast cancer with new immunological therapies, which does not yet exist for this group of tumors.

Primary leiomyosarcoma of the thyroid gland with prior malignancy and radiotherapy: A case report and review of literature.

BACKGROUND: Leiomyosarcoma (LMS) of the thyroid gland is a rarely presented tumor that offers poor prognosis. To the best of the authors' knowledge, there currently exist only 28 known cases described in the literature (limited to English). CASE SUMMARY: Herein a case is reported of a 60-year-old female patient who had an LMS of the thyroid, which was accompanied by periodic dysphonia and breathing disorder as well as the feeling of pressure in the chest and neck. At the time the disease was diagnosed, no metastases were detected. Prior to the diagnosis, the patient experienced a uterine adenocarcinoma that had been treated by surgical procedure and radiotherapy. For the LMS, a total thyroidectomy was performed, followed by radiotherapy. Since metastases were also discovered in the lungs, sternum, and femur, chemotherapy was administered as well. Immunohistochemically, the tumor cells in the thyroid indicated positively for alpha smooth muscle actin, calponin, and H-caldesmon, but were negative for CD34, p63, estrogen receptor, progesterone receptor, and Epstein-Barr virus. CONCLUSION: Although the etiology of the LMS is as of yet unknown, prior malignancy and radiation should be considered as risk factors.

Time course and expression pattern of the neuronal markers in the developing human spinal cord.

The aim of this study was to examine the spatio-temporal appearance of different neuronal cell subtypes by analyzing expression patterns of several neuronal markers (calretinin, neurofilament 200 (NF200), vanilloid receptor 1(VR1) and calcitonin gene-related peptide (CGRP)) of the embryonic human spinal cord (SC). Developing human SCs from 11 human conceptuses beetwen 5-10 developmental weeks (DW) were examined by light and electron microscopy and immunofluorescence. Light and electron microscopy revealed different embryonic stages of recognizable structure of the SC. NF200, CGRP and VR1 positive cells were observed in SCs during 5th-6th DW. NF200 was predominantly expressed in the ventral part, indicating presence of motoneurons. As development advanced, NF200 was mainly expressed in the marginal zone. Expression of CGRP was intense during all of the investigated periods, predominantly during the 5th-6th DW pointing to neural sensory differentiation, as opposed to the last DW when reduced expression of CGRP in the marginal layer indicated the terminations of the sensory afferents. Expression of VR1 was highest in the intermediate zone, at the beginning and at the end of the investigated periods, pointing to VR1 spatial pattern in the visceral afferents in the grey matter, while the first signs of calretinin were found in the 9th-10th DW ventrally. Delineating the relationships between factors involved in processes of neuronal differentiation as well as spatial and temporal arrangement of SC interrelated neurons can provide a useful information about normal SC development as well as the insight in possible causes of anomalies and disorders during embryonic life.

Nonsteroidal Anti-Inflammatory Drug-Induced Colopathy in a Colorectal Cancer Screening Program.

OBJECTIVE: To present a case of colopathy related to the use of diclofenac in a patient with a positive immunochemical faecal occult blood test (iFOBT) and to discuss the influence of nonsteroidal anti-inflammatory drugs (NSAIDs) on iFOBT specificity. CLINICAL PRESENTATION AND INTERVENTION: A colonoscopy in a 56-year-old female presenting with a positive iFOBT revealed diaphragm-like strictures and ulcers in the right colon. While carrying out a detailed retrospective interview, she reported a chronic backache requiring long-term NSAID treatment. CONCLUSION: No association has been established between chronic use of NSAID and a false-positive iFOBT. There is no need to stop NSAIDs before performing an iFOBT in a colorectal cancer screening program.

Comparison of cytological categories atypical (C3) and suspected (C4) with histopathological diagnoses of breast lesions.

PURPOSE: Fine needle aspiration cytology (FNAC) is a diagnostic method characterized by high sensitivity, specificity and predictive value. In order to obtain uniformed results of FNAC breast changes, the following categories are introduced: C1 (non-representative), C2 (benign), C3 (atypical), C4 (suspected) and C5 (malignant). The purpose of this study was to establish which pathological processes are most frequently diagnosed as C3 and C4 categories, which carry a malignant tumor risk. METHODS: The frequency of all cytological categories was determined in a retrospective analysis which included 1605 patients, all of whom had undergone FNAC of breast lesions, over a period of 5 years (2012-2016). Furthermore, histopathological diagnoses of 212 patients with cytological categories C3 (77) or C4 (135) were compared. RESULTS: In the sample of 1605 patients, 212 belonged to C3 or C4 cytological category ( frequency for C3 4.8%, for C4 8.4%). Also, in the group of patients with cytological categories C3 and C4 there were 208 women. The patients with C3 were younger than C4 patients. There was a statistically significant difference between the number of benign and malignant diagnoses in patients diagnosed with C3 or C4 cytological category (p<0.001). In C3 category, in 57.1% of the cases a benign condition was histopathologically diagnosed, while in C4 category, in 90.4% of the cases malignant tumor was histopathologically diagnosed. CONCLUSIONS: After histopathological analysis, C3 category in FNAC breast lesions is most commonly diagnosed as a fibrocystic breast disease or fibroadenoma, while C4 category is diagnosed as well-differentiated malignant tumor.

Clinical significance of understanding lateral and medial circumflex femoral artery origin variability.

The common femoral artery (CFA) divides into the superficial femoral artery (SFA) and deep femoral artery (DFA). The lateral circumflex femoral artery (LCFA) and medial circumflex femoral artery (MCFA) are most often branches of the DFA, although a large number of different variations in their origin has been described. We performed microdissection on both lower limbs of 30 fetuses, gestational age from 7 to 10 lunar months. Our results show that the LCFA and MCFA usually arise from the DFA. In 78.3% of cases, the MCFA originated from the DFA. In 11.7% of cases, the MCFA originated from the CFA, and in 5% of cases from the SFA. One case showed a common trunk with the DFA. Also, the MCFA was missing in one case, and it had a common trunk with the LCFA in one case. In 83.3% of cases, the LCFA arose from the DFA and in 6.7% of cases from the CFA. In one case, it had a common trunk with the DFA, and in one case with the MCFA. In 3.3% of cases, the LCFA was missing. In 66.7% of cases, both arteries originated from the DFA, in 15% of cases one originated from the DFA and the other from the CFA or SFA. Our results are in accordance with some published studies but also differ from the outcomes of other studies. Comprehensive knowledge of different variation types is imperative in order to prevent complications during surgical and orthopedic interventions.

Clinical significance of microvessel density and proliferation in prostate cancer core biopsy.

PURPOSE: To investigate the microvessel density (MVD) and proliferation in prostate cancer (PC) core biopsies. METHODS: Core biopsy samples of PC tissue from 45 patients were routinely processed and embedded in paraffin. The samples of PC formed the investigated group (n=25), while samples of benign prostatic hyperplasia (BPH) served as controls (n=20). From paraffin blocks, 3-5 µm-thick sections were made and routine hematoxylin-eosin method and immunohistochemical ABC method with Ki67 and CD34 antibodies were applied. Immunohistochemical expression of Ki67 and CD34 was stereometrically quantified. RESULTS: The median number of Ki67 and CD34 positive cells per mm2 in PC were significantly higher in comparison to the median of these cells in BHP. The average age and Gleason score in patients with high proliferation index (proIDX) and MVD index (mvdIDX) was significantly greater in comparison to those with low proIDX and low mvdIDX. The absolute values of Ki67 expression were in highly positive and significant correlation with the absolute values of CD34 expression. Highly significant correlation was found between Gleason score and proIDX and mvdIDX. CONCLUSION: This study showed that PC expressed significantly higher values of Ki67 and CD34 in comparison to BPH. The values of proIDX and mvdIDX obtained by core biopsy could clearly show the level of cancer progression expressed through highly correlated Gleason score. In this way it is possible to identify the patients at high risk for disease progression.

Paraganglioma of the thyroid gland: a case report.

INTRODUCTION: Thyroid paraganglioma is a very rare malignant neuroendocrine tumor. Immunohistochemical features of thyroid paraganglioma are helpful for the diagnosis. CASE REPORT: A 69-year-old female came to hospital with the presence of a growing thyroid nodule of the left lobe. Ultrasonic neck examination showed 5 cm hypoechoic nodule in the left thyroid lobe. Thyroid scintigraphy showed a big cold nodule in the left lobe. Computed tomography (CT) scan showed left lobe thyroid tumor with tracheal deviation on the right site. Extended total thyroidectomy was done. Intraoperative consultation with the pathologist confirmed thyroid cancer. The pathologist diagnosed thyroid paraganglioma on the base of immuohistochemical investigation. This thyroid paraganglioma was positive for neuron-specific enolase, chomogranin A, synaptophysin, and S-100 protein highlighted the sustentacular cells. Tumor cells were negative for thyroglobulin, epithelial membrane antigen, cytokeratin, calcitonin, and carcinoembryonic. After the surgery the patient was treated with chemotherapy, peptide receptor radionuclide therapy, and permanent TSH suppressive therapy. The patient was followed with measurements of thyroid hormone and serum neuron-specific enolase, chromogranin A level, every 6 months. Gastroscopy, colonoscopy, chest and abdomen CT scan as well as further tests (chest xray, ultrasound of the neck, and whole body octreotide scintigraphy) were done. No primary neuroendocrine tumor in digestive sistem or in the chest was found. After more than 3 years the patient has no evidence of the recurrent disease. CONCLUSION: Radical resection of thyroid paraganglioma, followed by chemotherapy and peptide receptor radionuclide therapy, should be considered the treatment of choice in patients with thyroid gland paraganglioma.

Bleeding gastroduodenal ulcers in patients without Helicobacter pylori infection and without exposure to non-steroidal anti-inflammatory drugs.

BACKGROUND/AIM: A high risk of bleeding in Helicobacter pylori (H. pylori)-negative, non-steroidal anti-inflammatory drugs (NSAID)-negative ulcers highlights the clinical importance of analysis of the changing trends of peptic ulcer disease. The aim of the study was to investigate the risk factors for ulcer bleeding in patients with non-H. pylori infection, and with no NSAIDs use. METHODS: A prospective study included patients with endoscopically diagnosed ulcer disease. The patients were without H. pylori infection (verified by pathohistology and serology) and without exposure to NSAIDs and proton pump inhibitors (PPI) within 4 weeks before endoscopy. After endoscopy the patients were divided into 2 groups: the study group of 48 patients with bleeding ulcer and the control group of 47 patients with ulcer, but with no bleeding. Prior to endoscopy they had completed a questionnaire about demographics, risk factors and habits. The platelet function, von Willebrand factor (vWF) and blood groups were determined. Histopathological analysis of biopsy samples were performed with a modified Sydney system. The influence of bile reflux was analyzed by Bile reflux index (BRI). RESULTS: Age, gender, tobacco and alcohol use did not affect the bleeding rate. The risk of bleeding did not depend on concomitant diseases (p = 0.509) and exposure to stress (p = 0.944). Aspirin was used by 16/48 (33.3%) patients with bleeding ulcer, as opposed to 7/47 (14.9%) patients who did not bleed (p = 0.036). Abnormal platelet function had 12/48 (25.0%) patients who bled, as opposed to 2/47 (4.3%) patients who did not bleed (p = 0.004). Patients with BRI < 14 bled in 79.2%, and did not bleed in 57.4% of the cases (p = 0.023). There was no statistical difference between groups in regards to blood groups and range of vWF. Antrum atrophy was found in 14/48 (29.20%) patients with bleeding ulcer and in only 5/47 (10.6%) patients who had ulcer without bleeding (p = 0.024). CONCLUSION: Abnormal platelet function, aspirin use and antrum atrophy were the risk factors for ulcer bleeding in non-H. pylori, non- NSAIDs ulcer disease.