Sinonasal Hamartoma and Chronic Laryngeal Edema Causing Severe Dyspnea.

Background: Sinonasal hamartomas, according to the 5th edition of the World Health Organisation classification of head and neck tumours are divided into respiratory epithelial adenomatoid hamartoma (REAH), seromucinous hamartoma and chondromesenchymal hamartoma. Seromucinous hamartoma are benign proliferations of small eosinophilic glands surrounded by fibrous stroma and cuboidal cells. Hamartomas of the nasal cavity and paranasal sinuses are rare entities, clinically presenting as sinonasal polyposis. Case Presentation: A 79- year-old female patient was referred to our emergency room due to severe dyspnea. Anterior rhinoscopy revealed unilateral greyish polypoid mass obstructing the middle, inferior and common nasal meatus. Systemic corticosteroids and oxygen therapy were administered under observation. Computerized tomographic imaging of the paranasal sinuses with contrast on all three planes showed an opacified polypoid mass in all meatus and the maxillary, anterior ethmoidal and sphenoidal sinus posteriorly extending to the choanae. On the coronal plane a widening of the olfactory clefts about 12 mm was described. FESS visualized that the polypoid mass originated from the posterior septum and extended to all meatus anteriorly and to the choanae posteriorly. The polypoid lesion was endoscopically completely excised. Histopathological analysis revealed a seromucinous hamartoma. Conclusion: Seromucinous hamartoma are rare benign tumors of the sinonasal region with potential of malignant alteration. Unfortunately, they share symptoms and clinical appearance with other benign conditions of the sinonasal region. Therefore, it is even more important to consider them as a differential diagnose.

Gray-Level Co-occurrence Matrix Analysis of Nuclear Textural Patterns in Laryngeal Squamous Cell Carcinoma: Focus on Artificial Intelligence Methods.

Gray-level co-occurrence matrix (GLCM) and discrete wavelet transform (DWT) analyses are two contemporary computational methods that can identify discrete changes in cell and tissue textural features. Previous research has indicated that these methods may be applicable in the pathology for identification and classification of various types of cancers. In this study, we present findings that squamous epithelial cells in laryngeal carcinoma, which appear morphologically intact during conventional pathohistological evaluation, have distinct nuclear GLCM and DWT features. The average values of nuclear GLCM indicators of these cells, such as angular second moment, inverse difference moment, and textural contrast, substantially differ when compared to those in noncancerous tissue. In this work, we also propose machine learning models based on random forests and support vector machine that can be successfully trained to separate the cells using GLCM and DWT quantifiers as input data. We show that, based on a limited cell sample, these models have relatively good classification accuracy and discriminatory power, which makes them suitable candidates for future development of AI-based sensors potentially applicable in laryngeal carcinoma diagnostic protocols.

Ligamentum flavum analysis in patients with lumbar discus hernia and lumbar spinal stenosis.

The normal ligamentum flavum (LF) is a well-defined elastic structure with specific innervation. Several studies investigated LF in patients with lumbar spinal stenosis (LSS) and used lumbar discus hernia (LDH) patients as control group, only on the presumed thesis that LF in this patients have normal morphology. In patients with LSS thickening of the LF is the main cause of stenosis, which is most often presented with neurogenic claudication, whose pathophysiological mechanism is not completely understood. We conducted observational cohort study of 60 operated patients divided into two groups. The first group of 30 patients underwent micro-discectomy (LSH group), and second group with 30 patients underwent decompression, after which analysis of harvested LF was performed. Patients from the LDH group and LSS group differed significantly in the frequencies of chief complaints, duration of symptoms, physical examination, and specific morphological/radiological parameters. The LF analysis showed that the groups differed significantly in the amount of collagen and elastic fibers, as well as in the histological appearance/architectonics of elastic fibers. Also, groups differ in the presence of LF nerve fibers. Our findings speak in favor of the recently postulated inflammatory theory in the origin of spinal neurogenic claudication's.

Late diagnosis of a submandibular gland carcinoma in Covid-19 pandemic.

The Covid-19 pandemic has created exceptional challenges for patients and medical care systems. Among many factors influencing postponed cancer diagnosis, mask-wearing created difficulties in initial diagnosis of head and neck tumours. This report features a patient who had been covering a submandibular tumour under a surgical mask for more than 6 months. He visited his general practitioner due to a significant weight loss, but he neither took his mask off, nor was he asked to do so. When he reported to our emergency room, we noticed a massive ulcerous mass in the right submandibular region. Histological examination confirmed primary squamocellular carcinoma of submandibular salivary gland. During the Covid-19 pandemic, significant clinical observations may be missed if a surgical mask or respirator are not removed during examination with the potential for increased incidence of medical malpractice claims.

Loss of Expression of Antiangiogenic Protein FKBPL in Endometrioid Endometrial Carcinoma: Implications for Clinical Practice.

Background and Objectives: FK506 binding protein like (FKBPL) is a member of the immunophilin family, with anti-angiogenic effects capable of inhibiting the migration of endothelial cells and blood vessel formation. Its role as an inhibitor of tumor growth and angiogenesis has previously been shown in studies with breast and ovarian cancer. The role of FKBPL in angiogenesis, growth, and carcinogenesis of endometrioid endometrial carcinoma (EEC) is still largely unknown. The aim of this study was to examine the expression of FKBPL in EEC and benign endometrial hyperplasia (BEH) and its correlation with the expression of vascular endothelial factor-A (VEGF-A) and estrogen receptor alpha (ERα). Materials and Methods: Specimens from 89 patients with EEC and 40 patients with BEH, as well as histological, clinical, and demographic data, were obtained from the Clinical Hospital Centre Zemun, Belgrade, Serbia over a 10-year period (2010−2020). Immunohistochemical staining of the tissue was performed for FKBPL, VEGF-A, and ERα. Slides were analyzed blind by two pathologists, who measured the intensity of FKBPL and VEGF-A expression and used the Allred score to determine the level of ERα expression. Results: Immunohistochemical analysis showed moderate to high intensity of FKBPL expression in 97.5% (n = 39) of samples of BEH, and low or no expression in 93.3% (n = 83) of cases of EEC. FKBPL staining showed a high positive predictive value (98.8%) and a high negative predictive value for malignant diagnosis (86.7%). The difference in FKBPL expression between EEC and BEH was statistically significant (p < 0.001), showing a decrease in intensity and loss of expression in malignant tissues of the endometrium. FKBPL expression was positively correlated with ERα expression (intensity, percentage and high Allred score values) and negatively correlated with the expression of VEGF-A (p < 0.05 for all). Conclusions: FKBPL protein expression demonstrated a significant decrease in FKBPL in EEC in comparison to BEH tissue, with a high predictive value for malignancy. FKBPL might be emerging as a significant protein with antiangiogenic and antineoplastic effects, showing great promise for the diagnostic and therapeutic applications of its therapeutic derivatives in gynecological oncology.

Life-Threatening Stridor due to Laryngeal Tuberculosis in the COVID-19 Era: Report of a Case.

Laryngeal tuberculosis is the most frequent granulomatous disease of the larynx and it is prone to be diagnosed as cancer. COVID-19 pandemic caused considerable disruption in tuberculosis service provisions both in the primary care and hospital settings. This report describes a rare case of life-threatening stridor in a patient who presented with an ulceroproliferative laryngeal mass later confirmed as laryngeal tuberculosis. Urgent tracheostomy was performed. The patient's sputum and the computed tomography of the chest revealed a pulmonary, as well as laryngeal tuberculosis. The patient was commenced on a 24 week course of anti-tuberculous treatment which was interrupted because of a mild course of hospital-acquired coronavirus infection. 3 months after initial treatment for tuberculosis, his sputum cultures became negative. Flexible laryngoscopy was performed at our department 4 months after commencement of treatment, demonstrating complete regression of the lesion and symmetrical laryngeal mobility, hence the patient was successfully decannulated and discharged to be followed up to his community hospital. In the time of COVID-19 pandemic, we should never underestimate other severe infectious diseases.

Decreased ERß expression and high cyclin D1 expression may predict early CRC recurrence in high-risk Duke's B and Duke's C stage.

PURPOSE: Despite many known risk factors for the colorectal cancer (CRC) recurrence, significant differences in disease-free survival (DFS) impose the need to look for new explanations. This study aimed to determine the degree of expression of ERα, ERß, PR, Cyclin D1, and Bcl-2 and their association with early CRC relapse. METHODS: This retrospective study included 101 radically operated CRC patients in high-risk Duke's B and Duke's C stage. Tissue samples were retrieved from paraffin blocks and clinical and diagnostic data from medical records obtained during further clinical treatment and follow up. Patients were divided into DFS≤24 months group and DFS≥48 months group. Immunostaining of ERα, ERß, PR, Cyclin D1, and Bcl-2 was performed and analyzed. RESULTS: ERα was not expressed in all patients. ERß moderate expression was present in 25% of all patients, more often in the DFS≥48 group (p=0.001). PR and Bcl-2 showed only moderate expression in 1/5 and 1/3 of the patients, respectively, without significant difference between groups (p=0.145;p=0.566). Cyclin D1 was expressed in the whole sample of patients with strong expression statistically more often in DFS≤24 group (p=0.011) and had 5.2 higher odds of having DFS˂24 months. Moderate expression of ERß was joined with 79.2% smaller odds for shorter DFS. Advanced T stage had 11.3 times higher odds of having DFS˂24 months. CONCLUSION: Early recurrence of CRC in high-risk Duke's B and Duke's C stage relates with reduced ERß expression and the high cyclin D1 expression, so they could be considered independent prognostic factors, especially in patients in advanced T stage.

Macrophage migration inhibitory factor deficiency aggravates effects of fructose-enriched diet on lipid metabolism in the mouse liver.

Dietary fructose can disturb hepatic lipid metabolism in a way that leads to lipid accumulation and steatosis, which is often accompanied with low-grade inflammation. The macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine with important role not only in the regulation of inflammation, but also in the modulation of energy metabolism in the liver. Thus, the aim of this study was to investigate the role of Mif deficiency in fructose-induced disturbances of hepatic lipid metabolism and ectopic lipid accumulation. Wild type (WT) and Mif deficient (MIF-/- ) C57Bl/6J mice were used to analyze the effects of 9-week 20% fructose-enriched diet on hepatic lipid metabolism (both lipogenesis and ß-oxidation) and histology, inflammatory status and glucocorticoid receptor (GR) signaling. The results showed fructose-induced elevation of lipogenic genes (fatty acid synthase (Fas) and stearoyl-CoA desaturase-1 (Scd1) and transcriptional lipogenic regulators (liver X receptor (LXR), sterol regulatory element binding protein 1c (SREBP1c), and carbohydrate response element-binding protein (ChREBP)). However, microvesicular fatty changes, accompanied with enhanced inflammation, were observable only in fructose-fed Mif deficient animals, and were most likely result of GR activation and facilitated uptake and decreased ß-oxidation of FFA, as evidenced by elevated protein level of fatty acid translocase (FAT/CD36) and decreased carnitine palmitoyl transferase 1 (CPT1) level. In conclusion, the results show that Mif deficiency aggravates the effects of energy-rich fructose diet on hepatic lipid accumulation, most likely through enhanced inflammation and activation of GR signaling pathway.