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Concept: Mucous membrane

170

Neuroendocrine tumor (NET) in adenoma of the gastrointestinal tract is a rare mixed glandular-endocrine neoplasm and has uncommonly been described mostly in the colon. Histologically, this tumor is composed of a predominant proportion of benign adenomatous component and a small portion of well-differentiated NE component. Only three cases of NET in gastric adenoma have been reported in the literature. We present 4 cases of NET in gastric adenoma mimicking invasive adenocarcinoma. The NETs were 0.62 mm to 4.1 mm in size and located at the basal lamina propria, muscularis mucosa and submucosa. Histologically, NETs consisted of nests, cords, tubules, and clusters of cells that predominantly interposed between the foveolar base without disturbing the overall polyp architecture. The lesions were completely removed by endoscopic submucosal dissection in three cases and in one case, subtotal gastrectomy was performed because endoscopic biopsy was invasive adenocarcinoma. The patients' clinical course was uneventful without an evidence of recurrence or metastasis. The recognition of NET in gastric adenoma will help avoid potential diagnostic pitfalls masquerading as invasvie adenocarcinomas posed by their infiltrative pattern into submucosa. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1688552293761001.

Concepts: Cancer, Oncology, Mucous membrane, Anatomical pathology, Adenocarcinoma, Esophagus, Lamina propria, Muscularis mucosae

28

In patients with celiac disease, gluten-induced lesions of the small-bowel mucosa develop gradually. However, it is not clear whether clinical presentation correlates with the degree of mucosal damage based on histology analysis. We investigated whether the degree of mucosal damage to the small bowel correlates with clinical presentation and serum markers of celiac disease.

Concepts: Medicine, Auerbach's plexus, Mucous membrane, Lamina propria

28

Theileriosis is an economically important hemoprotozoal disease with high morbidity and mortality in cattle. The present study reported the pathological features of a natural outbreak of tropical bovine theileriosis due to Theileria annulata in Fars Province, southern Iran. T. annulata was confirmed by the presence of T. annulata piroplasms in the blood smears and also by polymerase chain reaction test. On necropsy, pale mucous membranes and petechial and ecchymotic hemorrhages in the mucosal and serosal surfaces together with lymphadenopathy were observed. The liver was friable, yellowish, and larger than normal. Hemorrhages and punched-out ulcers were observed in the abomasal mucous membrane. Severe petechial hemorrhages were seen in the skin particularly in the hairless areas. Pulmonary edema and emphysema with petechial and ecchymotic hemorrhagic foci in the lungs were evident. The main histological changes were proliferation of lymphocytes in the lymph nodes and proliferation of macrophages, lymphocytes, and plasma cells in the spleen, Peyer’s patches, portal tracts of the liver, and interstitial tissue of the kidneys. The mucous membrane of the abomasum showed numerous multifocal areas of necrosis and ulceration, and the submucosal area and lamina propria adjacent to these lesions showed hyperemia and hemorrhages, with mononuclear cell infiltration. The skin showed multifocal necrotic changes, petechial and ecchymotic hemorrhages, and chronic dermatitis. The schizonts of Theileria were evident in the cytoplasm of the lymphocytes and macrophages of the lymph nodes, spleen, and skin. Molecular examination revealed that these animals were infected with T. annulata. The present study describes the clinicopathological findings of bovine tropical theileriosis in an unpredictable weather condition.

Concepts: Blood, Mucous membrane, Lymphatic system, Membrane biology, Mucus, Lamina propria, Muscularis mucosae

28

The major strides accomplished in elucidating the pathophysiology of rheumatoid arthritis (RA) have translated into therapeutic breakthroughs in clinical practice. However, currently available treatments work only for as long as they are taken. The development of curative treatments will probably require a better understanding of the earliest phases of RA and perhaps the identification of the etiological factors, which are probably numerous. These objectives are being pursued in studies of preclinical RA. The literature review presented herein indicates that the immunological conflict probably originates outside the joints, at mucous membrane sites and, more specifically, in the upper aerodigestive tract. The preclinical phase of RA can last for many years, and some patients probably never progress to arthritis. An immunological conflict develops then spins out of control, causing increases in autoantibody titers and subsequently in levels of serum markers for inflammation, before the development of the first joint symptoms. Improved knowledge of the preclinical phase, together with information from genetic markers, will allow the identification of profiles associated with susceptibility to RA and perhaps, in the future, the development of preventive strategies.

Concepts: Medicine, Mucous membrane, Rheumatoid arthritis, Rheumatology, Osteoarthritis, Philosophy of science, Phase, Rheumatoid factor

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OBJECTIVES/HYPOTHESIS: Immunoglobulin (Ig)G4-related disease is a systemic syndrome, characterized by sclerosing lesions that mainly affect the exocrine tissue. Although some patients with IgG4-related disease complain of nasal symptoms, there are few reports concerning the nasal manifestations of this disease. We investigated the clinical and pathological features of the nasal manifestations of IgG4-related disease. STUDY DESIGN: Retrospective review in a tertiary referral hospital. METHODS: Twenty-three consecutive patients with IgG4-related disease, six allergic rhinitis (AR) patients, and eight healthy subjects (HS) were evaluated. Nasal symptoms, local findings of the nasal cavity, and laboratory data were examined. Mucosal tissues from the inferior turbinate were obtained from all subjects before treatment. The level of IgG4-positive plasma cells and other infiltrating cells, and the number of nasal glands in the nasal subjects were compared among the three groups. RESULTS: Ten (43.4%) of 23 cases had some nasal symptoms, such as nasal obstruction and nasal crusting. Thirteen cases (56.5%) had numerous IgG4-positive plasma cell infiltration in the nasal mucosa. IgG4-positive plasma cells, CD3, and CD4 were significantly higher in the IgG4-related disease group than in the HS and AR groups, whereas the number of nasal glands in the IgG4-related disease group was significantly lower than in the HS and AR groups. CONCLUSIONS: The inflammatory lesions associated with IgG4-related disease exist on the nasal membrane. Thus, the nasal manifestations of IgG4-related disease were thought to be different from AR.

Concepts: Protein, Mucous membrane, Secretion, Allergy, Mucus, Nose, Somatic hypermutation, Tertiary referral hospital

27

Abstract Although povidone-iodine (PVP-I) has been used as a gargle since 1956, its effectiveness and material safety have been remained controversial. The aim of this study was to investigate the toxicity of PVP-I to epithelial cells in a concentration range significantly lower than that used clinically. Study design was in vitro laboratory investigations and in vivo histological and immunologic analysis. We examined the effects of PVP-I at concentrations of 1 × 10(-2) to 1 × 10(3 )μM and 1 × 10(-4) to 1 × 10 μM on HeLa cells as a model of epithelial cells and rat oral mucosa, respectively, after 1 or 2 days of exposure. Annexin V/FLUOS was used to distinguish live, apoptotic and necrotic cells. The terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) method was also used to observe whether apoptotic epithelial cells exist in rat oral mucosa after 1 day of exposure of PVP-I. HeLa cells developed concentration-dependent cytotoxicity, and epithelium of rat oral mucosa was thinned in a concentration-dependent manner. HeLa cell apoptosis increased after 1 × 10(0) μM of PVP-I exposure for 2 days. In the TUNEL method, many apoptotic epithelial cells were observed in the rat oral mucosa after 1 day of exposure to diluted 1 × 10(-2) μM of PVP-I, but minimal apoptotic epithelial cells were observed using 1 × 10(-3) μM of PVP-I. Our findings suggest that exposure to PVP-I, of which concentrations are even lower than those used clinically, causes toxicity in epithelial cells. This knowledge would help us better understand the risk of the use of PVP-I against mucosa.

Concepts: Scientific method, Mucous membrane, Oral mucosa, Apoptosis, Cell culture, Skin, Necrosis, Programmed cell death

27

Microstomia is a term used to describe a small oral aperture. Most of the reported cases are caused by scar contracture after facial trauma, burn injury, and tumor excision. We experienced a rare case of microstomia in a patient with antilaminin 332 mucous membrane pemphigoid, which was an acquired autoimmune disease and showed blisters and erosive lesions mainly on the mucous membranes. The patient had recurrent aphthous stomatitis and presented microstomia caused by scar contracture of oral mucosa. We surgically corrected microstomia by 5-flap Z-plasty for commissuroplasty and 2 Z-plasty of both upper and lower lips for an enlargement of oral aperture. The patient could achieve an enough oral aperture and was satisfied with the result. There was no recurrence of microstomia for 2 years.

Concepts: Mucous membrane, Oral mucosa, Aphthous ulcer, Lip, Stomatitis

26

Colorectal cancer (CRC) can be divided into non-mucinous and mucinous subtypes, of which the latter portends to have a worse clinical prognosis. A previous study suggested a putative link between SOX2 expression observed selectively in mucinous CRC and the induction of the gastric mucin MUC5AC. In this study, we re-evaluated the expression behavior of SOX2, MUC5AC, and CDX2 in both types of CRC. We performed immunohistochemical analysis on 90 cases of non-mucinous CRCs, 57 cases of mucinous CRCs, and 15 case-matched normal intestinal mucosa. In contrast to the previously suggested link between SOX2 and mucinous CRC, we observe aberrant expression of SOX2 at equal levels in both subtypes. Fluorescence in situ hybridization (FISH) analysis shows that expression is not attributed to genomic amplification. While SOX2 and CDX2 are normally expressed in a reciprocal manner, SOX2-positive tumor cells co-express CDX2. Furthermore, we show that MUC5AC is expressed independently of SOX2. In conclusion, we show that aberrant SOX2 expression is specifically linked neither to mucinous CRCs nor to the induction of MUC5AC, in contrast to previous suggestions.

Concepts: Scientific method, Gene expression, Cancer, Mucous membrane, Anatomical pathology, Colorectal cancer, Tumor, In situ hybridization

25

The association between smoking and postoperative complications is compounded in patients who have oral and maxillofacial operations by an additional local effect, and patients often continue to smoke after operation despite advice to stop. Recent studies have suggested that nicotine may reduce inflammation and improve angiogenesis, so topical application may be beneficial for smokers. The electronic cigarette is increasing in popularity and more patients ask whether they can vape after operation. We investigated the effect of electronic cigarettes (of which half contained nicotine and half did not) on blood flow in the buccal mucosa in 10 volunteers immediately after vaping. Smokers were excluded as this was considered an additional variable in a small pilot study and our Trust has a no-smoking policy. After vaping for 5minutes, capillary blood flow was measured in the buccal mucosa at 5-minute intervals using a laser Doppler probe, and the results were expressed as arbitrary perfusion units. There was a wide variation in results and a small but significant rise (p=0.008) as a result of nicotine vaping, but these fell to the same levels as before within 30minutes. Electronic cigarettes may have an effect on blood flow to the oral mucosa, although further studies are needed to show whether they improve healing time after operation. Additional work is also needed to compare them with cigarettes.

Concepts: Mucous membrane, Oral mucosa, Smoking, Tobacco, Cigarette, Nicotine, Electronic cigarette, Buccal mucosa

25

Summary Oral mucositis (OM) is a debilitating side effect of chemotherapy, which can be relieved by phototherapy. Antimicrobial Photodynamic Therapy (aPDT) may be used for the treatment of OM, when infection is present. However, there are no studies showing that aPDT affects tissue repair process when used in the treatment of lesions caused by OM. This work aims to evaluate the effect of aPDT in healing OM induced by 5-Fluorouracil (5-FU). Two hundred forty-five hamsters were divided into two groups, control © and experimental, which were subdivided into 4 subgroups (Ch, ChP, ChL, aPDT). C group received only the vehicle of chemotherapy and anesthesia, whereas all animals of the experimental groups received anesthesia and chemotherapy agent 5-FU to induce OM. Ch group received no OM treatment; ChP group received an application of methylene blue (MB) 0.01%; ChL received irradiation with low-power-laser (LPL-660nm/120J/cm(2)/40mW/4.4J per point); and aPDT received MB and LPL irradiation. OM Clinical severity were daily assessed by a blinded examiner. The animals were sacrificed after 5, 7 and 10 days of experiment and their oral mucosa were removed for biochemical (enzymatic activity of SOD and catalase) and histological analyzes (light microscopy). After statistical analysis was performed, results showed that aPDT reduced the severity of OM on the tenth day of the experiment, when compared to the initial OM score (p<0.05), as well as increased keratinization with organized collagen deposition in the lamina propria. In conclusion, aPDT can be safely used in animals with infected OM because it does not affect lesion-repairing processes.

Concepts: Cancer, Mucous membrane, Chemotherapy, Affect, Hematopoietic stem cell transplantation, Basal cell carcinoma, Mucositis, Fluorouracil