Focal Hyperplasia Research Articles

Optimization of surgical selection in the treatment of irritation fibroids

Irritation fibroma is a benign, non-neoplastic lesion that arises in the oral mucosa due to chronic irritations or trauma. This focal hyperplasia of collagenized fibrous connective tissue typically presents as an exophytic, firm, asymptomatic, pink nodule with a smooth surface and a well-defined border. Removing this lesion not only allows for diagnostic confirmation, it also prevents additional complications, relieves symptoms in symptomatic cases, and improves the patient's aesthetics and comfort. Surgical intervention is the recommended treatment and can be carried out using various techniques, such as conventional surgical excision, laser surgery, electrosurgery and cryosurgery. The choice of surgical method is based on specific characteristics of the fibroid and physician preferences, with conventional surgical excision frequently preferred as it allows complete control over tissue removal. This study details the case of a patient with an irritation fibroma located in the lateral region of the tongue, for which the VIKOR method was used as a multi-criteria decision-making tool to select the most appropriate surgical technique. The final decision favored conventional surgical excision, based on multicriteria assessment that included aspects such as the size and location of the lesion, available resources, risks, and aesthetic results. The management of irritation fibroma must be careful and well-founded, favoring techniques that ensure complete removal of the lesion with minimal complications and ensuring adequate postoperative follow-up to evaluate the patient's evolution and prevent recurrences

S2130 Rectal Xanthoma: A Rare Clinical Finding

Introduction: Xanthomas are localized lipid deposits within an organ system. They are more commonly found as cutaneous lesions and less likely to appear in the gastrointestinal tract. The incidence of gastrointestinal xanthomas is not well documented, but the vast majority of authors agree they occur more frequently in the stomach. Colonic xanthomas are rare and usually incidental endoscopic findings. There are several case reports that present gastrointestinal xanthomas, however a small subset of these cases are located in the rectum. Here we present a case of rectal xanthoma and discuss its macroscopic and microscopic features. Case Description/Methods: A 55-year-old female with a recent diagnosis of atrophic metaplastic autoimmune gastritis presents for colonoscopy. Per chart review, patient had a normal colonoscopy in 2012. During the colonoscopy in 2022, one 10 mm sessile polyp was resected in the cecum; pathology returned as hyperplastic polyp. In the rectum was an area concerning for a submucosal lesion, encompassing about one quarter of the rectal circumference. Overlying it was an area of mucosa with hues of yellow which was biopsied. Pathology showed fragments of colonic mucosa with mild chronic inactive inflammation with histiocytic aggregate and focal surface glandular hyperplasia suggestive of xanthoma. Lipid panel available from 2019 showed LDL 100 with other levels within normal range (Figure). Discussion: Colorectal xanthomas are intestinal lesions with aggregates of lipid laden macrophages called foamy histiocytes. These cells are distributed in the lamina propria, between the colonic glands and muscularis mucosa. Unlike cutaneous xanthomas, gastrointestinal xanthomas are not associated with dyslipidemia. There has been a reported case of colonic xanthomas presenting as submucosal masses in the rectum and sigmoid. In a case series of 28 patients with colorectal xanthomas, 23 were sessile and 5 were pedunculated. Twelve xanthomas appeared reddish in color, 5 were white, and 2 were of a yellow hue. The relationship between colorectal xanthomas and malignancy is unclear. Of the 28 colorectal xanthomas, 4 hyperplastic lesions were found within the xanthoma, while 4 adenomas and 2 adenocarcinomas were found adjacent to xanthomas. Chronic injury is believed to be associated with the cause of colorectal xanthomas. In our case, a sigmoidoscopy with EUS is planned to rule out a submucosal mass. Adding case reports to the literature will help assess potential correlation with polyps and malignancies.Figure 1.: (Top) Rectum with appearance of submucosal lesion and localized area of yellow hue in mucosa (bottom) Foamy histiocytes confined to the lamina propria.

The clinicopathological features of adult orbital xanthogranulomatous disease with lacrimal gland reactive lymphoid hyperplasia

Objective: To investigate the clinicopathological features of adult orbital xanthogranulomatous disease (AOXGD) with lacrimal gland reactive lymphoid hyperplasia. Methods: Retrospective case series study. The clinical and pathological data of AOXGD cases diagnosed and treated in Tianjin Eye Hospital from January 2002 to December 2021 was reviewed, and the clinical characteristics, radiologic findings and pathological characteristics of periocular and lacrimal gland lesions of 5 cases were retrospectively analyzed. The expression of IgG4 and IgG protein in periocular and lacrimal gland lesions was detected by immunohistochemical staining, and the role of IgG4 in AOXGD was preliminarily studied. Results: There were four females and one male with an average age of 53.8 years (39 to 77 years). Among the five AOXGD cases, there were three cases of adult-onset xanthogranuloma, one case of adult-onset asthma and periocular xanthogranuloma, and one case of necrobiotic xanthogranuloma. All cases involved both eyes. The swelling of eyelids was observed in five cases, and the yellow or pale yellow eyelid skin was found in two cases. Imaging examinations showed the tumor mainly involved the eyelids, subcutaneous tissues, anterior orbit and lacrimal gland. A large number of foam cells and typical Touton giant cells were found in the periorbital lesions, accompanied by different degrees of fibrosis. The fibrinoid necrosis was detected in one case of necrobiotic xanthogranuloma. The lacrimal gland lesions showed different types of reactive lymphoid hyperplasia, including IgG4-related disease in two cases, follicular lymphoid hyperplasia in two cases and focal lymphoid hyperplasia in one case. IgG4 levels of periorbital and lacrimal gland lesions were elevated in four cases. Asthma and elevated serum IgG4 were found in one case of adult-onset periocular xanthogranuloma. Three patients underwent surgical resection and adjuvant hormone or immunosuppressive therapy, and two patients underwent simple surgical resection. The patients were followed up for 1.5 to 10.0 years, one patient was lost, and four patients had no recurrence. Conclusions: AOXGD with lacrimal gland reactive lymphoid hyperplasia is a group of rare diseases. The periorbital lesions of that are characterized by proliferation of foamy histiocytes and Touton giant cells, and the lacrimal gland lesions of that manifest as IgG4-related disease in some cases.

Structure of Hyperplastic Processes of the Uterus in Menopausal Women According to the Results of an Echographic Study

The purpose of the study was to evaluate the results of ultrasound scanning in menopausal women with endometrial hyperplastic processes. Materials and methods. Ultrasound protocols of 67 menopausal women with uterine hyperplastic processes were analyzed. Endometrial imaging data were assessed as corresponding to focal endometrial hyperplasia in 53 (79.1%) women. Uterine fibroids in combination with endometrial hyperplasia were found in 42 (62.7%) menopausal patients. According to the transvaginal ultrasound protocols, only endometrial polyp was detected in 20.9% of women (n=14). Results and discussion. The main complaints of patients with endometrial hyperplastic processes were abnormal uterine bleeding and abdominal pain. Every third (n=22; 32.8%) woman in the menopausal period noted uterine bleeding. Every second patient complained of lower abdominal pain of varying intensity (n=34; 50.7%). 11 (16.4%) women had no complaints. All the women studied underwent transvaginal and transabdominal ultrasound (in 3D mode). Ultrasound examination of the pelvic organs in order to differentiate endometrial pathology in 54% of cases was performed twice and more often. Ultrasound examination of the uterus was performed in standard projections. Endometrial polyps in most cases were oval in shape and were visualized quite clearly due to high echogenicity, homogeneous structure, the presence of a base that has no connection with the myometrium, and the integrity of the basal layer in the area of attachment of the polyp base. The sizes of endometrial polyps ranged from 1 mm to 90 mm (12.6 ± 3.5 mm). Small polyps were more often of increased echogenicity and homogeneous structure. At the same time, patients with endometrial polyps in the menopausal period often lack their visualization during transvaginal ultrasound. They are often verified as a focal or diffuse form of endometrial hyperplasia, while the low frequency of diagnosis of polyps in the menopausal period is determined. Ultrasound results were interpreted as corresponding to a combination of focal hyperplasia and endometrial polyp in 16.4% of cases (n=11). Ultrasound with color Doppler mapping in endometrial cancer revealed a sharp increase in the blood flow rate in the arсuate arteries (Vmax = 0.33 ± 0.06 m/s, Vmin = 0.16 ± 0.1 m/s). Conclusion. Ultrasound is an affordable method for diagnosing hyperplastic processes of the uterus. In the diagnosis and determination of the structure of hyperplastic processes of the uterus, combined transabdominal and transvaginal ultrasound is a highly informative non-invasive method. There is a need for further investigation of the management tactics of patients with endometrial pathology during menopause

Case Report: Rare Acute Abdomen: Focal Nodular Hyperplasia With Spontaneous Rupture

Focal nodular hyperplasia (FNH) of the liver is a benign lesion characterized by hypertrophic nodules with central star-shaped fibrous scars. The etiology and pathogenesis of FNH are not completely understood. A 43-year-old man was hospitalized because of acute abdominal pain. Emergency computed tomography(CT) showed hepatic tumor rupture and bleeding. The patient’s condition improved following arteriographic embolization to stop bleeding. Laparotomy confirmed spontaneous rupture and hemorrhage of focal hyperplasia and the patient remains asymptomatic after an uneventful recovery. FNH with spontaneous rupture and bleeding is extremely rare. Currently, there is no unified management standard for FNH and most previous studies recommend observation and follow-up. We recommend consideration of surgical treatment of cases with spontaneous rupture and bleeding.

Traumatic tongue fibroma treated with individualized homeopathic remedies: A case report with a brief literature review

Reactive hyperplastic lesions are commonly seen in the oral cavity as a result of chronic irritation by plaque, calculus, overhanging margins, trauma and dental appliances. Tongue fibroma represents a reactive focal fibrous hyperplasia due to recurrent trauma or local irritation. It can possibly occur at any age group from almost any soft tissue site, buccal mucosa tongue and gingival where, the buccal mucosa is more commonly involved. Over the past few years several studies have reported an increased burden of oral-exophytic lesions in different parts of the world. In this case, a patient complained of a swelling (12mm x 9mm) on the right side dorso-lateral aspect of his tongue, which bled frequently when he ate solid foods and/or was touched. Because the patient refused to undergo conventional treatment through surgery and a biopsy of the lesion, he chose homeopathy as an alternate therapy option. Relevant history taking and careful clinical examination led us to diagnose the lesion as traumatic tongue fibroma. The case was treated with homeopathic medications, Arnica Montana 200C, Acid Nitric 1000C and Sulphur 200C and a complete remission of the lesion was achieved. From the literature survey, we did not encounter any other record of homeopathic cure of tongue fibroma published in any peer-reviewed journal.

Persistent γ-H2AX Formation and Expression of Stem Cell Markers in N-Butyl-N-(4-Hydroxybutyl)Nitrosamine-Induced Bladder Carcinogenesis in Rats.

We investigated γ-H2AX formation, a biomarker of DNA damage, and expression of stem cell markers (SCMs), including cytokeratin 14, aldehyde dehydrogenase 1A1 (ALDH1A1), and CD44, in the development of rat bladder tumors induced by short-term administration of N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). Histopathological examination showed that diffuse simple hyperplasia of the bladder urothelium induced by BBN recovered to the normal-appearing urothelium after withdrawal, whereas focal proliferative lesions were newly developed and subsequently progressed to benign papilloma and carcinoma. Immunohistochemical analysis revealed that BBN-induced γ-H2AX formation and ALDH1A1 and CD44 expression persisted at higher levels in the normal-appearing urothelium than those in the control group for long periods after withdrawal. Since persistent chronic inflammation was observed even after withdrawal, targeted gene expression analysis of inflammation-related factors revealed 101 genes, including Stat3 and Myc, that showed persistent high expression. Pathway analysis suggested that Stat3 and/or Myc activation may be associated with SCM expression. We focused on hepatocyte growth factor (Hgf), one of the genes predicted in relation to Stat3/Myc, and confirmed that HGF-positive cells increased by BBN persisted in the normal-appearing urothelium after withdrawal and colocalized with γ-H2AX and SCMs. These results suggested that the long-term persistence of γ-H2AX formation and SCM expression, which occurred during the early stages of bladder tumorigenesis, is not a transient response to exposure and might contribute to bladder tumorigenesis. Although further studies are needed, BBN-induced rat bladder tumors may originate from focal hyperplasia arising from SCM-positive cells via activation of the STAT3/MYC pathway after DNA damage involving γ-H2AX formation.

Chronic gastroduodenitis associated with Helicobacter pylori in combination with giardiasis in children

Background. The results of most scientific studies in recent years have made it possible to reconsider the traditional ideas about the pathogenesis of chronic gastroduodenitis (CGD) from a new perspective. The purpose was to investigate the clinical and endoscopic features of СGD associated with Helicobacter pylori (H.pylori) in combination with giardiasis. Materials and methods. The study included 105 children aged 7–16 years divided into two groups: I — patients with СGD associated with H.pylori (n = 29), II — children with СGD associated with H.pylori in combination with giardiasis (n = 76). The study was conducted on the basis of the gastroenterology department of the Chernivtsi Regional Clinical Hospital during 2020–2021 and included esophagogastroduodenofibroscopy, ultrasound examination of the abdominal cavity, rapid urease test, determination of specific M, A and G immunoglobulins to H.pylori CagA antigen in the blood serum and in feces, fecal examination for Giardia lamblia (G.lamblia) antigen by polymerase chain reaction. Results. The most severe infection of G.lamblia occurred in children aged 9–13 years (17 people out of 29 positive). The number of children with G.lamblia increased between the ages of 7–9 and 10–12 years (p < 0.05, χ2 = 5.236, z = 1.899) and decreased in the age of 13–16 years (p < 0.05, χ2 = 7.144, z = 2.567). Patients with giardiasis complained of irritability (p < 0.05), headache, dizziness, restless sleep, heart pain, and they were more likely to show signs of intoxication and skin syndromes. Children of group I were most often diagnosed with corpus gastritis (p < 0.05), antral gastritis (p < 0.05) or pangastritis (p < 0.05) with focal hyperplasia (p < 0.05), and children of group II — with mainly antral gastritis, as well as severe duodenitis (p < 0.05). A characteristic endoscopic feature in children of group II was follicular duodenitis. Inflammatory process in group II significantly more often (p < 0.05) was severe (81.5 %) and active (77.6 %) and was associated with eosinophilic infiltration (51.3 %), microerosions and foci of lymphoid tissue hyperplasia (6.5 %). Conclusions. The clinical course of СGD associated with H.pylori in combination with G.lamblia is characterized by more pronounced dyspeptic symptoms with signs of intoxication and skin syndromes. According to the results of endoscopic examination, patients suffered from СGD associated with H.pylori infection had esophagitis, corpus gastritis, antral gastritis and pangastritis (p < 0.05) significantly more often. Children with G.lamblia invasion had severe follicular duodenitis (p < 0.05).

Chemical structure characterization of polysaccharide from Osmunda japonica Thunb and its inhibitory activity on uterine fibroids

The active component polysaccharide of Osmunda japonica Thunb was extracted and its chemical structure was detected by FT-IR, 1D-NMR and 2D-NMR spectra, in order to have a positive preventive and therapeutic effect on uterine fibroids. The physicochemical properties of Osmunda japonica Thunb polysaccharides (OPP) were analyzed, and the results showed that OPP was heteropolysaccharides composed of six monosaccharides. Ara and Glc were the main monosaccharides of the polysaccharide, with a molecular weight of 252.54 ± 10.84 kDa. The main chain was connected by 1,3-linked Ara f , which had a high degree of branching, and was connected to the branch at the O-2 and O-3 positions. The mice model of uterine fibroids was established by the estrogen load method. The coefficient of the uterus in the mice model increased significantly, irregular nodular processes were observed in the uterus, focal hyperplasia appeared in the smooth muscle layer, cell enlargement, disordered arrangement of smooth muscle cells, and endometrial hyperplasia was obvious. Furthermore, this work found that the serum estradiol (E2) and progesterone (P) concentrations in the model group were significantly higher than those in the normal group ( P < 0.01 ), indicating successful modeling. OPP decreased serum E2 and P levels in a dose-dependent manner. Collectively, OPP had an obvious inhibitory effect on uterine fibroids in estrogen-loaded mice.

Exposure to perfluorooctanoic acid leads to promotion of pancreatic cancer.

Pancreatic cancer is the fourth leading cause of cancer deaths in the United States. Perfluorooctanoic acid (PFOA), a persistent environmental pollutant, has been shown to induce pancreatic acinar cell tumors in rats. Human epidemiologic studies have linked PFOA exposure to adverse chronic health effects including several types of cancer. Previously, we demonstrated that PFOA induces oxidative stress and focal ductal hyperplasia in the mouse pancreas. Here, we evaluated whether PFOA promotes pancreatic cancer using the LSL-KRasG12D;Pdx-1 Cre (KC) mouse model of pancreatic cancer. KC mice were exposed to 5ppm PFOA in drinking water starting at 8 weeks of age and analyzed at 6 and 9 months of age. At the 6-month time point, PFOA exposure increased pancreatic intraepithelial neoplasia (PanIN) area by 58%, accompanied by a 2-fold increase in lesion number. Although PanIN area increased at 9 months, relative to 6 months, no treatment effect was observed. Collagen deposition was enhanced by PFOA at both the 6- and 9-month time points. PFOA also induced oxidative stress in the pancreas evidenced by elevated antioxidant activity of superoxide dismutase (Sod), catalase and thioredoxin reductase, and a ~3-fold increase in Sod1 mRNA and protein levels at 6 months. Although antioxidant activity was not enhanced by PFOA exposure at the 9-month time point, increased pancreatic oxidative damage was observed. Collectively, these results show that PFOA elicited temporal increases in PanIN lesion area and desmoplasia concomitant with the induction of oxidative stress, demonstrating that it functions to promote pancreatic cancer progression.

Detection of hepatocarcinogens by combination of liver micronucleus assay and histopathological examination in 2-week or 4-week repeated dose studies

BackgroundCurrently, revisions to the ICH S1 guidance on rodent carcinogenicity testing are being proposed. Application of this approach would reduce the use of animals in accordance with the 3Rs principles (reduce/refine/replace). The method would also shift resources to focus on more scientific mechanism-based carcinogenicity assessments and promote safe and ethical development of new small molecule pharmaceuticals. In the revised draft, findings such as cellular hypertrophy, diffuse and/or focal cellular hyperplasia, persistent tissue injury and/or chronic inflammation, preneoplastic changes, and tumors are listed as histopathology findings of particular interest for identifying carcinogenic potential. In order to predict hepatocarcinogenicity of test chemicals based on the results from 2- or 4-week repeated dose studies, we retrospectively reanalyzed the results of a previous collaborative study on the liver micronucleus assay. We focused on liver micronucleus induction in combination with histopathological changes including hypertrophy, proliferation of oval cells or bile duct epithelial cells, tissue injuries, regenerative changes, and inflammatory changes as the early responses of hepatocarcinogenesis. For these early responses, A total of 20 carcinogens, including 14 genotoxic hepatocarcinogens (Group A) and 6 non-liver-targeted genotoxic carcinogens (Group B) were evaluated.ResultsIn the Group A chemicals, 5 chemicals (NPYR, MDA, NDPA, 2,6-DNT, and NMOR) showed all of the 6 early responses in hepatocarcinogenesis. Five chemicals (DMN, 2,4-DNT, QUN, 2-AAF, and TAA) showed 4 responses, and 4 chemicals (DAB, 2-NP, MCT, and Sudan I) showed 3 responses. All chemicals exhibited at least 3 early responses.Contrarily, in the Group B chemicals (6 chemicals), 3 of the 6 early responses were observed in 1 chemical (MNNG). No more than two responses were observed in 3 chemicals (MMC, MMS, and KA), and no responses were observed in 2 chemicals (CP and KBrO3).ConclusionEvaluation of liver micronucleus induction in combination with histopathological examination is useful for detecting hepatocarcinogens. This assay takes much less time than routine long-term carcinogenicity studies.

Effect of docosahexaenoic acid as a chemopreventive agent on experimentally induced hamster buccal pouch carcinogenesis

PurposeThe current study was directed to investigate the effectiveness of docosahexaenoic acid (DHA) as a chemopreventive agent on experimentally induced hamster buccal pouch (HBP) carcinogenesis. Material and methodsIn this study we used 40 Syrian male hamsters, five weeks old, were divided into 4 groups (GI, GII, GIII, and GIV) of 10 animals in each as follows, GI: Topical application of liquid paraffin alone (thrice a week for 14 weeks), GII: Topical application of 7, 12 dimethyl benz[a]anthracene (DMBA) alone (0.5% in liquid paraffin, thrice a week for 14 weeks), GIII: Topical application of DMBA (0.5% in liquid paraffin, thrice a week for 14 weeks) + Oral administration of DHA (125 mg/kg b.w. in 1 ml distilled water by oral gavage, thrice a week for 14 weeks on alternative days of DMBA application), GIV: Oral administration of DHA alone (125 mg/kg b.w. in 1 ml distilled water by oral gavage, thrice a week for 14 weeks). ResultsGross observations and histopathological findings revealed that, in GI: normal stratified squamous epithelium, in GII: well and moderately differentiated squamous cell carcinoma (SCC), in GIII: variable results ranges from hyperkeratosis, hyperkeratosis and focal hyperplasia, mild dysplasia, and well differentiated SCC with superficial invasion of tumor cells not extended to deeper areas, while in GIV: normal similar to GI. Immunohistochemical results indicated that oral DHA treatment to DMBA treated hamsters restored the normal expression of bcl-2. ConclusionOur results indicated that DHA has the potential to be a dietary chemopreventive agent due to its capacity to improve carcinogen detoxification and to block/suppress the initiation and promotion stages of experimentally produced HBP carcinogenesis.

Oral biopsies in a Portuguese population: A 20-year clinicopathological study in a university clinic.

Performing a biopsy is very important in oral medicine and the anatomopathological examination is fundamental to obtain or to confirm the diagnosis in oral and maxillofacial pathology. The purpose of this study is to analyse the frequency and characteristic patterns of biopsied oromaxillofacial lesions in a Portuguese population. A descriptive statistical analysis of the data from the anatomopathological reports of the biopsies performed between 1999 and 2019 at the university clinic of the Faculty of Dental Medicine of the University of Lisbon was performed, regarding the patient's gender and age, type of biopsy, location of lesions, clinical and histological diagnosis, and the results were obtained. Association relationships were studied using the chi-square test and the Kruskal-Wallis test to correlate variables. P<0.05 was considered statistically significant. From a total sample of 1448 patients, 826 (57.1%) were female, 610 (42.1%) were male, and 12 (0.8%) had no gender information, with a mean age of 50.14 years (standard deviation ± 17.61). The preferred location was the buccal mucosa, vestibule fundus and alveolar mucosa (20.7%). Benign lesions (BL) were the most common, in 82,8% of the cases, followed by oral potentially malignant disorders (OPMD) in 15,5%, and finally, malignant lesions (ML) in 1.7%. Focal fibrous hyperplasia was the most frequent diagnosis in the total sample (25.6%). In the young group, the most common entity was mucocele (34.0%), with a predominance of the lower lip (32.9%). In OPMD, leukoplakia was the most frequently diagnosed (48,7%). The most common ML was squamous cell carcinoma (92.0%), appearing mainly in the tongue (34.8%). A statistically significant relation between ML and older age was found. This study included biopsies analysed over a period of 20 years, being BL the main pathology to affect the oral cavity. Although less frequent, OPMD and ML should not be neglected and must be correctly diagnosed and treated. Key words:Oral biopsies, Oral and maxillofacial pathology, Oral medicine, Clinicopathological analysis, Epidemiological study, University clinic.

Hepatic pseudolesions caused by alterations in intrahepatic hemodynamics

Hepatic pseudolesion may occur in contrast-enhanced computed tomography and magnetic resonance imaging due to the unique haemodynamic characteristics of the liver. The concept of hepatic arterial buffer response (HABR) has become mainstream for the understanding of the mechanism of the reciprocal effect between hepatic arterial and portal venous flow. And HABR is thought to be significantly related to the occurrence of the abnormal imaging findings on arterial phase of contrast enhanced images, such as hepatic arterial-portal vein shunt and transient hepatic attenuation difference, which mimic hypervascular tumor and may cause clinical problems. Third inflow to the liver also cause hepatic pseudolesion, and some of the cases may show histopathologic change such as focal hyperplasia, focal fatty liver, and focal sparing of fatty liver, and called pseudotumor. To understand these phenomena might be valuable for interpreting the liver imaging findings.

Asymptomatic Postmenopausal Endometrial Thickening: A Comparison between Transvaginal Ultrasound and Hysteroscopy

<h3>Study Objective</h3> Compare the ultrasonography and the hysteroscopy findings in asymptomatic postmenopausal patients showing endometrial thickening. <h3>Design</h3> Observational study (Canadian Task Force Classification II-2). <h3>Setting</h3> San Salvatore Hospital of L'Aquila, Department of Obstetrics and Gynecology. <h3>Patients or Participants</h3> 315 asymptomatic postmenopausal women with endometrial thickening >4 mm. <h3>Interventions</h3> Diagnostic hysteroscopy, endometrial biopsy. <h3>Measurements and Main Results</h3> That patients had normal endometrium (8.6%), atrophic endometrium (26.7%), single benign polyp (47.6%), multiple polyps (8.6%), myoma (1.9%), focal hyperplasia (3.8%), diffuse hyperplasia (0.9%) and endometrial carcinoma (1.9%). In 30 women under therapy for breast cancer (thickening >5 mm) the hysteroscopic exam showed normal endometrium (50%), multiple polyps (20%), focal hyperplasia (20%) and diffuse hyperplasia (10%). For this subcategory of patients, the histopathological analysis confirmed the hysteroscopic diagnosis in 100% of case. It is not statistically valid to give to the homogeneity data of the endometrial thickening a direct association with the suspicion of polyp, as well as the ascription of a direct association with all the other suspicions except polyp to a non-homogeneous thickening cannot be considered statistically valid. The ROC analysis shows that the best cut-off for suspected polyp in ultrasonography is ≤6 mm (sensibility of just 66.0%, specificity of just 58.18%). By the ROC analysis, an 8 mm cut-off of ultrasound thickness was identified, above which the suspicion of endometrial carcinoma is strongly solid (specificity of 84.47% and a sensibility of 100%). <h3>Conclusion</h3> Hysteroscopy has a positive predictive value (PPV) of 100%and a negative predictive value (NPV) of 97.952% in detecting a risk of malignancy, with a specificity of 100% and a sensibility of 77.78%, demonstrating that hysteroscopy is the gold standard for the diagnosis of malignant endometrial pathology or an endometrial condition at severe risk of malignancy. A direct endoscopic exam is the only valid exam in the diagnosis of the intracavitary pathologies, especially in asymptomatic postmenopausal patients.

Структурно-функциональное состояние щитовидной железы у пациентов с предраковыми состояниями желудка

Актуальность. Механизмы функционального взаимодействия желудка и щитовидной железы (ЩЖ) базируются на биологическом действии тиреоидных гормонов. Согласно европейским рекомендациям MAPS II, к предраковым состояниям желудка относятся атрофия и кишечная метаплазия (КМ) слизистой оболочки желудка (СОЖ). Цель: оценить структурно-функциональные изменения паренхимы ЩЖ у больных с предраковыми состояниями желудка. Материалы и методы. Исследование проведено у 44 больных с предраковыми состояниями желудка. Среди обследованных больных было 32 (72,7 %) женщины и 12 (27,3 %) мужчин в возрасте от 33 до 76 лет, в среднем (59,7 ± 1,7) года. Верхнюю эндоскопию выполняли с использованием системы EVIS EXERA III с гастроскопом Olympus 190 (Япония). По результатам эндоскопического исследования пациенты были распределены на группы: I группа — 11 больных с атрофией СОЖ без КМ; II группа — 13 пациентов с атрофией СОЖ с КМ, ограниченной антральными отделом или телом желудка; III группа — 8 человек с диффузной КМ на фоне атрофии СОЖ. Группы были репрезентативны по возрасту и полу. Всем обследованным проводилось сонологическое исследование ЩЖ на ультразвуковом сканере Toshiba Xario (Япония) с использованием мультичастотного линейного трансдюсера с частотой 5–12 МГц. Для оценки функционального состояния ЩЖ в сыворотке крови определяли уровень тиреоглобулина и тиреотропного гормона иммуноферментным методом. Результаты. Установлено существенное увеличение частоты диффузных и очаговых изменений в ЩЖ у пациентов с диффузным распространением КМ в желудке (p &lt; 0,05), что подтверждено корреляционной связью частоты КМ тела и антрального отдела желудка с наличием узлов в ЩЖ (r = 0,44, p = 0,003 и r = 0,40, p = 0,006 соответственно). В то же время увеличение частоты очаговых гиперплазий СОЖ ассоциировалось с неровностью контуров ЩЖ (r = 0,41, p = 0,03) и увеличением плотности капсулы ЩЖ (r = 0,49, p = 0,04), что является признаками хронического воспалительного процесса. Распространение КМ сопровождалось увеличением уровня тиреоглобулина в более чем 3 раза (р = 0,0134). При этом содержание тиреотропного гормона достоверно снижалось по мере углубления перестроечных изменений СОЖ (р = 0,0474), а установленная корреляционная связь уровня этого гормона с наличием КМ в теле желудка (r = –0,46, р &lt; 0,05) свидетельствует о необходимости дальнейшего изучения роли гормонов ЩЖ в развитии предраковых состояний желудка. Выводы. У больных с предраковыми состояниями желудка наблюдается высокая частота структурных изменений паренхимы ЩЖ (81,8 %) как диффузного (75,0 %), так и очагового (43,2 %) характера. Распространение КМ СОЖ коррелирует со структурными изменениями паренхимы ЩЖ, что сопровождается достоверным увеличением содержания тиреоглобулина и снижением уровня тиреотропного гормона в сыворотке крови. Частота структурных изменений ЩЖ увеличивается по мере углубления перестроечных изменений желудка, что подтверждается положительной корреляционной связью между изменениями структуры ЩЖ и наличием ксантом СОЖ, которые являются маркерами предраковых состояний СОЖ (r = 0,52, p = 0,03).

Abstract 2661: Role of NKX2-1 in thyroid neoplasms induced by iodine-deficiency and radiation

Abstract The multi-step carcinogenesis model, including the adenoma-carcinoma sequence, has been proposed in many cancers including those of colon, pancreas, and thyroid. BRAF activation is among the reported gene mutations important for thyroid carcinogenesis. However, the role of NKX2-1, a master regulator of thyroid development and function, in thyroid carcinogenesis remains elusive. In this study, we investigated the role of NKX2-1 in thyroid neoplasm formation using thyroid-specific Nkx2-1 conditional KO mice, Nkx2-1(fl/fl);TPO-Cre (cKO mice). Nkx2-1(fl/fl) (WT) and cKO mice were each allotted to four groups: 1. Control Diet, 2. Control Diet + Radiation, 3. Low Iodine Diet (LID), 4. LID + Radiation. Whole body gamma-irradiation (2 Gy, 3 times every other day) was carried out at 4-8 weeks of age, followed by switching the diet to either Control Diet or LID. Thyroid histology was examined at 1.1-1.3 years after the start of the diet. In both WT and cKO mice, iodine-deficiency, regardless of radiation, induced diffuse hyperplasia (goiter) in more than 50% of the mice, and increased the incidence of focal hyperplasia considered as a preneoplastic lesion. Adenoma formation was only observed in LID-treated mice regardless of radiation, suggesting that iodine-deficiency, but not radiation, is a key factor for mouse thyroid adenoma formation. The incidence of adenoma formation was significantly higher in cKO mice than WT mice in LID + Radiation group (14% for WT vs 52% for cKO, in progress). In addition, carcinoma formation was observed only in LID + Radiation-treated mice, suggesting that radiation is necessary to proceed from adenoma to cancer in thyroid carcinogenesis. Further, there is a tendency for higher incidence of carcinoma in LID + Radiation-treated cKO mice (4% for WT vs 11% for cKO, in progress). These results suggest that the loss of Nkx2-1 can promote adenoma formation induced by iodine-deficiency, and possibly facilitate carcinogenesis induced by LID + Radiation. In summary, our results suggest that NKX2-1 may function as a tumor suppressor in thyroid carcinogenesis. We are now trying to investigate the molecular mechanisms by which loss of NKX2-1 affects thyroid proliferation and facilitates neoplasm formation by examining the molecular profiles of mouse thyroids after LID and/or radiation treatment. Citation Format: Yo-Taro Shirai, Yoshinori Takizawa, Manabu Iwadate, Jorge Paiz, Shigetoshi Yokoyama, Masaaki Miyakoshi, Jerrold M. Ward, Shioko Kimura. Role of NKX2-1 in thyroid neoplasms induced by iodine-deficiency and radiation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2661.

GENERAL PROFILE OF THE GINGIVAL LESIONS PRESENTED BY EPULIS: AN ANALYSIS OF 90 CASES

<h3>Background</h3> Epulis is a nonspecific historical term applied to localized enlargement of gingiva. Although gingival enlargement often develops because of simple reactive lesions, it sometimes may also be the clinical presentation form of malignant and benign neoplastic lesions. <h3>Objective and Methods</h3> A total of 90 cases with a clinical diagnosis of "epulis" were included in the study. Histopathologic findings of the cases were analyzed with demographic and clinical information. <h3>Results</h3> Of the 90 patients, 65 were female (72.2%) and 25 were male (27.8%). The mean age was 40.13 ± 18.04 years (range, 6 days to 78 years) and about one-third of cases were discovered in the fifth decade. The most frequent localization was mandibular gingiva (50 cases) compared to the maxillary gingiva. Histopathologically, reactive lesions were detected in the vast majority of cases and only 11 cases had a neoplastic lesion (12.2%). The most detected reactive lesion was peripheral giant cell granuloma (38.9%), followed by focal fibrous hyperplasia (35.6%) and pyogenic granuloma (13.3%). Of the 11 neoplastic lesions, 6 benign tumors (2 congenital granular cell tumor, 1 lipoma, 1 osteoma, 1 peripheral developing odontoma, and 1 peripheral ossifying fibroma) and 5 malignant tumors (2 Langerhans cell histiocytosis, 1 malignant melanoma, 1 mucoepidermoid carcinoma, and 1 osteosarcoma) were diagnosed. <h3>Conclusions</h3> In our study, neoplastic lesions were detected in 12.2% of patients and the risk of malignancy was determined as 5.5% in lesions presented by epulis. Histopathologic examination is a gold standard for differentiation of such lesions.

Identification of Cellular Damage in Uteri From Hyperinsulinemic Mice Treated With Unopposed Estradiol

Abstract Unopposed estradiol and obesity are known risk factors for endometrial adenocarcinoma (EC). Endometrium from women with obesity was found to have an increase in mutations relative to tissue from normal weight women, indicating DNA damage may be accelerated in the setting of obesity. Since obesity is associated with high levels of insulin and anovulatory cycles, we sought to mimic these conditions in a mouse model. We previously found that hyperinsulinemic MKR mice, without the confounder of obesity, have an increased incidence of nuclear atypia in endometrial glands. We hypothesized that hyperinsulinemia and unopposed estradiol have a synergistic effect on inducing abnormal architecture and DNA damage in the endometrium, than either alone. At 8-10 weeks old, cohorts of MKR (n=20) and WT (n=20) mice underwent ovariectomy and placement of either an estradiol (E2) or placebo (P) pellet. Metabolic profiling included insulin tolerance testing and MR for body composition. At 3 months post-implantation, mice received a partial hysterectomy and second pellet replacement. At 6 months, the remaining uterus was bisected into pieces. A blinded histological analysis was conducted by a gynecology pathologist. A marker of DNA damage due to oxidative stress, 8-oxoguanine-DNA-glycosylase (8-OHdG), was quantified by ELISA. Data was analyzed using Kruskal-Wallis test with multiple test correction, or Fischer’s exact test. By 6 months, MKR-E2 treated mice had a 27% lower body weight than MKR-P mice (p&amp;lt;0.05), and 31% lower than WT-E2 mice (p&amp;lt;0.01). WT-E2 and WT-P had similar weight, and were similar to MKR-P (p=ns). Percent body fat was similar across all 4 cohorts of mice (p=ns). Since placebo-treated mice had small, atrophied uteri with minimal gland formation, E2 pellet failure was determined by the presence of small, atrophied uteri and occurred in 4 MKR and 3 WT mice at either 3 or 6 months. All other MKR and WT E2 treated mice had enlarged uteri. The frequency of endometrial gland dilation was similar in MKR-E2 and WT-E2 uteri (p=ns), but all MKR mice had moderate-severe dilation, whereas WT mice had 50% mild and 50% moderate-severe dilation (p=0.07). Focal hyperplasia was present in one MKR-E2 mouse, and nuclear atypia was present in one WT-E2 mouse. MKR-P uteri had a 7-fold higher mean 8-OHdG relative to MKR-E2 uteri (5.0±3.7 vs 0.7±1.6, p&amp;lt;0.002). WT-E2 and WT-P uteri had similar 8-OHdG (1.6±0.8 vs 1.8±0.6, p=ns), as did MKR-E2 and WT-E2 uteri (p=ns). Our findings show that hyperinsulinemia exacerbates the cystic dilation induced by chronic unopposed estradiol, indicating a synergy of insulin and estradiol in promoting abnormal glandular growth in the endometrium. Surprisingly, uterine DNA damage was highest in the setting of hyperinsulinemia alone, in a hormonal state mimicking post-menopause. Further work is needed to understand the effect of estradiol on intrauterine oxidative stress-induced damage.

FOCAL FIBROUS HYPERPLASIA: A CLINICAL AND HISTOLOGICAL INSIGHT

Fibrous type gingival overgrowth is commonly seen in oral cavity and can be either benign or malignant lesions. Chronic irritation is one of the most common causes of nonneoplastic type of lesion. Focal fibrous hyperplasia also called as irritational or traumatic fibroma usually can be self limiting in nature or sometimes excision is recommended. Present case report demonstrates clinical and histological insight on the lesion.