Focal Epithelial Hyperplasia Research Articles

The molecular-based differentiation of Heck's disease from its mimics including oral condyloma and white sponge nevus

Heck's disease (focal or multifocal epithelial hyperplasia) is a benign, rare condition of the skin and mucous membranes induced by human papillomavirus (HPV) infection. Other entities that can induce large papillomatous lesions that involve the mucous membranes and skin include condyloma acuminatum, which is sexually transmitted, and white sponge nevus, often due to a mutation of cytokeratin 4 or 13. Six cases diagnosed as either Heck's disease (n = 2) or white sponge nevus (n = 4) and 6 oral condyloma were compared on histologic grounds and analyzed in situ for HPV DNA, including HPVs 6,11, and 13, as well as cytokeratins 4 and 13. Each case showed marked acanthosis, and para/hyperkeratosis. More variable histologic findings included rete ridge elongation, keratinocyte degeneration, and perinuclear halos. High copy HPV 13 DNA was evident in the squamous cells towards the surface in the two cases diagnosed as Heck's disease and in two cases diagnosed as white sponge nevus on clinical grounds. HPV 6/11 was found in each of the six condyloma. Marked decrease in either cytokeratin 4 or 13 was evident in the two cases diagnosed as white sponge nevus that were HPV DNA negative. It is concluded that in situ hybridization analyses including HPVs 6, 11, and 13 as well as immunohistochemistry for cytokeratins 4 and 13 can differentiate Heck's disease from condyloma and white sponge nevus, which can be difficult to differentiate on clinical and histologic grounds.

Immunohistochemical study of Ki-67, PHH3, and CK15 protein expression in oral epithelial malignancy

To investigate the expression of Ki-67, phosphohistone H-3 (PHH3), and cytokeratin 15 (CK15) proteins in the cells of the oral mucosa (OM) according to the degree of its malignant transformation. OM biopsy specimens from 69 patients diagnosed with focal epithelial hyperplasia, intraepithelial squamous cell neoplasia, cancer in situ, and squamous cell carcinoma were examined. Tissue antigens were determined using mouse Ki-67 monoclonal antibodies, rabbit PHH3 polyclonal antibodies, and mouse CK15 monoclonal antibodies. There was an increase in epithelial proliferative and mitotic activities in squamous cell carcinoma and a sharp decrease in the expression of CK15 in the cytoplasm in cancer in situ and squamous cell carcinoma of the OM. The protein CK15 can be used for the differential diagnosis between high-grade dysplasia and OM epithelial malignancy at the stage of carcinoma in situ and squamous cell carcinoma.

Oral manifestations of human papillomavirus infections.

Papillomaviruses are one of the oldest viruses known, dating back 330 million years. During this long evolution, human papillomaviruses (HPV) have developed into hijackers of human cellular and immune systems in which they replicate and remain silent. Systematic studies on oral HPV infections and their outcomes are still scarce. Oral HPV infections have been linked to sexual behaviour, but recent evidence supports their horizontal, mouth‐to‐mouth, transmission. Most HPV infections in infants are acquired vertically from the mother during the intrauterine period, during delivery, or later via saliva. The best‐known benign clinical manifestations of HPV infection are oral papilloma/condyloma and focal epithelial hyperplasia. Evidence is emerging which suggests that some oral HPV infections might persist. Persistent HPV infection is mandatory for HPV‐associated malignant transformation. However, progression of HPV‐induced lesions to malignancy requires additional cofactors. In the early 1980s, we provided the first evidence that a subset of oral cancers and other head and neck cancers might be causally linked to HPV infection. This review summarizes current knowledge on the virus itself, its transmission modes, as well as the full spectrum of oral HPV infections – from asymptomatic infections to benign, potentially malignant oral lesions, and squamous cell carcinoma.

Focal Epithelial Hyperplasia (Heck's Disease): an Unexpected Finding

Focal Epithelial Hyperplasia (Heck's Disease): an Unexpected Finding

A Case Report of Multifocal Epithelial Hyperplasia (Heck's Disease) Treated with CO2 Laser

Focal epithelial hyperplasia or Heck’s disease is a rare benign lesion of oral mucosa caused by human papilloma virus especially subtypes 13 and 32. The disease is predominantly found in children and adolescents with indigenous heritage. This paper reports a unique case of Heck's disease in an 11-year-old Iranian girl with multiple, bilateral and elevated lesions on the buccal and labial mucosa. The lesions had persisted for a year. The disease was diagnosed as focal epithelial hyperplasia through the clinical examination. Considering esthetic and functional problems, CO2 laser (Wavelength: 10600 nm) surgery was determined as a suitable choice of treatment. The patient was followed up over 1 year with no signs of lesion recurrence.

HECK DISEASE: REPORT OF CASE

Heck’s disease or focal epithelial hyperplasia is a proliferation caused by viruses, which settles in the oral squamous epithelium, rare, benign disease, which affects the oral mucosa of children and young adults. It is correlated with human papilloma virus (HPV). Female patient with 10 years history, reported not present systemic and oral problems. On clinical examination revealed well-defined lesions of rounded form, located on the lower lip. Excisional biopsy of the lesion was performed and sent for histopathologic analysis, which found mitosis cells, epithelial changes and rete ridges as in “golf club”. Histopathologic and clinical aspects diagnosis was focal epithelial hyperplasia (Heck disease). After removal of the lesion, was observed no occurrence during the short observation period.

Exotic "Gill Lice" Species (Copepoda: Lernaeopodidae: Salmincola SPP.) Infect Rainbow Trout (Oncorhynchus mykiss) and Brook Trout (Salvelinus fontinalis) in the Southeastern United States.

Salmincola californiensis infected 25 of 31 (prevalence 0.8; intensity 2-35 [mean 6.6 ± standard deviation 7.7; n = 25]) rainbow trout, Oncorhynchus mykiss, from a private trout farm connected to the Watauga River, North Carolina. Salmincola edwardsii infected all of 9 (1.0; 2-43 [9.3 ± 13.0; 9]) brook trout, Salvelinus fontinalis, from Big Norton Prong, a tributary of the Little Tennessee River, North Carolina. Both lernaeopodids are well-known salmonid pathogens, but neither is native to, nor has been previously taxonomically confirmed from, the southeastern United States. Herein, we (1) use light and scanning electron microscopy to identify and provide supplemental morphological observations of these lernaeopodids, (2) furnish complementary molecular sequence data from the 28S rDNA (28S), and (3) document the pathological effects of gill infections. We identified and differentiated these lernaeopodids by the second antenna (exopod tip with large [S. californiensis] vs. slender [S. edwardsii] spines; endopod terminal segment with subequal ventral processes shorter than [S. californiensis] vs. longer than or equal to [S. edwardsii] dorsal hook), maxilliped palp (length typically ≤1/3 [S. californiensis] vs. 1/3-1/2 [S. edwardsii] subchela length exclusive of claw), and bulla (sub-circular and concave on manubrium's side [S. californiensis] vs. non-stellate [S. edwardsii]). Analysis of the 28S rDNA sequences confirmed our taxonomic assignments as demonstrated by 100% sequence similarity among the sympatric, morphologically-conspecific isolates. Histopathology revealed focal gill epithelial hyperplasia, obstruction of interlamellar water channels, lamellar fusion, and crypting of gill filaments. High intensity infections by either lernaeopodid are surveillance-worthy because they are potentially pathogenic to trout in the southeastern United States.

Focal Epithelial Hyperplasia Prevalence in an Endemic Population, Molecular Association of HPV-13 to Asymptomatic Patients and Comparison Between Three Elementary Schools of Different Income Levels

Heck’s disease, or Focal Epithelial Hyperplasia (FEH), caused by Human Papilloma Virus (HPV) subtypes 13 and mainly 32, is a rare and benign pathology of the oral mucosa; diagnosis is confirmed by PCR analysis. This is a common disease in the Mayan and other Native-American populations, most frequently between 2-13 years. Risk factors include lower income class, poor hygiene and genetic predisposition. This cross-sectional study aims to determine the prevalence of clinically compatible lesions of FEH in children from low, middle and high-income in 3 elementary schools in Yucatan, Mexico. Clinical evaluation was conducted and documented for later analysis by a dermatologist familiar with FEH. Samples were taken and HPV-13 was identified by PCR. The total of 186 subjects were analyzed from the low-income elementary school, with 41 subjects presenting FEH lesions and 76 presented HPV-13 upon PCR analysis. In the middle-income school, of the 144 subjects studied, 3 had FEH lesions and 8 presented HPV-13 upon PCR analysis. In the high-income elementary school, 96 students were studied, and none presented FEH lesions, however, 6 had HPV-13 positivity. FEH and HPV-13 prevalence were inversely proportional to socioeconomic status. Lacking an association to a particular gender or difference in the age groups studied.

Case Report of Focal Epithelial Hyperplasia (Heck's Disease) with Polymerase Chain Reaction Detection of Human Papillomavirus 13.

Case Report of Focal Epithelial Hyperplasia (Heck's Disease) with Polymerase Chain Reaction Detection of Human Papillomavirus 13.

Effectiveness of trichoroloacetic acid in treatment of focal epithelial hiperplasia lesions

Objective: The aim of the present study was to assesseffectiveness of trichloroacetic acid therapy in the treatment of oral lesions produced in focal epithelial hyperplasia cases. Material and methods: In the present study 11 patients were included. Patients exhibited clinical and histopathological characteristics of focal hyperplasia and were willing to participate in the study. Convenience sampling was executed in patients attending clinical consultation at the Dental Clinic of the Rafael Nuñez University Corporation and the University of Cartagena. Patients underwent excision biopsy in oneof the lesions so as to establish anatomical-pathological diagnosis.Subsequently, 80% trichloroacetic acid was applied every twoweeks on the lesions, until lesions disappeared. Results: Out of 11 pediatric patients 63.64% were female, average age nine years.Locations of greater involvement in the mouth were upper andlower labial mucosa (representing 100%). Anatomical-pathological study revealed in all cases presence of epithelial acanthosis, papillomatosis and koilocytiosis. The greatest number of acid applications was three and four episodes with 27%, average time for lesion disappearance was 61.3 days. No relapse was observed in 100% of cases. Conclusion: Trichloroacetic acid application in focal epithelial hyperplasia cases is an effective technique which achieves rapid, atraumatic stress-free lesion resolution which did not generate fear in involved patients.

Abstract 1210: Preclinical pharmacology and repeated dose toxicity of the novel agonistic TWEAK receptor binding antibody BAY-356

Abstract TWEAK receptor (TWEAKR, FN14) is a member of the tumor necrosis factor receptor superfamiliy and is highly expressed in a variety of human solid tumor types, and its overexpression is associated with poor prognosis and metastasis. To explore targeting of TWEAKR for cancer therapy we have generated the novel, anti-TWEAKR antibody BAY-356. Its potent agonistic activity leads to TWEAKR hyperactivation and subsequent induction of cell death in vitro and tumor growth inhibition in vivo. BAY-356 is a fully human aglycosylated antibody (Kd ∼ 10nM) that binds to a novel epitope within the TWEAKR ectodomain of various species as determined by BiaCore. In vitro, BAY-356 showed strong agonistic activity on TWEAKR-positive tumor cells, including activation of NFκB- and STAT1 pathways, increase of TWEAKR protein expression, increased IL-8 secretion, caspase 3/7 activation, and proliferation inhibition in a dose-dependent manner. BAY-356 inhibited tumor growth in several TWEAKR-positive tumor models (NCI-H1975, WiDr, ScaBER, and HN10321) with growth inhibition rates of 49-71% when treated with 3-10 mg/kg BAY-356 twice weekly for up to 3 weeks. The activity of BAY-356 was independent of ADCC activation. In a preventative syngeneic CT26-tumor model in Balb/c mice, BAY-356 induced complete responses. Anti-tumor activity of BAY-356 was associated with high tumor levels of TNF alpha protein. To investigate the toxicity of BAY-356, a repeated dose-toxicity study was performed in Cynomolgus monkeys. Animals were dosed with 10, 20, and 40 mg/kg by weekly intravenous injection for 4 weeks. Compound-related clinical findings consisted of an increase of the serum markers amylase and lipase from 10 mg/kg onwards, urea and creatinine from 20 mg/kg onwards and the transaminases ALT and GDPH at 40 mg/kg. Histopathological evaluation revealed focal ductular epithelial hyperplasia with periductular fibrosis in the exocrine pancreas (at 10 & 20 mg/kg), renal tubular hyperplasia and degeneration, Bowman capsule hyperplasia, and glomerulosclerosis in the kidney starting at 10 mg/kg and bile duct hyperplasia in liver at 20 mg/kg and higher. The HNSTD was set as the highest tested dose of 40 mg/kg. Immunohistochemical analysis of TWEAKR expression in these organs demonstrated a dose dependent induction and increase when compared to untreated controls which correlated with the histopathological findings. From these data it can be concluded that hyperactivation of TWEAKR signaling by BAY-356 leading to strong anti-tumor efficacy in various mouse models is invariably accompanied by target-mediated side-effects originating from enhanced TWEAKR induction in in particular in kidneys, pancreas, and liver of sensitive species such as Cynomolgus monkeys. Citation Format: Sandra Berndt, Christian Votsmeier, Ruprecht Zierz, Jakob Walter, Anna-Lena Frisk, Stefanie Hammer, Heiner Apeler, Bertolt Kreft. Preclinical pharmacology and repeated dose toxicity of the novel agonistic TWEAK receptor binding antibody BAY-356. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1210.

Caudate lobe as the sole remnant liver following anatomical hepatectomy for the treatment of hepatolithiasis

Objective To investigate the safety and short-term effect of anatomical hepatectomy for the treatment of hepatolithiasis with the caudate lobe as the sole remnant liver. Methods The clinical data of 1 patient with hepatolithiasis combined with liver atrophy-hypertrophy syndrome who was admitted to the Hunan Provincial People's Hospital in April 2014 were retrospectively analyzed.The stones were located in the left and right liver, the involved liver became fibroatrophy, and the hepatic caudate lobe not containing stones became hypertrophy.The body surface area of the patient was 1.65 m2, standard total liver volume was 1 167.63 mL. According to the result of CT, expected residual liver volume after hepatectomy was 706.12 mL, and the ratio of residual liver volume over the standard total liver was 60.47%.The radio of residual liver volume over the body mass index was 1. 21%.The patient received the second exploration of common bile ducts, hepatectomy with the caudate lobe as the sole remnant liver and T tube drainage.The follow-up including recurrence of calculus was performed by outpatient examination and telephone interview up to April 2015. Results The patient underwent caudate lobe as the sole remnant liver following anatomical hepatectomy successfully without blood transfusion.The operation time and volume of intraoperative blood loss were 380 minutes and 350 mL.The peritoneal drainage tube was removed at postoperative day 2 and the patient was discharged at postoperative day 8 with a good recovery of liver function.The postoperative pathological examination showed that there were focal biliary epithelial papillary hyperplasia combined with light-medium atypical hyperplasia and no canceration.The T tube cholangiography two month later showed that there were unobstructed lower bile duct and no residual intra-and extra-hepatic stones. The liver function was normal.Then T tube was removed and patient resumed normal life.During the 1-year follow-up, no chills and fever, jaundice and abdominal pain occurred, no calculus was detected by Bultrasonography, and computed tomography reexamination showed that remnant liver volume was increased and no intra-and extra-hepatic bile duct stones were detected. Conclusion Anatomical hepatectomy for the treatment of hepatolithiasis with the caudate lobe as the sole remnant liver is safe and feasible, with a good curative effect. Key words: Hepatolithiasis; Anatomical hepatectomy; Surgical procedures, operative

Exophytic Verrucous Hyperplasia of the Oral Cavity – Application of Standardized Criteria for Diagnosis from a Consensus Report

Verruco-papillary lesions (VPLs) of the oral cavity described in the literature involve a spectrum of conditions including squamous papilloma, verruca vulgaris, focal epithelial hyperplasia, condyloma, proliferative verrucous leukoplakia and verrucous carcinoma. A majority of the VPLs are slow growing, benign in nature and have a viral aetiology. Virus associated benign mucosal outgrowths are not too difficult to diagnose either clinically or by microscopy. Apart from virus-associated lesions, VPLs harboring malignant potential or behaviour such as verrucous carcinoma, proliferative verrucous leukoplakia, oral verrucous hyperplasia (OVH), oral papillary squamous cell carcinoma (PSCC) and oral conventional squamous cell carcinoma with papillary features (CSCC) need to be further clarified for better understanding of their predictable biologic behavior and appropriate treatment. Current understanding of potentially malignant VPLs is perplexing and is primarily attributed to the use of confusing and unsatisfactory terminology. In particular, the condition referred to as oral verrucous hyperplasia (OVH) poses a major diagnostic challenge. OVH represents a histopathological entity whose clinical features are not well recognised and is usually clinically indistinguishable from a verrucous carcinoma and a PSCC or a CSCC. A consensus report published by an expert working group from South Asia as an outcome of the ‘First Asian Regional Meeting on the Terminology and Criteria for Verruco-papillary Lesions of the Oral Cavity’ held in Kuala Lumpur, Malaysia, recognised the clinical description of these OVH as a new entity named ‘Exophytic Verrucous Hyperplasia’. Previously described clinical features of OVH such as the ‘blunt’ or ‘sharp’ variants; and the ‘mass’ or ‘plaque’ variants can now collectively fall under this newly described entity. This paper discusses in detail the application of the standardized criteria guidelines of ‘Exophytic Verrucous Hyperplasia’ as published by the expert group which will enable clinicians and pathologists to uniformly interpret their pool of OVH cases and facilitate a better understanding of OVH malignant potential.

The frequency of human papillomavirus findings in normal oral mucosa of healthy people by PCR

SummaryThe human papillomavirus (HPV) is a DNA virus, which belongs to papillomaviridae family, being of low and high risk, which infect the skin and mucous membranes and can induce benign and malign tumor formation. In the oral mucosa they have been associated with oral papilloma, focal epithelial hyperplasia, leucoplakia and oral neoplasia.Aimto study the frequency of HPV finding in oral mucosa of normal people.Materials and methodsProspective study, cross-sectional cohort. One hundred volunteers, young adults, healthy, aged between 20 and 31 years, university students with no history, no complains, without oral or oropharyngeal lesions. They were submitted to a questionnaire with questions regarding HPV infection epidemiology. The samples were harvested by brushing and analyzed by PCR.ResultsThe results were negative for HPV in all samples.ConclusionIt seems we had high social and economical class individuals, with nutrition rich in carotenoyds and vitamin C, low smoking and alcohol consumption and heterosexual habits with predominant monogamy and regular use of condoms.

FOKAL EPİTELYAL HİPERPLAZİ -HECK HASTALIĞI: OLGU SUNUMU

Focal Epithelial Hyperplasia (FEH) is a rare seen disease which is caused by human papilloma virus (HPV). In this disease, small papules or nodules of mucosa membrane color or in a more white color occur inside mouth. FEH-related lesions are usually asymptomatic, in some cases it can cause painful and cosmetic concerns. Spontaneous regression or progression of the disease can be seen. While, among treatment options, electrocautery, cryotherapy, surgical excision and laser take place for localized lesions, in widespread-involvement seen cases, it was informed that successful results are obtained by systemic treatments like topical interferon-β, interferon-a2b and imiquimod retinoids. In this case report, we purpose to present the clinical, histopathological features of heck disease, its treatment and its 6 months-follow-up after treatment

Molecular biology for hpv typing in focal epithelial hyperplasia

Parichehr Ghalayani and colleagues (Volume 31, Number 1, Pages:060-063) report three interesting cases of focal epithelial hyperplasia (FEH) diagnosed through clinical and microscopic analysis (1). We would like to emphasize that, although the age and ethnicity of the patient may support the clinical suspicion of FEH, the histopathological features of FEH might be similar to that of condyloma acuminatum and oral squamous cell papilloma (2).

HPV and oral lesions: preventive possibilities, vaccines and early diagnosis of malignant lesions.

The importance of HPV in world healthy is high, in fact high-risk HPV types contribute significantly to viral associated neoplasms. In this article we will analyze vary expression of HPV in oral cavity both benign and malignant, their prevalence and the importance in early diagnosis and prevention. The classical oral lesions associated with human papillomavirus are squamous cell papilloma, condyloma acuminatum, verruca vulgaris and focal epithelial hyperplasia. Overall, HPV types 2, 4, 6, 11, 13 and 32 have been associated with benign oral lesions while HPV types 16 and 18 have been associated with malignant lesions, especially in cancers of the tonsils and elsewhere in the oropharynx. Transmission of the virus can occur with direct contact, genital contact, anal and oral sex; latest studies suggest a salivary transmission and from mother to child during delivery. The number of lifetime sexual partners is an important risk factor for the development of HPV-positive head-neck cancer. Oral/oropharyngeal cancer etiologically associated with HPV having an increased survival and a better prognostic (85%-90% to five years). There is no cure for the virus. There are two commercially available prophylactic vaccines against HPV today: the bivalent (16 and 18) Cervarix® and the tetravalent (6, 11, 16 and 18) Gardasil® and new vaccine Gardasil 9 (6, 11, 16, 18, 31, 33, 45, 52, 58) was approved in the United States. To be effective, such vaccination should start before "sexual puberty". The vaccine could be an important preventive strategy, in fact the scientific community is in agreement on hypothesis that blocking the contagion it may also limit the distance complications as the oropharyngeal cancer.

HUMAN-PAPILLOMA VIRUS IN ORAL MUCOSA: AN OVERVIEW

Since 20 years there been an ever - increasing interest in human papillomaviruses HPV for the reason that of their impending charact er in the pathogenesis of malignant tumors. HPV was undeniably confirmed a s an independent risk factor which leads to oral carcinoma . Up to now , totally more than 200 different strains and 170 types of HPV have been identified with their genomes and of the m generally very less leads to the cancerous stage . As in HPV type 16 is the most prevalent type in oral carcinomas. The benign oral lesions, related with HPV infection, include Oropharyngeal squamous cell carcinoma , verrucca vulgaris and focal epithelial hyperplasia ( FEH ) and benign warts (genital, plantar and flat warts) . These Oral

Focal epithelial hyperplasia in Yemeni families: Three case reports

This is the first time to get the opportunity to report and study three cases from three families with focal epithelial hyperplasia (FEH) in Yemen. Clinically they presented as focal and/or diffuse papillomatous lesions in the oral mucosa in children. The purpose of this paper is to add information concerning clinical feature, the possible etiologic factors and diagnosis of this disease which is totally unknown to the general Yemeni medical professionals and to raise dentist’s awareness about these rare conditions.

Focal epithelial hyperplasia associated with human papillomavirus 13 and common human leukocyte antigen alleles in a Turkish family

Focal epithelial hyperplasia (FEH) is a rare and benign papillomatous disease of the oral cavity, which is closely associated with human papillomavirus (HPV) type 13 and 32. Genetic susceptibility to HPV infections are supported by recent studies involving the human leukocyte antigen system (HLA). In this report, we aimed to determine the clinicopathological features of a Turkish family with FEH and to detect the shared HLA DR and DQ types. HPV DNA typing of tissue samples and HLA determination from blood samples of four family members were performed by polymerase chain reaction. Histopathological examination of all patients revealed acanthotic papillomatous epidermis, koilocytes, apoptotic keratinocytes, and mitosoid bodies. HPV13 was detected by polymerase chain reaction. HLA DQA1*0501, HLA DQB1*0302, and HLA DRB1*11 alleles were common in all family members. HLA DRB1*04 was detected in three of them. This report is the first step for the investigation of involvement of HLA types in the pathogenesis of Turkish patients with FEH.