Multifocal epithelial hyperplasia confined to the interdental papilla of an adult Chinese man: a rare case report and literature review.

BACKGROUND: Multifocal epithelial hyperplasia (MEH), or focal epithelial hypertension (FEH), or Heck's disease, is an uncommon, benign oral mucosal disease associated with human papillomavirus infection. It is mostly observed in indigenous populations of the world, and has been rarely reported in China. However, previous research suggested there might be a greater prevalence of MEH in the Chinese population. While predominantly involves the lips, buccal mucosa and tongue, MEH was occasionally reported to affect the hard palate and gingiva as well. CASE PRESENTATION: This paper reports a case of extensive MEH lesions that confined to the interdental papilla of a Chinese male without detection of HPV, and summarizes the published gingiva-involved MEH reports from 1966 until present. The lesions were excised with an Er: YAG laser after scaling and root planning, no recurrence was observed after 6-month follow-up. CONCLUSIONS: The present report illustrates the need for clinicians to be aware of rare presentations of MEH to facilitate a prompt diagnosis and proper management. More reports are encouraged to determine a correct prevalence rate of MEH in China.

Photodynamic therapy in focal epithelial hyperplasia.

Focal epithelial hyperplasia (FEH) is an uncommon benign disorder affecting the oral mucosa. It is primarily associated with human papillomavirus (HPV) infection and presents as multiple white or pink soft papules or nodules. Typically, FEH is asymptomatic. Conventional treatment approaches for FEH include topical medication, surgical excision, CO2 laser ablation, cryotherapy, etc., but their efficacy varies. Photodynamic therapy (PDT) is a non-invasive and selective photochemotherapy method widely utilized in clinical practice. By employing specific light wavelengths to activate photosensitizers and induce the generation of reactive oxygen, PDT exerts cytotoxic effects. However, the application of PDT in treating FEH has not been previously documented. In this study, we present a case demonstrating the complete remission of FEH lesions using PDT, with no recurrence observed over a period of 9 months. This compelling outcome suggests that PDT may be a preferred treatment modality for FEH.

Mechanical removal of epithelial hyperplasia leads to successful treatment of irregular astigmatism.

BACKGROUND: Corneal epithelium remodeling in response to changes in the anterior corneal surface (keratoconus, corneal refractive surgery) is well-documented in the literature. However, several conditions may induce a different behavior of the epithelium, in which focal areas of epithelial thickening induce irregular astigmatism. This case report presents a highly unusual case of irregular astigmatism induced by an epithelial hyperplasia of unknown etiology, which was treated by the mechanical removal of only the epithelium. CASE PRESENTATION: A 29-year-old woman underwent implantable collamer lens implantation to correct myopia. The patient provided written informed consent. The procedure was uneventful in both eyes. Twenty months later, she complained of decreased visual acuity in the left eye (uncorrected distance visual acuity (UCDVA) was 20/30; corrected distance visual acuity was 20/20 with + 1.00 -2.25 × 170). Corneal topography revealed a nasal steepening in the left eye. Although the corneal thickness map was normal, epithelial thickness mapping revealed a localized nasal area of epithelial hyperplasia in the left eye that matched the area of steepest curvature. Slit lamp examination showed a total clear cornea with no signs of abnormality. The patient´s medical history was unremarkable and a case of epithelial hyperplasia of unknown etiology, without active inflammation, was considered. The decision was made to perform a mechanical removal of the corneal epithelium after application of diluted alcohol. One month after the procedure, the topography of the epithelized cornea showed a regular bow tie pattern and UCDVA improved to 20/20. No recurrence of the epithelial hyperplasia was detected after twenty-one months. CONCLUSIONS: Focal epithelial hyperplasia may induce irregular astigmatism. Epithelial thickness mapping is a very helpful technological tool to assess cases with irregular topography. De-epithelization as an isolated procedure may be useful for the successful management of these cases. Further research is required to understand the mechanism that triggers the spontaneous development of a focal epithelial hyperplasia.

Lesiones papilomatosas orales: hiperplasia epitelial focal / Oral papillomatous lesions: Focal epithelial hyperplasia

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Useful cytological confirmation of HPV 13 in lesional mucosa enhances diagnosis of focal epithelial hyperplasia.

An 11-year-old female presented with multiple oral lesions for several months. Histopathological findings suggested focal epithelial hyperplasia (FEH), also known as Heck disease. FEH is strongly associated with Human papillomavirus (HPV), especially genotypes 13 and 32. An oral swab of a mucosal lesion was subsequently obtained for cytology, immunohistochemistry and in situ hybridization. In addition, in situ hybridization and immunohistochemistry were also performed retrospectively on the biopsy specimen for correlation. The cytology specimen showed squamous cells with enlarged, slightly atypical nuclei and rare perinuclear halos. The histology findings included papillomatosis with acanthosis, mild nuclear atypia and focal perinuclear halos. The immunohistochemistry for the consensus HPV L1 capsid protein was found in both the cytology and biopsy specimens indicating that the lesion was HPV-related. High viral copy numbers of HPV 13 were detected by in situ hybridization in both the cytology and histology specimens. Although histologic features of FEH have been well characterized in the literature, to our knowledge, this is the first case to describe in FEH with adjunct immunohistochemistry and in situ hybridization results. Furthermore, these findings assisted in our diagnosis since the patient's clinical presentation was a diagnostic challenge with smooth dome-shaped papules instead of the typically described flat-topped verrucous lesions seen in FEH. In summary, our case reveals that there is a high concordance between the HPV 13 detection in the cytology and histology of FEH, and that performing cytology in addition to histology can be used to optimize diagnostic evaluation towards appropriate patient care.

Refractory focal epithelial hyperplasia successfully treated with novel use of nano-pulse stimulation technology.

Focal epithelial hyperplasia (FEH), or Heck's disease, is an uncommon HPV-related dermatosis that presents with multiple discrete papules or nodules on the lips, tongue, and gingival or oral mucosa. Treatment is often sought due to cosmesis, social stigma, and functional impairment. Treatment is challenging and a variety of treatment modalities have been attempted with varying degrees of success. This report describes the novel use of nano-pulse stimulation in the successful treatment of recalcitrant FEH of the upper and lower vermillion lip.

Hiperplasia epitelial focal: relato de caso clínico / Focal epithelial hyperplasia: case report

Introdução: a hiperplasia epitelial focal (HEF) ou doença de Heck, caracteriza-se por ser uma lesão benigna rara da mucosa bucal. Geralmente, está associada a proliferação do epitélio pavimentoso atribuída principalmente ao papiloma vírus humano (HPV) dos subtipos 13 e 32. Objetivo: relatar o caso de um paciente, com suspeita diagnóstica de HEF, descrever suas manifestações clínicas bucais e histopatológicas. Metodologia: homem, 38 anos, melanoderma, compareceu no Serviço Universitário com queixa de ardência em mucosa bucal. Ao exame clínico, apresentava múltiplas lesões papulares, firmes à palpação, de coloração rósea, com pápulas aglomeradas ou isoladas, localizadas em rebordo alveolares, gengiva inserida e livre da arcada superior e inferior, mucosas jugais e labiais, compatíveis com lesões causadas por HPV. Realizou-se biópsia incisional das lesões bucais, o laudo histopatológico descreveu o fragmento de mucosa bucal que estava revestida por epitélio pavimentoso estratificado paraceratinizado com acantose proeminente, projeções focais confluentes para o tecido conjuntivo, confirmando a suspeita diagnóstica clínica. Conclusão: a HEF é uma patologia rara, benigna da mucosa, indolor e que pode se resolver espontaneamente. Portanto, é necessário o diagnóstico adequado através da biopsia e laudo histopatológico.

Introduction: focal epithelial hyperplasia (FEH) or Heck's disease is characterized as a rare benign lesion of the oral mucosa. It is usually associated with proliferation of the squamous epithelium, mainly attributed to human papillomavirus (HPV) subtypes 13 and 32. Objective: to report the case of a patient with a diagnostic suspicion of HEF, to describe its oral clinical and histopathological manifestations. Methodology: hale, 38 years old, black, attended the University Service with a complaint of burning in the oral mucosa. On clinical examination, she presented multiple papular lesions, firm to palpation, pink in color, with agglomerated or isolated papules, located in the alveolar ridge, inserted gingiva free from the upper and lower arch, jugal and labial mucosa, compatible with lesions caused by HPV. An incisional biopsy of the oral lesions was performed, the histopathological report described the fragment of oral mucosa that was lined with parakeratinized stratified squamous epithelium with prominent acanthosis, focal projections confluent to the connective tissue, confirming the clinical diagnostic suspicion. Conclusion: FEH is a rare, benign mucosal pathology, painless and can resolve spontaneously. Therefore, proper diagnosis through biopsy and histopathological report is necessary.

An update on Heck's disease-a systematic review.

BACKGROUND: Previous research has suggested an ethnic association of Heck's disease with a prominent genetic and familial inheritance pattern, but no systematic review has been reported, which has collected all the evidence in one paper. The aim was estimation of the updated age estimates and gender predilection of this disease and also questioning its proposed link to ethnic and geographical factors. METHODS: Heck's disease from 1966 until present are tabulated, including various descriptive characteristics. After removal of duplicates and adhering to all the inclusion criteria, we shortlisted 95 case reports. The quality assessment of all included studies has been done following STROBE (STrengthening the Reporting of OBservational studies in Epidemiology) guidelines. RESULTS: We found an age range of 3-92 years (mean: 23.1 years) with a male to female ratio of 3:4. Geographical distribution revealed one of the main findings of this study, which was an increased incidence of Heck's disease in the European region. CONCLUSIONS: As already observed and established, there is a much greater prevalence of this disease in the indigenous populations of the world and more research should be encouraged to understand the correct transmission and pattern of spread of this disease.

FAK Shutdown: Consequences on Epithelial Morphogenesis and Biomarker Expression Involving an Innovative Biomaterial for Tissue Regeneration.

By employing an innovative biohybrid membrane, the present study aimed at elucidating the mechanistic role of the focal adhesion kinase (FAK) in epithelial morphogenesis in vitro over 4, 7, and 10 days. The consequences of siRNA-mediated FAK knockdown on epithelial morphogenesis were monitored by quantifying cell layers and detecting the expression of biomarkers of epithelial differentiation and homeostasis. Histologic examination of FAK-depleted samples showed a significant increase in cell layers resembling epithelial hyperplasia. Semiquantitative fluorescence imaging (SQFI) revealed tissue homeostatic disturbances by significantly increased involucrin expression over time, persistence of yes-associated protein (YAP) and an increase of keratin (K) 1 at day 4. The dysbalanced involucrin pattern was underscored by ROCK-IISer1366 activity at day 7 and 10. SQFI data were confirmed by quantitative PCR and Western blot analysis, thereby corroborating the FAK shutdown-related expression changes. The artificial FAK shutdown was also associated with a significantly higher expression of filaggrin at day 10, sustained keratinocyte proliferation, and the dysregulated expression of K19 and vimentin. These siRNA-induced consequences indicate the mechanistic role of FAK in epithelial morphogenesis by simultaneously considering prospective biomaterial-based epithelial regenerative approaches.

Focal Epithelial Hyperplasia.

Focal epithelial hyperplasia (FEH) or Heck's disease is a rare, benign, oral condition that is associated with infection by human papillomavirus type 13, 32 or both. The whiteish to mucosal-colored, soft, papular or nodular elevated lesions in the oral cavity are normally asymptomatic but can grow to a size or at a location where treatment is needed. The diagnosis is often based on clinical presentation and histopathology, and the HPV genotype can be determined using PCR utilizing specific primers or DNA sequencing. While FEH was reported to often affect several members of the same family and exist primarily among indigenous populations around the world, the number of reported cases within the European region is increasing. This contemporary review summarizes the main findings in relation to HPV genotypes, impact of superinfection exclusion and vaccination, transmission, diagnosis, geographical and ethnical distribution, comorbidities and treatment of FEH with an emphasis on including the most recent case reports within the field. Furthermore, we describe for the first time a FEH lesion infected with the low-risk HPV90.

The spectrum of focal epithelial hyperplasia-a report of two cases.

Focal epithelial hyperplasia is a rare, benign, and asymptomatic disorder, characterized by soft papules on the oral cavity. It is primarily associated with human papillomavirus genotypes 13 and 32. It most commonly affects children and young adults. When it affects young adults, it is important to differentiate it from oral condyloma acuminata. Its diagnosis may be made clinically, but histologic examination and PCR genotyping are often useful. Treatment is not always mandatory.

Unusual oral multifocal epithelial hyperplasia in an adult African-American lung transplant patient.

Oral multifocal epithelial hyperplasia (MEH), or Heck's disease, is a rare benign proliferation of the oral mucosa associated with human papillomavirus (HPV). It clinically presents as multiple asymptomatic papules and nodules that mostly affect the lips, buccal mucosa, and tongue. MEH is predominantly found in children and young adults while relatively few cases have been reported in the elderly population. Here, we report a case of oral MEH in a 65-year-old man with history of lung transplantation. This case highlights the potential susceptibility of organ transplant recipients to the development of MEH. Since MEH that does not require treatment unless the lesion bothers the patient, clinicians should promptly establish a definitive diagnosis to rule out other HPV-related precancerous lesions.

Genomic characterization of human papillomavirus type 13, associated to multifocal epithelial hyperplasia, in a Mayan community.

Human papillomavirus type 13 (HPV13) is a low-risk HPV type associated with Multifocal Epithelial Hyperplasia (MEH). It is considered a rare pathology of oral mucosa, more prevalent in certain ethnical groups, such as the Maya from Yucatan in Mexico. As for 2020 only two complete genomes of HPV13 are publicly available in Genbank database (one from Turkey one from the Amazonian). We aimed to obtain the complete genome sequence of HPV13 associated to MEH, obtained from a community in the Mayan area from Mexico. A bank of oral swabs from children with MEH were used. To enrich the sample, a Rolling Cycle Amplification (RCA) method was performed followed by overlapping end-point PCR of 500 bp fragments, Sanger sequencing and assembly. Eight open reading frames (ORFs) were annotated (E1, E2, E4, E5, E6, E7, L1 and L2 genes). When compared with the other two previously reported genomes the identity at nucleotide level is high 98.9% and 99.6%, respectively. The phylogenetic tree shows that Yucatan HPV13 is more closely related to HPV13 obtained from the Amazonian. Most changes identified at amino acid level are substitutions derived from nucleotide variations or SNPs in coding regions. Amino-acid changes were observed in E2 and E1 proteins (n ≥ 8), and in L1, L2, E6 and E5 proteins (n ≤ 5). E7 protein from Yucatan has 100% identity with the reported from Amazonian and differs (94.1% identity) with the one from Turkey due to 3 substitutions and three missing amino acids. In conclusion, the genome from HPV13 (7831 bp, 49 nt missing) associated to MEH in the Mayan area from Yucatan was obtained from stored swabs; this is the first effort in Mexico, the second in Latin America, and the third of the world. More research that contributes to the knowledge of the determinants underlying this neglected pathology are urged.

Heck's disease occurring after Epstein-Barr virus-associated smooth muscle tumors in an immunosuppressed child.

A 10-year-old Guatemalan girl with past medical history of Epstein-Barr virus-associated smooth muscle tumors (EBV-SMT) and combined immunodeficiency presented for evaluation of painful intraoral lesions. On examination, she was noted to have multiple, white to flesh-colored, soft, flat-topped papules, and plaques on the buccal and labial mucosa. Human papillomavirus type 13 was detected on PCR with PGMY primers of previously biopsied buccal tissue, confirming a diagnosis of Heck's disease (multifocal epithelial hyperplasia). We present an immunosuppressed, pediatric patient with two rare, virus-associated neoplastic disorders that have not been previously reported to occur in the same individual.