Epstein-Barr virus oral shedding and viremia and their association with oral hairy leukoplakia in HIV+ individuals.

OBJECTIVE: To assess the oral shedding and viremia of Epstein-Barr virus (EBV) in HIV-positive patients and their relationship with oral hairy leukoplakia (OHL). METHODOLOGY: A total of 94 HIV-positive patients were included in the study, in which blood and saliva samples were collected for EBV quantification. Data on gender, age, time of HIV seropositivity, combined antiretroviral therapy (cART), CD4+ T-cell counts, and HIV viral load were collected. OHL diagnosis was based on histopathological examination and EBV in situ hybridization. RESULTS: The EBV load in the 94 HIV-positive patients was higher in saliva than in blood (2.4 and 1.6, respectively), and there was a positive correlation between EBV oral shedding and viremia (p = 0.001). Twenty (21.27%) patients had OHL and also a higher EBV load in saliva (mean log10  = 3.11) compared to those who had no OHL (p = 0.045). Presence of OHL was only associated with age (p = 0.030). CONCLUSION: In HIV-positive patients, the presence of OHL was associated with EBV oral shedding but not with viremia, regardless of the amount of circulating CD4+ T cells.

Second primary tumors in proliferative verrucous leukoplakia: a series of 33 cases.

OBJECTIVES: To describe the number of second primary malignancies in a series of 33 patients with proliferative verrucous leukoplakia (PVL), detailing the mean time between primary malignancies and their clinical characteristics. MATERIALS AND METHODS: Two groups of patients were included in this study: group 1 comprised 33 PVL patients who had developed ≥ 2 oral squamous cell carcinoma (OSCC) and group 2 comprised 48 PVL patients without malignant degeneration. We compared the groups with regard to age, gender, oral location, and number of oral sites affected. For patients in group 1, we determined the locations, clinical forms, and TNM stages of oral cancers. We also recorded the intervals of time between instances of oral cancer for all patients. RESULTS: The groups did not differ significantly in age; however, group 1 included more women (p < 0.05). The follow-up period and number of oral PVL locations were greater in group 1 (p < 0.01). Moreover, in group 1, as the number of OSCCs increased, the intervals between them became shorter. The gingiva was the most common site. The mean number of cancers in group 1 was 3.15; five second primary tumors were diagnosed in one patient. CONCLUSIONS: Multiple cancers in PVL patients were more frequently located on the gingiva in the form of erythroleukoplastic areas. In addition, the interval between new cancers decreased over time. CLINICAL RELEVANCE: This is the series with the highest number of cases described with second primary tumors in PVL.

The development of proliferative verrucous leukoplakia in oral lichen planus. A preliminary study.

BACKGROUND: Was to describe 14 cases of a proliferative verrucous leukoplakia as a clinical evolution of oral lichen planus. MATERIAL AND METHODS: The clinical and histopathological characteristics of 14 cases of OLP that progress towards a plaque-like and verrucous form were indicated, with monitoring over a period of six to 24.3 years. RESULTS: The female/male ratio was 11/3, (78.6 and 21.4%). The mean age when the first biopsy was undertaken was 56.4 years old. None of the patients smoked during the study. As bilateral reticular was clinically diagnostic criterion, the second most frequent clinical form was the plaque form (n=10; 71.4%), followed by the atrophic (n=6; 42.8%), and erosive forms (n=4; 28.5%). Clinically it spread towards attached gingival mucosa and the hard palate. In the histopathologic study, there were a predominance of hyperkeratosis and verrucous epithelial hyperplasia. Three of the cases progressed to a squamous cell carcinoma, and one patient developed two verrucous carcinoma. CONCLUSIONS: Further research is needed to demonstrate if proliferative multifocal oral lichen planus and proliferative multifocal oral leukoplakia are the same disorder but have different behaviour of malignancy for reasons of origin.

Dyschromatosis Universalis Hereditaria with Oral Leukokeratosis--A Case of Mistaken Identity and Review of the Literature.

Dyschromatosis universalis hereditaria (DUH) is a rare pigmentary genodermatosis characterized by reticulated hyper- and hypopigmented macules distributed over the trunk and extremities in otherwise healthy patients. DUH presents in a fashion similar to that of a variety of reticulate and pigmentary dermatoses, some of which are associated with precancerous entities and other comorbidities. It is therefore imperative that the clinician recognize and differentiate these disorders so that appropriate screening and counseling can be offered to the patient. We report a case of DUH in a 13-year-old boy presenting with oral leukokeratosis, with a review of the literature exploring the differential diagnoses.

Lichenoid Features and Fibrosis: Coexistence in Quid-induced Oral Lesions.

BACKGROUND: Oral submucous fibrosis (OSF) and quid associated oral lichenoid lesions (QOLL) are caused because of areca nut chewing and both show very characteristic histological changes. The present study aims to determine the histopathological presence of lichenoid features in cases of OSF as well as to determine the presence of fibrosis in cases of QOLL. MATERIALS AND METHODS: The study involved the retrospective analysis of hematoxylin and eosin stained slides of OSF (n = 50) and QOLL (n = 16). RESULTS: Seven cases of OSF revealed histopathological features of lichenoid reaction and four cases of QOLL revealed the presence of fibrosis in the underlying connective tissue. CONCLUSION: This study put forths a new finding that is, the presence of concomitant disease processes seen in the same patient at a histological level. It thus, stresses the need to evaluate all cases of OSF and QOLL for additional features which may be induced by areca nut chewing.

[Integrated approach to the treatment of oral mucosa diseases in patients with chronic gastritis].

The article presents data on the clinical and microbiological short and long term efficacy of treatment of the oral mucosa diseases in patients with Helicobacter pylori associated and not associated chronic gastritis depending on the chosen treatment regimen.

Spectrum of Liver Pathology in Dyskeratosis Congenita.

Dyskeratosis congenita (DC) is a rare multisystemic disorder associated with defective telomere maintenance. Frequent clinical manifestations of DC include reticular skin pigmentation, dystrophic nails, oral leukoplakia, and bone marrow failure. Hepatic disturbances are reported to occur in 7% of DC patients. This study aimed to evaluate the histopathologic spectrum of hepatic involvement in this disorder. DC patients with liver tissue in the pathology database at Boston Children's Hospital from 1995 to 2022 were identified. Clinical and pathologic information was documented. Thirteen specimens from 11 DC patients were included (M:F = 7:4; median age at the time of liver tissue evaluation: 18 y). DC-associated gene mutations were identified in 9 patients; TERF1-interacting nuclear factor 2 ( TINF2) was the most frequently represented gene mutation, seen in 4 patients. All patients had bone marrow failure, whereas dystrophic nails, cutaneous abnormal pigmentation, and oral leukoplakia were noted in 73%, 64%, and 55% of patients, respectively. Seven patients underwent bone marrow transplants before biopsy/autopsy (median interval of 45 mo). Histologically, 3 of 4 patients who presented with portal hypertension showed noncirrhotic changes (nodular regenerative hyperplasia and/or obliterative portal venopathy), whereas prominent central and sinusoidal fibrosis was noted in patients with intrahepatic shunting and those showing features of chronic passive congestion. All cases showed hepatocyte anisonucleosis. One patient developed hepatic angiosarcoma, and another 1 had colorectal adenocarcinoma metastatic to the liver. DC patients show heterogeneous histologic findings in their liver. The findings of noncirrhotic portal hypertension, intrahepatic shunting, and angiosarcoma suggest vascular functional/structural pathology as a possible unifying etiology of hepatic manifestations of DC.

Phenotype and genotype features of Vietnamese children with pachyonychia congenita.

BACKGROUND: Pachyonychia congenita (PC) is a group of autosomal dominant disorders caused by mutations in one of five keratin genes (KRT6A, KRT6B, KRT6C, KRT16, or KRT17). PC is an extremely rare condition. To our knowledge, this is the largest genotype-phenotype study of PC in a Vietnamese population to date. MATERIALS AND METHODS: We investigated keratin gene mutations and clinical features of seven Vietnamese children with PC. RESULTS: The seven Vietnamese patients were from six different families (two patients in the same family) from across Northern, Central, and Southern Vietnam. All children displayed PC symptoms before 1 year of age, but diagnosis was delayed in 4/7 patients. Thick fingernails, thick toenails, oral leukokeratosis, and follicular hyperkeratosis were the most common features recorded by all seven patients. Plantar keratoderma and thick fingernails were the clinical features associated with the most significant effect on daily function. All patients had mutations in KRT6A (PC-K6a) focused on the 1A and 2B domains. We found three distinct types of mutations (K6a R466P, K6a N171K, and K6a N172del). One mutation (N172del) was common to 5/7 (71.4%) of the patients. CONCLUSIONS: Individuals displaying nail dystrophy, oral leukokeratosis, follicular hyperkeratosis, and plantar keratoderma should be referred for genetic testing given the high likelihood of a PC-K6a-related mutation in patients with this constellation of clinical signs.

Reactive and Nonreactive White Lesions of the Oral Mucosa.

White lesions in the oral cavity may be diverse in etiology and may present with significant clinical and sometimes histologic overlap between categories, making accurate diagnosis difficult at times. Although white lesions of immune and infectious etiology are covered in another article, this article discusses the differential diagnosis between developmental, reactive, idiopathic, premalignant, and malignant white lesions focusing on clinical features of each category.

Etiology of Oral Potentially Malignant Disorders and Squamous Cell Carcinoma Based on Cellular Stress Regulation and Matrix Stiffness.

The oral cavity serves as the initial segment of the digestive system and is responsible for both nutritional supplementation and the mechanical breakdown of food. It comprises distinct hard and soft tissues; the oral mucosa is subject to mechanical stress and interaction with microbiota. In oral cancer, tumors exhibit abnormal cellular networks and aberrant cell-cell interactions arising from complex interplays between environmental and genetic factors. This presents a challenge for clinicians and researchers, impeding the understanding of mechanisms driving oral cancer development and treatment strategies. Lesions with dysplastic features are categorized under oral potentially malignant disorders, including oral leukoplakia, erythroplakia, oral submucous fibrosis, and proliferative verrucous leukoplakia, carrying a high malignancy risk. In this review, we discuss oral cancer cell characteristics and the stiffness of the surrounding matrix. We also discuss the significance of stiffness equilibrium in oral potentially malignant disorders, particularly oral submucous fibrosis, possibly triggered by mechanical stress such as betel quid chewing.

Liver Transplant for Management of Hepatic Complications of Dyskeratosis Congenita: A Case Report.

Dyskeratosis congenita, a rare genetic disorder typified by progressive bone marrow failure, is classically characterized by the triad of abnormal skin pigmentation, nail dystrophy, and oral leukoplakia; however, it is a multisystem disease. Although hepatic involvement occurs in about 7% of patients with dyskeratosis congenita, end-stage liver disease is rare. Treatment of dyskeratosis congenita generally involves hematopoietic stem cell transplant. For patients with hepatic failure, liver transplant can be an option. Here, we describe a case of a patient with dyskeratosis congenita who presented with liver failure and pulmonary failure, precluding him from hematopoietic stem cell transplant. After liver transplant, the patient had significant improvements in pulmonary function and transfusion requirements, allowing the patient to qualify for hematopoietic stem cell transplant. Although hematopoietic stem cell transplant is typically the first step in the management of dyskeratosis congenita, for patients with severe hepatic manifestations of the disease, a liver transplant first approach may result in better disease management.

Multisystemic Manifestations in Rare Diseases: The Experience of Dyskeratosis Congenita.

Dyskeratosis congenital (DC) is the first genetic syndrome described among telomeropathies. Its classical phenotype is characterized by the mucocutaneous triad of reticulated pigmentation of skin lace, nail dystrophy and oral leukoplakia. The clinical presentation, however, is heterogeneous and serious clinical complications include bone marrow failure, hematological and solid tumors. It may also involve immunodeficiencies, dental, pulmonary and liver disorders, and other minor complication. Dyskeratosis congenita shows marked genetic heterogeneity, as at least 14 genes are responsible for the shortening of telomeres characteristic of this disease. This review discusses clinical characteristics, molecular genetics, disease evolution, available therapeutic options and differential diagnosis of dyskeratosis congenita to provide an interdisciplinary and personalized medical assessment that includes family genetic counseling.

Dyskeratosis congenita with portal hypertension of unknown etiology.

Dyskeratosis Congenita (DKC) is a rare progressive bone marrow disorder associated with multi-systemic involvement. It is also characterized by triad of abnormal skin pigmentation, nail dystrophy and mucosal leukoplakia. Liver cirrhosis and portal hypertension are said to be uncommon among these patients. We hereby report a case of an adult male who presented with pancytopenia, abnormal skin pigmentation, nail dystrophy and mucosal leukoplakia. Skin biopsies along with clinical features confirmed the case. Imaging studies were reported as suggestive of and portal hypertension. Liver biopsy done but non-conclusive. Patient's one son and one daughter also had similar skin pigmentation.

Alteration in the expression of cdk4 and cdk6 proteins in oral cancer and premalignant lesions.

BACKGROUND: Cdk4 and cdk6, key players in G1 phase, have been shown to play an important role in the development of oral squamous cell carcinoma (OSCC). This study investigated the expression of these two proteins in OSCC and premalignant lesions including oral leukoplakia (OL) with and without dysplasia and determined if alterations in the expression of these two proteins could be used as markers of malignant transformation. METHODS: Expressions of cdk4 and cdk6 were evaluated in 61 samples including OSCC, OL with and without dysplasia and normal oral mucosa using immunohistochemistry method. Nuclear staining of the keratinocytes was considered positive and the percentage of positive cells was calculated. RESULTS: Expression of cdk4 was found in 11/15 (73.33%) OSCC, 13/14 (92.85%) OL with dysplasia, 13/20 (65%) OL without dysplasia and 3/12 (25%) normal mucosa. Expression of cdk6 was detected in 9/15 (60%) OSCC, 3/14 (21.43%) OL with dysplasia, 5/20 (25%) OL without dysplasia and 1/12 (8.33%) normal mucosa. In cdk4 stained specimens, the frequency of positive cases and the percentage of positive cells in normal mucosa was significantly lower than OL with dysplasia and OSCC. For cdk6 staining, the prevalence of positive cases and the percentage of positive cells in normal mucosa were significantly lower than OSCC. CONCLUSIONS: Overexpressions of cdk4 and cdk6 were observed in OSCC, indicating that these two proteins play a crucial role in OSCC. The aberrant expression of cdk4 was found in OL with dysplasia, suggesting that cdk4 may be involved in the early event of carcinogenesis.

Annual malignant transformation rate of oral leukoplakia remains consistent: A long-term follow-up study.

OBJECTIVES: Numerous clinical and histopathological characteristics have been associated with malignant transformation (MT) of oral leukoplakia (OL), including classic and differentiated epithelial dysplasia, but MT predictions remain suboptimal. The objective of this study was to determine the annual MT rate of OL and to identify clinicopathological risk factors associated with MT. PATIENTS AND METHODS: 170 patients with OL were included in this retrospective cohort study, 117 females and 53 males. Follow-up ranged from 12 to 219 months (median 54). The analyzed variables included age, gender, smoking habits, clinical presentation, subsite, size and treatment. In a subgroup of 140 patients, histopathological diagnoses were reviewed with regard to the presence of dysplasia, discerning both classic dysplasia and differentiated dysplasia. RESULTS: MT occurred in 23% of the patients, resulting in an annual MT rate of 4.9% (95% CI: 3.5 - 6.6) which remained consistent. High-risk subsite (tongue and floor of mouth) was the only clinical predictor for MT (Hazard Ratio = 2.7, 95% CI: 1.3 - 5.5, p = 0.007). In 140 patients, classic dysplasia (Hazard Ratio = 7.2, 95% CI: 1.6 - 33.1, p = 0.012) and differentiated dysplasia (Hazard Ratio = 6.6, 95% CI: 1.2 - 25.4, p = 0.026) were predictors for MT. Binary grading between dysplasia and no dysplasia was significant for predicting MT (Hazard Ratio = 6.4, 95% CI: 1.5 - 27.5, p = 0.013). CONCLUSION: Since annual MT rate of OL remains stable during follow-up, regular long-term or even life-long follow-up is advocated. Specific oral subsites and epithelial dysplasia are predictors for MT of OL.

Oral verrucous hyperplasia: histologic classification, prognosis, and clinical implications.

BACKGROUND: Oral verrucous hyperplasia (OVH) is a premalignant lesion that may transform into an oral cancer. METHODS: Sixty consecutive OVH cases were collected from 2003 to 2004. Clinicopathological features and the 5-year malignant transformation rate of these 60 OVH lesions were evaluated and analyzed. RESULTS: We found that 84% of OVH lesions occurred in patients between 40 and 69 years of age. The most common site for OVH lesions was the buccal mucosa (48%), followed by the tongue (20%), palate (18%), gingiva (7%), and labial mucosa (7%). Approximately 91% of OVH patients were areca quid chewers and 89% were smokers. When 60 OVH lesions were classified into 30 plaque-typed and 30 mass-typed OVH lesions, the mass-typed OVH lesions had a higher malignant transformation rate of 17% (5/30) than the plaque-typed OVH lesions (3%, 1/30) during a mean follow-up period of 59 +/- 7 months. The mean time for malignant transformation was 22 +/- 11 months. Of the 6 OVH lesions with malignant transformation, 2 underwent total surgical excision and 4 did not receive any form of therapy. CONCLUSIONS: We conclude that OVH lesions occur more commonly on the buccal mucosa and are highly associated with the areca quid chewing and cigarette smoking habits. The overall 5-year malignant transformation rate of 60 OVH lesions was 10%. The mass-typed OVH lesions had a higher malignant transformation rate than the plaque-typed OVH lesions and thus should receive an immediate treatment, such as total surgical excision or photodynamic therapy, after the histopathologic diagnosis.

Assessment of influence of smoking, drinking, leukoplakia and dental irritation on local control of early oral tongue carcinoma treated with brachytherapy: age and dental factors are potential prognostic factors.

BACKGROUND: To examine the background characteristics of elderly patients (65 years or older) with node-negative mobile tongue cancer (T1-2N0M0) who showed worse local control than a younger group. MATERIALS AND METHODS: We retrospectively analyzed background data for 265 patients treated with brachytherapy with or without external radiotherapy between 1967 and 1999. We examined dental factors (such as irritation by prosthesis), leukoplakia, tobacco smoking and alcohol consumption for comparisons between the elderly (age > or = 65 years; n = 83) and a control group (64 years or younger; n = 182). RESULTS: The elderly patients showed a worse outcome than the control group (respectively 86% and 70% at 5 years; P < 0.05). Incidence of dental factors tended to be higher for elderly patients (53%) than the control group (40%, P = 0.07). Dental factors proved to have prognostic importance for local control. Five-year local control rate was 85% for patients with and 76% for patients without dental factors (P = 0.04). The elderly group positive for dental factors showed a lower 5-year local control rate (61%) than the other three groups [(elderly without the dental factor (-) group (80%), control with the dental factor (+) group (84%), and control without the dental factor (-) group (87%)] (P < 0.05). Leukoplakia was found more frequently in the control (23%) than in the elderly group (5%) (P = 0.006) but had no effect on treatment outcome. CONCLUSIONS: Age and dental factors (including prosthesis irritation) are potentially important prognostic factors for local control of oral tongue cancer treated with brachytherapy, especially for elderly patients.

Oral mucosal conditions in chronic hepatitis C Brazilian patients: a cross-sectional study.

OBJECTIVE: Our purpose was to carry out an epidemiological study to assess the prevalence of oral mucosal conditions in Brazilian patients with chronic hepatitis C. METHODS: A cross-sectional survey was carried out on 215 patients with chronic hepatitis C who were examined for oral mucosal conditions, including oral mucosal lesions and variations of normality. RESULTS: The prevalence of patients with chronic hepatitis C presenting oral mucosal conditions was 96.3 percent (207 patients). Oral mucosal lesions were present in 147 patients (68.4 percent), whereas variations of normality were observed in 173 patients (80.5 percent). The most common lesions included cheek biting in 42 cases (19.5 percent), candidiasis in 39 cases (18.1 percent), and leukoplakia in 28 cases (13.0 percent). The association of oral lichen planus with hepatitis C virus (HCV) infection proved to be statistically significant (P = 0.002). The most frequent variations of normality included Fordyce's spots in 96 cases (44.7 percent), lingual varicosities in 67 cases (31.2 percent), and fissured tongue in 60 cases (27.9 percent). CONCLUSION: The prevalence of patients with chronic hepatitis C presenting oral mucosal conditions was 96.3 percent. Despite this high prevalence, only the association between oral lichen planus and hepatitis C showed statistical significance. Considering that HCV infection may be associated with extrahepatic disorders, such as oral manifestations, efforts should be made to clarify the possible relation between oral conditions and HCV infection. This may be helpful in the earlier diagnosis of the infection mainly in asymptomatic patients.

[Squamous cell carcinoma and potentially malignant disorders of the oral mucosa]. / Plattenepithelkarzinom und potenziell maligne Veränderungen der Mundschleimhaut.

Squamous cell carcinoma is the most frequent malignant tumor of the oral mucosa. Various endogenous and exogenous factors promote its development. Therapy and prognosis depend mainly on tumor stage. Early detection is therefore of utmost importance. In most cases cancer develops from "leukoplakia". Both homogeneous leukoplakias as well as "erythroleukoplakias" should be biopsied. The"brush-biopsy", imaging techniques, molecular biologic or DNA tests are not reliable enough at present, often technically demanding and not applicable in daily practice. In extensive lesions "field cancerization" has to be considered. Further important precursor lesions are proliferative verrucous leukoplakia and erosive lichen planus. The management of oral precancerous lesions should be individually tailored: Low-grade dysplasia can be observed. If indicated, patients at risk should be biopsied in intervals. High-grade dysplasia ("carcinoma in situ") should be surgically removed.