The use of E-cigarettes as a risk factor for oral potentially malignant disorders and oral cancer: a rapid review of clinical evidence.

BACKGROUND: The popularity of e-cigarettes has increased rapidly in the last decade, particularly among teens and young adults, being advertised as a less harmful alternative to conventional tobacco products. However, in vitro and in vivo studies have evidenced a variable quantity of potentially harmful components and some recognized carcinogens which may cause DNA damage in oral cells. Additionally, evidence suggests that e-cigarettes may play active roles in the pathogenesis of other malignancies, such as lung and bladder cancers. Therefore, this rapid review aimed to assess the available clinical evidence about using e-cigarettes as a risk factor for oral potentially malignant disorders (OPMD) and oral cancer. MATERIAL AND METHODS: A systematic search for English language articles published was performed in PubMed (MEDLINE), Embase, Scopus, and Web of Science. After the study selection process, the authors included twelve clinical studies about OPMD and oral cancer risk in e-cigarette users. RESULTS: The main findings showed the presence of carcinogenic compounds in saliva and morphologic changes, DNA damage, and molecular pathways related to carcinogenesis in the oral cells of e-cigarette users. However, results were inconsistent compared to tobacco smokers and control groups. CONCLUSIONS: the current clinical evidence on this topic is limited and insufficient to support using e-cigarettes as a risk factor for OPMD and oral cancer. Nevertheless, dental care professionals should advise patients responsibly about the potentially harmful effects of e-cigarettes on the oral mucosa cells. Future long-term and well-designed clinical studies are needed.

Lymphomas affecting the submandibular glands.

BACKGROUND: Lymphomas affecting the submandibular glands are very uncommon and few reports are currently available in the literature. Therefore, the aim of the current study is to describe the clinical and microscopic features of an original series of lymphomas affecting the submandibular glands. MATERIAL AND METHODS: The pathology files of two institutions were searched for lymphoma cases affecting the submandibular glands. The original hematoxylin and eosin, and immunohistochemical slides were revised by a pathologist for diagnosis confirmation following the revised 4th edition of the World Health Organization classification of tumours of haematopoietic and lymphoid tissues. Clinical data regarding age, sex, clinical manifestation, treatment, follow-up and status at last appointment were retrieved from the patients' medical charts. RESULTS: During the period investigated, 16 cases were included in the study. Females predominated (10:6) with a mean age of 57.8 years-old. Tumors usually presented as asymptomatic swellings. MALT lymphoma represented the most common subtype, followed by diffuse large B cell lymphoma and follicular lymphoma. Three patients died, one of them affected by plasmablastic lymphoma, one by DLBCL and one by MALT lymphoma. CONCLUSIONS: Low-grade B cell lymphomas predominate in the submandibular glands, but DLBCL and other subtypes may also be rarely diagnosed in this salivary gland.

Synchronous cemento-ossifying fibromas: a systematic review.

BACKGROUND: This systematic review aimed to incorporate published data regarding synchronous cemento-ossifying fibromas (COF), with an analysis of their demographic and clinicopathological characteristics. MATERIAL AND METHODS: Case reports and case series of synchronous COF were searched in PubMed, Web of Science, Scopus, EMBASE, and LILACS according to the PRISMA (2020) statement. Also, a manual search was carried out and the grey literature was assessed. A descriptive statistical analysis was performed. RESULTS: Nineteen studies comprising 20 cases of synchronous COF were included. The mean age at diagnosis was 35 years (±13.8), with a predominance of female patients (n=12/60%). In 13 cases (65%) the mandible and the maxilla were affected simultaneously. In two cases (10%) first-degree relatives (parents or siblings) had been previously diagnosed with COF. The diagnostic hypotheses were reported in 8 cases (40%), with florid cemento-osseous dysplasia, ameloblastic fibroodontoma, calcifying cystic odontogenic tumor, osteoma and cementoblastoma being cited in the differential diagnosis. Among the cases with details about management (n=17), eleven were treated by surgical enucleation and/or excision (64.7%). Follow-up was provided for 10 cases (50%), with a mean period of 44.7±62.19 months. Recurrence occurred in three of informed cases. CONCLUSIONS: Synchronous manifestation of COF is rare. Female patients around the 3rd decade of life are more commonly affected. Bilateral involvement of the mandible and maxilla is the most common clinical presentation.

Estimating the burden of care for oral potentially malignant disorders and oral cancer in Brazilian dental practice.

BACKGROUND: Oral cancer (OC) and oral potentially malignant disorders (OPMD) pose significant challenges to public health in Brazil. This study aimed to estimate the prevalence of oral cancer (OC) and oral potentially malignant disorders (OPMD) among patients who would be treated by Brazilian dentists during their careers. MATERIAL AND METHODS: Data on the number of dentists in Brazil were extracted from the 2022 census data, while incidence rates for OC cases were sourced from the Brazilian National Cancer Institute (INCA). Population estimates for Brazil and data on dental check-up rates were obtained from relevant national sources. RESULTS: Our analysis indicates that a general dentist in Brazil can expect to encounter on average two to three OC patients and on average 675 patients with OPMDs over a 35-year career. Regional disparities were observed, with certain regions showing higher than the average number of encounters due to low density of dentists in some rural districts. CONCLUSIONS: Brazilian dentists are likely to confront a substantial number of OPMD cases during their professional tenure, emphasizing the need for public health policies aimed at enhancing dental surgeons' education in oral cancer prevention and early detection.

Head and neck myofibroma: A case series of 16 cases and literature review.

BACKGROUND: This study aimed to explore the clinical, histopathologic, and immunohistochemical characteristics of myofibromas (MFs) affecting the head and neck region. MATERIAL AND METHODS: Formalin-fixed paraffin-embedded tissue blocks of patients diagnosed with MFs in the head and neck were retrieved from the archives of three oral and maxillofacial pathology laboratories. Data including clinical, radiographic, microscopic and immunohistochemical findings, treatment employed, and follow-up status were retrieved from the patient's medical records or pathology reports. RESULTS: Sixteen cases were included in the study. Females were slightly more affected than males. The first and second decades of life were more prevalent. The most common locations were the alveolar ridge and cheek. Although rare, some of the patients were presented with intraosseous lesions. Microscopically, tumors consisted of plump, spindle-shaped myofibroblasts arranged in whorls or fascicles with varying degrees of differentiation. Immunohistochemically, diffuse positivity for vimentin and α-SMA was observed, while Ki-67 mostly showed low immunoreactivity (<5%). Treatment primarily involved complete excision. CONCLUSIONS: MFs in the head and neck region are rare and predominantly affect female patients during the second decade of life. Despite their rarity, central MFs should be considered in the differential diagnosis of intraosseous lesions in infants.

Histopathological parameters reported in microinvasive oral squamous cell carcinoma: a systematic review.

BACKGROUND: Microinvasive oral squamous cell carcinoma (OSCCmi) is an incipient stage of oral cancer. Through this systematic review, we aim to assess patterns of histopathological outcomes reported in OSCCmi cases. MATERIAL AND METHODS: An online search in major databases was performed without period restriction, and 2,024 publications in English, Spanish and Portuguese were obtained. After screening and eligibility, 4 studies were selected. The risk of bias was assessed using Joanna Briggs Institute Critical Appraisal Checklist. A descriptive synthesis was conducted. RESULTS: All 4 publications included were retrospective, reporting a total of 116 OSCCmi patients, with a male predominance (1.6:1) and a mean age of 55.9 years. The main parameters considered for microinvasion were tumor thickness (TT) (range 4-10mm) and depth of invasion (DOI) (range 0,02-5mm). Definition, cut-off values, and assessment of microscopic features were not standardized. Other relevant measures such as perineural or lymphovascular invasion and pattern of invasive front were barely described, and cytological/architectural characteristics were not discussed. CONCLUSIONS: TT and DOI are currently the primary histopathological criteria used to define OSCCmi. Nonetheless, the outcomes of this systematic review showed the absence of standardized quantitative parameters to render the diagnosis of microinvasive OSCC. Therefore, additional studies aiming to standardize histopathological features to diagnose OSCCmi are paramount.

Evaluation of remote teaching in master programs in the Oral Pathology and Oral Medicine during the COVID-19 pandemic. Brazilian multicentric study.

BACKGROUND: With the COVID-19 pandemic, there was a need to adopt online teaching methods in a generalized and sudden way, a situation that led to unprecedented changes in the routine of post-graduate students and research development. This study aimed to analyze the evaluation of remote teaching by graduates of master's degrees and advisors in master's programs in the Oral Pathology and Oral Medicine who needed to adapt to a remote teaching methodology in the pandemic. MATERIAL AND METHODS: This quantitative study evaluated the remote teaching in the perception of master's graduates and advisors from postgraduate programs in Oral Pathology and Oral Medicine. Data were collected through an online Google forms® questionnaire. RESULTS: Participated in the study 14 master graduates and 14 master's advisors. Master graduates evaluated that the professors had a good performance (p=0.001), that the duration of the classes was adequate (p=0.015), that the interaction with professors was satisfactory (p=0.007), that they had good interaction with the advisor (p=0.001), that they were satisfied with the remote guidance process (p=0.038) and that face-to-face practical activities were missed (p=0.002). Master's advisors reported satisfaction with remote teaching, good adaptation (p=0.018) and motivation for remote teaching (p=0.016), they evaluated that students were cooperative in activities (p=0.019) and that face-to-face practical activities were missed (p=0.002). CONCLUSIONS: Despite the difficulties, remote teaching proved to be an effective alternative to face-to-face teaching.

Gingival neoplasms: a multicenter collaborative study of 888 patients in Brazil.

BACKGROUND: To evaluate the prevalence and clinicopathological features of a large series of gingival neoplasms in Brazil. MATERIAL AND METHODS:  All gingival benign and malignant neoplasms were retrieved from the records of six Oral Pathology Services in Brazil, during a 41-year period. Clinical and demographic data, clinical diagnosis, and histopathological data were collected from the patients' clinical charts. For statistical analysis, the chi-square, median test of independent samples and the U Mann-Whitney tests were used, considering a significance of 5%. RESULTS:  From 100,026 oral lesions, 888 (0.9%) were gingival neoplasms. There were 496 (55.9%) males, with a mean age of 54.2 years. Most cases (70.3%) were malignant neoplasms. Nodules (46.2%) and ulcers (38.9%) were the most common clinical appearance for benign and malignant neoplasms, respectively. Squamous cell carcinoma (55.6%) was the most common gingival neoplasm, followed by squamous cell papilloma (19.6%). In 69 (11.1%) malignant neoplasms, the lesions were clinically considered to be inflammatory or of infectious origin. Malignant neoplasms were more common in older men, appeared with larger size, and with a time of complaint shorter than benign neoplasms (p<0.001). CONCLUSIONS:  Benign and malignant tumors may appear as nodules in gingival tissue. In addition, malignant neoplasms, especially squamous cell carcinoma, should be considered in the differential diagnosis of persistent single gingival ulcers.

Epidemiology and survival outcomes of lip, oral cavity, and oropharyngeal squamous cell carcinoma in a southeast Brazilian population.

BACKGROUND: Lip, oral cavity, and oropharyngeal squamous cell carcinoma (SCC) represent a major health problem in the global scenario. In South America, the highest incidence rates are seen in Brazil. Therefore, the epidemiological and clinical profile and survival outcomes of lip, oral cavity, and oropharyngeal SCC was studied in São Paulo State, Brazil. MATERIAL AND METHODS: The clinicopathological data of 12,099 patients with lip, oral cavity, and oropharyngeal SCC were obtained from hospital cancer registries of the Fundação Oncocentro de São Paulo, Brazil (2010-2015). Survival rates and other analyses were performed using SPSS software. RESULTS: A clear male predominance was observed, particularly for patients with oropharyngeal SCC (88.3%). The average age of patients was higher for lip cases (65 ± 13.5 years) compared to other sites. The schooling level was low for most patients, especially in lip cases (87.9%). Most of the patients with oral cavity (71.8%) and oropharyngeal (86.3%) SCC had advanced-stage (III-IV) disease. However, the majority of lip cases (83.3%) were at an early stage (I-II). Surgical excision was the main treatment for lip (72%) and oral cavity SCC (23.5%), and chemoradiotherapy was the main treatment for oropharyngeal SCC (40.2%). The 5-year overall survival (OS) for patients with lip, oral cavity, and oropharyngeal SCC were 66.3, 30.9, and 22.6%, respectively. Multivariate analysis revealed that the determinants of OS were different for lip, oral cavity, and oropharyngeal SCC, except for those at the clinical stage, which was an independent predictor for all sites. CONCLUSIONS: OS-independent determinants varied according to the affected site. Oral cavity and oropharyngeal SCC presented worse survival rates than those for lip SCC.

MutSα expression predicts a lower disease-free survival in malignant salivary gland tumors: an immunohistochemical study.

BACKGROUND: Appropriate DNA replication is vital to maintain cell integrity at the genomic level. Malfunction on DNA repair mechanisms can have implications related to tumor behavior. Our aim was to evaluate the expression of key complexes of the DNA mismatch-repair system MutSα (hMSH2-hMSH6) and MutSß (hMSH2-hMSH3) in a panel comprising the most common benign and malignant salivary gland tumors (SGT), and to determine their association with disease-free survival. MATERIAL AND METHODS: Ten cases of normal salivary gland (NSG) and 92 of SGT (54 benign and 38 malignant) were retrieved. Immunohistochemistry was performed for hMSH2, hMSH3, hMSH6. Scanned slides were digitally analyzed based on the percentage of positive cells with nuclear staining. Cases were further classified in MutSαhigh and MutSßhigh based on hMSH2-hMSH6 and hMSH3-hMSH6 expression, respectively. RESULTS: hMSH3 expression was lower in malignant SGT compared to NSG and benign cases. Adenoid cystic carcinoma (ACC) cases with perineural invasion presented a lower percentage of hMSH3 positive cells. hMSH6 was downregulated in both benign and malignant SGT compared to NSG. Malignant SGT cases with MutSαhigh expression had lower disease-free survival compared to MutSαlow cases. A 10.26-fold increased risk of presenting local recurrence was observed. CONCLUSIONS: Our findings suggest that a lack of hMSH3 protein function is associated with a more aggressive phenotype (malignancy and perineural invasion) and that MutSα overexpression predicts a poor clinical outcome in malignant SGT.

Salivary gland cancer in Southern Brazil: a prognostic study of 107 cases.

BACKGROUND: Salivary gland cancers (SGC) represent an uncommon group of heterogeneous tumors. We performed a retrospective survey of SGC diagnosed in a reference center for treatment of malignant tumors from the south of Brazil aiming to determine the prognostic value of demographic, clinic and pathologic features. MATERIAL AND METHODS: Cases diagnosed as SGC between 2006 and 2016 were retrospectively collected. Medical records were examined to extract demographic, clinic, pathologic and follow-up information. RESULTS: One-hundred and seven cases of SGC were identified. The most common SGC were mucoepidermoid carcinoma (MEC) (n = 39) followed by adenoid cystic carcinoma (AdCC) (n = 29). Among AdCCs, 55.2% of cases were classified as cribriform, 27.6% as tubular and 17.2% as solid. The tubular subtype had the highest percentage of cases with perineural invasion (p=0.01). Among MEC, 61.5% of cases were classified as low grade, 15.4% as intermediate grade and 19.9% as high grade. Low grade MEC had the lowest percentage of cases with perineural invasion (p=0.04). The 5-year survival for loco-regional control, disease-free survival (DFS) and disease-specific survival were 75%, 70% and 84%, respectively. The following features were associated with poor DFS: advanced age (p=0.03), rural residency (p=0.01), being a smoker or former smoker (p=0.01), pain (p=0.03), nodal metastasis (p<0.001), need for chemotherapy (p=0.02), neck dissection (p=0.04), perineural invasion (p=0.01), and being diagnosed with AdCC compared to MEC (p=0.02). CONCLUSIONS: The clinco-demographic and pathologic features identified as prognostic factors reveal the profile of patients at increased risk of recurrence and who would benefit from closer follow-up.

What is the frequency of floor of the mouth lesions? A descritive study of 4,016 cases.

BACKGROUND: The aim of this study was to investigate the frequency of oral lesions in the floor of the mouth from representative oral pathology centres in Latin America. MATERIAL AND METHODS: This study was conducted on biopsies obtained from January of 1978 to December of 2018 at nine Latin America oral and maxillofacial pathology centres. Gender, age and histopathological diagnosis were evaluated. Data were analysed using descriptive methods. Chi-square test was used for pairwise comparisons. RESULTS: From 114,893 samples, 4,016 lesions (3.49%) occurred in the floor of the mouth. Brazil showed 3,777 cases (94%), Mexico 182 cases (4.5%) and Argentina 57 cases (1.4%). Benign lesions represented 65.1% (2,617 cases), followed by 34.9% (1,404 cases) of malignant disorders. Lesions of epithelial origin were more frequent (1,964 cases; 48.9%), followed by salivary glands (1,245 cases; 31%) and soft tissue lesions (475 cases; 11.7%). The most common histological subtypes were oral squamous cell carcinoma (1,347 cases; 33.5%), ranula (724 cases; 18%), oral leukoplakia (476 cases; 11.8%) and inflammatory fibrous hyperplasia (239 cases; 5.9%). The lesion affected males in 2,129 cases and females in 1,897 cases. CONCLUSIONS: In the current study, lesions in the floor of the mouth represented 3.49% of biopsies submitted to oral pathology services and oral squamous cell carcinoma, ranula and leukoplakia were the most common lesions.

Oral pigmented lesions: a retrospective analysis from Brazil.

BACKGROUND: Pigmented lesions are uncommon in the oral mucosa, and studies investigating the incidence and types of these lesions are desired to improve the diagnostic knowledge of clinicians. The aim of this study was to analyze the distribution of oral pigmented lesions in a Brazilian population. MATERIAL AND METHODS: A retrospective descriptive cross-sectional study was performed. Oral pigmented lesions were retrieved from the files of two oral and maxillofacial pathology services from Brazil over a 45-year period (1974-2019). The clinical data and the diagnoses of each case were retrieved and included in a Microsoft Excel® database. RESULTS: From 77.074 lesions diagnosed in this period, 761 (0.99%) represented pigmented lesions of the oral mucosa, including 351 (46.1%) melanocytic and 410 (53.9%) non-melanocytic lesions, with a higher incidence in females (73.2%) between the fourth and seventh decades of life. Amalgam tattoo (53.6%) represented the most common lesion, followed by melanotic macule (18.3%) and racial pigmentation (10.8%). Other pigmented lesions included nevus (9.9%), post-inflammatory pigmentation (3%), melanoma (2.1%), melanoacanthoma (1.4%), smoker's melanosis (0.4%), drug-induced pigmentation (0.3%), and melanotic neuroectodermal tumor of infancy (0.1%). The buccal mucosa was the most commonly affected site (25.2%), followed by the alveolar ridge (14.5%), and gingiva (11.8%). CONCLUSIONS: The current findings were similar to previous studies with minor differences due methodology and characteristics of the services from where lesions were retrieved. The knowledge of these data may contribute to a better understanding of oral pigmented lesions and assist clinicians to better recognize and manage them.

CD1a+ and CD207+ cells are reduced in oral submucous fibrosis and oral squamous cell carcinoma.

BACKGROUND: The objective of this study investigated the distribution of immature dendritic cells (DCs), Langerhans cells and plasmacytoid DCs in oral submucous fibrosis (OSMF), OSMF associated with oral squamous cell carcinoma (OSMF-OSCC), oral leukoplakia (OL), and oral squamous cell carcinoma (OSCC). MATERIAL AND METHODS: Fourteen cases of OSMF, 9 of OSMF-OSCC, 8 of OL¸ 45 of OSCC and 8 of normal epithelium were retrospectively retrieved and their diagnoses confirmed. Immunoreactions against CD1a, CD207 e CD303 were performed and the number of positive cells quantified. RESULTS: A significant decrease of CD1a+ was found in OSMF (p≤0.05), OSMF-OSCC (p ≤ 0.01), and OSCC (p ≤ 0.001) when compared to normal epithelium. For CD207+ the significance decrease was observed in OSMF-OSCC (p ≤ 0.05), and OSCC (p ≤ 0.01) when compared with normal epithelium, and in OSMF when compared with OL (p ≤ 0.05). There was no significant difference for CD303, but increased in CD303+ was observed in OSCC when compared with normal epithelium. CONCLUSION: The decrease in the number of CD1a+ and CD207+ cells may be associate to the development of oral OSCC, and in OPMDs they might be indicators of malignant transformation.

Different methods of cell quantification can lead to different results: a comparison of digital methods using a pilot study of dendritic cells in HIV-positive patients.

BACKGROUND: Although new digital pathology tools have improved the positive cell quantification, there is a heterogeneity of the quantification methods in the literature. The aim of this study was to evaluate and propose a novel dendritic cells quantification method in squamous cell carcinoma comparing it with a conventional quantification method. MATERIAL AND METHODS: Twenty-six squamous cell carcinomas HIV-positive cases affecting the oropharynx, lips and oral cavity were selected. Immunohistochemistry for CD1a, CD83, and CD207 was performed. The immunohistochemical stains were evaluated by automated examination using a positive pixel count algorithm. A conventional quantification method (unspecific area method; UA) and a novel method (specific area method; SA) were performed obtaining the corresponding density of positive dendritic cells for the intratumoral and peritumoral regions. The Mann-Whitney U test was used to verify the influence of the quantification methods on the positive cell counting according to the evaluated regions. Data were subjected to the ANOVA and Student's t-test to verify the influence of the tumour location, stage, histological grade, and amount of inflammation on the dendritic cells density counting. RESULTS: The cell quantification method affected the dendritic cells counting independently of the evaluated region (P-value <0.05). Significant differences between methods were also observed according to the tumour features evaluations. CONCLUSIONS: The positive cell quantification method influences the dendritic cells density results. Unlike the conventional method (UA method), the novel SA method avoids non-target areas included in the hotspots improving the reliability and reproducibility of the density cell quantification.

The impact of head and neck radiotherapy on the dentine-enamel junction: a systematic review.

BACKGROUND: Radiotherapy is widely used in contemporary head and neck cancer treatment protocols. The ability of head and neck radiotherapy (HNRT) to cause direct radiogenic destruction to the teeth is one of the most controversial topics in the field of oral oncology. Therefore, this systematic review aimed to investigate ionising radiation as an independent factor for physical and chemical changes on the dentine-enamel junction (DEJ), a pivotal dental topography for the onset and progression of radiation-related caries (RRC) and enamel delamination. MATERIAL AND METHODS: Systematic searches were conducted on three databases: Scopus, MEDLINE (Via PubMed) and Embase (Elsevier). Laboratory studies evaluating the effects of simulated or in vivo HNRT on the DEJ were included. The GRADE tool adapted for in vitro studies was used to assess the methodological quality. RESULTS: Of the 154 initially selected studies, eight met the inclusion criteria, from which five studies were graded as high quality of evidence, two studies were graded as moderate quality and one as low quality. Two studies did not demonstrate DEJ alterations following HNRT while the other six articles described several organic and inorganic changes in the DEJ of irradiated teeth samples. These radiogenic events were mostly detected through micro and nanoindentation, Raman micro-spectroscopy, confocal microscopy, Western blotting and optical coherence tomography. CONCLUSIONS: HNRT may have a negative impact on the physical and chemical aspects of the DEJ, predisposing cancer patients to RRC and enamel delamination.

Radiographic estimation of the growth rate of initially underdiagnosed ameloblastomas.

BACKGROUND: To evaluate the specific growth rate (SGR) of ameloblastoma. MATERIAL AND METHODS: cases of ameloblastoma initially underdiagnosed (e.g. cases overlooked or diagnosed as reactive lesions) which had adequate radiographic documentation to evaluate their progression were retrospectively selected. Two panoramic radiographs were analyzed to determine the specific growth rate (SGR) of each tumor, defined as the logarithm of the ratio of final tumor area (when the diagnosis of ameloblastoma was made) to the initial tumor area (when the lesion was underdiagnosed), divided by the time interval between the radiographic images. The tumor area was measured using the software ImageJ. RESULTS: Twelve patients with mandibular ameloblastomas were selected, including 5 males and 7 females, with a mean age of 24.9 years (range: 14-61 years). In four cases, the lesion was associated with the crown of an impacted third molar. In three cases, it was initially diagnosed as a periapical lesion. Three cases were extrafollicular and were not noticed in the initial radiographs. Two cases were initially diagnosed as ameloblastoma, but the surgery was delayed for personal reasons. The mean interval of time between the two radiographic images was 4.3 years (range: 0.4-9 years). Based on our analysis, ameloblastoma grows in average 40.4% per year (range: 14.9-88.7%). CONCLUSIONS: Ameloblastoma is a progressively growing tumor, but its growth rate seems to be smaller than initially reported in the literature. Better understanding the radiographic progression of ameloblastoma might improve its early diagnosis, management, and prognosis.

The depth of follicular extension in actinic keratosis correlates with the depth of invasion in squamous cell carcinoma: implication for clinical treatment.

BACKGROUND: Actinic keratosis (AK) may show extension down follicles, not only in cases with full-thickness epidermal atypia ('bowenoid' AK), but also in cases with atypia limited to the epidermal basalis. Previous studies have demonstrated that, in bowenoid AK, follicular extension is usually superficial, being limited to the upper follicular segment. Little is known about the depth of follicular involvement in cases of invasive squamous cell carcinoma of the skin (iSCC) arising from AK and the role of the follicle in iSCC pathogenesis. OBJECTIVE: This study investigated the relationship between follicular extension of atypical keratinocytes in an AK and the development of iSCC from the follicular wall. The depth of follicular extension was correlated with the depth invasion of iSCC. Differences between the differentiated and classical pathways of iSCC were also examined. METHODS: We performed a retrospective histologic review of 193 biopsy specimens of iSCC with an associated AK. We assessed the presence and depth of follicular extension of atypical keratinocytes in the AK, using tumour (Breslow) thickness and the follicular unit level (infundibular, isthmic and subisthmic), as well as iSCC being present directly adjacent to the follicular basalis. RESULTS: Follicular extension was present in 25.9% of the cases (50 cases), usually extending into the lower follicular segment. The iSCC was present directly adjacent to the follicular basalis in 58% of the cases (29 cases), correlating highly with the depth of follicular extension (infundibular: 3/12; isthmic: 21/33; subisthmic 5/5). CONCLUSION: The depth of follicular extension of atypical keratinocytes in an AK correlates with the development of depth of invasion of an associated iSCC, irrespective of the pathway of origin. It is therefore important to note the presence and the depth of follicular extension when diagnosing an AK, as follicular extension likely accounts for a significant proportion of recurrent AK and the development of iSCC following superficial treatment modalities.

Benign oral vascular lesions treated by sclerotherapy with ethanolamine oleate: A retrospective study of 43 patients.

BACKGROUND: Although sclerotherapy is a common treatment for benign oral vascular lesions, there is no well-standardized protocol for this purpose. The aim of the present study was to describe the clinical characteristics of patients treated by sclerotherapy with ethanolamine oleate (EO), in order to contribute to a better understanding of this technique. MATERIAL AND METHODS: Medical records and images of 90 patients treated by the same sclerotherapy protocol were retrieved and analysed. Thus, 43 cases with complete information were selected and described. RESULTS: The most affected age group was 41-70 years, with a female predominance and 86% of patients being Caucasian. Lips were the most affect site (70%) followed by the tongue (16%). Regarding clinical appearance, approximately 90% of lesions were classified as nodules, and 90% of patients reported no pain. Approximately 40% of lesions were 0.5-1.0 cm in size. In 58% of the patients, only one application of ethanolamine oleate was necessary. The application doses varied according to the lesion size and number of applications. Complete clinical regression occurred in 91% of cases, whereas 9% showed partial regression. CONCLUSIONS: Sclerotherapy with EO is an acceptable, effective and affordable treatment for benign oral vascular lesions.

Phylogenetic and paleobotanical evidence for late Miocene diversification of the Tertiary subtropical lineage of ivies (Hedera L., Araliaceae).

BACKGROUND: Hedera (ivies) is one of the few temperate genera of the primarily tropical Asian Palmate group of the Araliaceae, which extends its range out of Asia to Europe and the Mediterranean basin. Phylogenetic and phylogeographic results suggested Asia as the center of origin and the western Mediterranean region as one of the secondary centers of diversification. The bird-dispersed fleshy fruits of ivies suggest frequent dispersal over long distances (e.g. Macaronesian archipelagos), although reducing the impact of geographic barriers to gene flow in mainland species. Genetic isolation associated with geographic barriers and independent polyploidization events have been postulated as the main driving forces of diversification. In this study we aim to evaluate past and present diversification patterns in Hedera within a geographic and temporal framework to clarify the biogeographic history of the genus. RESULTS: Phylogenetic (biogeographic, time divergence and diversification) and phylogeographic (coalescence) analyses using four DNA regions (nrITS, trnH-psbA, trnT-trnL, rpl32) revealed a complex spatial pattern of lineage divergence. Scarce geographic limitation to gene flow and limited diversification are observed during the early-mid Miocene, followed by a diversification rate increase related to geographic divergence from the Tortonian/Messinian. Genetic and palaeobotanical evidence points the origin of the Hedera clade in Asia, followed by a gradual E-W Asian extinction and the progressive E-W Mediterranean colonization. The temporal framework for the E Asia - W Mediterranean westward colonization herein reported is congruent with the fossil record. Subsequent range expansion in Europe and back colonization to Asia is also inferred. Uneven diversification among geographic areas occurred from the Tortonian/Messinian onwards with limited diversification in the newly colonized European and Asian regions. Eastern and western Mediterranean regions acted as refugia for Miocene and post-Miocene lineages, with a similar role as consecutive centers of centrifugal dispersal (including islands) and speciation. CONCLUSIONS: The Miocene Asian extinction and European survival of Hedera question the general pattern of Tertiary regional extinction of temperate angiosperms in Europe while they survived in Asia. The Tortonian/Messinian diversification increase of ivies in the Mediterranean challenges the idea that this aridity period was responsible for the extinction of the Mediterranean subtropical Tertiary flora. Differential responses of Hedera to geographic barriers throughout its evolutionary history, linked to spatial isolation related to historical geologic and climatic constraints may have shaped diversification of ivies in concert with recurrent polyploidy.