Oral and maxillofacial tuberculosis: A systematic review.

OBJECTIVES: This study aimed to analyze the demographic, clinical, histopathological, diagnosis, treatment, and follow-up data on the occurrence of oral and maxillofacial tuberculosis (OMTB). METHODS: Electronic searches without publication date restrictions were undertaken in four databases. Case reports and case series describing the occurrence of OMTB were included. Critical evaluation of studies was done using the Joanna Briggs Institute - University of Adelaide tool for case reports or case series. RESULTS: A total of 217 studies were included in the qualitative synthesis, for a total of 301 cases of OMTB. Of these patients, 192 (63.7%) were male, with an average age of 39.6 ± 19.8 (15 months to 81 years). The tongue (n = 80/26.6%) represented the most common affected site, followed by the mandible (n = 43/14.3%). The clinical presentation consisted mainly of a painful ulcerated lesion (n = 156/56.5%). Histopathological analysis showed a granulomatous inflammation in most cases (n = 156/63.1%). The main diagnostic methods used were sputum test (n = 53/26.8%), culture (n = 49/24.7%) and purified protein derivative (PPD), or Mantoux test (n = 49/24.7%). Antituberculosis therapy was used in 244 cases (100.0%) and 5.2% of patients died. CONCLUSIONS: This systematic review provided clinical, demographic data and information about diagnostic methods of OMTB lesions and served as an important guide to assist health professionals in the early diagnosis of these lesions.

Synchronous odontogenic tumors: A systematic review.

This systematic review aimed to incorporate published information about synchronous odontogenic tumors (SOTs) with an analysis of the demographic and clinical characteristics from the cases published in the literature. Case reports and case series of SOT were searched in PubMed, Web of Science, Scopus, and EMBASE. A descriptive statistical analysis was performed. Twenty-eight studies comprising 30 cases of SOTs were included. Considering all cases published, SOTs mostly occurred simultaneously in the maxilla and mandible (n = 19/63.3%). Lesions were bifocal in 13 (43.3% of all the 30 cases) and multifocal in 17 cases (56.7% of all the 30 cases). All SOTs available in the literature presented the same type of lesion, and two of them also involved another different SOT (n = 2/6.7% of all the 30 cases). Out of all published cases, the most frequent SOTs in the literature were odontomas (n = 10/33.3% of all the 30 cases), squamous odontogenic tumors (OTs) (n = 8/26.7% of all the 30 cases), calcifying epithelial OTs (n = 8/26.7% of all the 30 cases), and adenomatoid OTs (n = 2/6.7% of all the 30 cases). Considering all SOTs cases included, the overall recurrence was 13.3%. Inside a subgroup of the lesion, synchronous calcifying epithelial OT presented the highest (25%). Five cases (16.7% of all the 30 cases) had a previously associated syndrome, with two cases of Schimmelpenning syndrome being reported. Among published SOTs, odontomas were the most common. All SOTs available in the scientific literature showed the same type of OT and mainly affected both jaws simultaneously. Only a few of these cases were associated with a syndrome.

Association between perceived self-confidence and abilities to distinguish oral mucosal lesions amongst dental students.

INTRODUCTION: Dentists usually refer to difficulties in performing the diagnosis of oral mucosal lesions. This may be attributed to limited access to theoretical lectures and practical training on this subject along the graduation course. The primary aim of this cross-sectional study was to verify if there is an association between the perception of time dedicated to lectures/training and oral diagnosis abilities in oral medicine. The secondary aim was to evaluate the association between self--confidence to perform oral mucosal lesions diagnosis and performance in a diagnostic abilities test. MATERIALS AND METHODS: The sample comprised 36 final-year dental students of a South-Brazilian dental school. The participants answered a questionnaire on their perception of time dedicated to lectures on oral medicine along the course (sufficient or insufficient) and their self-confidence to diagnose oral mucosal lesions or oral cancer (yes or not). The students were also submitted to a diagnostic abilities test based on 30 clinical photos of oral lesions, which should be classified as benign, potentially malignant or malignant. Moreover, the participants had to inform their clinical impression for each case. Finally, the participants informed their decision making for the case (refer the patient to a specialist or not). RESULTS: Students with higher self-confidence showed a higher percentage of correct answers on classification of the nature of lesions (81.1% vs. 68.5%, p = .03, teste t de Student) and on their clinical impression (66.3% vs. 41.7%, p < .01, Student's t-test). The perception of time dedicated to theoretical lectures on oral medicine as sufficient did not influence the students' diagnostic abilities (p > .05, Student's t-test) CONCLUSION: It may be concluded that self-confidence to diagnose oral lesions is associated with dental students' diagnostic abilities.

Malignant peripheral nerve sheath tumour of the oral and maxillofacial region-A systematic review.

To integrate the available data published on malignant peripheral nerve sheath tumours (MPNST) of the oral and maxillofacial region. Searches in Embase, PubMed, Web of Science and Scopus were conducted for the identification of case reports/case series in English language. The risk of bias was assessed using the Joanna Briggs Institute tool. Outcomes were evaluated by Cox regression and Kaplan-Meier methods. A total of 306 articles were retrieved, 50 of which reporting 57 MPNST were included. The lesion showed a predilection for the mandible (n = 18/31.57%) of middle-aged adults (~40.5 years) with a male/female ratio of 1.1:1. The individuals were mostly symptomatic with a mean evolution time of 9.6 months. Surgical removal plus adjuvant therapy (especially radiotherapy) was the main approach (51.86%). Recurrence was reported in 39.62% of cases. Nodal and distant metastases were identified in 28.26% and 26.66% of cases, respectively. The 2-year cumulative survival rate was 55%. Independent predictors of poor survival were the presence of neurofibromatosis type 1 (p = 0.04) and distant metastases (p = 0.004). The diagnosis of MPNST is challenging due to the variety of its clinical and histopathological presentations. Local aggressiveness and the potential for metastases are common outcomes of this neoplasm.

Potentially carcinogenic effects of hydrogen peroxide for tooth bleaching on the oral mucosa: A systematic review and meta-analysis.

STATEMENT OF PROBLEM: Little is known about the extent to which hydrogen peroxide as used for tooth bleaching could be carcinogenic to the oral mucosa. PURPOSE: The purpose of this systematic review and meta-analysis was to evaluate whether hydrogen peroxide as used for tooth bleaching has carcinogenic effects on the oral mucosa. MATERIAL AND METHODS: PubMed, Web of Science, Scopus, and Embase electronic databases were searched. Studies evaluating different outcomes potentially related to the carcinogenic effects of hydrogen peroxide for tooth bleaching on the oral mucosa were included. Risk of bias was assessed by the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE), Risk Of Bias in Non-randomized Studies of Interventions (ROBINS-I), or Risk of Bias 2 (RoB 2) tools. The strength of the evidence was assessed by using the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) protocol. The quantitative analysis was performed with means, standard deviations, and 95% confidence intervals (CIs). Heterogeneity was analyzed by using I-squared statistics. RESULTS: Thirteen articles comprising 5 animal and 8 clinical studies met the inclusion criteria. Three of the 5 animal studies associated the bleaching agents with a carcinogen and demonstrated an enhancement of the carcinogenic effect, but probably with the bleaching agent acting only as a promoter. Five clinical studies concluded that the bleaching agents did not cause mutagenic stress on the oral mucosa by using the micronucleus test. The meta-analysis demonstrated that the frequency of micronuclei did not differ significantly between baseline and 30 days after bleaching (mean difference: 0.48; 95% CI, -1.49, 2.46; P=.63). CONCLUSIONS: This systematic review indicated that hydrogen peroxide does not appear to have carcinogenic effects on the oral mucosa.

Pigmented lesion with characteristics of malignancy: a case report.

Pigmentations of the oral mucosa include a range of lesions or conditions that manifest as changes in the color of oral tissues; these changes may show melanocytic activity. A melanotic macule is a small, well-circumscribed melanocytic benign lesion. It can occur on the lips and intraorally and ranges in color from brown to black. Microscopically, it is characterized by elevated levels of melanin production by basal melanocytes, which appear normal in terms of number, morphology, and distribution. A 48-year-old woman sought treatment for a pigmented lesion that had been present for 4 months. Intraoral examination revealed a non-homogenous brownish spot (measuring 0.7 cm) with irregular borders on the left side of the soft palate. Since the lesion had an atypical clinical appearance, melanocytic nevus, oral melanoacanthoma, and oral malignant melanoma were considered in differential diagnoses. After an incisional biopsy, the lesion was diagnosed as a melanotic macule. Due to their varying clinical appearance, benign pigmented lesions can be mistaken for malignant tumors, especially when the lesions exhibit similar coloration, symmetry, and borders. Through this report on a case with atypical clinical characteristics, we aim to reinforce the ubiquitous nature of oral pigmented lesions, and the importance of employing different approaches to diagnosing these lesions.

Virtual learning object about oral ulcerative lesions: controlled educational intervention study.

The aim of this study was to develop a virtual learning object (VLO) to teach undergraduate dental students about the diagnostic and therapeutic approaches to oral ulcerative lesions. The VLO was developed with information on the diagnostic process, lesion classification, and clinical-surgical management of oral ulcerative lesions. The VLO content was initially validated by a group of specialists. Learning was evaluated in a sample of 58 undergraduate dental students, divided into control group (conventional theoretical class, n = 29) and intervention group (interaction with VLO, n = 29). All students answered a pre-test and post-test questionnaire. The VLO group also answered a specific questionnaire on the evaluation of the VLO. Both quantitative and qualitative descriptive analyses were performed. The validation showed that professors and students considered the VLO adequate. The use of the VLO was recommended by 100% of professors and 86.6% of students. In the intervention group, the results showed a significantly higher number of correct answers in the post-test (p < 0.01). In conclusion, the VLO proved to be a useful tool for teaching oral medicine, contributing significantly to the knowledge of ulcerated lesions in the mouth.

Risk factors for jaw osteoradionecrosis: a case control study.

There are divergences among studies regarding features associated to increased risk of osteoradionecrosis (ORN). Our objective was to identify factors that predispose to the development of ORN of the jaw. This was a retrospective, hospital-based, case-control study involving patients with head and neck cancer who had been treated with ≥ 60 Gy external radiotherapy (RT) to the jaw. A total of 19 cases of ORN and 43 controls were included. The patients' demographic data, tumor type, staging, treatment and outcome information, and pre-treatment oral status were collected. Univariate analysis showed that the oral cavity/oropharynx sites were associated with 9.77-fold increased risk of ORN development compared to other sites (p = 0.005). Being an active smoker was associated with 3.95-fold increased risk of ORN development (p = 0.01). A tendency towards increased risk of ORN was observed particularly when tooth extraction occurred after RT (odds ratio (OR): 3.04; p = 0.08). Multivariable analysis showed that tumor site was the only significant risk factor (OR: 21.03, p = 0.01). The oral and oropharyngeal primary site is an important risk factor for ORN. Dental extraction, which did not occur in 28% of the sample, was not an essential event for ORN development.

Distance learning course improves primary care dentists' diagnosis and self-efficacy in the management of oral lesions.

Oral cancer represents a public health issue because of its high mortality rate, resulting mainly from diagnostic delays. Insufficient training in oral diagnosis is usually perceived by dentists. Distance learning could be used as an auxiliary tool to bridge that gap. This study evaluated the impact of a distance learning course on oral mucosal lesion diagnosis offered to public healthcare dentists. Participants of an online course answered a pretest/posttest comprising clinical images of 30 clinical cases. Participants were questioned about the diagnosis and informed their decision on the cases (referring the cases to a specialist or managing them themselves), as a parameter of perceived self-efficacy. A total of 442 dentists enrolled in the course. Their pass rate was 97%. Classification of the nature of the lesions, diagnostic hypotheses, sensitivity, and specificity improved by 13.4%, 10.0%, 13.4%, and 6.6%, respectively (p<0.01, Wilcoxon test). Regarding management, there was a 16.6% reduction in the intention to refer cases, while confidence in the diagnosis of benign lesions increased by 40%. A distance learning course may be useful in continuing education actions for primary care dentists, improving their diagnostic abilities and encouraging them in the management of oral lesions. Moreover, this strategy could contribute to disseminating knowledge to remote regions, particularly among primary health care professionals.

Oral and Maxillofacial Neuroendocrine Carcinoma: A Systematic Review.

The aim of the present study was to integrate the available data published in the literature on oral and maxillofacial neuroendocrine carcinomas concerning the demographic, clinical and histopathological features of this condition. An electronic search with no publication date restriction was undertaken in April 2021 in four databases. Eligibility criteria included reports published in English having enough data to confirm a definite diagnosis, always showing a neuroendocrine marker. Cases originating in the oropharynx, including base of the tongue and tonsils, were excluded. Outcomes were evaluated by the Kaplan-Meier method along with Cox regression. Twenty-five articles (29 cases) from nine different countries were detected. Mean patient age was 56.3 (± 17.5) years, with a slight male predilection. Symptomatology was present in 72.2% of informed cases. Regarding clinical presentation, a non-ulcerated nodule located in the gingiva with a mean size of 3.4 (± 2.0) cm was most frequently reported. Concomitant metastasis was identified in seven individuals. Histopathologically, most neoplasms were of the small cell type, and immunohistochemistry for both epithelial and neuroendocrine differentiation was used in 65.5% cases. Radical surgery was the treatment of choice in almost all cases, with or without adjuvant therapy. Mean follow-up was 20.5 (± 21.2) months, and only four patients developed recurrences. Eleven (44.0%) individuals died due to the disease. Ulcerated lesions were a prognostic factor. This study provides knowledge that can assist surgeons, oncologists, and oral and maxillofacial pathologists with the diagnosis and management of neuroendocrine carcinomas. Our findings demonstrated that the long-term prognosis of this lesion continues to be poor.

Expression of DNMTs and H3K9ac in Ameloblastoma and Ameloblastic Carcinoma.

Objectives: DNA methyltransferases (DNMTs) and the histone modification H3K9ac are epigenetic markers. This study aimed to describe the immunohistochemical expression of DNMT1, DNMT3A, DNMT3B, and H3K9ac in the dental follicle (DF), ameloblastoma (AME), and ameloblastic carcinoma (AC), correlating these expressions with the recurrence and aggressive behavior in ameloblastoma. Study Design: Immunohistochemical reactions were performed in 10 human DFs, 38 ameloblastomas, and 6 AC samples. Another 59 ameloblastomas assembled in a tissue microarray were used to compare the immunoexpression with the clinical, radiographic, and histopathological characteristics and the presence of BRAFv600e mutation. Each slide was digitized as a high-resolution image and quantified by Aperio ScanScope Nuclear V9 software. All statistical analyzes were performed using GraphPad Prism statistical software. Results: DNMT3B expression was higher in ameloblastomas than in the DFs, while the AC overexpressed all proteins. The ameloblastomas with BRAFv600e mutation, vestibular/lingual, or vestibular/palatine bone cortical disruption and maxilla involvement showed DNMT1 overexpression, while recurrent cases had high DNMT3B levels. Conclusions: DNA methylation and histone modification might play a role in the development, clinical aggressiveness, and recurrence rates of ameloblastoma, such as the progression to AC. Further investigation about gene methylations in ameloblastomas is needed to better understand its relationship with aggressiveness and recurrence.

Central odontogenic fibroma: an international multicentric study of 62 cases.

OBJECTIVE: The aim of this study was to report the clinicopathologic features of 62 cases of central odontogenic fibroma (COdF). STUDY DESIGN: Clinical and radiographic data were collected from the records of 13 oral pathology laboratories. All cases were microscopically reviewed, considering the current World Health Organization classification of tumors and were classified according to histopathologic features. RESULTS: There were 43 females and 19 males (average age 33.9 years; range 8-63 years). Clinically, COdF lesions appeared as asymptomatic swellings, occurring similarly in the maxilla (n = 33) and the mandible (n = 29); 9 cases exhibited palatal depression. Imaging revealed well-defined, interradicular unilocular (n = 27), and multilocular (n = 12) radiolucencies, with displacement of contiguous teeth (55%) and root resorption (46.4%). Microscopically, classic features of epithelial-rich (n = 33), amyloid (n = 10), associated giant cell lesion (n = 7), ossifying (n = 6), epithelial-poor (n = 3), and granular cell (n = 3) variants were seen. Langerhans cells were highlighted by CD1a staining in 17 cases. Most patients underwent conservative surgical treatments, with 1 patient experiencing recurrence. CONCLUSIONS: To the best of our knowledge, this study represents the largest clinicopathologic study of COdF. Most cases appeared as locally aggressive lesions located in tooth-bearing areas in middle-aged women. Inactive-appearing odontogenic epithelium is usually observed within a fibrous/fibromyxoid stroma, occasionally exhibiting amyloid deposits, multinucleated giant cells, or granular cells.

Virtual learning object about oral ulcerative lesions: controlled educational intervention study

Abstract The aim of this study was to develop a virtual learning object (VLO) to teach undergraduate dental students about the diagnostic and therapeutic approaches to oral ulcerative lesions. The VLO was developed with information on the diagnostic process, lesion classification, and clinical-surgical management of oral ulcerative lesions. The VLO content was initially validated by a group of specialists. Learning was evaluated in a sample of 58 undergraduate dental students, divided into control group (conventional theoretical class, n = 29) and intervention group (interaction with VLO, n = 29). All students answered a pre-test and post-test questionnaire. The VLO group also answered a specific questionnaire on the evaluation of the VLO. Both quantitative and qualitative descriptive analyses were performed. The validation showed that professors and students considered the VLO adequate. The use of the VLO was recommended by 100% of professors and 86.6% of students. In the intervention group, the results showed a significantly higher number of correct answers in the post-test (p < 0.01). In conclusion, the VLO proved to be a useful tool for teaching oral medicine, contributing significantly to the knowledge of ulcerated lesions in the mouth.

Acinic cell carcinoma of the oral and maxillofacial region: an international multicenter study

Abstract The aim of this study was to describe the prevalence, clinicopathological, and prognostic features of acinic cell carcinoma (AciCC) of the oral and maxillofacial region. AciCC cases were retrospectively retrieved from 11 pathology centers of three different countries. Medical records were examined to extract demographic, clinical, pathologic, and follow-up information. A total of 75 cases were included. Females (65.33%) with a mean age of 45.51 years were mostly affected. The lesions usually presented as an asymptomatic (64.28%) nodule (95.66%) in the parotid gland (70.68%). The association of two histopathological patterns was the most common finding (48.93%) and the tumors presented mainly conventional histopathological grades (86.11%). Surgical treatment was performed in the majority of the cases (59.19%). Local recurrence was observed in 20% of the informed cases, regional metastasis in 30.43%, and distant metastasis in 12.50%. The statistical analysis showed that the cases with a solid histopathological pattern (p=0.01), high-grade transformation (p=0.008), recurrence (p=0.007), and regional metastasis (p=0.03) were associated with poor survival. In conclusion, high histopathological transformation, presence of nodal metastasis, and recurrence were prognostic factors for AciCC of the oral and maxillofacial region.

Titanium Activates the DNA Damage Response Pathway in Oral Epithelial Cells: A Pilot Study.

PURPOSE: To evaluate the effect of titanium (Ti) particles on oral epithelial cell homeostasis and the potential of dental implants to release Ti debris upon insertion. MATERIALS AND METHODS: Dental implants with varying surface treatments were employed to determine the feasibility of particle release during implant placement as well as the impact of free Ti debris on oral epithelial cells. Ti particles derived from implant surfaces were isolated and cultured in direct contact with normal oral epithelial cells for 48 hours. Further, cells were fixed and processed for immunofluorescence assay to detect the activation of the DNA damage response (DDR) using CHK2 and BRCA1 molecular markers. Positive cells demonstrating DNA damage were quantified and statistically analyzed. RESULTS: Ti particles derived from implants containing phosphate-enriched titanium oxide (PETO), fluoride-modified (FM), and grit-blasted (GB) surface treatments were able to activate CHK2 and trigger the recruitment of BRCA1 in oral epithelial cells. Also, implants with GB surfaces were able to release Ti particles upon implant placement. CONCLUSION: The results indicate that Ti debris may be detached from the implant surface upon placement. Also, free Ti particles can trigger DDR signaling in oral epithelial cells. These findings suggest that Ti particles/debris released into a surgical wound may contribute to the disruption of epithelial homeostasis, and potentially compromise the oral epithelial barrier.

Risk factors for jaw osteoradionecrosis: a case control study

Abstract There are divergences among studies regarding features associated to increased risk of osteoradionecrosis (ORN). Our objective was to identify factors that predispose to the development of ORN of the jaw. This was a retrospective, hospital-based, case-control study involving patients with head and neck cancer who had been treated with ≥ 60 Gy external radiotherapy (RT) to the jaw. A total of 19 cases of ORN and 43 controls were included. The patients' demographic data, tumor type, staging, treatment and outcome information, and pre-treatment oral status were collected. Univariate analysis showed that the oral cavity/oropharynx sites were associated with 9.77-fold increased risk of ORN development compared to other sites (p = 0.005). Being an active smoker was associated with 3.95-fold increased risk of ORN development (p = 0.01). A tendency towards increased risk of ORN was observed particularly when tooth extraction occurred after RT (odds ratio (OR): 3.04; p = 0.08). Multivariable analysis showed that tumor site was the only significant risk factor (OR: 21.03, p = 0.01). The oral and oropharyngeal primary site is an important risk factor for ORN. Dental extraction, which did not occur in 28% of the sample, was not an essential event for ORN development.

Distance learning course improves primary care dentists' diagnosis and self-efficacy in the management of oral lesions

Abstract Oral cancer represents a public health issue because of its high mortality rate, resulting mainly from diagnostic delays. Insufficient training in oral diagnosis is usually perceived by dentists. Distance learning could be used as an auxiliary tool to bridge that gap. This study evaluated the impact of a distance learning course on oral mucosal lesion diagnosis offered to public healthcare dentists. Participants of an online course answered a pretest/posttest comprising clinical images of 30 clinical cases. Participants were questioned about the diagnosis and informed their decision on the cases (referring the cases to a specialist or managing them themselves), as a parameter of perceived self-efficacy. A total of 442 dentists enrolled in the course. Their pass rate was 97%. Classification of the nature of the lesions, diagnostic hypotheses, sensitivity, and specificity improved by 13.4%, 10.0%, 13.4%, and 6.6%, respectively (p<0.01, Wilcoxon test). Regarding management, there was a 16.6% reduction in the intention to refer cases, while confidence in the diagnosis of benign lesions increased by 40%. A distance learning course may be useful in continuing education actions for primary care dentists, improving their diagnostic abilities and encouraging them in the management of oral lesions. Moreover, this strategy could contribute to disseminating knowledge to remote regions, particularly among primary health care professionals.

Prognostic significance of hMSH2, hMSH3, and hMSH6 expression in ameloblastoma.

OBJECTIVE: The aim of this study was to investigate hMutS proteins in developing human tooth, ameloblastomas, and ameloblastic carcinoma and to determine whether the expression of these proteins has any prognostic potential. STUDY DESIGN: Ten cases of developing human tooth, 39 ameloblastomas, and 2 ameloblastic carcinomas were used to determine the distribution of the proteins during the process of carcinogenesis. Simultaneously, another sample of 73 ameloblastomas was arranged in tissue microarray, and their clinical, microscopic, and radiographic features; treatment outcome; presence of BRAF-V600E mutation; and follow-up data were assessed to determine the prognostic relevance of the expression of hMutS (hMSH2, hMSH3, hMSH6) and Ki-67. hMSH2 and hMSH6 were significantly downexpressed in ameloblastomas (P = .0059) compared with developing human tooth (P < .0001). RESULTS: hMSH2, hMSH3 expression were significantly associated with BRAF-V600E mutation (P < .05). Simultaneous overexpression of hMutS was associated with recurrence (P = .035); however, these did not predict the disease-free survival of patients (P > .05). CONCLUSIONS: hMutS proteins are downregulated in ameloblastoma; moreover, simultaneous overexpression of these proteins in ameloblastoma was associated with recurrence but did not predict disease-free survival.

Impact of highly active antiretroviral therapy in the development and remission of oral plasmablastic lymphoma.

Plasmablastic lymphoma (PBL) represents a rare type of non-Hodgkin lymphoma associated with human immunodeficiency virus (HIV) infection. The impact of highly active antiretroviral therapy (HAART) in this tumor is poorly known due to its small incidence. This study reports a case of a 33-year-old HIV-positive woman who was referred to the Stomatology Department complaining about a painful gingival growth and cervical nodule both with 20 days of evolution. The lesions appeared 7 months after the patient stopped HAART. The final diagnosis was PBL. After resuming HAART for 45 days, the gingival lesion presented complete remission. The patient continued with HAART alongside chemotherapy. At 24 months follow-up, the patient was stable. The dental surgeon plays an essential role in orientation and retention in care of HIV patients once the adherence of HAART seems to play an important role in PBL development and response to treatment.